Your Doc Is In

Oral HPV Infection: Higher in Men, Transmitted by Sex

2012-01-27T20:43:00.001-08:00

From Medscape Medical News > Oncology

January 27, 2012 — A major study of oral infection with human papillomavirus (HPV) — now known to cause of a subset of oropharyngeal cancer — has found a much higher incidence in men than in women and has established sexual transmission as the main way it spreads. It also raises questions about whether existing HPV vaccines offer protection.Zosia Chustecka

There is a rising incidence in oral HPV infection and in HPV-positive oropharyngeal cancer in the United States. "The curves are a little bit frightening," said lead author Maura Gillison, MD, PhD, from Ohio State University in Columbus. But she pointed out that vaccines against HPV are already marketed, so "we have the means to prevent this already sitting on our pharmacy shelves."

The HPV vaccines (Gardasil and Cervarix) were developed to offer protection against cervical cancer after the link between cervical HPV infection and cervical cancer was firmly established, and are targeted mainly to girls.

The link between oral HPV infection and oral HPV cancer was established more recently; Dr. Gillison reported that the research is about 20 years behind that for cervical cancer. There is speculation — although no hard data — that the same vaccines could offer protection against HPV-associated oral cancer. Because this is more prevalent in men, it would make sense to vaccinate boys as well as girls.

"We need to have thorough and accurate discussions about HPV vaccination," Dr. Gillison said. "We have identified a new cancer...and we have identified its Achilles heel," she added.

Dr. Gillison spoke at a presscast at the 2012 Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Therapeutic and Radiation Oncology and held in Phoenix, Arizona. The study waspublished online January 26 in JAMA: The Journal of the American Medical Association to coincide with its presentation.

Sexual Transmission

This the first major prevalence study of oral HPV infection in the United States, according to an accompanying editorial, subtitled "Hazard of Intimacy."

Editorialist Hans Schlecht, MD, MMSc, from Drexel University College of Medicine in Philadelphia, Pennsylvania, writes that the "results are remarkable for a number of reasons," including the fact that they allow estimation of oral HPV prevalence based on sexual experience, smoking status, and immune suppression.

One of the main findings from this study is that the main method of transmission is sexual, and that the prevalence of oral HPV infection increases with the number of sexual partners reported.

Another finding is "a striking bimodal pattern with age" in men, with peaks in men 30 to 34 and 60 to 64 years of age.

During the presscast, Dr. Gillison speculated that these peaks in oral HPV infection might be partially explained by a "birth cohort" effect. The peak in older men could be related to the fact that they would have been making their sexual debut during the sexual revolution of the 1960s; the dip in middle-aged men could be the result of the dampening impact that the HIV epidemic had on sexual behavior. The peak in younger men could be related to one result of that epidemic — the perception that oral sex is "safe sex."

The new data showing a rising incidence of HPV oropharyngeal cancer raise questions about exactly how safe oral sex is.

In his editorial, Dr. Schlecht suggests that "clinicians should encourage their patients who engage in oral sex to use barrier protection."

First Major Prevalence Study

This study used 2009/10 data from the National Health and Nutrition Examination Survey (NHANES), and analyzed tissue collected from an oral rinse and gargle collected from 5579 people 14 to 69 years of age.

The overall prevalence of HPV oral infection was 6.9%; the particular strain associated with oropharyngeal cancer, HPV16, was found in 1%. "Although this 1% may sound small, this means that around 2.1 million individuals in the United States are infected," Dr. Gillison explained.

However, the incidence in men is significantly higher than it is in women (10.0% vs 3.6%; P < .001).

In addition, the bimodal distribution, with peaks in younger and older individuals, was seen only in men. Why the incidence of oral HPV infection in men is so much higher is not clear, Dr. Gillison said.

Men did report having more sexual partners than women, but this difference in sexual behavior explains only about 16% of the difference in prevalence, the authors note. Another explanation could be higher rate of transmission to men performing oral sex on woman than to women performing oral sex on men; there is some evidence for this in the data. But there are also many other factors, including the fact that women who have already been exposed to cervical HPV infection have greater protection against subsequent oral HPV infection.

The bimodal distribution of oral HPV infection in men is different than that of cervical HPV infection, which peaks in women in their 20s and then generally drops off, although a later peak in older women is seen in some populations.

"It is clear that the natural history of HPV is different in the 2 genders," Dr. Gillison reported.

There was a higher prevalence of oral HPV infection in black than in white people, although this did not reach statistical significance (10.5% vs 6.5%; P = .06). There was also a higher prevalence in current smokers and heavy consumers of alcohol (which increased with intensity of use for both), as well as in current and former marijuana users.

There was little HPV oral infection in individuals who had no history of any sexual contact. Compared with this group, the prevalence was 8 times higher in sexually experienced individuals, and increased significantly with the number of sexual partners. For instance, the prevalence was 20% in people who reported having more than 20 sexual partners.

"These data indicate that transmission by casual, nonsexual contact is likely to be unusual," the authors write.

They note that previous studies have suggested a link between oral sexual behavior and an increased risk for HPV-positive oropharyngeal cancer, but the way the data were collected in the current study precluded association with any particular behavior. However, the data did show that oral HPV infection is more common in sexually experienced people who do not report performing oral sex than in those who were not sexually experienced, which suggests that transmission occurs through other sexually associated contact, such as deep kissing.

This adds weight to the notion that HPV vaccination should be targeted at individuals who are 9 to 13 years of age, in an effort to reach them before any sexual behavior, including deep kissing, begins. This suggestion has been made previously by Dr. Gillison, although she emphasized that protection against oral HPV infection with the existing HPV vaccines has not been proven. She has been trying to conduct such a study for the past 5 years, but has run into funding problems; she hopes to hear soon about funding from the National Cancer Institute, she told journalists in the audience.

Extending HPV vaccination to offer protection against oropharyngeal cancer was discussed by several experts, in addition to Dr. Gillison, last year when it was highlighted by the American Society for Clinical Oncology.

The study was supported by an unrestricted grant from Merck, and was also funded by Ohio University and the Intramural Research Program of the National Cancer Institute. Dr. Gillison reports acting as a consultant to Merck and GlaxoSmithKline, both manufacturers of HPV vaccines. Dr. Schlecht has disclosed no relevant financial relationships.

JAMA. Published online January 26, 2012. Abstract, Editorial

2012 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstract LBPL1. Presented January 26, 2012.

Sexual Activity and Cardiovascular Disease

2012-01-27T17:44:00.000-08:00

American Heart Association Scientific Statement "Sexual Activity and Cardiovascular Disease" in 2012

Summary

Sexual activity is an important component of patient and partner quality of life, and it is reasonable for most patients with CVD to engage in sexual activity.

It is reasonable that patients with CVD who wish to engage in sexual activity undergo a comprehensive history and physical examination beforehand.

Those with stable symptoms and good functional capacity generally have a low risk of adverse cardiovascular events with sexual activity.

Patients with unstable or severe symptoms should first be treated and stabilized before engaging in sexual activity.

Exercise testing can provide additional information as to the safety of sexual activity in patients with indeterminate or unclear risk.

Cardiovascular medications are uncommonly the true cause of ED, and those that can improve symptoms and survival should not be withheld because of concerns about the potential impact on sexual function. PDE5 inhibitors have proved safe and effective in many patients with stable CVD; however, nitrate use is an absolute contraindication for PDE5 inhibitor administration.

Anxiety and depression are important considerations in patients with CVD and can contribute to reduced or impaired sexual activity.

Sexual counseling of CVD patients and their partners is an important component of recovery; unfortunately, it is rarely provided.

General Recommendations
1. Women with CVD should be counseled regarding the safety and advisability of contraceptive methods and pregnancy when appropriate
2. It is reasonable that patients with CVD wishing to initiate or resume sexual activity be evaluated with a thorough medical history and physical examination
3. Sexual activity is reasonable for patients with CVD who, on clinical evaluation, are determined to be at low risk of cardiovascular complications
4. Exercise stress testing is reasonable for patients who are not at low cardiovascular risk or have unknown cardiovascular risk to assess exercise capacity and development of symptoms, ischemia, or arrhythmias
5. Sexual activity is reasonable for patients who can exercise >3 to 5 METS without angina, excessive dyspnea, ischemic ST-segment changes, cyanosis,hypotension, or arrhythmia
6. Cardiac rehabilitation and regular exercise can be useful to reduce the risk of cardiovascular complications with sexual activity for patients with CVD
7. Patients with unstable, decompensated, and/or severe symptomatic CVD should defer sexual activity until their condition is stabilized and optimally managed
8. Patients with CVD who experience cardiovascular symptoms precipitated by sexual activity should defer sexual activity until their condition is stabilizedand optimally managed

Sexual Activity and Specific Cardiovascular Conditions

Coronary Artery DiseaseRecommendations
1. Sexual activity is reasonable for patients with no or mild angina
2. Sexual activity is reasonable 1 or more weeks after uncomplicated MI if the patient is without cardiac symptoms during mild to moderate physical activity
3. Sexual activity is reasonable for patients who have undergone complete coronary revascularization, and, may be resumed (a) several days after percutaneous coronary intervention (PCI) if the vascular access site is without complications or (b) 6 to 8 weeks after standard coronary artery bypass graft surgery (CABG), provided the sternotomy is well healed
4. Sexual activity is reasonable for patients who have undergone noncoronary open heart surgery and may be resumed 6 to 8 weeks after the procedure,provided the sternotomy is well healed
5. For patients with incomplete coronary revascularization, exercise stress testing can be considered to assess the extent and severity of residual ischemia
6. Sexual activity should be deferred for patients with unstable or refractory angina until their condition is stabilized and optimally managed

Valvular Heart DiseaseRecommendations
1. Sexual activity is reasonable for patients with mild or moderate valvular heart disease and no or mild symptoms
2. Sexual activity is reasonable for patients with normally functioning prosthetic valves, successfully repaired valves, and successful transcatheter valveinterventions
3. Sexual activity is not advised for patients with severe or significantly symptomatic valvular disease until their condition is stabilized and optimally managed

Heart FailureRecommendations
1. Sexual activity is reasonable for patients with compensated and/or mild (NYHA class I or II) heart failure
2. Sexual activity is not advised for patients with decompensated or advanced (NYHA class III or IV) heart failure until their condition is stabilized and optimally managed .

Congenital Heart DiseaseRecommendation
1. Sexual activity is reasonable for most CHD patients who do not have decompensated or advanced heart failure, severe and/or significantly symptomatic valvular disease, or uncontrolled arrhythmias.

Hypertrophic CardiomyopathyRecommendations
2. Sexual activity should be deferred for patients with HCM who are severely symptomatic until their condition is stabilized

Arrhythmias, Pacemakers, and ICDsRecommendations
1. Sexual activity is reasonable for patients with atrial fibrillation or atrial flutter and well-controlled ventricular rate
2. Sexual activity is reasonable for patients with a history of atrioventricular nodal reentry tachycardia, atrioventricular reentry tachycardia, or atrialtachycardia with controlled arrhythmias
3. Sexual activity is reasonable for patients with pacemakers
4. Sexual activity is reasonable for patients with an ICD implanted for primary prevention).
5. Sexual activity is reasonable for patients with an ICD used for secondary prevention in whom moderate physical activity (>3–5 METS) does not precipitateventricular tachycardia or fibrillation and who do not receive frequent multiple appropriate shocks
6. Sexual activity should be deferred for patients with atrial fibrillation and poorly controlled ventricular rate, uncontrolled or symptomatic supraventricular arrhythmias, and spontaneous or exercise-induced ventricular tachycardia until the condition is optimally managed .
7. Sexual activity should be deferred in patients with an ICD who have received multiple shocks until the causative arrhythmia is stabilized and optimally controlled.

Cardiovascular Drugs and Sexual FunctionRecommendation
1. Cardiovascular drugs that can improve symptoms and survival should not be withheld because of concerns about the potential impact on sexual function

Pharmacotherapy for Sexual Dysfunction PDE5 InhibitorsRecommendations
1. PDE5 inhibitors are useful for the treatment of ED in patients with stable CVD
2. The safety of PDE5 inhibitors is unknown in patients with severe aortic stenosis or HCM
3. PDE5 inhibitors should not be used in patients receiving nitrate therapy
4. Nitrates should not be administered to patients within 24 hours of sildenafil or vardenafil administration or within 48 hours of tadalafil administration

Herbal MedicationsRecommendation
1. It may be reasonable to caution patients with CVD regarding the potential for adverse events with the use of herbal medications with unknown ingredients that are taken for treatment of sexual dysfunction

Psychological Issues of Sexual Activity and CVDRecommendation
1. Anxiety and depression regarding sexual activity should be assessed in patients with CVD

Patient and Partner CounselingRecommendation
1. Patient and spouse/partner counseling by healthcare providers is useful to assist in resumption of sexual activity after an acute cardiac event, new CVDdiagnosis, or ICD implantation

Milk Supplements Might Prevent Gout Flares

2012-01-25T18:48:00.000-08:00

NEWS REFERENCEEDUCATION Medical News
Janis C. KellyJanuary 24, 2012

A proof-of-concept clinical trial by New Zealand researchers suggests that skim milk powder (SMP) enriched with 2 dairy fractions may prevent gout flares.
Lead author Nicola Dalbeth, MD, associate professor of medicine at the University of Auckland, New Zealand, and colleagues report in an article published online January 23 in the Annals of the Rheumatic Diseases that a daily dose of SMP enriched with glycomacropeptide (GMP) and
The supplement was compared with SMP alone, as well as with lactose powder.
The enriched SMP also reduced mean pain scores during the 3-month period.
The SMP/GMP/G600 treatment did not boost weight gain or increase the levels of potentially harmful blood lipids.Dr. Dalbeth told Medscape Medical News that "[SMP] enriched with GMP and G600 led to a greater reduction in gout flares, and to greater improvements in the pain of gout flares and fractional excretion of uric acid.
I think that this research raises interesting questions about the advice that we give our patients about diet interventions for gout.
Most of the dietary advice is based on observational studies (which have been very well-conducted), rather than clinical trial data, and this study is the first randomized controlled study of a dietary intervention for gout.
This is quite surprising, given the strong perception within the community, and also within the medical profession, that gout is a disease that is caused, in large part, by diet."
The study was a 3-month randomized double-blind controlled trial in 120 patients aged 18 years or older with recurrent gout flares, defined as at least 2 flares in the preceding 4 months.
Exclusion criteria included lactose intolerance and severe renal impairment (estimated glomerular filtration rate, <30 mL/minute).
The primary end point was change in the frequency of gout flares.
The patients were randomly assigned to daily treatment with lactose powder, SMP, or SMP enriched with GMP and G600. Each powder was mixed in 250 mL of water as a vanilla-flavored shake."This is the first reported randomized controlled trial of dietary intervention in gout management, and suggests that daily intake of skimmed milk powder enriched with GMP and G600 may reduce the frequency of gout flares," conclude the authors.

Dr. Dalbeth said, "This study has highlighted a potential new dietary intervention for managing gout, which may be useful as an adjunct to medical treatment. I think it is important to recognize that the effects seen in this study were modest, and that SMP/GMP/G600 will not replace treatments such as allopurinol for effective management of gout.
However, for patients with gout who wish to try a dietary approach as part of their gout management plan, this may be a very useful option. We spend quite a lot of time in the clinic advising people with gout what they shouldn't eat, so it would be nice to have some positive advice to give to patients."

Dr. Dalbeth's group initially became interested in the potential of milk products for gout after reports by Hyon Choi, MD, that intake of low-fat dairy was protective in the development of gout and was associated with lower serum urate levels.
"The specific fractions were identified in a previous study in our lab, where we screened a number of milk fractions for anti-inflammatory properties in models of gout," Dr. Dalbeth said.
"GMP and G600 were found to have anti-inflammatory properties in the laboratory assays, and for this reason we took these fractions into the clinical trial."Dr. Dalbeth said that the supplement is not currently commercially available, but that the researchers are working with the Fonterra Dairy Research Center to develop the product for commercial use.
S. Louis Bridges Jr, MD, PhD, Marguerite Jones Harbert-Gene V. Ball Professor of Medicine and director of the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham, reviewed the study for Medscape Medical News.Dr. Bridges found this research "definitely worth pursuing," but stressed the need for validation studies."This proof-of-concept study was well designed and well done, but like most proof-of-concept studies, it was of short duration with small numbers of patients: only 40 per group," Dr. Bridges said. "We have known for some time that decreased dairy intake is associated with increased gout risk, but this is the first randomized controlled trial to raise the question of whether more dairy intake would lower the frequency of gout flares. The fact that flare incidence decreased in all 3 study groups does also raise the question of whether the effect was due to the posited anti-inflammatory effects of the GMP and G600 supplements added to the skim milk powder...or more an overall result of more dairy intake, but this approach clearly deserves more study."The study was supported in part by LactoPharma, a joint venture between Fonterra Ltd, Fonterra R&D Ltd, and Auckland Uniservices Ltd. Lactose, SMP, and G600 milk fat extract were provided by Fonterra Co-operative Group Ltd. GMP was provided by Arla Foods Ingredients.
Dr. Dalbeth and one coauthor are named inventors on a patent application related to milk products and gout. Three coauthors are employees of Fonterra. Dr. Bridges has disclosed no relevant financial relationships.
Ann Rheum Dis. Published online January 23, 2012. Abstract

Black Tea Lowers Blood Pressure in Small Trial

2012-01-25T18:43:00.000-08:00

From Heartwire
Michael O'RiordanJanuary 24, 2012 (Boston, Massachusetts)

Drinking black tea appears to reduce the risk of developing high blood pressure, research shows.

Three daily cups, which provided approximately 400 mg/day of polyphenols, reduced systolic and diastolic blood pressure between 2 to 3 mm Hg, according to researchers.
"A large proportion of the general population has blood pressure within the range included in this trial, making results of the trial applicable to individuals at increased risk of hypertension," write Dr Jonathan Hodgson (University of Western Australia, Perth) and colleagues in a research letter published in the January 23, 2012 issue of the Archives of Internal Medicine.

Black tea is a common source of flavonoids, which have been suggested to contribute to vascular health. The researchers point out that they have shown that flavonoids augment nitric-oxide status and reduce plasma concentration of endothelin-1, both of which could contribute to reductions in vascular tone and reduced blood pressure.
In their study, the group randomized 95 men and women with a daytime ambulatory systolic blood pressure between 115 and 150 mm Hg to three cups of black tea daily or to placebo that matched the tea in flavor and caffeine content (approximately 96 mg of caffeine per day).
There were no significant differences between patient groups at baseline.
Daily consumption of the tea resulted in a significantly lower 24-hour systolic and diastolic blood pressure compared with the control arm.
The net-effect difference in systolic blood pressure at three and six months was -2.7 mm Hg and -2.0 mm Hg, respectively (p=0.006 at three months, p=0.05 at six months).
Diastolic blood pressure was reduced 2.3 mm Hg and 2.1 mm Hg at three and six months, respectively (p<0.001 at three months, p=0.003 at six months).
"At a population level, the observed differences in BP would be associated with a 10% reduction in the prevalence of hypertension and a 7% to 10% reduction in the risk of cardiovascular disease," write Hodgson and colleagues. "Therefore, given the high prevalence of hypertension worldwide and the importance of hypertension as a risk factor for cardiovascular and total mortality, these findings have important public-health implications."

Statin Medications and Increased Risk for Diabetes Mellitus

2012-01-25T05:19:00.000-08:00

From Medscape Ob/Gyn > Manson on Women's Health

What Clinicians and Patients Need to Know
JoAnn E. Manson, MD, DrPH01/12/2012

Hello, this is Dr. JoAnn Manson, Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital. I would like to talk with you today about a recently published study on the link between cholesterol-lowering statin medications and an increased risk for new-onset diabetes.

A paper was just published online in the January 9 issue of Archives of Internal Medicine.
Along with my colleagues, I looked at this question in the Women's Health Initiative observational analysis of more than 153,000 women, ages 50-79 at baseline.
During follow-up, more than 10,000 cases of diabetes were diagnosed.
We found that statin therapy -- statins of all types -- were associated with an increased risk for diabetes, about 48% overall, or moderate increase in risk.
This was similar to the magnitude seen between rosuvastatin and diabetes risk in the JUPITER trial, and meta-analyses of randomized trials have further supported that there may be an increased risk for diabetes with a very wide range of statins.
This could be a medication class effect.
Our analyses similarly suggested that this could be a medication class effect that was relevant to all forms of statins.
We found increased risk for diabetes with both low-potency and high-potency statins across the board, but no clear relationship with dose or with duration of therapy.
What are the implications of these findings?
We don't think the findings should change clinical practice guidelines, because for the vast majority of patients who are on statins, the benefits are expected to outweigh the risks.
Statins are very effective at lowering risk for heart disease and stroke.
We hope that the public and patients won't be alarmed about these findings and abruptly stop taking their statin medications. But we do believe that the findings should lead to increased vigilance about testing for diabetes in patients who are on statins and that the awareness of this link is important.
Patients are aware of it and they are aware of some symptoms of diabetes to look for (increased thirst, increased frequency of urination, blurred vision, etc.) and they may be more likely to report these symptoms to their clinicians and have diabetes diagnosed earlier than it might be otherwise.
We hope this research will stimulate additional studies to understand the mechanisms involved.
Is this at the level of the liver, the pancreas, the tissue's response to insulin?
We also hope that it will spur development of new statins or new medications that won't be associated with these adverse events.
For those who advocate even more widespread use of statins -- virtually "putting statins in the water supply" -- these findings give pause and suggest that perhaps if statins are used even more widely in those at lower risk and from very early ages, at some point this increased risk for diabetes could begin to offset some of the benefits of statins, unless new statins are developed without this risk or new medications are found to be of comparable benefit without the increased risk for diabetes.
So, overall, there are some clinical implications, but we definitely do not think that this should lead to abrupt stopping of statin medications.
Thank you very much for listening. This is Dr. JoAnn Manson.

http://www.medscape.com/viewarticle/756688?src=mp&spon=17Related Link: Statins Associated With Significant Increase in Diabetes Risk

'Exergaming' Helps Older Adults Improve Cognitive Function

2012-01-24T22:31:00.001-08:00

From Medscape Medical News > Neurology
Allison ShelleyJanuary 19, 2012 —

Virtual reality–enhanced exercise can delay cognitive decline more than traditional exercise, report investigators.
The technique combines physical training with a computer-simulated environment and interactive videogame features.
Virtual reality–enhanced exercise games such as the Wii Fit and PlayStation Move have become popular and tend to increase the appeal of exercise.
These so-called "exergames" have the potential to increase fitness by shifting attention away from some of the aversive aspects of working out, and toward motivating features such as competition and 3-dimensional scenery.
In this multisite cluster randomized trial, investigators compared a new approach using this concept, called "cybercycling," with the standard stationary bike."We anticipated that seniors would enjoy cybercycling, which they did, but we did not anticipate such a robust and significant cognitive effect from cybercycling compared with traditional exercise," lead investigator Cay Anderson-Hanley, PhD, from Union College, Schenectady, New York, told Medscape Medical News. "This gives us hope that there is more that can be done to both boost participation in exercise and increase the benefit of a workout through innovative exergames."

Results of the clinical trial were published in the February issue of the American Journal of Preventive Medicine.The trial included 102 older adults from retirement communities, ranging in age from 58 to 99 years. All rode identical recumbent bikes for an average of 3 rides per week, but the cybercycle participants had a virtual reality display that allowed them to ride in a 3-dimensional landscape and race against a ghost rider based on their own last best performance.
The main outcome measures were executive function, clinical status, exercise effort, fitness, and plasma brain-derived neurotrophic growth factor.Intent-to-treat analyses, controlling for age, education, and cluster randomization, revealed a significant group × time interaction for composite executive function (P = .002).Cybercycling yielded a medium effect over traditional exercise (d = .50).
Patients in this group also experienced a 23% relative risk reduction in clinical progression to mild cognitive impairment.
"Exercise can make a meaningful difference in brain health in later life, and interactive mental and physical exercise appears to yield additional cognitive benefit," Dr. Anderson-Hanley said during an interview.
"In our study, older adults who used the cybercycle 2 to 3 times a week for 3 months garnered significantly greater cognitive benefit for the same effort as those who rode a traditional stationary bike."With dementia on the rise, no cure yet available, and an estimated 100 million affected worldwide by 2050, "we need every tool available to curb progression and enhance cognitive function," Dr. Anderson-Hanley explained.
She pointed out that the exercise effort and fitness were comparable between groups, suggesting another underlying mechanism. A significant group × time interaction for brain-derived neurotrophic growth factor indicated enhanced neuroplasticity among cybercyclists (P = .05).

NeuroplasticitySerge Gauthier, MD, a spokesperson for the Alzheimer Society and director of the research unit at the McGill Center for Studies in Aging in Montreal, Quebec, Canada, complimented the work. "This exergaming study is a good one," he said to Medscape Medical News. Dr. Gauthier acknowledged that although the findings will need to be replicated in a different and larger group, they are in line with recent work performed by his team.Reporting in the June 2011 issue of Brain (2011;134:1623-1634), researchers led by Sylvie Belleville, PhD, from the Research Centre, Institut Universitaire de Gériatrie de Montréal, found that despite the presence of mild cognitive impairment, the brains of the participants remained highly plastic, and training resulted in significant neural changes that were measurable with brain imaging.
One explanation for the greater cognitive benefit found with cybercycling compared with traditional cycling is the added mental exercise required.
Navigating a 3-dimensional landscape, anticipating turns, and competing with others requires additional focus, expanded divided attention, and enhanced decision making.
"We are hopeful that older adults will be encouraged to pursue regular exercise and perhaps maximize the cognitive benefit of their workouts by simultaneously enjoying the interactive gamelike components of cybercycling," Dr. Anderson-Hanley told Medscape Medical News. "Researchers have shown that slowing the onset of dementia by 1 year through combined behavioral interventions such as exercise and diet can trim 1 million off of the 8 million expected to be diagnosed in the United States in 2050."

This study was funded by the Robert Wood Johnson Foundation, through the Health Games Research national program, and by faculty and student grants from Union College, Schenectady, New York, and Skidmore College, Saratoga Springs, New York. The investigators have declared no relevant financial relationships.Am J Prev Med. 2012;2:109-119. Abstract

Cognitive Decline Detectable Even in Middle-Aged Adults

2012-01-24T21:10:00.000-08:00

From Medscape Education Clinical BriefsNews Author: Emma Hitt, PhDCME Author: Charles P. Vega, MDCME Released: 01/11/2012; Clinical ContextThere is no known cure for dementia, but there is debate as to when the process of cognitive decline begins among adults. The authors of the current study describe that neurofibrillary tangles and amyloid plaques, the pathologic hallmarks of dementia, can be found in the brains of young adults. Although cognitive performance earlier in life can help to predict an individual's future risk for dementia, there are no reliable biomarkers that indicate a higher risk for dementia. Nonetheless, there is evidence that controlling traditional cardiovascular risk factors can have a salutary effect in the prevention of dementia.But when should clinicians be concerned regarding the incipient stages of cognitive decline? The current study by Singh-Manoux and colleagues addresses this issue.Study Synopsis and PerspectiveCognitive decline is detectable in persons aged 45 to 49 years and may not uniformly start later, in persons aged approximately 60 years, as previously thought, new research suggests.The study, using data from the longitudinal Whitehall II cohort study, followed participants aged 45 to 70 years at baseline using 3 cognitive assessments over a period of 10 years. The investigators report that average performance in all cognitive domains except vocabulary, which is known not to be affected by age, declined over the follow-up period in all age groups, including persons aged 45 to 49 years.Archana Singh-Manoux, MD, with the Hôpital Paul Brousse, Villejuif, France, and colleagues from the University of London, in the United Kingdom, reported their findings online January 5 in the BMJ.The Subject of DebateAccording to the researchers, "the age at which cognitive decline becomes evident at the population level remains the subject of debate." They add that some studies suggest that there is little evidence of cognitive decline before the age of 60 years, but they note that "this point of view…is not universally accepted."They sought to determine whether cognitive decline begins before the age of 60 years using a large sample of middle-aged adults from the longitudinal Whitehall II cohort study.The prospective cohort study, beginning in 1985 to 1988, included participants who worked in civil service departments in London. All participants (5198 men and 2192 women) were aged 45 to 70 years at the beginning of cognitive testing in the period from 1997 to 1999.Participants underwent repeated measures of cognitive function over a decade of follow-up across multiple cognitive domains.They found that cognitive scores declined in all categories (memory, reasoning, and phonemic and semantic fluency) except vocabulary; the decline was faster among older people. Over the 10-year study period, there was also a -3.6% decline in mental reasoning in men aged 45 to 49 years and a -9.6% decline in those aged 65 to 70 years. The corresponding figures for women were -3.6% and -7.4%.According to the researchers, robust evidence showing cognitive decline before the age of 60 years has important ramifications because it demonstrates the importance of promoting healthy lifestyles, particularly cardiovascular health, because there is emerging evidence that "what is good for our hearts is also good for our heads."They add that targeting patients who suffer from one or more risk factors for heart disease (obesity, high blood pressure, and high cholesterol levels) could not only protect their hearts but also safeguard them from dementia in later life."Determining the age window at which potential interventions are likely to be most beneficial is also a crucial next step," they suggest.A "Slightly Different" Research AgendaIn an accompanying editorial, Francine Grodstein, MD, associate professor of medicine at Brigham and Women’s Hospital in Boston, Massachusetts, notes that the study suggests that "it may be possible to identify those at increased risk of dementia as early as in their 40s," and that "this finding potentially has profound implications for prevention of dementia and public health."By finding cognitive decline in young adults, these researchers "have set a new benchmark for future research, and eventually clinical practice," Dr. Grodstein writes. "That is, efforts to prevent dementia may need to start in adults as young as 45 years," whereas most research has focused on those aged 65 years and older."The major challenge will be to design prospective research studies that include much younger age groups — a dramatic change from the status quo," she writes. To begin studying risk factors for cognitive decline in middle-aged persons will require large sample sizes, "probably tens of thousands of participants," and more creativity in research methods, perhaps incorporating telephone interviews or computerized cognitive assessments."We are entering a new era of research and prevention in dementia," Dr. Grodstein concludes. "There is probably greater hope of identifying ways to intervene in the development of dementia, but the challenge will be to change the status quo and find creative approaches to a slightly different research agenda."The study was not commercially funded. The authors and editorialists report no relevant financial relationships.BMJ. 2011;343. Published online January 5, 2012. Abstract, EditorialStudy HighlightsResearchers focused on the Whitehall II cohort to examine the rate of cognitive decline among middle-aged adults. Study participants were British civil servants between the ages of 35 to 55 years during study enrollment in 1985.Participants underwent cognitive testing in 3 phases during 1997 to 1999, 2002 to 2004, and 2007 to 2009. Researchers used a variety of validated instruments to assess different domains of cognitive function.The main study outcome was cognitive performance as time progressed.7390 participants provided data for the current analysis. 70% of participants were men, and 90% were white. The cohort was fairly evenly divided among different educational levels, including achievement of less than secondary school.63% of the study cohort underwent cognitive evaluations at all 3 follow-up points.Older age at baseline was associated with lower cognitive scores in reasoning, memory, phonemic fluency, and semantic fluency. However, it did not affect vocabulary scores.There were trends toward worse performance on multiple cognitive domains with age, with a more pronounced effect among men vs women.Compared with men 45 to 49 years old at baseline, the average decline in reasoning skills was -3.6% at ages 55 to 59 years and -9.6% at ages 65 to 70 years. The corresponding average declines among women were -3.6% and -7.4%.Results from testing of all of the other cognitive domains also declined with age, with the exception of vocabulary.On examination of cross-sectional effects of the data, differences in the level of education led to an overestimation of cognitive decline with age among women, but not men.However, longitudinal analyses did not demonstrate a substantial effect of educational level in altering the main study results.Clinical ImplicationsNeurofibrillary tangles and amyloid plaques can be found in the brains of young adults. Although cognitive performance earlier in life can help to predict an individual's risk for dementia in the future, there are no reliable biomarkers that indicate a higher risk for dementia. Nonetheless, there is evidence that controlling traditional cardiovascular risk factors can have a salutary effect in the prevention of dementia.The current study by Singh-Manoux and colleagues suggests that cognitive decline begins in middle age and affects multiple domains, with the exception of vocabulary.

Statins for Primary Prevention?

2012-01-24T20:53:00.000-08:00

From HeartwireExperts Debate in WSJ: Prescribe Statins for Primary Prevention?Michael O'RiordanJanuary 23, 2012 (San Francisco, California and Baltimore, Maryland) — Are statins one of the greatest advances since the introduction of antibiotics, capable of preventing cardiovascular disease in a wide range of patients, even healthy ones, or are clinicians relying too heavily on the lipid-lowering medications, using the drugs too frequently in individuals who would be better treated with an overhaul of their diet and exercise habits?The two very different sides of the statin argument are debated today in the Wall Street Journal, with Dr Roger Blumenthal (Johns Hopkins University Medical Center, Baltimore, MD) arguing the drugs prevent heart disease in patients with cardiovascular risk factors as well as in those who have already had a cardiovascular event. Good diet and exercise are the foundations of good health, says Blumenthal, but they're simply not enough sometimes, especially in patients with increased LDL-cholesterol levels or other cardiovascular risk factors."Every major medical guideline calls for doctors to prescribe a statin to certain seemingly healthy people with high levels of 'bad' cholesterol, which signals elevated risk for a heart attack," according to Blumenthal. "Doing so is one of the certainties of life, like the Cubs falling out of the pennant race by Labor Day."Dr Rita Redberg (University of California, San Francisco), on the other hand, argues against the current practice of prescribing statins to patients with cardiovascular risk factors, including individuals with elevated cholesterol levels. To heartwire , she said that there are too many low-risk individuals taking statins, and they simply don't get a benefit. In these low-risk/low-benefit patients, given the residual risk of statins, benefit is exceeded by harm."Despite research that has included tens of thousands of people, there is no evidence that taking statins prolongs life, although cholesterol levels do decrease," she writes in the Journal. "Using the most optimistic projections, for every 100 healthy people who take statins for five years, one or two will avoid a heart attack. One will develop diabetes. But, on average, there is no evidence that the group taking statins will live any longer than those who don't."Aggressive Treatment of Risk FactorsJust last January, a controversial Cochrane review concluded that there was not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease, a conclusion that was challenged by other researchers and clinicians.To heartwire , Blumenthal said that it is extremely rare to "find a cardiologist, in this day and age, who thinks you shouldn't treat elevated cholesterol levels." Noting that Redberg is a close, personal friend, he said that she is simply not looking at the totality of the evidence, noting that the data support the use of statins in primary and secondary prevention. Waiting until the patient has had a clinical event is too late, argues Blumenthal, especially when the first manifestation of cardiovascular disease can often be sudden cardiac death."I agree that that less invasive testing and [fewer] interventions can be just as good or better in some settings, but to adopt a real conservative strategy you also need to have not only aggressive lifestyle changes, which Dr Redberg and I agree on, but an aggressive treatment of risk factors like high cholesterol and blood pressure," said Blumenthal. "We don't really have mortality data supporting the treatment of blood pressure to less than 160 [mm Hg], yet every authority would say that if you stopped treating these patients the rates of heart failure, stroke, and renal disease would go up."In her essay, as well as to heartwire , Redberg states that there is not a significant mortality reduction with statins when used in primary prevention and that the use of lipid-lowering medications might lead some patients to not change their lifestyle since they are now being treated with medication. Moreover, the blood-pressure analogy is not accurate as there are more data on the prevention of cardiovascular events with treatment of hypertension."If we were to spend a small fraction of the annual cost of statins on making fruits and vegetables and physical activity more accessible, the effect on heart disease, as well as high blood pressure, diabetes, cancer, and overall life span, would be far greater than any benefit statins can produce," she writes.WOSCOPS, JUPITERBlumenthal, however, disagrees with Redberg's interpretation of the data, noting that the West of Scotland Prevention Study (WOSCOPS) showed that there was a strong trend toward reduced mortality after five years of treatment with statin therapy. The more recent Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study was stopped early given significant reductions in cardiovascular morbidity and mortality in individuals with cardiovascular risk factors but without cardiovascular disease. Recently, long-term results from the Anglo-Scandinavian Cardiac Outcomes--Lipid-Lowering Arm (ASCOT-LLA) study showed that treatment with atorvastatin reduced all-cause mortality compared with placebo, mainly through a reduction in noncardiovascular death."The selective use of cholesterol-lowering medications is what every clinical guideline recommends, from Europe to Canada to the United States," said Blumenthal.In contrast, Redberg noted that WOSCOPS studied men only and that 80% of patients in the study were current or former smokers with a body-mass index in the obese/overweight range. In addition, some of the patients had cardiac or peripheral vascular disease. "This was an extremely high-risk population and it's not who we're talking about when we're talking about people taking statins," Redberg told heartwire . Regarding JUPITER, Redberg noted the trial was stopped prematurely after just 1.9 years of follow-up and that the use of C-reactive protein (CRP) levels to guide treatment remains controversial.Regarding the potential for a large-scale, long-term, randomized, clinical trial to definitively answer the questions about statins' benefit in primary prevention, Blumenthal said it would be impossible given how large, time-consuming, and expensive such a trial would be. Moreover, such a trial would also be stopped early because of the significant reductions in MIs, strokes, and revascularizations that would be observed in the statin-treated patients, he said."I don't think we should treat everybody who's 50 years of age, but I take the attitude that people with risk factors should be, especially those with dyslipidemia, hypertension, or a family history of heart disease," he said. "We're extremely aggressive in lifestyle changes, and I'm sure Dr Redberg is too, but she's taken the attitude of 'do no harm'--but she's also unfortunately taken the attitude of 'do no good,' especially if she's doesn't think we should be using medication."Blumenthal said that the emergence of cheap and potent statins, including simvastatin and atorvastatin, makes the drugs an affordable, low-risk option to reduce the risk of heart disease.What About the Side Effects of Statins?To Redberg, the availability of generic statins does not change the equation, given the risk of potential side effects, such as muscle pain and weakness. Regarding the attitude of statin proponents that large-scale trials would be prohibitively expensive and very long, Redberg calls this a "disappointing stance," citing the billions of dollars that have already been spent on statin prescriptions and advertising."Every week in clinic I see patients who are suffering severe adverse effects of statins, and most of them are incredibly low-risk patients," Redberg told heartwire . "Most of them are women, who I think, unfortunately, suffer more adverse effects from statins, which is ironic because women are at a much lower risk than men from coronary disease anyway. None of the trials in primary prevention have shown a reduction in heart disease and none of them in women. None of them have shown a reduction in mortality in men or women. What this means for women is that they are much more likely to be getting adverse events and not likely to get any benefit at all from treatment."Primary prevention, according to Redberg, should be based on proper diet and exercise, and these efforts should begin in the school system through physical education and improved nutritional content of lunches and snacks."Too often people feel that because lifestyle interventions are not always going to be successful they don't even try, and we can just write a prescription," said Redberg. "I don't think we're doing our best service to our patients with that type of approach. I think there is a lot to be gained from physician counseling on lifestyle changes as well as public-health measures."Blumenthal agrees about the importance of making healthy food choices available and promoting better dietary habits and physical activity, but these habits are best learned when patients are young. Moreover, physician counseling on physical activity and lifestyle changes does not negate the value of statins in middle-aged and older adults with cardiovascular risk factors, such as elevated LDL-cholesterol levels."It's sort of silly to have this conversation in 2012 about not giving a cholesterol-lowering medication to a person who has dyslipidemia and other risk factors," Blumenthal told heartwire . "I'm not sure why she and some of the others have taken an extreme point of view that would be considered malpractice in the 48 continental states, and probably in Alaska and Hawaii, too."

.Sleep Locks In Bad Memories, Emotions

2012-01-18T21:42:00.000-08:00

By KATIE MOISSE | ABC News – Tue, Jan 17, 2012 10:08 AM ESTSleeping after a traumatic event might lock in bad memories and emotions, a new study has found. Researchers from the University of Massachusetts at Amherst asked more than 100 healthy adults to rate their emotional responses to a series of images, some depicting unsettling scenes. Twelve hours later, they rated the images again. The difference: Half of the subjects slept during the break; the other half did not. "Not only did sleep protect the memory, but it also protected the emotional reaction," said Rebecca Spencer, a neuroscientist at UMass Amherst and co-author of the study that was published in the Journal of Neuroscience. Study subjects who stayed awake for 12 hours had a weaker emotional response to the unsettling images the second time around, suggesting sleep serves to preserve and even amplify negative emotions. Their memories were also weaker than those of their well-rested counterparts, as they struggled to remember whether they had seen the images before. "It's true that 'sleeping on it' is usually a good thing to do," said Spencer, citing evidence that sleep boosts memory and other cognitive functions. "It's just when something truly traumatic or out of the ordinary happens that you might want to stay awake." Spencer said people often find it difficult to sleep after a traumatic event. "This study suggests the biological response we have after trauma might actually be a healthy," she said. "Perhaps letting people go through a period of insomnia before feeding them sleeping meds is actually beneficial." While the findings may have implications for post traumatic stress disorder, Spencer emphasized that daily emotional ups and downs are not grounds for sleep deprivation. "Just because we have a bad day doesn't mean we should stay awake," she said. "We need to maintain some memories and emotional context to know what to avoid. We do learn something from them." Although sleep gives the body some much-needed rest, the brain stays active. Spencer used polysomnography to monitor brain activity in some sleeping subjects. "REM sleep in particular was associated with a change in how emotional you found something," she said. "We think there are parts of the brain being activated during sleep that allow us to process those emotions more than during day." Next, Spencer plans to study the link between sleep and memory in the context of aging. With age, the amount of time spent sleeping drops dramatically. "We want to know if those changes actually underlie some of the cognitive and behavioral changes that occur with age," she said-------------------------------------------------------------------------------------------------

Questions About Data Linking Breast Cancer and HRT

2012-01-18T19:44:00.000-08:00

From Medscape Medical News > OncologyZosia ChusteckaJanuary 17, 2012 — The link between breast cancer and hormone replacement therapy (HRT) is based on "unreliable evidence," assert the authors of a paper published online January 16 in the Journal of Family Planning and Reproductive Health Care. However, this criticism has been summarily dismissed by experts involved in the HRT studies.The authors note that the claim that HRT with estrogen plus progestogen is now an established cause of breast cancer is based principally on the findings of 3 studies — the collaborative reanalysis, the Women's Health Initiative, and the Million Women Study (MWS).The findings from these studies, which were reported in the early 2000s, led to warnings about the risk for breast cancer from HRT, and resulted in a dramatic fall in the use of these products.However, these studies do not prove causality, say the authors, headed by Samuel Shapiro, MB, visiting professor of epidemiology at the University of Cape Town Medical School in South Africa. They examined each of the studies in a series of articles, the latest of which focuses on the MWS."HRT may or may not increase the risk of breast cancer," the authors note, and conclude that these studies do not establish causality.The MWS study estimated a larger risk for breast cancer with HRT than either the collaborative reanalysis or the Women's Health Initiative, and it had a huge impact on regulatory authorities and on the public perception of safety, the authors note. It is the largest study of HRT and breast cancer ever conducted, and its name — the Million Women Study — implies an authority beyond criticism or refutation," they add.However, size alone dose not guarantee that the findings are reliable, they add. After examining the validity of the study in some detail, they conclude that the evidence from the MWS is "unreliable."Dr. Shapiro and colleagues report that there were defects in the study design, and find evidence of detection bias and confounding, issues with internal and external consistency, and other problems.However, the principal investigator of the MWS, Dame Valerie Beral, AC, DBE, FRS, MRCP, professor and head of the Cancer Epidemiology Unit at Oxford University, United Kingdom, dismissed the criticisms. "These issues are not new and have been refuted previously," she said in a statement.She describes the paper by Dr. Shapiro and colleagues as a "restatement of views held by many consultants to HRT manufacturers (as these authors are) attempting to dispute evidence about the adverse effects of HRT."The totality of the worldwide evidence is now overwhelming.The authors neglect to mention that "the MWS findings of an increased risk of breast cancer in users of HRT, especially of estrogen–progestogen combinations, have now been replicated in over 20 other studies," she continued. "The totality of the worldwide evidence is now overwhelming""In line with the findings from these studies, the recent large decrease in HRT use has been followed in many countries by a nationwide decline in the incidence of breast cancer," Dr. Beral said.In the related statement, Sir Richard Peto, FRS, cofounder and codirector of the Clinical Trial Service Unit, Oxford University, said that the MWS "provides strong biologically plausible evidence of causality — i.e., of an increased probability of getting breast cancer among otherwise similar women (and a rapid decrease after they stop).""HRT is one of the most important causes of breast cancer in the world, and women can easily change their risk by stopping," Dr. Beral and Dr. Peto conclude.Dr. Shapiro and several coauthors report acting as consultants to manufacturers of HRT products.J Fam Plann Reprod Health Care. Published online January 16, 2012. Abstract

How Doctors Die

2012-01-16T18:44:00.000-08:00

NexusHow Doctors DieIt’s Not Like the Rest of Us, But It Should Beby Ken MurrayYears ago, Charlie, a highly respected orthopedist and a mentor of mine, found a lump in his stomach. He had a surgeon explore the area, and the diagnosis was pancreatic cancer. This surgeon was one of the best in the country. He had even invented a new procedure for this exact cancer that could triple a patient’s five-year-survival odds—from 5 percent to 15 percent—albeit with a poor quality of life. Charlie was uninterested. He went home the next day, closed his practice, and never set foot in a hospital again. He focused on spending time with family and feeling as good as possible. Several months later, he died at home. He got no chemotherapy, radiation, or surgical treatment. Medicare didn’t spend much on him.It’s not a frequent topic of discussion, but doctors die, too. And they don’t die like the rest of us. What’s unusual about them is not how much treatment they get compared to most Americans, but how little. For all the time they spend fending off the deaths of others, they tend to be fairly serene when faced with death themselves. They know exactly what is going to happen, they know the choices, and they generally have access to any sort of medical care they could want. But they go gently.Of course, doctors don’t want to die; they want to live. But they know enough about modern medicine to know its limits. And they know enough about death to know what all people fear most: dying in pain, and dying alone. They’ve talked about this with their families. They want to be sure, when the time comes, that no heroic measures will happen—that they will never experience, during their last moments on earth, someone breaking their ribs in an attempt to resuscitate them with CPR (that’s what happens if CPR is done right).Almost all medical professionals have seen what we call “futile care” being performed on people. That’s when doctors bring the cutting edge of technology to bear on a grievously ill person near the end of life. The patient will get cut open, perforated with tubes, hooked up to machines, and assaulted with drugs. All of this occurs in the Intensive Care Unit at a cost of tens of thousands of dollars a day. What it buys is misery we would not inflict on a terrorist. I cannot count the number of times fellow physicians have told me, in words that vary only slightly, “Promise me if you find me like this that you’ll kill me.” They mean it. Some medical personnel wear medallions stamped “NO CODE” to tell physicians not to perform CPR on them. I have even seen it as a tattoo.To administer medical care that makes people suffer is anguishing. Physicians are trained to gather information without revealing any of their own feelings, but in private, among fellow doctors, they’ll vent. “How can anyone do that to their family members?” they’ll ask. I suspect it’s one reason physicians have higher rates of alcohol abuse and depression than professionals in most other fields. I know it’s one reason I stopped participating in hospital care for the last 10 years of my practice.How has it come to this—that doctors administer so much care that they wouldn’t want for themselves? The simple, or not-so-simple, answer is this: patients, doctors, and the system.To see how patients play a role, imagine a scenario in which someone has lost consciousness and been admitted to an emergency room. As is so often the case, no one has made a plan for this situation, and shocked and scared family members find themselves caught up in a maze of choices. They’re overwhelmed. When doctors ask if they want “everything” done, they answer yes. Then the nightmare begins. Sometimes, a family really means “do everything,” but often they just mean “do everything that’s reasonable.” The problem is that they may not know what’s reasonable, nor, in their confusion and sorrow, will they ask about it or hear what a physician may be telling them. For their part, doctors told to do “everything” will do it, whether it is reasonable or not.The above scenario is a common one. Feeding into the problem are unrealistic expectations of what doctors can accomplish. Many people think of CPR as a reliable lifesaver when, in fact, the results are usually poor. I’ve had hundreds of people brought to me in the emergency room after getting CPR. Exactly one, a healthy man who’d had no heart troubles (for those who want specifics, he had a “tension pneumothorax”), walked out of the hospital. If a patient suffers from severe illness, old age, or a terminal disease, the odds of a good outcome from CPR are infinitesimal, while the odds of suffering are overwhelming. Poor knowledge and misguided expectations lead to a lot of bad decisions.But of course it’s not just patients making these things happen. Doctors play an enabling role, too. The trouble is that even doctors who hate to administer futile care must find a way to address the wishes of patients and families. Imagine, once again, the emergency room with those grieving, possibly hysterical, family members. They do not know the doctor. Establishing trust and confidence under such circumstances is a very delicate thing. People are prepared to think the doctor is acting out of base motives, trying to save time, or money, or effort, especially if the doctor is advising against further treatment.Some doctors are stronger communicators than others, and some doctors are more adamant, but the pressures they all face are similar. When I faced circumstances involving end-of-life choices, I adopted the approach of laying out only the options that I thought were reasonable (as I would in any situation) as early in the process as possible. When patients or families brought up unreasonable choices, I would discuss the issue in layman’s terms that portrayed the downsides clearly. If patients or families still insisted on treatments I considered pointless or harmful, I would offer to transfer their care to another doctor or hospital.Should I have been more forceful at times? I know that some of those transfers still haunt me. One of the patients of whom I was most fond was an attorney from a famous political family. She had severe diabetes and terrible circulation, and, at one point, she developed a painful sore on her foot. Knowing the hazards of hospitals, I did everything I could to keep her from resorting to surgery. Still, she sought out outside experts with whom I had no relationship. Not knowing as much about her as I did, they decided to perform bypass surgery on her chronically clogged blood vessels in both legs. This didn’t restore her circulation, and the surgical wounds wouldn’t heal. Her feet became gangrenous, and she endured bilateral leg amputations. Two weeks later, in the famous medical center in which all this had occurred, she died.It’s easy to find fault with both doctors and patients in such stories, but in many ways all the parties are simply victims of a larger system that encourages excessive treatment. In some unfortunate cases, doctors use the fee-for-service model to do everything they can, no matter how pointless, to make money. More commonly, though, doctors are fearful of litigation and do whatever they’re asked, with little feedback, to avoid getting in trouble.Even when the right preparations have been made, the system can still swallow people up. One of my patients was a man named Jack, a 78-year-old who had been ill for years and undergone about 15 major surgical procedures. He explained to me that he never, under any circumstances, wanted to be placed on life support machines again. One Saturday, however, Jack suffered a massive stroke and got admitted to the emergency room unconscious, without his wife. Doctors did everything possible to resuscitate him and put him on life support in the ICU. This was Jack’s worst nightmare. When I arrived at the hospital and took over Jack’s care, I spoke to his wife and to hospital staff, bringing in my office notes with his care preferences. Then I turned off the life support machines and sat with him. He died two hours later.Even with all his wishes documented, Jack hadn’t died as he’d hoped. The system had intervened. One of the nurses, I later found out, even reported my unplugging of Jack to the authorities as a possible homicide. Nothing came of it, of course; Jack’s wishes had been spelled out explicitly, and he’d left the paperwork to prove it. But the prospect of a police investigation is terrifying for any physician. I could far more easily have left Jack on life support against his stated wishes, prolonging his life, and his suffering, a few more weeks. I would even have made a little more money, and Medicare would have ended up with an additional $500,000 bill. It’s no wonder many doctors err on the side of overtreatment.But doctors still don’t over-treat themselves. They see the consequences of this constantly. Almost anyone can find a way to die in peace at home, and pain can be managed better than ever. Hospice care, which focuses on providing terminally ill patients with comfort and dignity rather than on futile cures, provides most people with much better final days. Amazingly, studies have found that people placed in hospice care often live longer than people with the same disease who are seeking active cures. I was struck to hear on the radio recently that the famous reporter Tom Wicker had “died peacefully at home, surrounded by his family.” Such stories are, thankfully, increasingly common.Several years ago, my older cousin Torch (born at home by the light of a flashlight—or torch) had a seizure that turned out to be the result of lung cancer that had gone to his brain. I arranged for him to see various specialists, and we learned that with aggressive treatment of his condition, including three to five hospital visits a week for chemotherapy, he would live perhaps four months. Ultimately, Torch decided against any treatment and simply took pills for brain swelling. He moved in with me.We spent the next eight months doing a bunch of things that he enjoyed, having fun together like we hadn’t had in decades. We went to Disneyland, his first time. We’d hang out at home. Torch was a sports nut, and he was very happy to watch sports and eat my cooking. He even gained a bit of weight, eating his favorite foods rather than hospital foods. He had no serious pain, and he remained high-spirited. One day, he didn’t wake up. He spent the next three days in a coma-like sleep and then died. The cost of his medical care for those eight months, for the one drug he was taking, was about $20.Torch was no doctor, but he knew he wanted a life of quality, not just quantity. Don’t most of us? If there is a state of the art of end-of-life care, it is this: death with dignity. As for me, my physician has my choices. They were easy to make, as they are for most physicians. There will be no heroics, and I will go gentle into that good night. Like my mentor Charlie. Like my cousin Torch. Like my fellow doctors.Ken Murray, MD, is Clinical Assistant Professor of Family Medicine at USC.

FDA Okays Pneumococcal Vaccine for Older Adults

2012-01-03T17:19:00.000-08:00

From FDA Approvals > Medscape Medical NewsMegan BrooksJanuary 3, 2012 — The US Food and Drug Administration (FDA) on December 30 approved the pneumococcal 13-valent conjugate vaccine (manufactured by Wyeth Pharmaceuticals, marketed by Pfizer Inc) for adults aged 50 years and older for the prevention of pneumonia and invasive disease caused by the 13 Streptococcus pneumoniae serotypes contained in the vaccine.The move comes on the heels of the November 16, 2011, meeting of the FDA's Vaccines and Related Biologics Advisory Committee, in which the committee voted 14 to 1 in favor of expanding the indication for Prevnar 13 to adults.Prevnar 13 was first approved by the FDA in February 2010 for the prevention of invasive pneumococcal disease in infants and young children from age 6 weeks through 5 years."Substantial" Disease Burden in AdultsPneumococcal infections remain an important cause of morbidity and mortality among older adults, a population that is rapidly expanding."According to recent information for the United States, it is estimated that approximately 300,000 adults 50 years of age and older are hospitalized yearly because of pneumococcal pneumonia," Karen Midthun, MD, director of the FDA's Center for Biologics Evaluation and Research, notes in an agency press release."Pneumococcal disease is a substantial cause of illness and death. [This] approval provides an additional vaccine for preventing pneumococcal pneumonia and invasive disease in this age group," Dr. Midthun said.Until now, Pneumovax 23 from Merck was the only pneumococcal vaccine licensed in the United States for use in adults aged 50 years and older.In studies conducted among adults 50 and older in the United States and Europe, Prevnar 13 induced antibody levels that were similar to or higher than the levels induced by Pneumovax 23, the FDA notes.Common adverse reactions reported with Prevnar 13 include pain, redness, and swelling at the injection site; limitation of movement of the injected arm; fatigue; headache; chills; decreased appetite; generalized muscle pain; and joint pain. Similar reactions have been observed with Pneumovax 23.The FDA says an additional trial in 85,000 people aged 65 years and older with no history of receiving Pneumovax 23 is underway to confirm the clinical benefit of Prevnar 13 in the prevention of pneumococcal pneumonia.The FDA says the expanded indication for Prevnar 13 in adults 50 years and older supports the Department of Health and Human Services' Healthy People 2020 objectives.

Exercise Relieves Fibromyalgia Pain, Ups Cognitive Function

2012-01-02T22:03:00.001-08:00

From Medscape Medical NewsJanis C. KellyDecember 9, 2011 — Six weeks of aerobic exercise can relieve the pain typically experienced by patients with fibromyalgia (FM) who discontinue analgesic medications, according to imaging studies reported at the Neuroscience 2011, the Society for Neuroscience annual meeting. The exercise also improves their working memory. The researchers suggest that this is a result of the increased activation of task-related parts of the brain, as shown by functional magnetic resonance imaging (fMRI) data."These results are suggestive of the effect [of] exercise on not only self report of global change in pain sensation in FM but also improvement in the network of cortical areas recruited in working memory," report a research team led Manish Khatiwada, MS, from Georgetown University Medical Center in Washington, DC. "Thus, exercise may have benefit in both reducing FM symptoms and improving cognitive capacity." Khatiwada is working in the laboratory of coauthor John VanMeter, PhD, director of Georgetown University's Center for Functional and Molecular Imaging.Senior author Brian Walitt, MD, director of the university's Fibromyalgia Evaluation and Research Center, said in a statement: "This study demonstrates how these symptoms change with treatment and withdrawal of treatment, and what the neurological correlates of these changes are." Dr. Walitt said the study is not suggestive of a change in clinical care for fibromyalgia.The researchers studied 9 women with FM (8 right-handed, 1 left-handed; age, 45.8 ± 10.60 years). The study consisted of 4 visits:baseline: receiving current FM medications;washout: off all FM medications for 3 half-lives;no treatment: 6 weeks after stopping FM medications; andexercise: after a 6 weeklong aerobic exercise intervention.At each visit the participants completed an N-Back fMRI working memory task (serial letter recognition with 0 and 2 back). The researchers analyzed changes in neuronal activity across visits based on changes in their patient global impression change. Analysis of this change across visits revealed increased activation in left superior medial frontal, left dorsal lateral prefrontal, right midfrontal, right supplementary motor, left thalamus, left caudate, left inferior parietal, and bisuperior parietal, all of which are task-related areas.According to Dr. Walitt, in conditions similar to FM, the body perceives something by mistake. Unlike psychosomatic pain, the pain of FM is objectively verifiable and is probably produced by the central nervous system.The research team used fMRI to "provide a definitive measure of cognitive functioning, so that we can more scientifically measure the effect of exercise," said Khatiwada in a statement. "This is a novel approach to the study of fibromyalgia."The researchers concluded, "Our results indicate that as the patients discontinue their current medication treatment and transition into the exercise treatment their subjective rating of change in pain initially increases and then decreases. Neuronal activity in areas recruited for an N-Back [fMRI] working memory task follow[s] an inverse pattern with an initial drop following medication cessation that increases on subsequent visits."The authors have disclosed no relevant financial relationships.Neuroscience 2011: Abstract 258.08, Poster BB5. Presented November 13, 2011.

Building Healthy Adults Starts in Childhood

2011-12-30T20:26:00.001-08:00

From Medscape Medical News > PsychiatryMegan BrooksDecember 28, 2011 — Extensive evidence indicates that early childhood adversity and “toxic stress” have harmful effects on mental and physical health that can last a lifetime, warns a new technical report from the American Academy of Pediatrics (AAP).In an accompanying policy statement, the AAP advocates incorporating the growing scientific knowledge base that links childhood adversity to lifelong harm into the training of all current and future physicians.The report and policy statement were published online December 26 and will appear in the January 2012 print issue of Pediatrics."Potentially Transformational"Drawing on multiple lines of investigation in biological, behavioral, and social sciences, the authors of the technical report present an ecobiodevelopmental (EBD) framework that illustrates how early childhood experiences and environmental influences can shape lifelong learning, behavior, and health.The authors summarize what they call “extensive evidence” linking early adversity to later impairments in learning, behavior, and physical and mental well-being.The implications of this EBD framework for the practice of medicine are “potentially transformational,” Jack P. Shonkoff, MD, director of the Center on the Developing Child at Harvard University, Boston, Massachusetts, and colleagues note in the report.It suggests that many adult diseases “should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood,” they write.In the accompanying policy statement, the AAP says, “All health care professionals should adopt the proposed EBD framework as a means of understanding the social, behavioral, and economic determinants of lifelong disparities in physical and mental health.”Pediatrics. 2012;129: Published online December 26, 2011. Report, Policy Statement

Does the Cranberry Beat Antibiotics for Recurrent UTIs?

2011-12-28T18:24:00.000-08:00

From Medscape Internal Medicine > Medicine MattersMedicine Matters , MedscapeSandra A. Fryhofer, MDPosted: 12/22/2011 Hello. I'm Dr. Sandra Fryhofer. Welcome to Medicine Matters. The topic? Relief for recurrent urinary tract infections (UTIs): cranberries or antibiotics? A new study in the Archives of Internal Medicine explores which approach is best.Urinary tract infections are common. About half of all women have had at least one. For those who have had at least 2 or more UTIs per year, low-dose antibiotics are often prescribed for prevention, but this can create strains -- usually Escherichia coli -- that are resistant to most antibiotics.So, is a more organic treatment, such as cranberries, preferable? Cranberries have been used as the alternative treatment of choice for UTI prevention for years. Exactly how they work isn't totally clear. Cranberries contain both fructose and Type A proanthocyanadins (PACs) that prevent bacteria from attaching to the urinary tract lining. A combined look at 2 randomized control trials found that cranberry products do work better than placebo. They reduced risk of UTI recurrence by 39%.However, unlike these studies, the one discussed in this commentary compared cranberries to an antibiotic -- trimethoprim sulfa (Bactrim®). This was a year-long, double-blind, double-dummy, randomized, noninferiority trial of more than 200 premenopausal women with recurrent UTIs.Patients received either trimethoprim sulfa, 480 mg once a day, or cranberry capsules, 500 mg twice a day. The PAC dose in the cranberries was 9.1 mg. Antibiotics were better at preventing urinary tract infections in the women. However, bacteria did become more resistant to trimethoprim sulfa as well as amoxicillin and ciprofloxacin. Increased resistance was not seen in the cranberry group.There is a caveat. Research published in the journal BMC Infectious Diseases finds that 72 mg of PACs prevent bacteria from adhering to the urinary tract lining. This is much higher than the 9.1 milligrams used in this study.Does more cranberry equal more prevention? It might be worth another study.

DHEA Hormone May Help Women Through Menopause

2011-12-27T21:41:00.000-08:00

From Reuters Health InformationBy Kate KellandLONDON (Reuters) Dec 20 - A hormone called DHEA and mostly secreted by the adrenal glands might be able to help women who are going through menopause and could also give them better sex lives, according to a preliminary study out Tuesday.Italian researchers writing in the journal of the International Menopause Society, Climacteric, said they had found the first robust evidence that low doses of DHEA can help sexual function and menopausal symptoms, suggesting it may one day become an alternative to hormone replacement therapy (HRT).But they stressed that the trial was small, so far larger studies are needed to confirm the results."We must bear in mind that this is a pilot study with a small sample," Dr. Anna Fenton, co-editor of Climacteric, said in commentary on the work. "We can't yet say that this study means that DHEA is a viable alternative to HRT, but ... we should be looking to do larger studies to confirm these initial results."DHEA, or dehydroepiandrosterone, is a natural steroid hormone mostly made in the adrenal glands and has a variety of therapeutic uses.Sales of HRT drugs have fallen sharply since the Women's Health Initiative study in 2002 found higher rates of ovarian cancer, breast cancer and strokes in women who took the pills, and the search has since been on for alternatives.American researchers said in January that the antidepressant Lexapro, made by drugmaker Forest Laboratories, significantly cut the number and severity of hot flushes in menopausal women, and other antidepressants including GlaxoSmithKline's Paxil and the Pfizer drugs Prozac and Effexor also have been found to be effective.For this trial, a team of researchers led by Dr. Andrea Genazzani of the University of Pisa followed a group of 48 post-menopausal women with troubling symptoms.Over a year, 12 women took vitamin D and calcium, 12 took DHEA 10 mg daily, 12 took standard HRT (1 mg estradiol plus 5 mg dihydrogesterone daily), and 12 took a synthetic steroid called tibolone (2.5 mg daily) which is used to alleviate menopausal symptoms.The women's menopausal symptoms, sexual interest and activity were measured using a standard questionnaire that explores factors such as satisfaction with frequency of sex, vaginal lubrication, orgasm, and sexual partner.After 12 months, all the women on hormone replacements had improvements in menopausal symptoms, but those taking vitamin D and calcium did not show any significant improvement.At the start of the trial, all groups had similar sexual activity, but after the year, those taking calcium and vitamin D scored an average of 34.9 on the questionnaire scale, while those taking DHEA had a score of 48.6, showing that those on DHEA had more sexual interest and activity.The results for the HRT group were similar, and both the HRT and DHEA groups showed a higher level of sexual intercourse in comparison to the control group, the researchers said.Dr. Genazzani said the results showed DHEA has potential, especially for those women who may have problems in taking more conventional HRT."But this is a small study, a proof of concept," she cautioned. "What we need to do now is to look at a larger study, to confirm that these initial results are valid," she added.SOURCE: http://bit.ly/vuMZnp

French Breast Implant Fears Spread Around World

2011-12-27T17:50:00.000-08:00

From Reuters Health InformationBy Kate Kelland and Daniel FlynnLONDON/PARIS (Reuters) Dec 22 - Fears over the safety of silicone breast implants made by a now defunct French firm spread to Australia, South America and across Europe on Thursday as French officials prepared to decide if thousands of women should have their implants surgically removed.The silicone gel implants, made by a company called Poly Implant Prosthese (PIP) which was shut down in 2010, appear to have an unusually high rupture rate and have sparked an investigation in France into possible links to cancer.Some 300,000 PIP implants, which are used in cosmetic surgery to enhance breast size or replace lost breast tissue, were sold worldwide before PIP went bust last year."It's not just France that's concerned. We're looking at 300,000 to 400,000 potential victims in the world," said Alexandra Blachere, the leader of a French PIP implant patient group.She said women from Italy and Spain had been in touch with her with worries about their implants, and she'd seen reports of problems in Venezuela, Brazil and elsewhere.Britain's drugs watchdog the Medicines and Healthcare products Regulatory Agency (MHRA) said, however, that there was no reason for patients to be alarmed and stressed as there is currently no scientific evidence to suggest increased health risks.MHRA officials said they had talked to other health or regulatory experts from France, the Netherlands, Portugal, Italy, Ireland, Hungary, Austria, Denmark and Malta."They all agreed that there was no evidence of any increase in incidents of cancer associated with PIP breast implants and no evidence of any disproportionate rupture rates other than in France," it said in a statement.Founded in 1991, Poly Implants Prosthese was based in southern France and for a while ranked as the world's number three maker of implants, supplying around 100,000 a year.Some 80% were exported abroad, and health authorities around the world said they were watching closely for the results on Friday of an inquiry by France's National Cancer Institute into whether the implants can be linked to cancer.France has had reports of eight cases of cancer in women with breast implants made by PIP, which is accused of using industrial-grade silicone normally used in anything from computers to cookware.MHRA said there were also French reports of a woman with PIP implants who died from anaplastic large cell lymphoma (ALCL).France's drug and medical device regulatory authority, AFSSAPS, ruled last year that the state would pay for the removal of all the PIP implants but only fund replacements for victims of breast cancer, not those who used them for aesthetic purposes.A French victims association is pushing for the state to pay for replacements for all women with PIP implants.France's Health Ministry is expected to make an announcement on Friday following the National Cancer Institute's findings.BRITAIN MONITORING FRENCH DECISIONAustralia's healthcare watchdog, the Therapeutic Goods Administration (TGA), said around 8,900 of the PIP implants had been used in Australian women, some of whom had complained about the devices splitting and leaking."The TGA has received 45 reports relating to PIP implants, 39 of which relate to rupture," it said in a statement. It has had no reports of ALCL in Australian women with the implants.The TGA said women with PIP implants should continue to monitor them and consult their surgeons if they have any concerns. Brain's MHRA said the same, adding that it would be "looking carefully at the French safety statement when it comes out as a matter of priority."PIP was placed into liquidation in March 2010 with losses of 9 million euros after AFSSAPS recalled its implants when surgeons reported abnormally high rupture rates.During a subsequent inspection of its manufacturing site, officials found PIP had started using a type of silicone gel that was not approved by health authorities, but was around 10 times cheaper.A subsequent investigation found that a majority of implants made by PIP since 2001 contained the unapproved gel.A solicitor acting for at least 250 British women taking legal action over their PIP implants said the liquidation of the French company had limited the scope for patients' legal action."We're suing about half a dozen clinics that have been involved in implanting the PIP breast implants," Mark Harvey, a partner at legal firm Hugh James, told Reuters."We would have preferred to sue PIP, obviously, but they are bankrupt so they have no money and no assets."

Acetaminophen: Repeated Use of Slightly Too Much Can Be Fatal

2011-11-24T22:27:00.001-08:00

From Medscape Medical NewsLaurie Barclay, MDNovember 22, 2011 — Repeated doses of slightly too much acetaminophen (known as paracetamol in the United Kingdom and elsewhere in Europe) can be fatal, according to the results of a large, single-center cohort study published online November 22 in the British Journal of Clinical Pharmacology."On admission, these staggered overdose patients were more likely to have liver and brain problems, require kidney dialysis or help with breathing and were at a greater risk of dying than people who had taken single overdoses," senior author Kenneth J. Simpson, MBChB (Hons), MD, FRCP (Edin), from the University of Edinburgh and Scottish Liver Transplant Unit in the United Kingdom, said in a news release."They haven't taken the sort of single-moment, one-off massive overdoses taken by people who try to commit suicide, but over time the damage builds up, and the effect can be fatal," he adds.In the United Kingdom, acetaminophen hepatotoxicity is the leading cause of acute liver failure (ALF). However, the effect of a staggered overdose pattern or delayed hospital presentation on mortality or need for emergency liver transplantation was previously unknown.Of 663 patients admitted with acetaminophen-induced severe liver injury between 1992 and 2008, 161 (24.3%) had taken a staggered overdose. Compared with patients who took an overdose at a single time, patients with staggered overdose were significantly older and more likely to abuse alcohol.When asked why they repeatedly ingested more than the recommended dose of acetaminophen, patients with staggered overdose most often cited pain relief as their rationale (58.2%).Compared with patients who took an overdose at a single time, those who took staggered overdoses had lower total ingested doses and lower serum alanine aminotransferase (ALT) levels on admission. Nonetheless, they were more likely to be encephalopathic and to require renal replacement therapy or mechanical ventilation.Although mortality was higher in staggered overdoses than in single-time overdoses (37.3% vs 27.8%; P = .025), the staggered overdose pattern was not an independent predictor of mortality. For staggered overdoses, sensitivity of the King's College poor prognostic criteria was reduced (77.6%; 95% confidence interval [CI], 70.8% - 81.5%).Delayed presentation to medical services more than 24 hours after single-time overdose occurred in 44.9% of those in whom accurate timings could be determined, and was independently associated with death or liver transplantation (odds ratio [OR], 2.25; 95% CI, 1.23 - 4.12; P = .009).In their logistic regression analysis, the investigators controlled for signs and symptoms, such as hepatic encephalopathy and prothrombin time, as well as various demographic factors."Staggered overdoses or patients presenting late after an overdose need to be closely monitored and considered for the paracetamol antidote, N-acetylcysteine [NAC], irrespective of the concentration of paracetamol in their blood," Dr. Simpson said.Because both these groups are at increased risk of developing multiorgan failure, they should be considered for early transfer to specialist liver centers.Limitations of this study include reliance on patient recall regarding the time of last ingestion, total paracetamol dose, and suicidal intent; limited data regarding the use of concomitant P450 enzyme inducers or recent fasting; and selection bias for the more severe cases of acetaminophen toxicity in Scotland."[T]his large cohort study demonstrates the deleterious effects of delayed presentation and staggered overdose pattern upon outcome following paracetamol-induced acute liver injury," the study authors conclude. "Both delayed presentation > 24 hours and staggered overdoses are strongly associated with multiorgan injury and the need for [liver transplantation]. Patients presenting with these overdose patterns should be treated as high risk for progression to ALF, and should receive NAC in their presenting hospital whilst awaiting serial ALT and PT levels."This study received no external funding. The authors have disclosed no relevant financial relationships.Br J Clin Pharmacol. Published online November 22, 2011.

Pomegranate Juice Lowers Cardiovascular Risk Factors

2011-11-14T19:12:00.001-08:00

From Medscape Medical NewsDaniel M. Keller, PhDNovember 12, 2011 (Philadelphia, Pennsylvania) — Patients on hemodialysis consuming a moderate amount of pomegranate juice for a year saw a continuous, cumulative, beneficial effect on their lipid profile, their blood pressure, and the number of antihypertensive medications they required, Batya Kristal, MD, MHA, from the Nephrology Department at the Western Galilee Hospital in Nahariya, Israel, reported here at Kidney Week 2011: American Society of Nephrology 44th Annual Meeting.In addition to water, sugars, and pectin, pomegranates contain the antioxidants ascorbic acid and polyphenolic flavonoids.Hemodialysis patients were randomized to receive 100 mL of pomegranate juice (n = 66) or an equivalent-tasting placebo (n = 35) 3 times a week for 12 months. End points of the trial were lipid profile, including triglycerides (TGs), low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol (HDL), systolic and diastolic blood pressure, and the number of antihypertensive drugs required.At 12 months, all components of the lipid profile improved in the pomegranate juice group but not in the placebo group. In the juice group, there were statistically significant decreases in TGs from baseline to 12 months (P = .01), especially in patients with a baseline TG level of at least 200 mg/dL (P < .001). Over the same time period, HDL rose significantly (P = .005) in the juice group. There was no significant change in any of these parameters in the placebo group.During the study period, there was a significant decrease in systolic blood pressure in the juice group overall (P < .006), especially in patients who had a baseline systolic pressure of at least 140 mm Hg (P < .005); this was not the case in the placebo group.At 12 months, those in the juice group were taking significantly fewer antihypertensive drugs than those in the placebo group (P < .05). In the juice group, 22% of the subjects were taking fewer and 12.2% were taking more antihypertensive drugs; in the placebo group, 7.7% were taking fewer and 34.6% were taking more antihypertensive drugs.Dr. Kristal speculated that the consumption of pomegranate juice might lower the risk for cardiovascular disease in patients on hemodialysis, and recommended that it be added to diets that improve cardiometabolic risks, including low-salt diets, Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean diet.One safety concern is that pomegranate juice contains a high level of potassium, so potassium overload is a risk, especially in patients with chronic kidney disease and dietary potassium restrictions. Dr. Kristal recommended that such patients be monitored by a dietician and a nephrologist. In addition, pomegranate juice intake can interfere with the metabolism of certain drugs, raising their levels in the blood. However, no adverse effects were detected in the group taking pomegranate juice.Katherine Tuttle, MD, executive director for research at Providence Sacred Heart Medical Center and professor of medicine at the University of Washington School of Medicine in Spokane, who was not involved in the study, told Medscape Medical News that "it's an interesting preliminary study.... I think before we conclude that we should be giving our patients pomegranate juice, we need to do bigger studies in other settings [with] more diverse populations and, of course, look beyond just the risk factors that they measured."In light of the high levels of potassium in pomegranate juice, Dr. Tuttle advised that "if [patients] decide to use it, [they should] be sure to let their healthcare professionals know."The study had no commercial funding. Dr. Kristal and Dr. Tuttle have disclosed no relevant financial relationships.Kidney Week 2011: American Society of Nephrology 44th Annual Meeting. Abstract FR-PO1660. Presented November 11, 2011.

Statins Can Make Asthma Worse

2011-11-14T19:08:00.001-08:00

From Medscape Medical NewsFran LowryNovember 14, 2011 (Boston, Massachusetts) — Statins are among the most widely prescribed drugs in the world and help to stave off cardiovascular disease, but results from a small study suggest that they might worsen asthma control, researchers said here at the American College of Allergy, Asthma & Immunology 2011 Annual Scientific Meeting.Statin drugs, which are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are effective at lowering cholesterol, but they also influence allergic inflammation with immunomodulatory activities, said lead author Safa Nsouli, MD, director of the Danville Asthma and Allergy Clinic in California.These include the downregulation of the T helper (TH)1 phenotype response and the upregulation of the TH2 phenotype response.Dr. Nsouli said he noticed that some of his patients with asthma had exacerbations and worsening control. When he investigated, he observed that they were using statins.The observation prompted him to conduct this small study. He compared 20 patients with asthma who were taking statins with 20 matched patients who were not taking statins."The patients were very carefully selected and did not have any other medical factors that could interfere with asthma exacerbation," Dr. Nsouli told Medscape Medical News.The patients were seen at 3, 6, and 12 months. At each follow-up visit, measures of the following asthma factors were taken: forced expiratory volume in 1 second (FEV1), the use of beta agonists, nocturnal wakening, and daytime exacerbation symptoms.The investigators found that at 3 months, patients in the statin group had a 20% decrease in FEV1 from baseline, compared with patients in the nonstatin group, who had a 10% decrease. At 6 months, the decreases were 28% and 12%, respectively; at 12 months, the decreases were 35% and 14%.The use of beta-agonist rescue inhalers was also higher in the statin group than in the nonstatin group, Dr. Nsouli said. At 12 months, beta-agonist use was up by 72% in the statin group, compared with 9% in the nonstatin group.At 3 months, peak expiratory flow was decreased by 18% in the statin group, and by 4% in nonstatin group. At 6 months, it was decreased by 25% and 9%, respectively, and at 12 months, it was decreased by 39% and 11%.Finally, statin users had more nighttime wakening and a greater increase in daytime symptoms than nonusers. At 12 months, the increase in nighttime wakening was 31% and 3%, respectively, and the increase in daytime asthma symptoms was 35% and 3%."More studies are needed to demonstrate that statins cause possible immune changes that promote allergic diseases such as asthma," Dr. Nsouli said. "Statins inhibit proinflammatory cytokines, which is good for the cardiovascular system, but they also suppress the major histocompatibility complex, class II, which is detrimental for patients with asthma," he explained.Physicians who notice that their patients' asthma is worsening should find out if they are taking statins. Dr. Nsouli suggested.He also said that patients with asthma who are prescribed statins should be informed that, because of the adverse immunomodulatory effects that statins produce, their asthma might get worse."This does not mean that patients with asthma who need to take statins should stop taking these drugs. But it does mean that they should be treated more aggressively," Dr. Nsouli said.Chitra Dinakar, MD, from the University of Missouri School of Medicine in Kansas City, told Medscape Medical News that she thinks the observations from this study are interesting, but stressed their preliminary nature."He had 20 patients in each group. The dose of statins wasn't clear, neither was the patient profile, but the study is thought provoking," said Dr. Dinakar, who was comoderator of the oral session."It tells us that we need to be watching out for patients with asthma who are on statins to see if the statins do indeed affect their control. The data are preliminary at this point, but they do raise doubt. The subject merits further study."Dr. Nsouli has disclosed no relevant financial relationships. Dr. Dinakar reported financial relationships with AstraZeneca and GlaxoSmithKline.American College of Allergy, Asthma & Immunology (ACAAI) 2011 Annual Scientific Meeting: Abstract 30. Presented November 6, 2011.

Diabetes Epidemic on 'Relentlessly Upward Trajectory'

2011-11-14T17:37:00.001-08:00

From Medscape Medical NewsMartha KerrSeptember 13, 2011(Lisbon, Portugal) — The number of people diagnosed with and dying from diabetes continues "on a relentlessly upward trajectory," with no signs of abating, according to officials from the International Diabetes Federation (IDF) and the European Association for the Study of Diabetes (EASD) 47th Annual Meeting.Data from international studies demonstrate that the number of people with diabetes in 2011 has reached 366 million. This year, 4.6 million deaths will be attributed to diabetes, with 1 person dying from diabetes every 7 seconds. Healthcare spending on diabetes has reached $465 billion.The warning comes a week before the United Nations Summit on Non-Communicable Diseases, to be held September 19 and 20 in New York City, where world leaders will meet to discuss the global issues posed by diabetes, cancer, heart, and respiratory diseases.IDF president Jean Claude Mbanya and EASD vice president Andrew Boulton state that "without urgent research into improved care and prevention models, we stand little chance of meeting any long-term targets that arise from the summit.""Implementation of current knowledge will bring some improvements to [noncommunicable disease] care and prevention, but further research is essential if we are to truly defeat these diseases," the officials say, adding that increased funding for research is critical.The findings will be published in the 5th edition of the Diabetes Atlas. The figure of 366 million people with diabetes in 2011 is up almost 30% from the 285 million cited for 2010 in the 4th edition of the Atlas.More information on the call for action can be obtained at www.idf.org or www.easd.org.

Neuromuscular Warm-Ups Reduce Injuries in Female Athletes

2011-11-11T18:47:00.001-08:00

From Medscape Medical NewsJennifer GarciaNovember 7, 2011 — Coach-led neuromuscular warm-up training (NMT) reduces lower-extremity injuries in female high school basketball and soccer players in a low-income, mixed-ethnicity, urban setting, according to data from a large, cluster-randomized, controlled trial published in the November issue of the Archives of Pediatric and Adolescent Medicine.To find out whether NMT training could reduce lower-extremity injuries in this setting, Cynthia R. LaBella, MD, from the Children's Memorial Hospital, Chicago, Illinois, and colleagues invited girls' soccer and basketball head coaches from all Chicago high schools to participate in the study during the 2006-2007 season. Of the 258 coaches invited, 95 enrolled, and 90 completed the study, representing 105 teams. The study was approved by the Chicago Public Schools research review board and the Children's Memorial Hospital review board.After learning how to implement a 20-minute neuromuscular warm-up before team practices and a shorter pregame version, the coaches in the intervention group used the prescribed warm-up before an average of 80% (standard deviation [SD], 21%) of practices, with a median of 87%. The control coaches stuck to their standard warm-up protocol, including no warm-up exercises and having athletes jog or warm up on their own.Overall, 96 lower-extremity injuries occurred (4.19/1000 athlete exposures; 95% confidence interval, 3.35 - 5.02 per 1000 athlete exposures) in the control group and 50 lower-extremity injuries (1.78/1000 athlete exposures; 95% confidence interval, 1.29 - 2.28 per 1000 athlete exposures) in the intervention group.Compared with athletes in the control group, Dr. LaBella and colleagues noted a 44% decrease in acute noncontact lower-extremity injuries and a 34% decrease in noncontact ankle sprains among players in the intervention group.Moreover, 7 athletes in the control group sustained anterior cruciate ligament (ACL) injuries during the study, and 6 of those required surgery. Two athletes in the intervention group sustained ACL injuries; neither required surgery.NMT combines progressive strengthening with plyometric, balance, and agility exercises. Coaches instructed the athletes to avoid dynamic knee valgus and to land jumps with flexed hips and knees. The investigators taught coaches how to distinguish proper from improper form and how to use verbal cues to promote proper form.The study authors calculated that 189 athletes would need to be trained to use neuromuscular warm-up exercises to prevent 1 noncontact lower-extremity injury. This would require training 11 soccer coaches or 16 basketball coaches, which, at $80 per coach per session, would be far less expensive than the estimated treatment cost for 1 surgically treated ACL injury.A potential limitation of the study, the researchers note, is that it encompassed only 1 season, so whether compliance can be maintained for several seasons is unknown. In addition, parental consent to include personal health and background information was available for only 855 of the 1492 participating athletes; therefore the data may not be representative of the entire sample.Despite the limitations, Dr. Labella and colleagues conclude: "[T]o our knowledge, this is the first randomized controlled study to demonstrate that (1) high school coaches in a mixed-ethnicity, predominantly low-income, urban population can implement a neuromuscular warm-up; (2) the warm-up reduces noncontact [lower-extremity] injuries, including ACL injuries, in female basketball and soccer athletes in this population; (3) the effect is likely dose related; and (4) coach training seems cost-effective."M. Alison Brooks, MD, MPH, from the Department of Orthopedics and Pediatrics, and Timothy A. McGuine, PhD, ATC, from the University of Wisconsin Health Sports Medicine Center, University of Wisconsin–Madison, write in an accompanying editorial: "This study is indeed novel for targeting a group that is often ignored and understudied because of logistical barriers and lack of resources."Although the study does confirm that neuromuscular training programs can reduce lower-extremity injuries, Dr. Brooks and Dr. McGuine point out that a longer follow-up would be needed to evaluate whether coaches continue to implement NMT consistently for several seasons, or whether retraining will be needed.The editorialists also note that many of the coaches in the control group did not include any type of warm-up routine in their training. Whether this behavior extends to the large percentage of coaches who declined to participate in the study could provide qualitative information that may help identify barriers to successful implementation of injury prevention strategies.Additionally, the authors of the editorial point out that including cost analysis of other, more common lower-extremity injuries beyond ACL would actually demonstrate an even greater cost-savings if coaches were trained in how to implement a neuromuscular warm-up as part of their training regimen.Both the study authors and the editorialists point out that physical activity has significant benefits in adolescent girls, including improved academic success and lower rates of obesity, diabetes, pregnancy, and depression. This association underscores the importance of sports injury prevention, particularly in girls from mixed-ethnicity, predominantly low-income, urban populations who are at higher risk for adolescent obesity, diabetes, and pregnancy.This study was supported by grants from Children's Memorial Research Center and Office of Child Advocacy. Dr. Brooks and Dr. McGuine have disclosed no relevant financial relationships.Arch Pediatr Adolesc Med. 2011;165:1033-1040. Abstract

Some Probiotics Effectively Reduce Common GI Symptoms

2011-11-11T17:46:00.001-08:00

From Medscape Medical NewsSandra YinNovember 8, 2011 (National Harbor/Washington, DC) — Mounting evidence is building a strong case for the use of probiotics, or "good" bacteria, to alleviate common gastrointestinal (GI) symptoms, such as diarrhea, bloating, and inflammation, according to several studies highlighted during a press briefing here at the American College of Gastroenterology 2011 Annual Scientific Meeting and Postgraduate Course.In one meta-analysis, researchers from the Maimonides Medical Center in Brooklyn, New York, found that in 22 studies of more than 3000 patients, probiotic prophylaxis significantly reduced the odds of developing antibiotic-associated diarrhea and Clostridium difficile–associated diarrhea by about 60%.In another meta-analysis, researchers from Beth Israel Deaconess Medical Center and Harvard Medical School, in Boston, Massachusetts, analyzed 28 randomized controlled trials in which more than 3000 patients received a single or a combination of antibiotics for various indications. In adult and pediatric populations, the preventive effect of probiotic use was significant, regardless of the species used and regardless of the antibiotic administered.In the largest study to date on probiotics in a nonpatient population, researchers from the University of North Carolina at Chapel Hill evaluated the efficacy of Bifidobacterium infantis 35624, a probiotic that has relieved symptoms in patients with irritable bowel syndrome, to see how well it relieved abdominal discomfort and bloating in nonpatients.The double-blind randomized placebo controlled study involved a 2-week placebo phase followed by a 4-week intervention phase, and was conducted at 10 clinical centers in the United States. More than 300 nonpatients who had experienced abdominal discomfort and bloating more than twice weekly, on average, for at least 3 months were included in the study. They had not seen a physician or received prescribed medication for their symptoms in the previous 12 months.In contrast to previous clinical studies of irritable bowel syndrome patients, the researchers saw no statistically significant improvement in mean severity of abdominal discomfort or bloating after the nonpatient population took B infantis 35624.However, an Irish group found that a nonpatient population receiving B infantis 35624 experienced significantly more bloat-free days.The researchers hypothesized that microbial imbalance could explain the increased incidence of a wide range of inflammatory disorders. To test whether altering the balance between good and bad bacteria in the gut raises the immune regulatory response, which could lower inflammation, researchers from the Alimentary Pharmabiotic Centre at University College Cork, and Alimentary Health Ltd in Cork, Ireland, conducted a double-blind placebo controlled study. Their goal was to see if B infantis affects systemic proinflammatory biomarkers in patients with inflammatory disease.The results of their study suggest that probiotics exert antiinflammatory effects."By giving a specific probiotic orally, we could actually reduce the levels of these proinflammatory cytokines and actually enhance the production of an anti-inflammatory cytokine, which is the exact replication of what we identified in animal models and more basic models," said principal investigator Eamonn Quigley, MD, FACG, professor of medicine at the National University of Ireland in Cork.Plasma levels of the anti-inflammatory cytokine interleukin (IL)-10 rose significantly in healthy volunteers and patients with psoriasis, but not in those who took the placebo for 8 weeks.Plasma levels of 2 proinflammatory cytokines — tumor necrosis factor-alpha and IL-6 — dropped in all patients who received B infantis. C-reactive protein levels were also significantly lower in patients with psoriasis, ulcerative colitis, and chronic fatigue after treatment with the bacterium than after treatment with placebo.Although not everybody who takes an antibiotic should also take a probiotic, the institutionalized elderly should, to minimize the chance of getting something like antibiotic-associated diarrhea or antibiotic-associated C difficile, said Fergus Shanahan, MD, FACG, a researcher involved in the Irish B infantis 35624 study, and professor and chair of the Department of Medicine at University College Cork.Certain subsets of patients, such as those with cystic fibrosis or chronic urinary infections, who must take recurring courses of antibiotics might benefit from taking probiotics to minimize antibiotic-associated diarrhea."It's ironic that we would worry about taking an organism when we've got billions of organisms in the GI tract" and the amount is relatively small, Dr. Shanahan observed. Instead of worrying about drug toxicity in that population, "we're worried about something that has vanishingly low side effects. It can't be zero, but it is very, very low.""If we paid more attention to prescribing antibiotics, we wouldn't have a lot of these problems," added Dr. Quigley.According to Mark Mellow, MD, FACG, director of the Digestive Health Center at INTEGRIS Baptist Medical Center in Oklahoma City, Oklahoma, physicians aren't the only ones to blame for the indiscriminate use of antibiotics. Edicts from hospital compliance committees often establish rules that patients who come in with community-acquired pneumonia be placed on antibiotics soon after admission. These rules can have unintended consequences."Someone comes in with a fever and a cough and because there's not enough time to sort it out, they get put on an antibiotic," he said, whether or not they have a bacterial infection.Dr. Quigley reports financial relationships with Alimentary Health, Norgine, Merck, Procter and Gamble, Movetis/Shire, Shire, Yakult, and Ironwood/Almirall. Dr. Shanahan reports a financial relationship with Alimentary Health Ltd. Dr. Mellow has disclosed no relevant financial relationships.American College of Gastroenterology (ACG) 2011 Annual Scientific Meeting and Postgraduate Course: Abstracts P650, P120, P60, P283. Presented November 1, 2011.

TNF Blockers and Cancer: FDA Requires Increased Surveillance

2011-11-04T19:30:00.001-07:00

From Medscape Medical News > Alerts, Approvals and Safety Changes > Medscape AlertsEmma Hitt, PhDNovember 3, 2011 (UPDATED November 4, 2011) — The US Food and Drug Administration (FDA) announced today that it is requiring the manufacturers of tumor necrosis factor (TNF)-α blockers to perform enhanced safety surveillance of these drugs because of the potential risk for cancer in children and adults aged 30 years or younger.Manufacturers will be required to submit reports of all malignancies and, in the case of malignancy in pediatric and young adult patients, expedited reports (provided within 15 days)."This type of safety surveillance is important for our improved understanding of malignancies in pediatric and young adult patients treated with TNF blockers because it will allow FDA to more completely capture and analyze all reported malignancies based on more complete and consistent reports," the FDA states in an alert sent today from the Division of Drug Information of the FDA's Center for Drug Evaluation and Research'.The FDA recommends that healthcare professionals "remain vigilant" for TNF blocker–related malignancies and report them to the FDA's MedWatch program or to the manufacturer. They add that "healthcare professionals may be queried by FDA or the manufacturer for additional clinical and diagnostic information related to the malignancy cases."On November 4, 2011, MedWatch, the FDA's safety information and adverse event reporting program, sent out a new alert asking healthcare professionals to include specific information in its reports of malignancy in patients treated with TNF blockers. This information includes: patient characteristics (age, sex, no patient identifiers); risk factors for malignancy; exposure to other immune-suppressing products or products with risk for malignancy; indication for TNF blocker treatment; TNF blocker exposure (duration, dose); cancer diagnosis (date of diagnosis, stage); biopsy results; and outcomes of malignancy (treatments, event outcome)The FDA first warned of the increased risk for childhood and adolescent cancers associated with TNF blockers in 2008, and warnings were added to the product labels of these drugs in 2009.Today's announcement comes in the wake of several somewhat conflicting findings about TNF blockers and cancer risk.One report in the August 2010 issue of Arthritis & Rheumatism found that children treated with TNF-α blockers may have increased cancer risk but that cancer cases reported in these children were confounded by underlying illnesses and concomitant use of immunosuppressants.Likewise, another report found that TNF inhibitors used to treat rheumatoid arthritis (RA) may increase the risk for skin cancer (including melanoma) but did not appear to be associated with increased risk for other malignancies. The pooled analysis, published in the September 1, 2011, issue of the Annals of the Rheumatic Diseases, found negligible increase or no increase in overall risk of developing any cancer.However, several studies have demonstrated an increased risk with these agents. In the August 2011 issue of Rheumatology, a study including data from over 20,000 US military veterans showed that nonmelanoma skin cancer risk is about one third higher for patients with RA treated with TNF inhibitors than for similar patients treated with nonbiologic disease-modifying antirheumatic drugs.In addition, in April of this year, the FDA reported an association between hepatosplenic T-cell lymphoma in adolescents and young adults treated with TNF blockers, azathioprine, and/or mercaptopurine.Drugs included in the TNF blocker class include infliximab (Remicade, Centocor), etanercept (Enbrel, Amgen and Pfizer), adalimumab (Humira, Abbott Laboratories), certolizumab pegol (Cimzia, UCB), and golimumab (Simponi, Centocor Ortho Biotech Inc).Even in the absence of immunosuppressive drugs, a higher incidence of lymphomas has been found in patients being treated for RA, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.More information about the announcement is available on the FDA Web site and on the MedWatch Web site.Adverse events related to use of TNF blockers should be communicated to the MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

Distinguishing Alzheimer Disease From Other Major Forms of Dementia

2011-11-01T23:12:00.000-07:00

From Expert Review of NeurotherapeuticsStella Karantzoulis, PhD; James E. Galvin, MD, MPH10/20/2011 http://www.medscape.org/viewarticle/751357?src=cmemp Abstract and Introduction Distinguishing AD Dementia From Other Major Forms of Dementia Memory Language Visuospatial Skills Attention & Executive Functions Lack of Insight/Unawareness/Anosognosia Behavior, Mood, Personality & Psychiatric Symptoms Personality Extrapyramidal Symptoms Expert Commentary & Five-year View Key IssuesAbstractAlzheimer’s disease (AD) is the most common and most studied cause of dementia. Significant advances have been made since the first set of clinical criteria for AD were put forth in 1984 that are now captured in the new criteria for AD published in 2011. Key features include recognition of a broad AD spectrum (from preclinical to mild cognitive impairment to AD dementia) and requirement of AD biomarkers for diagnosis. Correctly diagnosing dementia type is increasingly important in an era when potential disease-modifying agents are soon to be marketed. The typical AD dementia syndrome has at its core, an amnestic syndrome of the hippocampal type, followed by associated deficits in word-finding, spatial cognition, executive functions and neuropsychiatric changes. Atypical presentations of AD have also been identified that are presumed to have a different disease course. It can be difficult to distinguish between the various dementia syndromes given the overlap in many common clinical features across the dementias. The clinical difficulty in diagnosis may reflect the underlying pathology, as AD often co-occurs with other pathologies at autopsy, such as cerebrovascular disease or Lewy bodies. Neuropsychological evaluation has provided clinicians and researchers with profiles of cognitive strengths and weaknesses that help to define the dementias. There is yet no single behavioral marker that can reliably discriminate AD from the other dementias. The combined investigation of cognitive and neurobehavioral symptoms coupled with imaging markers could provide a more accurate approach for differentiating between AD and other major dementia syndromes in the future.Key Issues Alzheimer’s disease (AD) is the most common form of dementia. There are 35 million individuals worldwide currently affected by the disease; and AD is projected to affect 115 million by 2050. Generally speaking, AD neuropathology initially involves medial temporal lobe structures (e.g., hippocampus and entorhinal cortex) and subsequently extends to temporal, parietal and frontal lobe association areas as the disease progresses. Neuropsychiatric symptoms are present throughout the course of AD. New diagnostic criteria for AD emphasize the importance of biomarker data in the definition of prodromal AD. The typical dementia syndrome continues to be described by prominent episodic memory impairment linked to early changes in the hippocampus and entorhinal cortex, with secondary deficits in word-finding skills, spatial cognition and executive functions. Atypical presentations of AD include posterior cortical atrophy, logopenic progressive aphasia and focal frontal variant AD. In posterior cortical atrophy, the onset is characterized by early, higher-order visual deficits and a higher density of neurofibrillary tangles in the occipital regions than in typical AD. Logopenic progressive aphasia is an atypical language variant defined as a primary phonological loop deficit leading to impaired memory, sentence repetition and comprehension, with sparse spontaneous speech and frequent prolonged word-finding pauses. Greater numbers of neurofibrillary tangles within the frontal lobes are seen in frontal variant AD, resulting in a more severe disease course. Episodic memory scores do not differ between behavioral variant frontotemporal dementia patients and AD patients, although the neural correlates of the memory impairment differs between the two patient groups. Lewy body dementia (LBD) tends to co-occur with AD in 80% of cases, with only 20% having pure LBD. Patients with pure Lewy body pathology have better verbal memory skills than those with pure AD or mixed LBD/AD. A fluctuating or step-wise course and history of strokes may help clinicians differentiate AD from mixed AD with cerebrovascular disease when their clinical profiles are otherwise indistinguishable. Subcortical vascular dementia is associated with primary deficits in information processing speed and executive functions, and secondary milder effects on memory. Personality changes are common among the dementias. They can occur in the very earliest stages of AD, prior to the onset of any obvious cognitive decline and can discriminate between AD and LBD (more passive traits in the LBD group). Personality changes appear to be more common in behavioral variant frontotemporal dementia than in AD. Current treatments for AD provide symptomatic relief either by improving symptoms or by delaying decline. Improving our understanding of the molecular mechanisms of AD has led to the identification of multiple potential targets for disease-modifying agents.

Pancreatic Cancer Possibly Detected by Salivary Bacteria

2011-11-01T23:03:00.000-07:00

From Medscape Education Clinical BriefsNews Author: Janis KellyCME Author: Charles P. Vega, MD10/20/2011 Clinical ContextPancreatic cancer is a solid tumor with particularly poor outcomes for patients, as reviewed by the authors of the current study. The 5-year survival rate of pancreatic cancer is only 5%, although this rate increases to approximately 20% among individuals with surgically resectable disease at the time of presentation.Cigarette smoking appears to be the most significant known risk factor for pancreatic cancer. Diabetes, insulin resistance, and obesity might also contribute to the risk for pancreatic cancer. The lack of biomarkers for early detection of pancreatic cancer contributes to its poor prognosis. The current study examines the value of changes in oral microbiota as an early warning sign for pancreatic cancer.Study Synopsis and PerspectiveA pair of bacteria in the saliva are associated with pancreatic cancer and chronic pancreatitis, according to a study published online October 12 in Gut. Although a press release from the journal attributes the suggestion that this finding "opens up the possibility of curbing the progress of one of the most difficult cancers to treat, by altering the balance of bacteria," to the researchers, they were, in fact, much more circumspect.According to lead author James J. Farrell, MD, MD, from the division of digestive diseases at the UCLA David Geffen School of Medicine in Los Angeles, California, the key finding is that the study provides proof of principle that differences in the microbiota in saliva can serve as noninvasive biomarkers for diagnosing and differentiating pancreatic cancer and chronic pancreatitis.Dr. Farrell told Medscape Medical News that "we need to validate the panel of salivary biomarkers, both bacterial and transcriptomic, in a larger prospective study, enrolling patients suspected of having pancreatic disease and cancer and following them over time. This is currently underway. The big unanswered question is: Are these bacteria causing or the result of the cancer? Most data from previous studies and studies in other disease suggest that the bacteria are directly or indirectly contributing to the development of pancreatic disease, likely through inflammation."Identifying BacteriaThe researchers used the human oral microbe identification microarray (HOMIM) to examine salivary microbiota in 10 patients with resectable pancreatic cancer and 10 matched healthy control subjects. They then used real-time quantitative polymerase chain reaction (qPCR) to identify the bacterial species or clusters that were notably different in the saliva of patients with pancreatic cancer and that of control subjects. Finally, they validated the candidate marker bacteria with qPCR on saliva from 28 patients with pancreatic cancer, 27 with chronic pancreatitis, and 28 control subjects.The initial analysis identified 31 bacterial species or clusters that were higher in the saliva of patients with pancreatic cancer than in control subjects, and 25 that were lower. Two of the 6 candidate bacteria validated in the independent samples were present at significantly different levels in the patient and control groups: Neisseria elongata and Streptococcus mitis. Furthermore, 2 bacteria (Granulicatella adjacens and S mitis) were present at different levels in patients with chronic pancreatitis and in control subjects.Causative Rather Than Reactive?Dr. Farrell's group then combined N elongata and S mitis and determined that the pair distinguished patients with pancreatic cancer from control subjects with 96.4% sensitivity and 82.1% specificity.The authors write that "whether a variation in bacterial abundance is a causative factor for cancer carcinogenesis or a derivational reflection of cancer onset due to the change of oral niches needs to be further explored in longitudinal.... Taken together [with the association between chronic pancreatitis and pancreatic cancer], these data suggest that the association between variations in oral microbiota and pancreatic disease may likely be causative rather than reactive."The authors note that they were unable to test for possible changes in oral bacteria after pancreatic cancer resection.They also note that "none of the bacterial biomarkers validated in this study was significantly altered in the microflora profile of lung cancer."Limitations in Study DesignHowever, Dominique Michaud, ScD, associate professor of community health at Brown University in Providence, Rhode Island, who reviewed the paper for Medscape Medical News, is more cautious. Dr. Michaud, whose research centers on causes of pancreatic and brain cancers, and who has studied periodontal disease and pancreatic cancer (J Natl Cancer Inst. 2007;99:171-175), said that although "this is an interesting preliminary study, it is far from conclusive. There are many limitations to the study design, including small numbers and lack of other diseased control subjects. These findings need to be replicated and cannot provide any information on causality. It is very possible that any immunocompromised patient would have the same profile of saliva bacteria, which means this would test would not be a useful clinical screening tool."Community HealthDr. Farrell told Medscape Medical News that his group is currently enrolling patients in a nested, case–control study to see how these biomarkers behave in a large general population to detect pancreatic disease, and that efforts are underway to convert the HOMIM, which is currently only a research tool, for patient and clinic-based salivary diagnostics.Dr. Farrell and Dr. Michaud have disclosed no relevant financial relationships. Coauthor David T.W. Wong, from the David Geffen School of Medicine, reports ownership of intellectual property related to the saliva diagnostics field.Gut. Published online October 12, 2011. Abstract

Thyroid Cancers Commonly Found Incidentally

2011-11-01T22:42:00.001-07:00

From Medscape Medical NewsNancy A. MelvilleOctober 31, 2011 (Indian Wells, California) — A significant increase in the incidence of thyroid cancer in recent decades might be largely attributable to cancers incidentally found with ultrasound and other types of imaging, according to research presented here at the American Thyroid Association 81st Annual Meeting.From 1975 to 2008, the incidence of thyroid cancer nearly tripled, increasing from 4.85 to 12.97 cases per 100,000. This increase is "more rapid than any other type of cancer," said coauthor Michael Malone, BS, a medical student at New York University Langone Medical Center in New York City.Recent studies have suggested that increasing diagnostic scrutiny largely explains the apparent rise in cancers.To evaluate the issue, Mr. Malone and his colleagues conducted a chart review of 404 patients who underwent initial surgery for well-differentiated thyroid cancer at the Langone Medical Center from January 2007 to August 2010.They found that of 307 (76%) patients with stage 1 or 2 thyroid cancer, 46% had their tumors initially detected with an imaging study; the rest were detected because the patient or physician felt a mass in the neck.Imaging studies were also the method of detection in 46 (47%) of the 97 (24%) patients with stage 3 or 4 well-differentiated thyroid cancer.Among the tumors detected with imaging, 58% were less than 1 cm, 53% were 1 to 2 cm, 31% were 2 to 4 cm, and 39% were greater than 4 cm, Mr. Malone noted.When tumors were detected with imaging, ultrasound was the leading modality, used in 104 (55%) patients, followed by computed tomography in 37 (20%) patients, magnetic resonance imaging in 19 (10%) patients, carotid duplex scan in 13 (7%) patients, and positron emission tomography or other imaging in 15 (8%) patients."It is important to note that these were sonograms that were not performed to evaluate something that was palpated on physical exam, but instead were performed for a variety of reasons, some appropriate and some not."Patients whose tumors were detected with imaging were more likely to be male (32% vs 21%; P = .013) and were older (median age, 52 vs 46; P = .0004) than those whose tumors were detected without imaging.The findings support the argument that imaging studies indeed heavily influence the rise in thyroid cancer incidence rates, Mr. Malone concluded."We feel that a substantial number of thyroid cancers are discovered by imaging rather than by palpation alone," he said. "This observation is true for small and large cancers, as well as early and advanced cancers.""As with small cancers, the increasing incidence of larger and more advanced thyroid cancers may be the result of increasing diagnostic scrutiny and may not necessarily represent a true increase in disease," he observed.Kenneth B. Ain, MD, professor of medicine and chair of cancer research at the University of Kentucky Medical Center, in Lexington, questioned whether the findings would hold true in a patient population outside of the New York City demographic."I think before you attempt to generalize, you should take into account the evidence of geography and different populations," said Dr. Ain."For example, the study deals with urban patients in population centers that have well-equipped medical centers, and many practitioners have unused ultrasound machines in their offices that have to generate money.""In that situation, I assure you that you'll have a huge number of case findings by ultrasound and not by palpation," he said.However, "if you take a rural population in eastern Kentucky, for instance, who have issues such as oxycontin use, smoking, and don't usually have ultrasound machines available, patients will generally present with palpable cancers and you will see the same increase in thyroid cancers among these patients as those in the big cities."He added that some of the data used for this study have also shown that thyroid cancer has the "second highest increasing cancer death rate among all ages and all sexes, and to merely state this increased case finding and not account for the fact that these cases are killing more people despite with our advanced therapeutics makes it a little curious."Kathryn G. Schuff, MD, of the Oregon Health & Science University in Portland, who moderated the session, said the study and the ensuing comments reflect a larger debate regarding the role of imaging in increasing thyroid cancer incidence rates."There are thyroidologists arguing on both sides of the issue," noted Dr. Schuff."Some say it's just imaging, others say it is a real increase, arguing that the increasing death rates indicate that this is not just an increase in 'small incidentally found' tumors. I don't think we have the answer to that particular question yet."Mr. Malone, Dr. Ain, and Dr. Schuff have disclosed no relevant financial relationships.American Thyroid Association (ATA) 81st Annual Meeting: Abstract 94. Presented October 28, 2011.

Yoga Improves Back Function in Patients With Low Back Pain

2011-11-01T22:39:00.000-07:00

From Medscape Medical News > NeurologyMegan BrooksOctober 31, 2011 — A study released today provides more evidence that yoga can help patients who suffer from chronic low back pain. Conducted in the United Kingdom, the study found that a 12-session, 3-month yoga program led to greater improvements in back function than usual care.However, yoga did not yield greater reductions in pain or improvements in overall health compared with usual care. "Although there was no evidence of pain reduction at 12 months, confidence in performing normal activities despite pain improved more in the yoga group than usual care group at 3 and 6 months," the study team notes.In terms of yoga studies for low back pain, this study is "the largest to date, with over 300 participants, and it has the longest follow-up of any trial," investigator David J. Torgerson, PhD, from the University of York's Department of Health Sciences, United Kingdom, told Medscape Medical News."We followed them up for 12 months (9 months after they had finished the yoga), and found that the benefit of yoga was sustained for this length of time, probably because a proportion of participants continued to practice yoga after they had completed their formal course," he said.Based on the findings in this study, "yoga could be recommended as a therapy for chronic low back pain," Dr. Torgerson said.The study was published November 1 in the Annals of Internal Medicine.Benefit "Sustained"The study involved 313 adults with chronic or recurrent low back pain. All of them received a back pain education booklet and usual care. In addition, 156 were offered Iyengar yoga classes (12 classes total, once weekly). The yoga classes were given by 12 yoga teachers who had extra training in back care. Each class lasted 75 minutes.In a statement, Iyengar yoga teacher and study investigator Alison Trewhela, DBL, said: "Yoga aims to treat the whole person — not just the physical." The yoga program offers "poses for pain-relief and mental calming; mobilizing, stretching, strengthening and relaxation; improving awareness of posture; education about how a healthy back functions; and positive mental focus," she explained.Sixty percent of patients in the yoga group attended at least 3 of the first 6 sessions and at least 3 other sessions. In the first 3 months, 82% said they practiced yoga at home on their own, 65% were practicing yoga at home at 6 months, and 60% were practicing yoga at home at 12 months.The researchers report that the yoga group had better back function at 3 months (the primary outcome) and at 6 and 12 months (secondary outcomes) than the usual care group."Although there is no consensus, a change of 1.1 to 2.5 on the RMDQ has been recommended as clinically important," the investigators note in their report. "In this trial, we found that individuals offered yoga benefited from, on average, 2.17 fewer limited activities at 3 months and by 1.57 fewer limited activities at 12 months."They note that they were missing data for the primary outcome for 21 yoga participants and 18 usual care participants, and differential missing data were observed (more so in the yoga group) for secondary outcomes.The yoga and the usual care groups had similar back pain and general health scores at 3, 6, and 12 months, and the yoga group had higher scores on the Pain Self-Efficacy Questionnaire at 3 and 6 months, but not at 12 months.Twelve (8%) of the 156 yoga patients reported adverse events; 1 adverse event was deemed as serious and possibly or probably related to yoga (the patient had experienced severe pain but had a history of severe pain after any physical activity).The other 11 adverse events in the yoga group were nonserious and were mostly related to increased pain. Adverse events were reported in 2 (1%) of the 157 patients in the usual care group (1 accident/injury, 1 death).Yoga Comparatively EffectiveOther interventions for low back pain that have been evaluated in randomized controlled trials include exercise and manipulation, the Alexander technique, and cognitive behavioral therapy, Dr. Torgerson and colleagues note in their report.Comparing the findings of their study with these other techniques, they say, "suggests that group yoga may improve back function (as measured by the RMDQ) more than exercise and manipulation, cognitive behavioral treatment, and 6 sessions of 1-on-1 Alexander technique but not as much as 24 sessions."They caution, however, against "overanalyzing these results because the comparisons are indirect." Further research is needed to compare yoga directly with these other treatments, they say.Additional support for yoga in chronic back pain comes from a study published online October 24 in the Archives of Internal Medicine.As reported by Medscape Medical News, the study found that stretching, regardless of whether it is achieved via yoga classes or conventional stretching exercises, has moderate benefits in adults with moderately impairing chronic low back pain.In a comparative effectiveness study, the researchers found that yoga classes were more effective than a self-help book, but not more effective than stretching classes, in improving function and reducing symptoms resulting from chronic low back pain, with benefits lasting at least several months.The author of a comment on the article in the Archives of Internal Medicine called the results from this trial "actionable" for practice because they reinforce the evidence that exercise is safe and moderately beneficial for chronic low back pain."Health care providers should feel comfortable referring patients to either yoga or [physical therapy–]led classes; either seems to be helpful," writes Timothy S. Carey, MD, MPH, from the Sheps Center for Health Services Research, University of North Carolina, Chapel Hill.The current study was supported by Arthritis Research UK. Disclosures can be viewed on the journal's Web site.Ann Intern Med. 2011;155:569-578. Abstract

Explaining Gender Differences in Non-fatal Suicidal Behaviour Among Adolescents

2011-10-26T20:21:00.000-07:00

From BMC Public HealthExplaining Gender Differences in Non-fatal Suicidal Behaviour Among AdolescentsA Population-based StudyMichael Kaess; Peter Parzer; Johann Haffner; Rainer Steen; Jeanette Roos; Martin Klett; Romuald Brunner; Franz ReschPosted: 09/27/2011; BMC Public Health. 2011;11(597) © 2011 BioMed Central, Ltd.Background While suicide is the second leading cause of death among young people in most industrial countries, non-fatal suicidal behaviour is also a very important public health concern among adolescents. The aim of this study was to investigate gender differences in prevalence and emotional and behavioural correlates of suicidal behaviour in a representative school-based sample of adolescents.Methods A cross-sectional design was used to assess suicidal behaviour and various areas of emotional and behavioural problems by using a self-report booklet including the Youth Self-Report. One hundred sixteen schools in a region of Southern Germany agreed to participate. A representative sample of 5,512 ninth-grade students was studied. Mean age was 14.8 years (SD 0.73); 49.8% were female.Results Serious suicidal thoughts were reported by 19.8% of the female students and 10.8% of the females had ever attempted suicide.In the male group, 9.3% had a history of suicidal thoughts and 4.9% had previously attempted suicide. Internalizing emotional and behavioural problems were shown to be higher in the female group (difference of the group means 4.41) while externalizing emotional and behavioural problems slightly predominated in male students (difference of the group means -0.65). However, the total rate of emotional and behavioural problems was significantly higher in the adolescent female group (difference of the group means 4.98). Using logistic regression models with suicidal thoughts or attempted suicide as dependent variables, the pseudo-R2 of gender alone was only 2.7% or 2.3%, while it was 30% or 23.2% for emotional and behavioural problems measured by the YSR syndrome scales. By adding gender to the emotional and behavioural problems only an additional 0.3% of information could be explained.Conclusions The findings suggest that gender differences in non-fatal suicidal behaviour among adolescents can to a large extent be explained by the gender differences in emotional and behavioural problems during this age.BackgroundSuicide and non-fatal suicidal behaviour are both well-recognized public health problems in young people.Whereas the prevalence of suicide and suicidal behaviour remains relatively low before puberty, adolescent suicide is one of the leading causes of death in the teenaged group.In Europe, suicide is the second leading cause of death in male and female adolescents. In the USA, suicide is reported to be the third leading cause of death after accidents and homicides.According to the findings of a WHO multi-centre study conducted in young people 15 to 24 years of age, the increase in suicide has been shown to be associated with an increase in suicide attempts. Results of a systematic review of 128 studies on the prevalence of suicidal phenomena in adolescents revealed that, on average, 9.7% (95% CI 8.5 to 10.9) of adolescents reported to have attempted suicide while even 29.9% (95% CI 26.1 to 33.8) of these adolescents indicated having thought about suicide at some point in their life.One of the strongest predictors of completed suicide or further suicide attempt has been found to be a previous suicide attempt.Therefore, suicide attempts and also suicidal thoughts in adolescents must always be taken seriously, in spite of the fact that for every death of a young person from suicide, many suicide attempts have already been undertaken, especially by girls.In most western countries, females are more likely to engage in suicidal behaviour, but are less likely to die as a result of a suicidal act than males.This "gender paradox" is known to be extremely distinctive in adolescents; during this period of life suicide attempts are 3–9 times more common in girls while completed suicides rates are 2–4 times higher in adolescent males.Many epidemiological studies so far have reported higher rates of non-fatal suicidal behaviour in females which could indicate a gender-specific predisposition for the experience of suicidal thoughts and suicide attempts during this life-period.As regards mental illness as one of the strongest risk factors for suicidal behaviour, depression and anxiety in particular seem to function as mediators of adolescent suicidal behaviour.But drug abuse, risk behaviours and other types of externalizing psychopathological behaviours are also associated with an increased risk of suicide among adolescents.There is only little empirical research which investigated the reasons underlying the correlation of being female and showing higher rates of suicidal thoughts and suicide attempts during adolescence. One theory is that gender differences in psychopathology could play an important role in this issue, suggesting that different types and characteristics of emotional and behavioural problems may primarily lead to unequal rates of suicidal behaviour in female and male individuals. Therefore, our hypothesis was that gender differences in non-fatal suicidal behaviour among adolescents could mainly be explained by the gender differences in emotional and behavioural problems.

Losing Weight by Midlife Reduces CVD Risk

2011-10-26T19:53:00.000-07:00

From HeartwireHarvard alumni study of early and midlife coronary disease riskReed MillerOctober 26, 2011 (Cambridge, Massachusetts) — A study of Harvard alumni shows that obesity early in life does not portend a coronary disease death in people who reach a healthier weight by their mid-40s.The National Institutes of Health–sponsored Harvard Alumni Health Study has followed nearly 19 000 men who began regular medical examinations during their undergraduate years at Harvard University between 1916 and 1950. The median follow-up period was 56.4 years and the maximum was 82.5 years. The authors report their findings in the October 24, 2011 issue of the Archives of Internal Medicine.Investigators Dr Linsay Gray (Medical Research Council, Glasgow, Scotland) and colleagues found that Harvard men who were obese in early adulthood had twice the risk of dying from coronary disease as men with a normal body-mass index as young men (18.5 to 28 years). The association between obesity as young men and cardiovascular mortality later on held even after adjustment for confounding variables in early adulthood such as smoking and physical activity and after adjustment for midlife risk factors including type 2 diabetes and hypertension.However, the link seen between early obesity (18.4 years) and later coronary disease death disappeared after taking into account midlife body-mass index (46.1 years), suggesting that men who were obese when they were young can reduce their risk by reaching a normal weight by middle age. The authors caution that their results should be replicated in more studies with a broader population.Commenting on the study, Archives editor Dr Rita Redberg (University of California, San Francisco) writes that this study "brings us some reason for hope that efforts to address childhood obesity are well worth it, [and] it is never too late to adopt healthy lifestyle changes."

Chest X-Ray Screening Does Not Reduce Lung Cancer Mortality

2011-10-26T19:51:00.000-07:00

From Medscape Medical NewsLaird HarrisonOctober 26, 2011 (Honolulu, Hawaii) — The largest study yet to examine the issue shows that screening with chest radiographs does not reduce mortality from lung cancer, researchers reported here at CHEST 2011: American College of Chest Physicians Annual Meeting.The results, which were also published online October 26 in JAMA, confirmed earlier research on the issue but still came as a disappointment. "We were hopeful the chest X-rays we did would make a difference," coauthor Paul A. Kvale, MD, told Medscape Medical News.Putting these findings together with a those of study published in August in the New England Journal of Medicine, health policy groups are likely to recommend screening with low-dose computed tomography (CT), but not chest X-ray, and only for patients at high risk for lung cancer, said Dr. Kvale, a pulmonologist at Henry Ford Hospital in Detroit, Michigan.For the current study, part of the Prostate, Lung, Colorectal and Ovarian Cancer Cancer Screening Trial, researchers enrolled 154,901 participants aged 55 through 74 years. "This was the biggest study of its kind ever done," said Dr. Kvale.The investigators randomly assigned 77,445 of the patients to receive annual screenings with chest X-rays, and 77,456 to receive usual care, at 1 of 10 centers across the United States between November 1993 and July 2001.They offered participants in the screening group annual posterio-anterior view chest radiographs for 4 years. The participants in the usual care group were not offered screenings as part of the study, although 11% undertook chest X-rays independent of the study.Between 79% and 87% of the participants in the screening group got the X-rays offered each year.Researchers followed-up the patients for a maximum of 13 years until December 31, 2009.They tallied a lung cancer incidence of 20.1 per 10,000 person-years in the screening group and 19.2 per 10,000 person-years in the usual care group, for a rate ratio (RR) of 1.05 (95% confidence interval, 0.98 - 1.12).They counted 1213 deaths from lung cancer in the screening group compared with 1230 in the usual care group, for an RR of 0.99 (95% confidence interval, 0.87 - 1.22).The study avoided problems of previous studies, such as a large number of screenings in the control group, but still came up with the same bottom line, said Dr. Kvale.Another important aspect of the study was its analysis of a subgroup of patients who were at high risk for lung cancer because of their age, smoking, and other factors. Just as in the study as a whole, researchers randomly assigned 15,183 members of this subgroup to screening, and the same number to usual care.After 6 years of follow-up, 518 members of the high-risk screening group got lung cancer, and 316 died of the disease. In the high-risk usual care group, 520 got lung cancer and 334 died of it, for an RR of 0.94 (95% confidence interval, 0.81 - 1.10).The high-risk group was intentionally selected to match a high-risk group in the National Lung Screening Trial, published in the New England Journal of Medicine. In that study, researchers compared high-risk participants screened with chest X-rays with high-risk patients screened with low-dose CT. They concluded that the low-dose CT screening reduced the mortality rate of these patients by 20%.If low-dose CT screening is 20% better than X-ray screening, and X-ray screening is the same as usual care, then it would be logical to assume that CT screening is 20% better than usual care. However, more statistical analysis should be done before reaching that conclusion, writes Harold C. Sox, MD, from Dartmouth Medical School in West Lebanon, New Hampshire, in an editorial published along with the study in JAMA. New studies should directly compare usual care to low-dose CT-screening, Dr. Sox writes.Still, the findings are already being taken into consideration by a coalition of groups working on new guidelines for lung cancer screening, said Frank C. Deterrbeck, MD, chief of thoracic surgery at Yale University, New Haven, Connecticut, and cochair of the coalition.The coalition, made up of the American College of Chest Physicians, the American Cancer Society, the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and to a lesser extent, the American Thoracic Society, will publish new guidelines within a few months, Dr. Deterrbeck told Medscape Medical News.However, he would not confirm that the guidelines will call for low-dose CT screening for everyone who is at high risk for lung cancer. "I think there is a potential benefit, as well as a potential harm," he said. "Selection of the appropriate population is something we have to pay careful attention to."Although low-dose CT poses a low risk from radiation, it often leads to other diagnostic procedures, some of which may not be necessary. "Low-dose CT picks up a lot of stuff that's nothing," he said.On the basis of the low-dose scans, patients may be referred for regular CT, with its higher doses of radiation, and for biopsies, which can cause complications.The cost questions are complicated, too, Dr. Deterrbeck said, as the expense of the screening must be weighed against the costs that are saved in treatment costs if cancer is caught earlier.However, the short-term implications of the study are clear, he said. "We have not employed X-rays as a screening tool for lung cancer, and I guess we won't."Dr. Kvale and Dr. Detterrbeck have disclosed no relevant financial relationships. Dr. Sox has disclosed that he is an unpaid member of advisory boards for the Southwest Oncology Group and the Fred Hutchinson University of Washington Cancer Consortium.JAMA. Published online October 26, 2011. Full text, EditorialCHEST 2011: American College of Chest Physicians Annual Meeting: Session 7225. Presented October 26, 2011.

Physical Activity Cuts Risk for Invasive Breast Cancer

2011-10-26T19:45:00.000-07:00

From Medscape Medical News > OncologyRoxanne NelsonOctober 26, 2011 (Boston, Massachusetts) — Data supporting the association between physical activity and a reduced risk for breast cancer are increasing. Adding to these data are the results of a large European study, presented here at the Tenth Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research.When the researchers compared the highest and lowest quartiles of physical activity, the risk for invasive tumors was inversely associated with high levels of total physical activity (hazard ratio [HR], 0.85; P trend < .001), especially recreational activity (HR, 0.88; P < .001).However, no association was seen between in situ carcinoma and any of the physical activity variables.The researchers also looked at the effect of physical activity on breast cancer risk by receptor status, and note that this is the largest prospective study to do so. Previous studies investigating this issue have yielded inconsistent results, explained study author Karen Steindorf, PhD, from the German Cancer Research Center in Heidelberg.The researchers found a significant protection of physical activity only for the estrogen-receptor (ER)-positive and progesterone-receptor (PR)-positive tumor types, said Dr. Steindorf. "These findings strengthen the hypothesis that lowering breast cancer risk with physical activity is at least partly related to hormonal pathways."The association between breast cancer risk and physical activity also differed by menopausal status. "There were significant risk reductions in postmenopausal breast cancer," she said, adding that the risk reductions were a little lower in premenopausal women.Among postmenopausal women, the risk reduction was significant for both total physical activity (HR, 0.81; P = .002) and recreational activity (HR, 0.89, P = .005). These results were slightly less robust for premenopausal breast cancer for total physical activity (HR, 0.87; P = .082) and for recreational activity (HR, 0.84; P = .032)."I would say that this adds to the evidence of what we have already seen in other research — that physical activity may reduce the risk of breast cancer," said Karen T. Liby, PhD, research assistant professor of medicine at Dartmouth Medical School, Hanover, New Hampshire, who was not involved in the study. "But it seems to be effective only in receptor-positive cancers."Exercise Linked to Lower RiskAs previously reported by Medscape Medical News, postmenopausal women who maintain a regular moderate to vigorous exercise program can reduce their risk for breast cancer by 20% to 40%.In addition, research has shown that physical activity can reduce the risk in premenopausal women; among the most active women, risk reduction can be as high as 23%.Other data have shown that obesity and lack of physical activity can increase the risk for triple-negative breast cancer.Protective Effects ConfirmedDr. Steindorf and colleagues used data from the European Prospective Investigation Into Cancer and Nutrition (EPIC), a large study designed to investigate the relation between diet, nutritional status, and lifestyle and environmental factors and the incidence of cancer and other chronic diseases. The trial has recruited 520,000 people from 10 European countries.Detailed information on recreational household physical activity, occupational physical activity, and other variables was assessed in a baseline examination conducted between 1992 and 2000. The cohort in this trial involved 283,680 women; within this group, at a median follow-up of 11.7 years, there were 9947 incident breast cancer cases, including 1060 cases of in situ carcinoma. Of the 8887 invasive breast cancer cases, it was possible to assess the ER status of the tumor in 6007 cases (67.6%), the PR status in 4814 cases (54.2%), and the combined status in 4798 cases (53.9%).When analyzed by hormone-receptor status, stronger effects of total physical activity were seen for ER-positive/PR-positive breast tumors than for other combinations (P = .043 for heterogeneity). A more detailed analysis revealed that it was primarily the PR status (P = .006 for heterogeneity), not the ER status (P = 0.235 for heterogeneity), that dominated this result.The protective effect of physical activity on breast cancer risk is confirmed with these results, note the researchers. "The results of this largest prospective study on physical activity and different hormone-receptor status indicate that physical activity primarily reduces the risk for PR-positive and ER-positive/PR-positive tumors," they conclude.Tenth Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research. Presented October 24, 2011.

PSA Screening: USPSTF Review

2011-10-24T19:25:00.000-07:00

From Medscape Education Clinical BriefsDraft Guidelines Recommend Against PSA Screening: USPSTF Review CME/CENews Author: Zosia ChusteckaCME Author: Charles P. Vega, MDClinical ContextFew topics in the field of preventive medicine are contentious as prostate cancer screening. Widespread screening for prostate cancer has had a remarkable effect on the epidemiology of this tumor, as demonstrated in a study by Welch and Albertsen published in the October 7, 2009, issue of the Journal of the National Cancer Institute. Their study found that the introduction of routine prostate cancer screening led to approximately 1.3 million more men being diagnosed with prostate cancer in the United States alone. Men younger than 60 years accounted for most of this surge in cases. The authors estimated that more than 20 additional men would have to be diagnosed with prostate cancer through screening to result in a single case of reduced mortality risk from prostate cancer.These findings are fairly pessimistic regarding the value of prostate cancer screening. The current study commissioned by the US Agency for Healthcare Research and Quality provides a more complete review of important issues in screening for prostate cancer.Study Synopsis and PerspectiveThe US Preventive Services Task Force issue draft recommendations against routine screening for prostate cancer using the prostate-specific antigen (PSA) test in the United States, where it is currently used more than in any other country in the world. As a result, prostate cancer is the most commonly diagnosed cancer in American men.The USPSTF draft recommendation against routine screening with the PSA test was to have been published October 11 in the Annals of Internal Medicine, but the entire draft paper was leaked and posted October 6 on the Cancer Letter Web site, in "an egregious breach of our embargo and media policies," according to the journal. The news has since been widely disseminated on the Internet; as a result, the journal published the paper early.The USPSTF already recommends against routine PSA screening in men older than 75 years. In the new draft recommendation, it extends this to all men. It now recommends against routine screening in men younger than 75 years, giving this a "D" rating, which means "there is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits."The news is likely to spark a furor in medical circles, not unlike the outcry that followed the USPSTF's recommendation in 2009 against routine mammography screening for breast cancer in women younger than 50 years. This provoked outrage from some breast cancer experts, patient advocates, and professional societies, with accusations that this was a move toward the "rationing" of healthcare.Angry reactions to the latest news have already begun. The "decision of no confidence on the PSA test by the US government condemns tens of thousands of men to die," said Skip Lockwood, CEO of ZERO, the Project to End Prostate Cancer. ZERO is sponsored by many organizations with a stake in prostate cancer, such as Abbott, Beckman Coulter, Accuray, CyberKnife, Dendreon, and the American Urological Association (AUA).Based on Reviews of TrialsThe recommended change is based on a review of 5 randomized trials of screening and 3 trials and 23 cohort studies of treatments. Included in the review were the 2 largest trials of PSA screening, which reported conflicting results, the USPSTF notes.The European study found a reduction in mortality after 9 years of screening, but the American trial, which had high crossover and contamination rates, found no reduction in mortality after 10 years of screening, as previously reported by Medscape Medical News.The review also noted that treatment for prostate cancer, such as prostatectomy and radiation, is associated with risks for problems such as erectile dysfunction, urinary incontinence, and bowel dysfunction.The USPTSF concludes that "after about 10 years, PSA-based screening results in small or no reduction in prostate-cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary."Delay in AnnouncementThis recommendation has been a long time coming, according to reports in the October 7 issue of the Cancer Letter and in the New York Times magazine. They assert that the timing of the release of this recommendation was influenced by political considerations. According to these reports, the task force first voted to recommend against routine PSA screening back in November 2009, but this "caused a violent political firestorm," and subsequent follow-up meetings were cancelled. The final vote was taken in March. After this, a paper summarizing the recommendation was submitted to the Annals of Internal Medicine, where is it expected to appear next week.PSA Test is Not SpecificThe main problems with the PSA test are that it is not specific for prostate cancer and it cannot differentiate between aggressive and indolent forms of the disease."It cannot distinguish cancer that will never make a difference in a man's lifetime from cancers that will make a difference," so might prompt men to undergo aggressive treatment unnecessarily, Virginia Moyer, MD, MPH, chair of the USPTSF panel that made the recommendation, stated in an interview yesterday with Bloomberg News. "So you go from being a guy who feels fine and who is potentially one of the majority who would never have known they had this disease, to being a guy who wears adult diapers," she said. Dr. Moyer is a professor of pediatrics at Baylor College of Medicine in Houston, Texas.The PSA test is "hardly more effective than a coin toss," said Richard Ablin, PhD, research professor of pathology at the University of Arizona College of Medicine in Tucson. Dr. Ablin discovered PSA in 1970. Using this test to screen for prostate cancer in the general population has been a "hugely expensive public health disaster," he wrote in an opinion piece in the New York Times last year."Drug companies continue peddling the tests, and advocacy groups push 'prostate cancer awareness' by encouraging men to get screened," he wrote. "The medical community must confront reality and stop the inappropriate use of PSA screening," he stated. "Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatment."Although PSA testing is recognized as being imperfect, it is the only test for prostate cancer that is widely available, and it does provide information that can be useful, proponents point out. One of the professional bodies that has long supported the use of the test, the AUA, emphasizes that it should not be used on its own, but needs to be combined with other information (such as family history).The AUA issued a statement in reaction to the new USPSTF recommendations: "We are concerned that the Task Force's recommendation will ultimately do more harm than good to the many men at risk for prostate cancer, both here in the United States and around the world.""The AUA's current clinical recommendations support use of the PSA test, and it is our feeling that, when interpreted appropriately, the PSA test provides important information in the diagnosis, pretreatment staging or risk assessment, and posttreatment monitoring of prostate cancer patients," according to the statement."Not all prostate cancers require active treatment and not all prostate cancers are life-threatening," the statement points out, and the decision of whether to proceed to active treatment or whether surveillance is an option needs to be discussed in detail with the patient.The Agency for Healthcare Research and Quality supported this study. Author disclosure information is available on the Annals of Internal Medicine Web site.Ann Intern Med. Published online October 7, 2011.

Testosterone May Not Treat ED

2011-10-24T18:39:00.000-07:00

From WebMD Health NewsStudy: Testosterone May Not Treat EDDenise MannOctober 24, 2011 — Many men may be taking supplements of the male sex hormone testosterone to boost their sex drive, but it may not be that helpful after all.A new study of men 60 and older who had low or borderline low levels of testosterone showed that testosterone replacement therapy did not improve erectile dysfunction (ED) or their ability to achieve and maintain an erection, compared to a placebo gel.Men who used either a low dose or a conventional dose of testosterone gel showed no improvements in their sexual function during the course of the year-long study, compared with men who used placebo gel.The findings were presented at the annual meeting of the American Society for Reproductive Medicine in Orlando, Fla."It appears that testosterone supplementation will not improve ED, though it may have other benefits on sexual function that were not evaluated with this data," says study researcher Lauren W. Roth, MD, an obstetrician/gynecologist at the University of Colorado in Denver, in an email.Sexual function is one of many reasons that many men are turning to testosterone therapy. With a laundry list of promises from a boost in sex drive and more energy to an increase in muscle mass and mental acuity, testosterone therapy can be tempting for many men who want to feel and look younger than they do.But, according to some experts, the hormone may be more harmful than helpful for some men."I am quite concerned about the rampant use of testosterone replacement therapy for very soft indications," says Rebecca Sokol, MD. She is a professor of medicine and obstetrics and gynecology and the director of the andrology program at the Keck School of Medicine of the University of Southern California in Los Angeles. "It is very much a buyer beware situation.""We have to be very cautious about who we do and do not start on testosterone," Sokol says.Risks of Testosterone SupplementsThere are risks attached to the use of testosterone, Sokol says. "This hormone may cause the prostate gland to increase in size, and there is also the theoretic risk that we can stimulate the growth of cancer cells in the prostate. We have been looking carefully to see if testosterone initiates prostate cancer and there is no data to indicate that it does at this point."Testosterone may also increase levels of LDL "bad" cholesterol while decreasing levels of HDL "good" cholesterol, she says.Men who are considering taking testosterone need to weigh the pros and cons carefully with their doctor."The patient really needs to be evaluated by a physician who is an expert in hormones and male reproduction," Sokol says. "The indication for treatment needs to be very clear and verified by evaluation and physical exam."Checking for Low Levels of TestosteronePart of the problem is that men are getting their testosterone from non-expert sources, including their buddies in the gym and online, says Joseph P. Alukal, MD. He is an assistant professor of urology and the director of male reproductive health at New York University's Langone Medical Center in New York City.Testosterone replacement does have a role in treating some men with erectile dysfunction who also have low levels of the hormone, he says."Testosterone is one of the treatments we have, but it's not the only one."The first step is to measure a man's testosterone levels to see if they are low. This needs to be done on more than one occasion to make sure the results are accurate, he says.If levels are low, and there are no other health problems that may be causing the problems with sexual functioning, testosterone replacement therapy is an option, Alukal tells WebMD.In some men, ED can be a red flag for heart problems. In these cases, men will likely need to see a cardiologist, he says."Hormones are powerful," Alukal says. "They have tremendous benefits and significant risks, so to go on them requires proper monitoring by a physician who understands their risks and benefits and knows how to monitor men."Doctors who prescribe testosterone should monitor the prostate gland closely, he says."We know that there is some relationship between testosterone and the growth of the prostate and the development of prostate cancer, but we don't fully understand the relationship," Alukal tells WebMD.SOURCES:Lauren W. Roth, MD, ob-gyn, University of Colorado, Denver.Joseph P. Alukal, MD, assistant professor of urology; director of male reproductive health, New York University Langone Medical Center.Annual Meeting of American Society for Reproductive Medicine, Orlando, Fla. Oct. 15-19, 2011.Rebecca Sokol, MD, professor of medicine and obstetrics and gynecology; director of andrology program, Keck School of Medicine, University of Southern California, Los Angeles.

Chronic Inflammation May Mean Early Menopause

2011-10-24T18:34:00.000-07:00

From Medscape Medical NewsMegan BrooksOctober 21, 2011 (Orlando, Florida) — Women with psoriasis, rheumatoid arthritis, inflammatory bowel disease, or systemic lupus erythematosus have an increased risk for both early menopause (before 45 years of age) and premature ovarian failure, new research confirms."Our findings support and add to existing studies," Janet F. McLaren, MD, from the division of reproductive endocrinology and infertility, University of Alabama, Birmingham, told Medscape Medical News. She presented the research here at the American Society for Reproductive Medicine 67th Annual Meeting.Dr. McLaren and colleagues from the University of Pennsylvania School of Medicine in Philadelphia reviewed the records of more than 1.7 million women of reproductive age (15 to 45 years). They accomplished this using The Health Improvement Network, an electronic medical records database.The researchers looked for diagnostic codes for psoriasis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. "These are the 4 most prevalent conditions in women of reproductive age," Dr. McLaren noted. Women without these conditions comprised the comparator group.Results of unadjusted analyses point to a 2- to 5-fold increased risk for both early menopause and premature ovarian failure in women with these common chronic inflammatory diseases, Dr. McLaren reported.IBD Finding Novel?"It's known that women with lupus have antiovarian antibodies and that they have premature ovarian failure," Dr. McLaren said. "Some studies have suggested that there is an earlier age at menopause in women with rheumatoid arthritis, and there are some older publications that show that the number of children they have is slightly lower than other women," she added.However, she said she has not been able to find any studies showing an increased risk for menopause in women with inflammatory bowel disease.The researchers controlled for smoking, body mass index, previous pelvic surgery, socioeconomic status, and drug therapy. After adjustment for these factors, psoriasis, rheumatoid arthritis, and inflammatory bowel disease were no longer associated with premature ovarian failure; lupus, however, remained associated, with an odds ratio of 2.5."It is still likely," Dr. McLaren said, "that all of these diseases are associated with premature ovarian failure. It's just when you control for the medications, you control for the severity of the disease; so it's 'confounding by indication' — the more severe patients are getting the more aggressive medications.""Further research is needed to [determine] if the effect is due to the underlying illness or treatment," the study team notes in a meeting abstract.Dr. McLaren said adjusted analyses for early menopause have not been completed yet. "The next step of the project is to look more specifically at the different disease exposures and see which of these exposures are highly associated with early menopause," Dr. McLaren said.The study was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships.American Society for Reproductive Medicine (ASRM) 67th Annual Meeting: Abstract 10. Presented October 17, 2011.

Exercise a Viable Treatment Option for Mental Illness

2011-10-21T18:59:00.000-07:00

Medscape Medical News from the: Canadian Psychiatric Association (CPA) 61st Annual ConferenceExercise a Viable Treatment Option for Mental IllnessAbsence of Guidelines Should Not Be a BarrierCaroline CasselsOctober 21, 2011 (Vancouver, British Columbia) — Exercise is an effective, but potentially underused, treatment option for mental illness, experts say.In a symposium presented here at the Canadian Psychiatric Association (CPA) 61st Annual Conference, Christopher Willer, MD, a senior psychiatry resident at the University of Toronto, Ontario, Canada, made the case for exercise as an adjunctive therapy.Emerging research, he said, strongly suggests that exercise can improve patients' physical and mental health and may help offset some of the metabolic effects associated with older antidepressants and newer atypical antipsychotics."It's not too soon to talk to patients about exercise as another treatment option, especially if they are asking about it or if they have a history of sport being important in their lives."There's often a time lag between the time research comes out and when treatment guidelines are published. Based on the quality of the research that has been published [on exercise and mental illness] in the last 5 years, I think it would be irresponsible to wait," Dr. Willer told Medscape Medical News.In his presentation, Dr. Willer reviewed the existing literature for aerobic exercise as a treatment for mental illness, some of which suggests it can be as effective as pharmacotherapy and/or talk therapies.However, potential mental health benefits aside, Dr. Willer noted that the physical benefits of exercise are clear and include reducing cardiovascular risk factors that are often associated with mental illness and the medications used to treat psychiatric disorders."Exercise mitigates certain illnesses; it protects against obesity, which certainly is a big problem with much of our patient population; and it has been shown to help with cognition and affective problems in well people."As psychiatrists, we have to remember that we're not just concerned with our patients' psychiatric symptoms but also their physical health. It is important that we promote an active lifestyle to our clients as part and parcel of good psychiatric treatment," he said.Antianxiety PropertiesEarly research examining exercise and depressive symptoms has been relatively simple, relying on case reports or short-term intervention studies. However, said Dr. Willer, in the past 5 years it has become more sophisticated."We've come a long way, and now there are randomized trials that are attempting to compare exercise to a sham version of exercise that include larger numbers of patients, so the studies are higher quality," he said.Most of the evidence to date supports the use of aerobic exercise in unipolar depression, he added.However, a Cochrane review published in 2010 and reported by Medscape Medical News at that time showed that regular physical exercise in individuals with schizophrenia and schizophrenia-like illnesses is feasible and may help improve the mental and physical well-being of these patients.Nevertheless, although the overall results were positive, the review included only 3 small studies, prompting the authors to point out that larger randomized trials are needed "before any definitive conclusions can be drawn."Dr. Willer also noted that physical activity has been shown to have antianxiolytic properties.In patients with anxiety, sometimes there is a concern that the somatic expression of exercise — elevated heart rate, sweating, and heavy breathing — may invoke a panic response, but the literature does not bear this out, said Dr. Willer."There are studies that suggest that in the moment, anxiety can be moderated by physical activity, and there are also studies showing 20 minutes of exercise a day for 10 weeks can modify on trait anxiety," he added.Worthwhile EndeavorDr. Willer pointed out that only about 30% of North Americans get the recommended amount of 150 minutes of exercise per week, and that the therapeutic dose for the treatment of mental illness is unclear. However, he noted, as the research becomes more refined, this will be elucidated.In the meantime, he said, encouraging psychiatric patients to become more physically active is a worthwhile endeavor."It is not expensive, and it can be independent of the healthcare system. It doesn't require [the psychiatrist] to be involved, other than to mentor patients and to check in with them," he said.Asked by Medscape Medical News to comment on Dr. Willer's presentation and assertion that psychiatrists should consider exercise as a viable treatment option, Saul Marks, MD, a practicing sports psychiatrist at North York General Hospital in Toronto, said it is a routine part of his practice."Exercise confers a definite benefit. I have a patient myself who was able to come off antidepressant medication by taking up running, and she is doing extremely well now. There is a growing body of literature that psychiatric patients are at particular risk of metabolic syndrome, especially if they are taking atypical antipsychotics, suggesting psychiatrists need to promote exercise as a treatment," said Dr. Marks.Dr. Marks added that he routinely talks to his patients about the importance of being physically active every day."Even if they do something as simple as walking for 45 minutes a day, that will keep them physically fit and also help their mental health," he said.Dr. Willer and Dr. Marks have disclosed no relevant financial relationships.Canadian Psychiatric Association (CPA) 61st Annual Conference: Abstract S11b Presented October 13, 2011.

EMA Reviewing Safety of NSAIDs, Clarifies on Pioglitazone

2011-10-21T18:35:00.000-07:00

From Heartwire > Alerts, Approvals and Safety Changes > AlertsMichael O'RiordanOctober 21, 2011 (London, United Kingdom) — The European Medicines Agency (EMA) has launched a new review of the cardiovascular safety of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), while also clarifying a previous opinion on the use of the antidiabetic agent pioglitazone (Actos, Takeda) and the risk of bladder of cancer.In 2011, the EMA recommended that new contraindications and warnings be added to the label of pioglitazone, noting there was a small increased risk of bladder cancer with the diabetes drug. Today, the agency confirmed their previous opinion, with the earlier warnings and contraindications remaining in place, but provided some clarification on its use. The EMA stated that pioglitazone should be used as a second- or third-line treatment, noting it "remains a valid treatment option for certain patients with type 2 diabetes, when certain other treatments (metformin) have not been suitable or have failed to work adequately."Based on the earlier recommendations, the EMA continues to recommend against the use of pioglitazone in patients with current or a history of bladder cancer, or those with uninvestigated macroscopic hematuria. Before use in any patient, physicians should take into account risk factors for bladder cancer, especially in older patients, according to the EMA.In June 2011, the US Food and Drug Administration informed physicians that using pioglitazone for more than 12 months was associated with an increased risk of bladder cancer, and revised the drug's label to highlight the risks. French regulators suspended sales of pioglitazone, also in June 2011, while German health authorities said it should not be started in new patients.NSAIDs Also Under ReviewIn a separate statement, the EMA also said that it has begun a new review of the latest data on the cardiovascular safety of nonselective NSAIDs. In 2006, the EMA's Committee for Medicinal Products for Human Use (CHMP) concluded the drugs were safe for use, with a positive overall risk–benefit profile, but was unable to rule out a small risk of thrombotic events, especially when used at high doses or for long durations.Since 2006, new studies on the cardiovascular safety of NSAIDs have been published, including data from the Safety of Nonsteroidal Anti-inflammatory Drugs (SOS) project, led by investigators from Erasmus University in Rotterdam, Germany, the EMA notes. CHMP is currently reviewing data from SOS, as well from other clinical trials, epidemiological studies, and post marketing reports, to determine if there is a need to update their 2006 opinion on the safety of NSAIDs.

Less Frequent Testing for Cervical Cancer Proposed

2011-10-20T20:57:00.000-07:00

From Medscape Medical News > OncologyZosia ChusteckaOctober 19, 2011 — Less frequent testing for cervical cancer is recommended in 2 separate proposed guidelines issued today — one from the United States Preventative Services Task Force (USPTF), and the other from the American Cancer Society (ACS), working in collaboration with the American Society for Colposcopy and Cervical Pathology (ASCCP) and the American Society for Clinical Pathology (ASCP).The 2 sets of guidelines are similar, and both recommend against testing every year, which has been the convention until now; instead, both recommend testing every 3 years for women 21 to 65 years of age. They also both endorse Papanicolaou (Pap) tests, as has been the convention, and say that testing for human papillomavirus (HPV) is not ready for prime time and should not be used alone, although it can provide additional useful information.The proposed guidelines from the ACS/ASCPP/ASCP are posted online and are open for comments. There are plans for discussion at a symposium in November, and the final guidelines will be issued in mid-2012.The USPSTF proposed guidelines are also posted online and are open for comments until November 16. These guidelines were based on 2 reviews of the literature just published in the Annals of Internal Medicine, as reported by Medscape Medical News.The 2 groups worked independent of each other to formulate their guidelines, but they coordinated the release of their draft recommendations, according to the ACS, "to enable stakeholders to consider both sets of recommendations concurrently with the goal of creating consistent guidance that will lead to less confusion for providers and the public."Proposed ACS/ASCCP/ASCP GuidelinesThe proposed guidelines from the ACS/ASCCP/ASCP contain several changes from the existing guidelines, as outlined below, which will result in women undergoing fewer tests during their lifetime.The changes include: Instead of beginning screening 3 years after starting sexual intercourse, the new starting age will be 21 years. This applies equally to women who have and have not been vaccinated against HPV. Pap testing (conventional or liquid based) is recommended every 3 years for women 21 to 29 years of age. This replaces the current recommendation for annual testing with a conventional Pap test or testing every 2 years with a liquid-based Pap test. Pap testing is recommended every 3 years for women 30 years and older, although the preferred strategy is Pap testing plus HPV testing every 3 to 5 years. It is recommended that women who have had normal results on 3 Pap tests in a row, or if over the past 10 years there have not been any abnormal Pap tests and 2 or more HPV tests have been negative, testing can be stopped at 65 instead of 70 years of age.In addition, the draft ACS/ASCCP/ASCP document states that there is insufficient evidence to recommend for or against a comprehensive program for primary screening with HPV testing alone.New Proposed USPSTF GuidelinesSimilarly, the draft document from the USPSTF recommends: no screening in women younger than 21 years of age, regardless of sexual history screening with Pap tests every 3 years in women 21 to 65 years of age no screening in women older than 65 years of age who have had adequate previous screening and who are not otherwise at high risk for cervical cancer.However, the USPSTF differs in its guidelines on the use of HPV testing, recommending against its use in women younger than 30 years of age, either alone or in combination with Pap tests. The USPFT concludes that there is "insufficient" evidence to assess the balance of benefits and harms of HPV testing, alone or in combination with cytology, for screening for cervical cancer in women 30 years and older.

Hereditary Breast and Ovarian Cancer: BRCA and Your Patient

2011-10-19T22:47:00.000-07:00

From CDC Expert CommentaryKatherine Kolor, PhD, CGCPosted: 10/10/2011Hello, I am Dr. Katherine Kolor from the Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC). I am speaking to you as part of the CDC Expert Commentary Series on Medscape.Today I would like to talk to you about hereditary breast and ovarian cancer. I will describe how basic family history information can be used to help determine whether your patients might be at increased risk for hereditary breast and ovarian cancer and could benefit from genetic counseling and evaluation.The US Preventive Services Task Force (USPSTF) issued a recommendation in 2005 that women whose family history indicates an increased risk for hereditary breast and ovarian cancer associated with mutations in the BRCA1 and BRCA2 genes be referred for genetic counseling and evaluation for BRCA genetic testing. This is a preventive service covered under the Affordable Care Act. Available research suggests that in the United States as many as 3 out of 4 women with relevant family histories who might benefit from genetic counseling for hereditary breast and ovarian cancer have not used these services.Most breast and ovarian cancers that occur in women in the general population are not hereditary. Only 3%-5% of women who develop breast cancer and about 10%-15% of women who develop ovarian cancer have an associated BRCA1 or BRCA2 mutation.For women who have a BRCA mutation, the risk of developing breast or ovarian cancer is greatly increased, with current risk estimates ranging from 50%-85% for breast cancer and 10%-40% for ovarian cancer by age 70, and important steps can be taken to help lower risk for cancer in these women.Women With BRCA Mutations Do Have OptionsFor women with BRCA mutations, the USPSTF found fair evidence that prophylactic bilateral mastectomy reduces breast cancer risk by 85% or more, and prophylactic oophorectomy reduces ovarian cancer risk by 85% or more and breast cancer risk by 53% or more. Thus, the potential benefits of genetics referral and evaluation for these women can be substantial. The USPSTF found insufficient evidence to determine the benefits of chemoprevention or intensive screening in improving health outcomes for these women. This continues to be an active area of research, and women who are at risk should carefully review their options with a healthcare provider knowledgeable about medical management of women with BRCA mutations.How Can We Identify Women Who Might Be at Risk?Your patient might be at increased risk of having BRCA mutations if her family history includes one or more of the following in her first- or second-degree relatives (Remember that the maternal and paternal sides of the family are equally important.): Several relatives with either breast or ovarian cancer -- generally, 2 or more with ovarian cancer and 3 or more with breast cancers on the same side of the family; Breast cancer at a young age (under 50 years); A combination of breast and ovarian cancer among relatives; A relative with primary cancers of both breasts; A relative who had both breast and ovarian cancer; A male relative with breast cancer; Ashkenazi Jewish ancestry and any first-degree or 2 second-degree relatives with breast or ovarian cancer on the same side of the family; and A relative with a known BRCA mutationTo help identify women who could benefit from referral to genetic counseling and evaluation, collect this information from your patient, and review it in the context of the family history patterns outlined in the USPSTF recommendation. Also, encourage your patients to verify and update this information from family members regularly, notifying you if additional cases of breast and ovarian cancer occur. Note that the family history patterns outlined in the USPSTF recommendation are provided as a guide and do not capture all possible families that could benefit from genetic counseling and evaluation for BRCA testing. If you or your patient is concerned about her family history, then a consultation with a cancer genetics specialist or counselor can help determine whether genetic testing might be helpful.While the USPSTF recommends genetic counseling and evaluation for BRCA testing for women whose family history is associated with an increased risk for BRCA mutations, it recommends against routine referral for women without an increased family history risk. It is also important to note that the USPSTF recommendations were focused on women without a personal history of breast or ovarian cancer. Women affected by these cancers may also benefit from genetic counseling and evaluation for BRCA testing.In closing, remember that: Most of your patients aren't at increased risk for BRCA mutations, but patients with increased family history risk patterns as recommended by the USPSTF could benefit from genetic counseling and evaluation for BRCA testing; Genetic counseling by a suitably trained health care provider is important to help women make informed decisions about BRCA genetic testing; Women with BRCA mutations can take effective steps to lower their risk for breast cancer and ovarian cancer; Genetic testing for BRCA mutations will not find all causes of hereditary breast or ovarian cancer; and Health insurance often, but not always, covers the cost of genetic counseling and BRCA testing.For additional information, links to the USPSTF recommendation and other resources are provided below, as well as a table to help determine your patient's family history risk category.Thank you.Table. Breast and Ovarian Cancer and Family History Risk Categorieshttp://www.medscape.com/viewarticle/749018?src=mp&spon=17

Hypertension Linked to First-Trimester Birth Defects

2011-10-19T22:03:00.000-07:00

From Medscape Medical NewsRicki Lewis, PhDOctober 18, 2011 — Pregnant women with treated or untreated hypertension are at higher risk of carrying fetuses with congenital anomalies than are normotensive women. The finding points to elevated blood pressure as the teratogen, rather than the drugs used to treat it, according to a report published online October 18 in the British Medical Journal.Angiotensin-converting enzyme (ACE) inhibitors are known to be teratogenic during the second and third trimesters. A 2006 study using data from the Tennessee Medicaid population associated first-trimester ACE inhibitor exposure with neural tube defects and cardiac malformations, but did not find association with other antihypertensives. Two subsequent studies implicated other drugs. The new investigation disentangles the effects of antihypertensive drugs from those of the condition they treat.De-Kun Li, MD, PhD, MPH, and colleagues at the Kaiser Foundation Research Institute in Oakland, California, conducted a population-based retrospective cohort study that evaluated 465,754 mother-infant pairs from northern California in the Kaiser Permanente database, from 1995 to 2008. This included electronic medical records of fetal malformations, maternal drug exposures, and potential confounding factors such as preexisting diabetes and overweight during pregnancy. The researchers compared 4 groups of pregnant women: those with hypertension who took ACE inhibitors during the first trimester, those with hypertension who took other antihypertensives during the first trimester, those with hypertension who took no antihypertensives during the first trimester, and pregnant women who did not have hypertension and did not receive antihypertensives for other indications.The offspring of women taking antihypertensives had elevated rates of cardiac anomalies and birth defects overall, but not of neural tube defects, compared with women not taking the drugs. However, the elevation was not seen when rates were compared with the cohort of women with untreated hypertension, implicating the underlying hypertension.Use of ACE inhibitors in women with hypertension was associated with increased risk for congenital heart defects compared with normal control participants (those with neither hypertension nor use of antihypertensives), at 15 of 381 (3.9%) v 6232 of 400,021 (1.6%) patients, with an odds ratio of 1.54 (95% confidence interval [CI], 0.90 - 2.62).Similar associations were found for other antihypertensives. However, compared with the 2.4% (708/29,735) of pairs with untreated hypertension that had congenital heart defects, the use of ACE inhibitors or other antihypertensives in the first trimester was not associated with increased risk (odds ratios, 1.14 [95% CI, 0.65 - 1.98] and 1.12 [95% CI, 0.76 - 1.64])."Compared with the hypertension controls, there was no increased risk of malformation associated with use of either ACE inhibitors or other antihypertensive drugs," the investigators conclude.Limitations of the study include not controlling for influences of diet and exposures to other medications and not delineating more specific types of birth defects.In an editorial, Allen Mitchell, MD, from the Slone Epidemiology Center at Boston University, Massachusetts, supports the findings, adding that we still have much more to learn about the precise effects of elevated maternal blood pressure on the fetus.The study was funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration. The authors have disclosed no relevant financial relationships.BMJ. Published online October 18, 2011.

Dieters Benefit More From Water Than From Diet Beverages: Study

2011-10-18T20:33:00.000-07:00

Medscape Medical News from:From Reuters Health InformationObesity 2011: The Obesity Society 29th Annual Scientific MeetingBy Rob GoodierNEW YORK (Reuters Health) Oct 12 - Cutting back on caloric beverages can help people lose weight, but replacing them with water, rather than diet beverages, seems to have additional metabolic benefits, new trial data show.Obese patients enrolled in the six-month CHOICE trial at the University of North Carolina, Chapel Hill, were twice as likely to lose 5% of their body weight no matter if they'd been randomly assigned to a water group or a diet drink group, as opposed to a control group.But the diet beverage drinkers consumed more carbohydrates and sugar than the water drinkers, researchers reported October 5 at the Obesity Society's annual meeting in Orlando, Florida."It has been unclear from previous research whether replacing sweetened beverages with diet beverages offers any benefits in terms of weight loss or health outcomes," Dr. Douglas Hill, who conducts obesity research at the Children's Hospital of Philadelphia, but was not involved in either of the new studies, told Reuters Health by email."These studies confirm that, while substituting artificially sweetened beverages for sweetened beverages may be an effective short-term weight loss strategy, water is still the healthiest choice," Dr. Hill said.The CHOICE trial involved 315 obese participants. The two intervention groups were instructed to replace at least 200 kcal of caloric beverages every day with either water or diet drinks.The study investigators, led by Dr. Barry M. Popkin at UNC, made two presentations at the Orlando conference. In one, they reported that the odds for losing 5% of body weight were significantly higher in patients who cut back on caloric beverages (OR: 2.07; p=0.04).At six months, they said, there was no difference in absolute weight between the two study groups -- but those who drank water had a significantly greater improvement in fasting glucose and a trend toward a lower diastolic blood pressure compared to the control group.In the other presentation, Dr. Popkin's group said that at three months into the trial, participants consuming diet drinks were more likely to be consuming more calories in general compared to the water drinkers (OR: 2.35; p=0.03).And after six months, the diet beverage drinkers were more likely to consume non-sugar carbohydrates compared to the water group (OR: 2.63; p=0.03).Diet beverage drinkers were also more likely to eat desserts, sweeteners and breads at three months, but not at six months, compared to the water drinkers."The diet beverages and consumption study suggests that one reason that previous research has not found a health benefit for diet beverages is that individuals who drink diet beverages also tend to consume more carbohydrates and sweet foods," Dr. Hill said. "Further research is necessary to investigate whether artificial sweeteners trigger a craving for more sugary foods."

Chronic pain in America remains underrecognized, underdiagnosed, and undertreated.

2011-10-18T20:16:00.000-07:00

This PainTV educational series is designed to address this significant public health problem by educating clinicians who treat patients with chronic pain through a series of short video commentaries that present clinical pearls and demonstrations on specific topics related to chronic pain management.Collectively, this series aims to raise clinician awareness of the impact of chronic pain; its assessment, treatment, and varied pathophysiologies; and factors that can influence patient functioning and quality of life.http://www.medscape.org/sites/advances/pain-tv?src=cmemp

New Guidelines to Urge Pap Tests Only for Women 20 to 65

2011-10-18T20:07:00.000-07:00

From Medscape Medical News > OncologyJanis C. KellyOctober 17, 2011 — Screening for cervical cancer is equally effective with conventional Pap testing and liquid-based cytology with human papillomavirus (HPV) testing. So concludes the upcoming update of the 2003 US Preventive Services Task Force (USPSTF) recommendations, based in part on 2 literature reviews published online October 17 in the Annals of Internal Medicine. In addition to concluding that liquid-based cytology HPV testing is generally not superior to conventional Pap tests, the reviewers conclude that routine cervical cancer screening is generally not needed in women younger than 20 years and older than 65 years.Evelyn P. Whitlock, MD, MPH, lead author of the first study, told Medscape Medical News that "cervical cancer screening using conventional cytology (Pap test) or liquid-based cytology would be expected to be equally effective. And, although 1-time testing comparisons show that HPV is more sensitive but less specific for precancerous lesions than cytology, trials comparing HPV-enhanced strategies with cytology have not shown a clear advantage after repeat screening, nor have they compared the impact on false-positive-related burden or harms."Dr. Whitlock, from the Oregon Evidence-Based Practice at Kaiser Permanente Northwest in Portland, also noted that HPV trials currently available are European and do not compare with current American practice for the management of abnormal screening results.The review consisted of 4 fair- to good-quality studies, with a total of 141,566 participants, and compared the evidence on liquid-based cytology and high-risk HPV screening with conventional cytology in population-based screening for cervical cancer.Dr. Whitlock said that "although this review pointed out the need for more complete information on the potential harms and benefits of adding on or substituting HPV testing for cytology, we also found that the research about HPV and cervical cancer is very active and is moving in some very interesting directions. In the future, this research may support using more specific types of HPV testing, along with cytology, screening history, and other information, to individualize screening recommendations, improve screening performance, and safely reduce screening intervals for many low-risk women. At the same time, the emergence of a young cohort of HPV-vaccinated women eligible for cervical cancer screening will raise new, important questions about appropriate approaches."Appropriate AgesThe second review focused on the ages at which to appropriately begin and end cervical cancer screening. Lead author Kimberly K. Vesco, MD, MPH, and colleagues presented a "narrative review" of risk factors and other epidemiologic considerations.Dr. Vesco, who is from the Center for Health Research at Kaiser Permanente Northwest, told Medscape Medical News that "the evidence suggests that the potential harms of screening outweigh the benefit of cervical cancer screening for women under 20." Current methods have higher false-positive rates in younger women, because the methods used to diagnosis and treat cervical intraepithelial neoplasia (CIN) have potential adverse effects, and because HPV infections and cytologic abnormalities have relatively high rates of regression in young women, she said.Dr. Vesco said that the data support discontinuing screening for women 65 years and older without a history of CIN or cervical cancer who have had recent negative cervical cancer screening."The evidence to define adequate prior screening is limited, but the American Cancer Society defines it as 3 or more documented consecutive negative screening tests and no abnormal/positive cytology tests within the last 10 years," Dr. Vesco said.Dr. Whitlock warned against discontinuing cervical cancer screening for older women who do not fit these guidelines, however."A 65-year-old women who has not been screened regularly or who has a history of abnormal Pap tests, CIN, or cervical cancer would be a candidate for continued screening. Before discontinuing screening, all women should speak with their clinician, particularly women known to be at increased risk due to a weakened immune system (like those with HIV) and women who were exposed to diethylstilbestrol in utero. Women of any age with vaginal bleeding, pain, or other symptoms related to possible cervical cancer should always seek prompt medical attention, regardless of screening history," Dr. Whitlock said.The new draft recommendations on starting and stopping screening, type of test, and intervals will be available for public comment on October 19 on the USPSTF Web site.Ann Intern Med. Published online October 17, 2011. Abstract

Noncommunicable Diseases: More Than a Health Crisis

2011-10-12T19:33:00.000-07:00

From Medscape Hematology-OncologyLinda Brookes, MSc; Eduardo L. Cazap, MD, PhDOn September 19-20, 2011, the United Nations (UN) General Assembly will hold a High Level Summit on Noncommunicable Diseases (NCDs) in New York to address the global threat posed by NCDs.The Summit is only the second UN meeting of its kind to focus on a global disease issue, the first being the special session on HIV/AIDS in 2001. This Summit will focus on the 4 most prominent NCDs: cancers, cardiovascular diseases, chronic respiratory diseases, and diabetes. The World Health Organization (WHO) has estimated that by 2030, NCDs will be the most common causes of death worldwide.Cancer, long considered a health threat in high-income countries, is now recognized as being an increasingly important cause of morbidity and mortality worldwide. In 2008, 7.6 million or 21% of NCD deaths were caused by cancer, and this number is projected to increase by 4 million over the next 20 years.By 2030, two thirds of all cancer diagnoses will occur in low- and middle-income countries.An Epidemic With Global Economic ImpactThe impending global epidemic of cancer will have far-reaching impact. "If action is not taken very soon," said Eduardo L. Cazap, MD, PhD, president of the Union for International Cancer Control (UICC), "a financial crisis like that of Lehman Brothers will be peanuts in comparison with a collapse of healthcare systems."http://www.medscape.com/viewarticle/748954?src=ptalk

Vitamin Supplements Associated With Increased Risk for Death

2011-10-12T05:25:00.000-07:00

From Medscape Medical NewsEmma Hitt, PhDOctober 10, 2011 — In women aged 55 to 69 years, several widely used dietary vitamin and mineral supplements, especially supplemental iron, may be associated with increased risk for death, according to new findings from the Iowa Women's Health Study.Although many vitamin supplements did not appear to be associated with a higher risk for total mortality, several were, including multivitamins, vitamins B6, and folic acid, as well as minerals iron, magnesium, zinc, and copper.Jaakko Mursu, PhD, from the Department of Health Sciences, Institute of Public Health and Clinical Nutrition at the University of Eastern Finland in Kuopio, Finland, and colleagues reported their findings in the October 10 issue of the Archives of Internal Medicine."Supplements are widely used, and further studies regarding their health effects are needed," Dr. Mursu and colleagues write. "Also, little is known about the long-term effects of multivitamin use and less commonly used supplements, such as iron and other minerals."The current study sought to evaluate the link between supplement use and total mortality rate, using data from the Iowa Women's Health Study. A total of 38,772 older women were included in the analysis. Women were aged between 55 to 69 years, with an average of 61.6 years at the beginning of the study in 1986. Self-reported data on vitamin supplement use were collected in 1986, 1997, and 2004.A total of 15,594 deaths were reported through December 31, 2008, representing about 40% of the initial participants. The use of multivitamins overall was associated with 2.4% increased absolute risk for death (hazard ratio, 1.06; 95% confidence interval, 1.02 - 1.10). Self-reported use of dietary supplements increased substantially between 1986 and 2004. In addition, supplement users had a higher educational level, were more physically active, and were more likely to use estrogen replacement therapy.Vitamin B6, folic acid, iron, magnesium, and zinc were associated with about a 3% to 6% increased risk for death, whereas copper was associated with an 18.0% increased risk for total mortality when compared with corresponding nonuse.In contrast, use of calcium was inversely related to risk for death (hazard ratio, 0.91; 95% confidence interval, 0.88 - 0.94; absolute risk reduction, 3.8%).The researchers assessed the findings for iron and calcium in more detailed analyses conducted during shorter periods (10-year, 6-year, and 4-year follow-up) and found results similar to those for the analyses conducted during the entire time."In agreement with our hypothesis, most of the supplements studied were not associated with a reduced total mortality rate in older women," Dr. Mursu and colleagues conclude. "In contrast, we found that several commonly used dietary vitamin and mineral supplements, including multivitamins, vitamins B6, and folic acid, as well as minerals iron, magnesium, zinc, and copper, were associated with a higher risk of total mortality.""Although we cannot rule out benefits of supplements, such as improved quality of life, our study raises a concern regarding their long-term safety," the authors add.In a related editorial, Goran Bjelakovic, MD, DMSc, and Christian Gluud, MD, DMSc, from the Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Rigshospitalet, Copenhagen University Hospital, Denmark, note that the current study adds "to the growing evidence demonstrating that certain antioxidant supplements, such as vitamin E, vitamin A, and beta-carotene, can be harmful.""We cannot recommend the use of vitamin and mineral supplements as a preventive measure, at least not in a well-nourished population," they add. "Those supplements do not replace or add to the benefits of eating fruits and vegetables and may cause unwanted health consequences."This study was partially supported by the National Cancer Institute and the Academy of Finland, the Finnish Cultural Foundation, and the Fulbright program’s Research Grant for a Junior Scholar. One study author is an unpaid member of the Scientific Advisory Board of the California Walnut Commission. The other authors and editorialists have disclosed no relevant financial relationships.Arch Intern Med. 2011;171:1625-1634.

Managing the Adverse Effects of Nonsteroidal Anti-inflammatory Drugs

2011-10-09T21:44:00.000-07:00

From Expert Review of Clinical PharmacologyPaola Patrignani; Stefania Tacconelli; Annalisa Bruno; Carlos Sostres; Angel LanasPosted: 09/28/2011; Expert Rev Clin Pharmacol. 2011;4(5):605-621. © 2011 Expert Reviews Ltd. Abstract and Introduction Mechanism of Action of Nonsteroidal Anti-inflammatory Drugs GI Toxicity of NSAIDs CV Effects of NSAIDs COX-inhibiting NO Donators Managing GI Toxicity Management of GI Risk With Asprin Management of Patients With Peptic Ulcers or Dyspepsia Associated With NSAID Use NSAIDs & Lower GI Damage Managing CV Toxicity Expert Commentary Five-year ViewAbstractConventional medical treatment for rheumatoid arthritis and osteoarthritis includes the use of NSAIDs (traditional and selective inhibitors of cyclooxygenase [COX]-2), because they provide unmistakable and significant health benefits in the treatment of pain and inflammation. However, they are associated with an increased risk of serious gastrointestinal (GI) and cardiovascular (CV) adverse events. Both beneficial and adverse effects are due to the same mechanism of action, which is inhibition of COX-dependent prostanoids. Since CV and GI risk are related to drug exposure, a reduction in the administered dose is recommended. However, this strategy will not eliminate the hazard owing to a possible contribution of individual genetic background. Further studies will be necessary to develop genetic and/or biochemical markers predictive of the CV and GI risk of NSAIDs.http://www.medscape.com/viewarticle/750226?src=mp&spon=27

Anti-Infective Agents in Periodontal Treatment

2011-10-02T20:55:00.000-07:00

From Medscape Dentistry & Oral HealthJorgen Slots, DDS, DMD, PhD, MBAPosted: 09/15/2011Periodontitis is a polymicrobial infectious disease associated with specific bacterial species[1] (Table 1) and herpesviruses.[2]The primary goal of periodontal therapy is to achieve a periodontal environment free of infectious pathogens. Anti-infective periodontal treatment includes mechanical pocket debridement (scaling and root planing) to remove dental calculus, periodontal pocket irrigation with potent antiseptics, systemic antibiotics for advanced disease, and proper patient self-care. Pharmacotherapeutics targeting subgingival microorganisms can significantly enhance treatment outcomes. However, because porous subgingival calculus comprises a protective reservoir for bacterial survival during anti-infective therapy, meticulous scaling and root planing must precede antiseptic and antibiotic periodontal treatment. The antimicrobials recommended here are readily available throughout the world, have been used in periodontal therapy for decades, offer significant benefits for individuals with limited financial resources, and are well accepted by most dental professionals and patients.Antiseptic Agents in Periodontal DiseaseAn increase in antibiotic-resistant bacteria has created interest in using inexpensive, safe, and highly bactericidal/virucidal antiseptics in periodontal therapy.Antiseptics attack multiple components of infectious agents, practically eliminating the risk for development of resistance, and do not interact with prescription medications. Antiseptics are particularly valuable in the treatment of biofilm infections, which may be unresponsive to even high concentrations of antibiotics. Moreover, because the contents of inflamed periodontal pockets are emptied into the oral cavity every 90 seconds, and relatively small amounts of antimicrobial agents are applied subgingivally, the risk for antiseptics entering the gingival tissue and causing systemic damage is virtually nonexistent. This high degree of safety allows frequent and broad use of antiseptics in periodontal treatment.Povidone-IodineAqueous (Lugol's iodine) and tincture (iodine in alcohol) solutions of iodine have been employed as dental antiseptics for more than 150 years, but the early iodine formulations caused surface staining and irritation of mucosa and skin. Iodophors (iodine-releasing agents) developed in the 1950s were solutions of iodine complexed with an organic carrier that largely overcame the negative aspects of iodine treatment. The most common commercial form of povidone-iodine (Betadine® or generic equivalent) is a 10% solution in water, yielding 1% (10,000 ppm) available iodine. Povidone-iodine can give rise to allergic reactions, including itching, burning, and reddening and blistering in the area of application, so a patient's history of allergy to iodine or shellfish must be evaluated. Prolonged iodide intake can inhibit thyroid hormone synthesis and cause goiter, myxedema, or hyperthyroidism; therefore, povidone-iodine should not be used in patients with thyroid dysfunction, pregnant woman, infants, or in routine patient self-care.Povidone-iodine kills in vitro all major periodontopathic bacteria within 15 to 30 seconds and exhibits a wide virucidal spectrum, covering both enveloped (eg, herpesviruses) and non-enveloped viruses. Several studies have shown a measurable improvement in periodontal status after treatment with full-strength povidone-iodine.[4] A study from Sweden[5] showed that patients who received a whole-mouth application of povidone-iodine at the time of initial therapy exhibited less periodontitis for up to 13 years after treatment.Povidone-iodine lavage together with thorough debridement of necrotic tissue has arrested the progression of noma in HIV-infected patients.[6] Of potentially great clinical significance, povidone-iodine can kill the major cariogenic bacterium Streptococcus mutans, and caries-prone children who received a povidone-iodine application to their entire dentition every 2-3 months experienced a marked reduction in new caries lesions compared with control children.[7]Povidone-iodine used in periodontal treatment is applied subgingivally using, for example, a 3-mL endodontic syringe with a 23-gauge cannula that has a blunt end and side ports. The cannula is inserted into the base of the periodontal pocket to ensure maximum drug delivery. A single course of subgingival irrigation of the entire dentition takes about 1.5 minutes and is repeated at least 3 times for a total application time of 5-10 minutes.Sodium HypochloriteSodium hypochlorite (NaOCl) is a highly active cytotoxic oxidant recognized to be among the most potent antiseptic and disinfectant agents against bacteria, fungi, and viruses. Sodium hypochlorite occurs naturally in human neutrophils and monocytes/macrophages therefore, it does not evoke allergic reactions; it is not a mutagen, carcinogen or teratogen; and it has a century-long safety record. Dilute sodium hypochlorite has no contraindications. Sodium hypochlorite is available globally at exceptionally low cost as household bleach in concentrations of 5%-6%.Sodium hypochlorite has been used as an antiseptic agent in dentistry for more than a century and remains a widely used root canal irrigant at concentrations ranging from 1.0%-5.25%. Sodium hypochlorite rinsing exerts broad antimicrobial activity against experimental oral biofilms and reduces biofilm by 80-fold compared with water. Dilute sodium hypochlorite rinse (0.5%) has produced a 47% greater reduction in dental plaque mass compared with water rinsing.Low gingivitis scores were maintained around teeth receiving sodium hypochlorite rinse, whereas the gingivitis score increased by 50% in control teethThe American Dental Association Council on Dental Therapeutics has designated dilute sodium hypochlorite a "mild antiseptics mouth rinse" and suggested its use for direct application to mucous membranes.The lowest concentration of sodium hypochlorite solution that reliably inactivates bacteria in vitro is 0.01%. Patients are advised to use an oral irrigator for subgingival application of sodium hypochlorite at a concentration of 0.5%. This is equivalent to 10 mL (2 teaspoonfuls or two thirds of a tablespoon) of 6% household bleach in 125 mL (one half glass) of water.Patients are also advised to rinse orally with 0.2% sodium hypochlorite for 30 seconds, 2 or 3 times per week. This is equivalent to 8 mL (2 reduced teaspoonfuls) of 6% household bleach in 250 mL (a full glass) of water. More frequent rinsing may produce a brown-black extrinsic discoloration of the teeth. Diluted hypochlorite solutions gradually lose strength, so fresh solutions should be prepared for each use.ChlorhexidineChlorhexidine, a bisbiguanide, has been an important oral antiseptic for more than 40 years, and numerous studies and meta-reviews have confirmed its antiplaque and antigingivitis effects. The ability of chlorhexidine to adhere to the dental pellicle and oral mucosa prolongs its antiplaque effect. Chlorhexidine gluconate is used in dentistry as a 0.12%-0.2% mouthwash applied in a volume of 15 mL for 30 seconds. Low-cost generic chlorhexidine in concentrations of 2% or higher can be diluted in water to the desired concentration for oral use.Chlorhexidine is inactivated by organic serum compounds in the gingival crevice fluid, and subgingival placement produces little change in microbial and clinical variables.As the antimicrobial action of the cationic chlorhexidine is neutralized by anionic compound surfactants in toothpastes, chlorhexidine should not be used in conjunction with toothbrushing. A major disadvantage of chlorhexidine is its propensity to dark stain tooth surfaces. Dark staining gaps along the margin of tooth-colored restorations may reflect into the filling material and necessitate replacement of affected restorations.Antibiotics in PeriodontitisSystemic antibiotic therapy for periodontitis aims at reducing or eradicating specific periodontopathic bacteria that are not readily reached by topical therapy, such as pathogens in gingival tissue, in furcation defects, at the base of periodontal pockets, and on the tongue, tonsils and buccal mucosa. The selection of effective and safe antibiotics can be challenging because periodontitis lesions usually harbor a constellation of periodontopathic bacteria that have diverse susceptibility profiles. The tradition in dentistry is to treat empirically (eg, institute antibiotic therapy on the basis of the "best estimate" of the most probable pathogen or pathogens and the usual antibiotic susceptibility pattern of the suspected pathogen or pathogens). Microbiological testing with antimicrobial susceptibility profiling allows dentists to move from a trial and error approach to the more predictable targeted therapy, but susceptibility testing depends on complex and relatively expensive culture methods in a reference laboratory.Antibiotic combination therapy with 2 antibiotics is used to take advantage of different mechanisms of action and to expand the spectrum of antimicrobial activity. Amoxicillin-metronidazole (250 mg amoxicillin-375 mg metronidazole, 3 times daily for 8 days) is the most common antibiotic combination in periodontics. Ciprofloxacin-metronidazole (500 mg of each, twice daily for 8 days) is indicated for periodontitis involving a mixture of enteric gram-negative facultative rods and anaerobic bacteria.Enteric gram-negative facultative rods are particularly prevalent in periodontal sites of older individuals and immunocompromised patients. Ciprofloxacin-metronidazole combination therapy is also a valuable alternative for penicillin-allergic patients. Metronidazole exerts activity against Clostridium difficile and thus reduces the risk for pseudomembranous colitis. Valacyclovir (500 mg, twice daily for 10 days) may be prescribed for patients with severe periodontitis, which is virtually always associated with a herpesvirus infection. The dosing recommendations are for healthy adults with normal weight and must be adjusted for body size to ensure optimal therapeutic effectiveness and safety. Interactions with other medications, toxicity, and hypersensitivity may restrict antibiotic use in individual patients.Tetracycline HCl, doxycycline HCl, and minocycline HCl embedded in various delivery systems have been marketed commercially for direct placement into the periodontal pocket. The usefulness of topical antibiotics in periodontal treatment is questionable.The chief drawbacks of topical antibiotic therapy are an insufficient range of antimicrobial activity for even broad-spectrum antibiotics, a modest and transient clinical effect, possible development of resistant bacteria, adverse host reactions, and high acquisition costs. Topical antibiotic agents are a less desirable choice than the topical use of broad-spectrum, low-cost antiseptic agents with low potential for adverse reactions.ConclusionMechanical debridement combined with subgingival povidone-iodine application in the dental office and sodium hypochlorite irrigation for patient self-care are valuable antimicrobial treatments in the management of virtually all types of periodontal disease. Systemic antibiotics or periodontal surgery may be required in the treatment of advanced periodontitis.

Peptic Ulcer Disease

2011-10-02T20:12:00.000-07:00

Author: BS Anand, MD; Chief Editor: Julian Katz, MD 20th June 2011BackgroundGastric and duodenal ulcers usually cannot be differentiated based on history alone, although some findings may be suggestive (see Diagnosis). Epigastric pain is the most common symptom of both gastric and duodenal ulcers. It is characterized by a gnawing or burning sensation and occurs after meals—classically, shortly after meals with gastric ulcer and 2-3 hours afterward with duodenal ulcer.In uncomplicated peptic ulcer disease (PUD), the clinical findings are few and nonspecific. “Alarm features" that warrant prompt gastroenterology referral[1] include bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia or odynophagia, recurrent vomiting, and family history of GI cancer. Patients with perforated PUD usually present with a sudden onset of severe, sharp abdominal pain. (See Clinical Presentation.)In most patients with uncomplicated PUD, routine laboratory tests usually are not helpful; instead, documentation of PUD depends on radiographic and endoscopic confirmation. Testing for H pylori infection is essential in all patients with peptic ulcers. Rapid urease tests are considered the endoscopic diagnostic test of choice. Of noninvasive tests, fecal antigen testing is more accurate than antibody testing and is less expensive than urea breath tests. A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison syndrome. (See Workup.)Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected PUD. Endoscopy provides an opportunity to visualize the ulcer, to determine the presence and degree of active bleeding, and to attempt hemostasis by direct measures, if required. Perform endoscopy early in patients older than 45-50 years and in patients with associated so-called alarm features.Most patients with PUD are treated successfully with cure of H pylori infection and/or avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs), along with the appropriate use of antisecretory therapy. In the United States, the recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy.[1] These regimens result in a cure of infection and ulcer healing in approximately 85-90% of cases.[2] Ulcers can recur in the absence of successful H pylori eradication. (See Treatment and Management.)In patients with NSAID-associated peptic ulcers, discontinuation of NSAIDs is paramount, if it is clinically feasible. For patients who must continue with their NSAIDs, proton pump inhibitor (PPI) maintenance is recommended to prevent recurrences even after eradication of H pylori.[3, 4] Prophylactic regimens that have been shown to dramatically reduce the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analog or a PPI. Maintenance therapy with antisecretory medications (eg, H2 blockers, PPIs) for 1 year is indicated in high-risk patients. (See Medication.)The indications for urgent surgery include failure to achieve hemostasis endoscopically, recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after 2 failed endoscopic attempts), and perforation.Patients with gastric ulcers are also at risk of developing gastric malignancy. http://emedicine.medscape.com/article/181753-overview

Ambulatory BP Monitoring Cheaper, Effective, and Gets Boost

2011-08-28T05:27:00.000-07:00

From HeartwireShelley WoodAugust 23, 2011 (London, United Kingdom) — A long-time "reference standard" for tricky blood-pressure readings, ambulatory monitoring should now become the go-to test for diagnosing hypertension in all patients, authors of a new analysis say .The study, now published online in the Lancet, was conducted jointly by independent researchers and an expert committee drafting an update to the UK's National Institute for Health and Clinical Excellence (NICE) Hypertension Guideline, officially launching on Wednesday.The guidelines are the first in the world to formally recommend ambulatory blood-pressure monitoring (ABPM) as a "key priority" in diagnosing suspected hypertension, particularly if a clinic BP reading is 140/90 mm Hg or higher, according to the chair of the writing committee.Works Better, Priced RightThe Lancet analysis, by Dr Kate Lovibond (National Clinical Guideline Centre, London, UK) et al, shows that using ABPM to diagnose hypertension is not only more effective than testing blood pressure at home or in the clinic, it also saved money in almost every patient group studied."Historically, ABPM been the reference standard when you've not been quite sure what to do," senior author on the Lancet analysis, Dr Richard J McManus (University of Birmingham, UK), told heartwire . "What we've realized from this and from a systematic review published in BMJ earlier this year is that actually the reference standard is quite a lot better than clinic blood-pressure and to a lesser extent home blood-pressure monitoring at making a diagnosis."Having established efficacy, investigators set out to see whether higher costs offset the value of ABPM--the devices are relatively expensive. "We were reasonably surprised when it showed just how cost-effective the ambulatory monitoring actually is," McManus said.Study coauthor Dr Bryan Williams (University of Leicester, UK), who also chaired the update of the NICE hypertension guidelines, explained that the cost saving comes both from speeding up a diagnosis in someone who needs medication swiftly and from eliminating treatment in people who do not, in fact, have hypertension but have been misdiagnosed in the clinic or at home."ABPM is likely to eliminate from treatment up to 25% of newly presenting people with elevation of BP," he said. "If you remove the drug costs from those individuals, what we found was that modeling on 100 000 people in the UK that the ABPM would cost about ₤2.5 million to implement in the first year [which includes acquisition of equipment and training of personnel], but after that there was a progressive net gain in terms of cost. By year two it is cost neutral, and by year five this would save ₤10 million."Williams continued: "So what we have here is a situation where we have a more effective way of diagnosing hypertension, it's better for patients, it eliminates unnecessary treatment in a significant number of patients, and at the same time it is potentially cost saving and at worst cost neutral. It's a no brainer to say: why aren't we doing this?"Highest Savings in Older PatientsLovibond, McManus, et al modeled cost-effectiveness in a hypothetical primary-care group undergoing 24-hour BP monitoring instead of clinic-based or home-based tests. They report that ABPM was the most cost-effective strategy across all age groups considered, and in both men in women. The lowest cost savings were in men over 75 years of age (an incremental saving of ₤56) compared with a diagnosis made with a clinic BP test, and highest among women aged 40 (₤323) per hypertension diagnosis.ABPM also came out on top for improving health outcomes in men and women over age 50; in younger subjects, ABPM led to higher cost savings but smaller reductions in quality-adjusted life-years."The bottom line is that using ABPM as a diagnostic strategy for high BP is both more effective in terms of making a diagnosis and saving costs," McManus said.There are no good data on just how commonly ABPM is used as the go-to test, he added. "We think that less than 5% of patients in the UK have ABPM as part of their diagnosis," he said. "There will be a few people for whom this won't be appropriate, particularly people with accelerated hypertension or people with very high BP who've had a stroke." In those patients, "you want to just get them on treatment, but in most people with suspected hypertension, particularly in the primary-care setting, we think this is the thing to do, and that's a big shift."Other jurisdictions are increasingly looking to the UK's NICE model, because it balances both the evidence base and cost efficacy. Both McManus and Williams stressed that the Lancet paper, as well as the new NICE hypertension guidance, will have a ripple effect, particularly in places like the US, where ABPM is not always reimbursed. "I think this may get people internationally thinking about their diagnostic strategies as well," McManus said.An editorial accompanying the study takes issue with some of the assumptions within Lovibond et al's analysis, saying further studies may be warranted to model specific scenarios, but if anything, writes Dr Thomas A Gaziano (Brigham and Women’s Hospital, Boston, MA), further studies might even strengthen the results.NICE Hypertension Update Also Includes Drug Choices, Age AdviceThe first NICE hypertension guideline was issued in 2004 and updated in June 2006. The new, simple, 16-page document lists "key priorities," provides a care "pathway," and encompasses different ways to measure and diagnose hypertension, assess risk and target-organ damage, use lifestyle and drug interventions, and educate patients.Speaking with heartwire , Williams pointed to a number of other novel elements of this update.For one, the update recommends the same antihypertensive drug treatment in people over aged 80 as in people aged 55 through 80, a change from previous guidance that urged caution in older subjects, out of concerns that adverse effects might offset benefits. A review of the evidence in older adults suggests there were reductions in stroke, hospitalizations for heart failure, and deaths and "no hint of any adverse offset" when a standard antihypertensive approach was applied, Williams said.Second, in a recommendation that Williams predicts will be hotly debated in the UK, the NICE reviewers reexamined advice for subjects over age 55 and recommend the use of a calcium-channel blocker (CCB) as first-line therapy, with thiazidelike diuretics reserved for patients with edema, CCB intolerance, or evidence of heart failure or at high risk of heart failure.And in a departure from previous recommendations, the new update recommends physicians use a thiazidelike diuretic, such as chlorthalidone or indapamide, in patients starting on or switching diuretics. These drugs should be used "in preference to" what is more commonly the first-line diuretic in the UK, bendroflumethiazide, says Williams, or the most common in the US, hydrochlorothiazide.This will "prompt a lot of debate" not only in the UK, predicts Williams, but in the US as well.References

Anti-TNF Agents and Cancer Risk: What to Tell Patients

2011-08-28T05:09:00.000-07:00

From Medscape Rheumatology > ViewpointsKevin Deane, MDPosted: 08/17/2011Does Cancer That Occurs During or After Anti-Tumor Necrosis Factor Therapy Have a Worse Prognosis?: A National Assessment of Overall and Site-Specific Cancer Survival in Rheumatoid Arthritis Patients Treated With Biologic AgentsRaaschou P, Simard JF, Neovius M, Askling J Arthritis Rheum. 2011;63:1812-1822BackgroundShortly after the introduction of anti-tumor necrosis factor (TNF) therapies for rheumatoid arthritis (RA) and other rheumatic diseases, concern was raised that these agents might increase the risk for cancer. Complicating the issue of anti-TNF therapy and cancer risk are biologic mechanisms of TNF that, when blocked, either improve or worsen cancer risk, depending on the type of cancer.Multiple studies have examined the association between anti-TNF therapy and cancer incidence; however, to date, data on the influence of such therapy on cancer outcomes are limited. Therefore, using a large registry of Swedish patients with RA along with controls, Raaschou and colleagues investigated the effects of anti-TNF therapy on cancer staging and survival. A study of this type is possible in Sweden because cancer reporting is mandatory, and the estimated under reporting is < 5%.Study SummaryUsing the Swedish Patient Register, the authors identified 78,483 patients with RA, treated with or without biologic therapy (nearly all with anti-TNF agents).From this group, 8562 patients started biologic therapy during the study period. The investigators performed a matched analysis of patients with both RA and cancer who were treated with biologic therapies (n = 302, of whom 300 were treated with anti-TNF agents), matched by cancer site, age, sex, and year of cancer diagnosis in a 1:2 fashion with patients with RA and cancer who had not received biologic therapy (n = 586). Cancer stage at diagnosis was similar between groups, although a larger proportion of patients treated with biologics had stage 3 cancer (20% vs 9%) and a smaller proportion had stage 4 cancer than did biologic-naive patients (20% vs 29%). For lung cancer in particular, a greater proportion of biologic-naive patients had stage 4 cancer at diagnosis than did patients treated with biologics (60% vs 26%). Conversely, for melanoma, a greater proportion of patients treated with biologics had stage 2 cancer or higher at diagnosis than did biologic-naive patients (28% vs 0%). In the 302 biologic-treated patients, 113 (37%) deaths occurred; in the 586 biologic-naive patients, 256 (44%) deaths occurred. In adjusted analyses (including accounting for comorbid conditions), no significant differences in overall survival (relative risk 1.1, 95% confidence interval, 0.8-1.6) or survival by specific type of cancer were found between biologic-treated and biologic-naive patients.Also analyzed in an unmatched fashion were the outcomes of first cases of primary cancer in biologic-treated patients (n = 314 cancers) compared with biologic-naive patients (n = 4650 cancers). In these analyses, no significant differences in overall outcomes or cancer-specific outcomes were found between groups.The investigators concluded that cancer outcomes following anti-TNF therapy do not significantly differ, in terms of stage at presentation or survival rates, from those of biologic-naive patients with RA.ViewpointThe findings of this study suggest that the use of anti-TNF agents in patients with RA does not significantly alter cancer stage at presentation or overall survival of patients with incident cancers. However, how these results will influence the management of specific patients in terms of cancer screening approaches or use of biologic therapy after a diagnosis of cancer is still unclear.In particular, what should a rheumatologist do with anti-TNF therapy in a patient who develops cancer? Moreover, does management of biologic therapy depend on the type of cancer -- for example, should patients with lung cancer continue to receive their anti-TNF agent, and should patients with melanoma or hematologic cancers have their therapy discontinued? These questions are not readily answered by this study because most patients discontinued biologic therapy after cancer was diagnosed, and numbers of the various subtypes of cancers were limited.Furthermore, as the author of an accompanying editorial points out, it is not clear how these results apply to all patients with RA, including those in the United States who may have received anti-TNF therapy for less-aggressive disease than what is seen in Europe because of differences in prescribing practices. In terms of applicability to direct patient care, data from this study can be used to counsel patients that if they develop cancer while receiving anti-TNF therapy, the outcomes will not clearly be worse than if they discontinued therapy. However, additional surveillance studies, and perhaps controlled studies where possible, are still necessary going forward to help guide biologic use (especially anti-TNF therapy) after cancer has been diagnosed.

Switching From Simvastatin 80 mg: How to Shop for Statins

2011-08-24T23:30:00.000-07:00

From Medscape Internal Medicine > Staying Well With Sandra Fryhofer, MDSandra A. Fryhofer, MD Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia; Past President, American College of Physicians, Philadelphia, PennsylvaniaPosted: 08/12/2011Savvy Statin ShoppingLet's go shopping. This edition of Staying Well focuses on how to be a savvy shopper in choosing a statin for your patients, a timely issue in light of the US Food and Drug Administration's (FDA's) new simvastatin warnings. Seasoned shoppers always check the sale racks first, but don't buy something -- even if on sale -- if the "size and style" aren't right. Apply this analogy to picking a statin. Although the first thing to look for is price, it should not be the only deciding factor. Simvastatin is certainly one of the cheapest statins, but is it the best choice for your patients?My Personal DisclaimerI admit that I have been a little lazy. For the last several years, when my patients needed statins I always started with simvastatin. It was generic. It was on all the pharmacy plans, so the price point for patients was right. Prescribing was hassle free: no cumbersome forms to fill out and explain. However, the recent FDA warnings about the dangers of high-dose simvastatin and additional warnings about dosing and drug interactions have led me to rethink this strategy and take a closer look at the different statins available. It is now time to find out the facts and make necessary changes in prescribing patterns. Maybe it's time for a new "style" of treatment. Here is some information to help you decide.Statin CharacteristicsThis statin dose equivalency guide gives equivalent doses of available statins along with generic and brand names and selected characteristics (Table 1).Table 1. Statin Dose Equivalency GuideMedication Dose Equivalent Pharmacotherapeutic Factor Metabolism MetabolitesRosuvastatin (Crestor®) 2.5 mg Hydrophilic CYP2C9 Active (minor) metaboliteAtorvastatin (Lipitor®) 5 mg Lipophilic P450 3A4 (CYP3A4) Active metaboliteSimvastatin (Zocor®)a 10 mg Lipophilic P450 3A4 (CYP3A4) Active metaboliteLovastatin (Altoprev®, Mevacor®) 20 mg Lipophilic P450 3A4 (CYP3A4) Active metabolitePravastatin (Pravachol®) 20 mg Hydrophilic Renal metabolism No active metabolitesFluvastatin(Lescol®, Lescol® XL) 40 mg Lipophilic CYP2C9 No active metabolitesPitavastatin (Livalo®) 1 mg Lipophilic Little metabolism by CYP3A4 No active metabolitesaAlso in combination medications: ezetimibe/simvastatin (Vytorin®) and niacin extended release/simvastatin (Simcor®) Table 2 is from the FDA Drug Safety Communication and gives relative low-density lipoprotein (LDL) efficacy for the different statins. Note that pitavastatin (Livalo®) is a newer statin and was FDA approved in 2009.Table 2. Relative LDL-Lowering Efficacy of Statin and Statin-Based TherapiesAtorva Fluva Pitava Lova Prava Rosuva Vytorin®a Simva %↓ LDL-C-- 40 mg 1 mg 20 mg 20 mg -- -- 10 mg 30%10 mg 80 mg 2 mg 40/80 mg 40 mg -- -- 20 mg 38%20 mg -- 4 mg 80 mg 80 mg 5 mg 10/10 mg 40 mg 41%40 mg -- -- -- 10 mg 10/20 mg 80 mg 47%80 mg -- -- -- 20 mg 10/40 mg -- 55% -- -- -- 40 mg 10/80 mg -- 63% Atorva = atorvastatin; Fluva = fluvastatin; LDL-C = low-density lipoprotein cholesterol; Pitava = pitavastatin; Lova = lovastatin; Prava = pravastatin; Rosuva = rosuvastatin; Simva = simvastatin aNo incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established. Data from US Food and Drug Administration. June 8, 2011. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htmAssociation of Pharmacologic Factors With Adverse EffectsStatins that are hydrophilic (pravastatin and rosuvastatin) are less likely to cross skeletal muscle membranes and are less likely to cause adverse effects.Statins that don't have active metabolites (fluvastatin, pravastatin, and pitavastatin) are less likely to cause adverse effects. Rosuvastatin has only a minor active metabolite.Drug metabolism pathway plays a role in drug-drug interactions and subsequent safety. This is especially important for patients on multiple medications: For statins metabolized by P450 3A4 (CYP3A4) (simvastatin, lovastatin, atorvastatin), concomitant administration of medications that inhibit the CYP3A4 pathways (protease inhibitors, cyclosporine, amiodarone, fibrates) is problematic. The result is increased statin levels and increased risk for muscle tissue injury. On the other hand, fluvastatin and rosuvastatin (metabolized by CYP2C9) and pravastatin (metabolized by the kidneys) are considered to be safer statin choices for patients on multiple medications.

Bedbugs: An Update on Recognition and Management

2011-08-24T22:31:00.000-07:00

From Skin Therapy LetterRobyn S. Fallen, BHSc; Melinda Gooderham MD, MSc, FRCPCPosted: 08/17/2011; Skin Therapy Letter. 2011;16(6) © 2011 SkinCareGuide.comhttp://www.medscape.com/viewarticle/745992?src=mp&spon=9 Abstract and Introduction Epidemiology Entomology Psychological Consequences Cutaneous Manifestation Diagnostic Considerations Disease Transmission Management ConclusionABSTRACTThe common bedbug (Cimex lectularius) is increasingly prevalent and a source of concern and questions for patients. In addition to a range of cutaneous presentations and potential for serious sequelae, bedbug bites cause significant psychological distress and create an economic burden associated with infestation control. Recognition of characteristic entomology, clinical presentation, diagnostic features and differential diagnosis can support expedient identification of patients exposed to infestations and support their appropriate management.IntroductionThe common bedbug, Cimex lectularius (C. lectularius), is a hematophagus arthropod. A pest to mankind for centuries, bedbug populations in industrial nations declined steadily with the advent of novel pesticides, improved sanitation practices, and economic conditions. In contrast, infestations in developing countries have persisted.However, pest control companies in Canada and the United States are reporting overwhelming increases in the number of new bedbug encounters compared with 10 years ago. This recent bedbug resurgence has been attributed to evolving pesticide resistance coupled with increased rates of international trade and travel, as travellers can bring the insects home in their clothing and luggage.Bedbugs have since established more widespread infestation of environments serving transient populations such as hotels, dormitories, hospitals, cruise ships, and homeless shelters. In addition to this increased prevalence, bedbugs are also widely discussed in popular media and may be presented as a concern by patients. Awareness of the entomology, diagnosis, and management of bedbugs can assist physicians in detecting affected individuals and providing concerned patients with education on this topic.ManagementUncomplicated bedbug bites usually resolve within 1–2 weeks and are self-limited. Although the evidence base is weak, management is otherwise symptomatic. Topical or oral antipruritic agents combined with an intermediate corticosteroid can bring some relief. For some patients, having prescription topicals compounded with menthol and camphor can be soothing. Superinfection can occur, especially in cases with significant excoriation, and can be treated with topical or oral antibiotics.[16]Systemic reactions to bedbug bites are treated with intramuscular epinephrine, antihistamines, and oral corticosteroids, as in insect-induced anaphylaxis.[16]In tandem with the control of symptoms, eliminating the infestation must be aggressively pursued to prevent further bites. Goddard et al. (2009) have outlined several steps that are useful in successful eradication of bedbugs:[16] Proper identification of the bedbugs species Education of the patient, other dwelling occupants, and landlord, as applicable Thorough inspection of both infested and other nearby areas Implementation of pesticide and non-chemical control measures Follow-up to ensure control of the infestation

Osteoporosis: Yesterday, Today and Tomorrow: Rapid Progress, but do not Forget the Simple things

2011-08-14T19:03:00.000-07:00

From Rheumatology

Nancy E. Lane

Introduction

Osteoporosis, a disease characterized by low bone strength and fractures that occur with very low-impact loads, has experienced many changes over the past 20 years and we should expect to see many more in the future. Prior to 1990, there was little activity in the field: although there were some small studies with sodium flouride, they set the field back because these compounds improved bone mass but increased bone fragility and fractures. While osteoporosis, or bone fragility, was generally accepted to be part of the normal process of ageing in post-menopausal women, an osteoporotic fracture diagnosed the disease, unfortunately at a very advanced stage.
Until the development of DPA followed by dual-energy X-ray absorptiometry (DEXA), there was no method to determine an individual's risk of an osteoporotic fracture before the event.
However, in 1992, T-scores (S.D.'s above and below peak bone mass) became a way to identify individuals who would, over time, be at increased risk of osteoporotic fractures.
This ability to identify individuals at risk for fractures prior to their occurrence by DEXA, coupled in 1990 with the first studies to find a reduction in incident vertebral fractures with the bisphosphonate etidronate, administered for 2 weeks every 3 months, followed by the approval of the bisphosphonate alendronate in the USA in 1995, really jump-started the field.
Post- and pre-menopausal women and men obtained BMD scans, and, based on a T-score of −1 or below at the lumbar spine or hip, were started on this anti-resorptive agent indefinitely. Over time, other bisphosphonates were approved, initially daily treatment, then weekly, then monthly, followed by i.v. therapies, first every 3 months and now annually
The past decade also saw the approval of the first 'anabolic' or bone-building agent that could increase bone strength by increasing both bone formation and bone resorption. The concept of an anabolic agent that could improve bone strength through increasing remodelling was difficult for the medical community to understand; we learned that the bone matrix is rich in growth factors for osteoblasts including Transforming Growth Factor-β, Insulin Growth Factor-1 and Fibroblast Growth Factor-2. The anabolic agent teriparatide allowed bone strength to increase by adding bone to existing trabeculae. However, with the discontinuation of teriparatide, the new bone would be rapidly lost; the addition of an anti-resorptive agent maintained or even increased BMD.
The addition of an anabolic agent as a treatment for osteoporosis came at nearly the same time as the Women's Health Initiative Study in the USA reported that HRT, while effective in reducing hip fractures and gastrointestinal cancer, had risks of cardiovascular events (MIs, strokes, deep venous thrombosis) that outweighed the benefits.
This dramatically changed how physicians treated post-menopausal women, especially in the prevention of oestrogen-deficient bone loss in early menopause. However, the number of new, generally non-hormonal medications to treat or prevent osteoporosis kept clinicians busy learning the biology of bone metabolism, and most became very good at identifying and prescribing for patients who should be treated for osteoporosis. However, other than the one anabolic agent, teriparatide, there was no information on how long to treat with anti-resorptive agents or information about drug holidays.

The Fracture Intervention Trial Long-term Extension (FLEX) study, sponsored by Merck, determined that women with osteopenia, and a hip T-score above −3.5, treated with alendronate for ~4.5 years, retained the majority of the bone gained at the hip and spine and showed no significant difference in morphometric fractures 5 years after discontinuation compared with subjects who continued treatment.
This information suggested to clinicians that after 5 years a potent anti-resorptive agent could be discontinued, but no guidelines were produced on how to monitor these subjects after therapy was discontinued: this has been left to clinicians to figure out.
In the past 3 years, quite unexpectedly, a number of series of cases of subtrochanteric or atypical fractures have been reported in women treated with bisphosphonates for a number of years. The reports from multiple centres are strikingly similar. The American Society of Bone and Mineral Research convened a task force to investigate the problemand the Food and Drug Administration made recommendations.
One of the major risk factors appears to be the length of time a patient has taken the bisphophonate. While pharmaceutical manufacturers were successful in convincing clinicians that these medications would improve patients' bone strength, no guidance was provided on the length of time that the medication should be prescribed. The Phase III studies carried out to seek FDA approval of the bisphosphonates were only 3 years in duration. However, many of the patients' subtrochanteric fractures had been treated with these medications for much longer.
So we have learnt a lesson in the treatment of osteoporosis: 3 years is effective, and much longer might cause some harm. This story is not finished.
The use of the T-score to identify patients who might be at risk for osteoporotic fractures, and using a T-score of −1 or less as a threshold to treat patients with bone-active medications, was not satisfying. For a woman at menopause, a T-score of −1 might just reflect her peak bone mass.
At her young age, nearly 20 years before, she would be at risk of osteoporotic fractures; medication to prevent osteoporosis might not be worthwhile. The development of the Fracture Assessment Tool (FRAX) has greatly aided clinicians in determining the risk of osteoporotic fracture in individual patients.By sitting with a patient and identifying risk factors on the computer, adding the hip BMD, and then being presented with the 10-year risk of a hip fracture and major osteoporotic fracture, we can identify the most appropriate patients to treat to prevent osteoporotic fractures. The fracture risk thresholds for treatment vary by country; however, the most significant risk factor is age, and with use of the FRAX to identify subjects to treat, we are treating fewer women around the age of menopause.
The future is bright for the development of osteoporosis treatments. New anti-resorptive therapies including denosumab and odanocatib (still in development), to name a few, are potent but have a much shorter half-life in the bone. Denosumab, an inhibitor of Receptor Activator of NF-B Ligand, is given by s.c. injection every 6 months. Odanocatib, an anti-resorptive agent that inhibits the enzyme cathepsin K, a collagenolytic, is given by mouth daily in clinical trials.
A new anabolic agent, also in development, inhibits sclerostin, synthesized primarily in osteocytesterminally differentiated osteoblast cells within the bone matrix, which connect to each other through dendritic processes and to the bone surface. Sclerostin is produced by osteocytes and released into the bone marrow, where it inhibits the maturation of osteoblasts. In rodents, an inhibitor of sclerostin increases bone formation dramatically and has been able to rapidly restore peak bone mass.
Phase II clinical trials are ongoing. However, as with teriparatide, the new bone mass gained from inhibition of sclerostin is lost rapidly, so either maintenance treatment or prolonged use of an anti-resorptive agent will be needed. Agents that can direct mesenchymal stem cells to move to the bone surface and differentiate into osteoblasts to form bone are also in development. This type of therapy may be useful in accelerating fracture healing.
Since 1995, with the approval of alendronate for treatment and prevention of osteoporosis, and the availability of DEXA to determine risk of osteoporosis, clinicians have been busy diagnosing and treating this disease. Today, we have many highly effective agents to improve bone strength, some by reducing remodelling and others by increasing it. We have increased our bone cell vocabulary to include osteoclasts, osteoblasts and even osteocytes. We also know that these cells work together to build and maintain a strong skeleton. In the next few years, we will improve our understanding of osteoporosis and bone fragility, and hopefully refine the length of time we use bone active agents to maximize efficacy and reduce toxicity. However, while medications can improve bone strength, a patient generally has to fall to suffer a hip fracture. Clinicians, almost as a reflex, institute medications to treat osteoporosis, and fail to do an assessment of a patient's risk of falling.
A thorough evaluation for osteoporosis and fracture risk includes: a review of the patient's medications for sedatives/hypnotics that impair balance and increase fall risk; a physical examination to determine muscle strength and balance; and a review of laboratory tests including haemoglobin, haematocrit and electrolytes. Lastly, a review of the home should be done to determine whether there is anything that could increase fall risk. Preventing a fall through the use of an assistive device like a cane or a walker may do as much as any medication.
Going forward, this author would like to believe clinicians will be more thorough in their assessment of fracture risk both with FRAX and an assessment of fall risk, and interventions may be both pharmacological and non-pharmacological. Osteoporosis is a chronic degenerative disease, and screening is recommended at the age of 60 years with risk factors and at the age of 65 years without.
Since most women live into the mid-eighties, clinicians will be monitoring and treating their bone health for 25 years. The unmet need is to understand how to monitor bone strength so that clinicians know when to start, stop and reinstitute medications to maintain skeletal health. We have come a long way, but we have much left to do.

Promising Developments in Osteoporosis Treatment

2011-08-14T18:36:00.000-07:00

From International Journal of Clinical Rheumatology

Manuel Sosa; Esther González-Padilla

Abstract and Introduction
New Assessment Tools for Fracture Risks & Treatment Decisions
Anabolic Agents
New Resorption Inhibitors
Future Perspective

Abstract

Osteoporosis is a very common disease that affects both men and women and produces an important burden. Fracture prevention is the primary treatment goal for patients with osteoporosis. There are several treatments available nowadays with anabolic, antiresorptive or dual actions. A great number of new drugs are under study. In this brief review, we highlight the knowledge regarding them so far.

Introduction

The concept of osteoporosis was introduced in 1990 as "a skeletal disorder characterized by low bone mass and compromised bone strength, resulting in increased bone fragility and susceptibility to fracture".This definition comments on the intimate association between fractures and bone strength and provides a useful framework for reviewing recent developments and advances involving the diagnosis and management of individuals with compromised bone strength.Osteoporosis is a very common disease that can occur in populations of all types and ages, having significant physical, psychosocial and financial consequences.
Fracture prevention is the primary treatment goal for patients with osteoporosis.
Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls.
In this article we briefly review some promising new treatments for osteoporosis.

New Assessment Tools for Fracture Risks & Treatment Decisions

New tools have been developed in order to facilitate both the diagnosis and management of bone metabolic diseases. They are useful to estimate the long-term risk of suffering a fracture and sometimes would advise to indicate a treatment or even sometimes to discontinue them. These tools are FRAX®, Study of Osteoporosis Fractures (SOF) and QFracture™.

FRAX & SOF

The WHO developed a computer-generated algorithm, FRAX, which will supply clinicians with a tool to estimate absolute, time-specific fracture risk quantitatively.^[4–6] This useful tool provides country- and ethnic-specific 10-year hip and major osteoporotic fracture (hip, distal forearm, shoulder, vertebral body) risks, based on information entered into the calculator, which is available for free online.^[101] The information requested can be easily obtained from simple questioning; it includes age, sex, weight, height, personal and family history of fracture, current tobacco and alcohol consumption, corticosteroid usage, previous conditions associated with secondary osteoporosis, and history of rheumatoid arthritis. In the USA, bone density values at the hip are also included in the data. Threshold values for the instauration of bone-strengthening medication are established for those individuals who have a 3% or more risk of a hip fracture and/or 20% risk or more of a major osteoporotic fracture. The FRAX calculator is particularly useful for younger, healthy, postmenopausal females with osteopenia, a group of people with a relatively low 10-year fracture risk.
The American SOF Research Group has also created another assessment tool for fracture risk. The SOF model, unlike FRAX, is based only on BMD and age. However, it predicts the 10-year risk of hip and major osteoporotic fracture as well as the FRAX tool in a group of postmenopausal females, 65 years and old.^[7,8] These findings highlight the importance of age as a risk factor for fragility fractures.
Both the FRAX and SOF models have demonstrated that older people with low bone density and a history of fragility fracture are at highest risk for sustaining further fragility fractures.

QFracture

A third tool, named QFracture, was also published recently. It has some similarities to FRAX, and estimates 10-year risks of fracture (major osteoporotic fracture and hip fracture) from a number of risk factors,^[9] accessible free at.^[102] It has the advantage of not requiring densitometry. For a given patient, the estimated risks obtained with both tools can sometimes be similar but sometimes not. The differences between FRAX and QFracture can be seen in Box 1. The exact value of QFracture in the management of osteoporosis and the advantages or disadvantages compared with FRAX need to be studied.
The greater concerns regarding the potential adverse effects and costs of long-term use of antiresorptive agents is likely to be increasing the interest in identifying and treating those individuals who have a significantly increased absolute fracture risk. Fracture assessment tools provide critical quantitative information on fracture risk and may aid in this endeavor.

Future Perspective

Treatment of osteoporosis has changed substantially in recent years. Only 15 years ago, we had calcitonin, estrogen, etidronate and alendronate. Today, the therapeutic arsenal is huge and varied and we have a deeper understanding of the side effects that occur as a consequence of prolonged use of some drugs such as bisphosphonates.
New drugs are emerging for the treatment of osteoporosis, characterized by acting on very specific bone cell physiology, and sometimes it is almost a true therapy with monoclonal antibodies that regulates bone cell pathophysiology. Perhaps the most important aspect that remains is to check there are no major side effects in the long term.

Music Lowers Anxiety and Boosts Mood in Cancer Patients

2011-08-12T21:25:00.000-07:00

From Medscape Medical News > Oncology

Roxanne Nelson

August 12, 2011 — Listening to music may have a beneficial effect on anxiety, pain, mood, and quality of life in cancer patients, according to a new Cochrane systematic review.
The findings from the review, which included 30 trials and a total of 1891 patients, suggested that music therapy and music medicine interventions might also have a beneficial effect on heart rate, respiratory rate, and blood pressure in cancer patients.
"The evidence suggests that music interventions may be useful as a complementary treatment to people with cancer," said lead researcher Joke Bradt, PhD, MT-BC, associate professor in the Department of Creative Arts Therapies at Drexel University, Philadelphia, Pennsylvania.
"Music interventions provided by trained music therapists as well as listening to prerecorded music both have shown positive outcomes in this review, but at this time there is not enough evidence to determine if one intervention is more effective than the other," she noted in a release.
Dr. Bradt also pointed out that when patients can't be blinded to an intervention, there is an opportunity for bias when they are asked to report on subjective measures such as anxiety, pain mood, and quality of life. Therefore, these results need to be interpreted with caution.
The researchers point out that the quality of evidence for some outcomes was low because of the small numbers of trials that have been performed. Further trials could help increase certainty in the findings and improve understanding of music's impact on distress, body image, and other aspects, for which research is currently too scarce to draw any conclusions.

Therapeutic Across Specialties
During the past 2 decades, there has been an increasing interest and a growth of research on the effects of music and music therapy for medical patients, which encompassed a variety of specialty areas, note the authors. For example, music has been used to lessen anxiety for both adults and children before or during surgical procedures and to decrease tension during chemotherapy or radiation therapy. It has also been used to reduce the adverse effects of treatment, to improve mood, to enhance pain management, to boost immune system functioning, and to improve quality of life.
As recently reported by Medscape Medical News, music therapy can improve the symptoms of depression when added to standard antidepressant treatment.
Music stimulates the mind and triggers images, metaphors, and emotions that often are preconscious by nature, explained the lead author Jaakko Erkkilä, PhD, from the Finnish Centre of Excellence in Music Research, University of Jyväskylä, Finland.

Music is kind of an emotional language.

"In other words, music is kind of an emotional language with a lot of abstract, unformed psychic ideas," Dr. Erkkila told Medscape Medical News. "It enriches communication, stimulates and even evokes speech, and through these qualities is an excellent way to deal with and consider mental problems that are emotional by nature. Making music is also a physical activity, thus enabling functioning and bodily communication."
Benefits Mood, Physiologic Responses
In the current review, the Cochrane authors examined the effects of music therapy or music medicine interventions on psychological and physical outcomes in cancer patients with cancer.
A total of 36 references reporting on 30 trials were included in the review. Nine trials included participants who underwent chemotherapy or radiation therapy, 8 examined the effects of music during procedures or surgery, and 13 trials included general cancer patients. In addition, 4 studies evaluated music interventions with pediatric patients.
The results of 16 trials suggest that music therapy and music medicine interventions may have a beneficial effect on anxiety, which is consistent with the findings from 2 previous Cochrane systematic reviews that evaluated the use of music with coronary heart disease patients and the use of music with patients receiving mechanical ventilatory support.
The pooled estimate from 3 trials suggested that music might help improve the mood of people with cancer, but 5 studies that specifically looked at depression did not find evidence of an effect of music.
When looking at physical symptoms, 6 trials showed that music may have a moderate pain-reducing effect, although no effect was noted for fatigue or physical status.
The authors also found evidence that music interventions may have a beneficial effect on several physiologic responses, including reducing heart and respiratory rates. These results are also consistent with findings from another Cochrane systematic review on the use of music with coronary heart disease patients, which also found a reduction in heart rate.
Single trials that were included in this review supported a beneficial effect of music on mean arterial pressure and immunologic function, but not for oxygen saturation level. Furthermore, although the results suggested that music may benefit quality of life, there was no support for an effect on spirituality.
Cochrane Database Syst Rev. 2011;8:CD006911.

Women Smokers Have Higher Risk of Heart Disease Than Men

2011-08-12T20:54:00.000-07:00

From Heartwire

Michael O'Riordan

August 11, 2011 (Minneapolis, Minnesota) — A large meta-analysis suggests that the harmful effects of tobacco smoking affect men and women differently. In a study of more than two million people, researchers showed that the pooled adjusted female-to-male relative risk of coronary heart disease in smokers vs nonsmokers is 25% higher in women.

"It's an unusually large study," lead investigator Dr Rachel Huxley (University of Minnesota, Minneapolis) told heartwire . "In the main analysis, there are about 2.4 million people with data on 44 000 coronary heart disease events, and what was very nice about the study is that the results were very consistent across all of the studies. There was no heterogeneity between them, adding to the robustness of the findings. We're pretty confident that the estimate we came up with is a real approximation of the true risk."

If anything, said Huxley, the 25% increased risk might be on the conservative side. Women have not been smoking as long as men, so the true impact of smoking on women's health might not yet have manifested entirely, and women don't smoke as many cigarettes as men when they do smoke. In addition, it's still taboo for women to smoke in many cultures, and as a result women might underreport their smoking habits. "All three factors combined would suggest that the 25% is an underestimate," said Huxley.
The results of the study are published online August 11, 2011 in the Lancet.

Females Still a Growth Market for Tobacco Companies
In the analysis, the researchers performed a systematic review and meta-analysis of prospective cohort studies published between 1966 and 2010. Studies that stratified by sex with measures of relative risk for coronary heart disease and current smoking compared with not smoking were included in the analysis.

As we all know, prevention is far better and far easier than trying to cure somebody of a habit.

In the 75 cohorts, which included 2.4 million participants, the pooled adjusted female-to-male relative risk ratios of smoking compared with not smoking for coronary heart disease was 1.25 (95% CI 1.12–1.39, p<0.0001). The relative risk ratio increased by 2% for every additional year of study follow-up, a finding that suggests the longer a woman smokes, the greater her risk of developing coronary heart disease compared with a man who has smoked the same length of time.
"If you looked at some countries, such as Asian-Pacific countries, this is still a growth market for tobacco companies, because the prevalence of smoking in women is still in the single digits," said Huxley. "For example, in China, about 60% of men smoke, whereas just 4% to 9% of women smoke. Tobacco-control programs really need to develop a female perspective to dissuade women from starting to smoke in the first place, because women often find it more difficult to quit smoking compared with men."

In an editorial accompanying the published study [2], Drs Matthew Steliga and Carolyn Dresler (University of Arkansas Medical Sciences, Little Rock) point out that coronary heart disease is predicted to remain the leading cause of death globally and is expected to cause approximately 14% of deaths annually by 2030. Most of coronary heart disease is attributable to lifestyle-related factors, including smoking.
"Thus, a large proportion of the most common cause of death worldwide is attributable to behavior or addiction," they write. "Although some people might view this statistic as discouraging, it can also be seen as a great opportunity to reduce the burden of disease through behavior modification and smoking-cessation programs."
The editorialists note that national and international organizations such as the International Network of Women Against Tobacco and the World Health Organization Tobacco Free Initiative are important reference organizations that can help promote more effective tobacco cessation in women.
To heartwire , Huxley said that an understanding of sex differences in smoking-cessation initiatives has not been fully explored. However, researchers are aware there are differences in smoking-related behavior between men and women. Men, for example, start smoking at a younger age, smoke more cigarettes than women, and always have a higher smoking prevalence across different age groups, the lone exception being adolescent and teenage girls.
"That's a particular concern, because more young girls will start to smoke than young boys, so we really do need to develop effective campaigns that can dissuade young girls from starting in the first place," said Huxley. "As we all know, prevention is far better and far easier than trying to cure somebody of a habit."

Curry Spice Offers Hope for Tendinitis Pain

2011-08-11T19:02:00.000-07:00

From WebMD Health News

Moira Dower

August 9, 2011 — Curcumin, which gives the curry spice turmeric its bright yellow color, could be helpful in treating painful inflammatory conditions, such as tendinitis and arthritis, according to researchers at the University of Nottingham in the U.K. and Ludwig-Maxmillians University in Munich, Germany. Their studies show that curcumin can be used to suppress inflammation in tendon diseases.

Not a Cure
Ali Mobasheri, DPhil, of the University of Nottingham’s School of Veterinary Medicine and Science, who co-led the research, says, "Our research is not suggesting that curry, turmeric, or curcumin are cures for inflammatory conditions such as tendinitis and arthritis. However, we believe that it could offer scientists an important new lead in the treatment of these painful conditions through nutrition."
Turmeric has been used for centuries in traditional Indian, or ayurvedic, medicine as an anti-inflammatory agent and remedy for symptoms related to irritable bowel syndrome and other disorders. Based on its potential anti-inflammatory and antioxidant properties, researchers in several countries are investigating curcumin for use in a variety of diseases, including some types of cancer and cirrhosis of the liver.

Blocking Inflammation
The Nottingham-Munich study, due to be published in the Journal of Biological Chemistry, used a culture model of human tendon inflammation to study the anti-inflammatory effects of curcumin on tendon cells. The main objective of the study was to observe the effects that curcumin had on the inflammatory and degenerative properties induced by molecules called interleukins. The results showed that curcumin prevents interleukins from promoting inflammation.
Tendons, the tough cords of fibrous connective tissue that join muscles to bones, are essential for movement because they transfer the force of muscle contraction to bones. However, they are prone to injury, particularly in athletes who overstretch themselves and overuse their joints.
Tendinitis is a form of tendon inflammation that causes pain and tenderness close to the joints, and it is particularly common in the shoulders, elbows, knees, hips, heels, and wrists. Examples of common tendon disease include tennis elbow, golfer’s elbow, and Achilles tendon injury.
The global incidence of tendinitis is on the increase in line with the rise in aging and inflammatory diseases. It is also linked to other arthritic and rheumatic diseases such as rheumatoid arthritis or metabolic diseases such as diabetes.
Nonsteroidal anti-inflammatory drugs (NSAIDS), such as aspirin or ibuprofen, are used to relieve the pain and inflammation of tendinitis. In more serious cases of tendon injury, steroid injections can be given directly into the tendon sheath to control pain and enable physiotherapy to start. However, NSAIDS and steroids are associated with side effects, such as stomach ulcers, nausea, vomiting, and other problems affecting the digestive system, as well as headaches, drowsiness, and fatigue.

Music Therapy Hits the Right Note for Depression

2011-08-11T18:43:00.000-07:00

From Medscape Medical News > Psychiatry

Fran Lowry

August 10, 2011 — Music therapy can improve the symptoms of depression when added to standard antidepressant treatment, according to a study by Finnish researchers published in the August issue of the British Journal of Psychiatry.
"Music therapy is noninvasive, and just 20 biweekly sessions produce a beneficial effect," lead study author Jaakko Erkkilä, PhD, from the Finnish Centre of Excellence in Music Research, University of Jyväskylä, Finland, told Medscape Medical News.
Moreover, "you don't have to be a musician nor musically talented in order to get benefit from this treatment," Dr. Erkkilä said.

Dr. Jaakko Erkkilä

Researchers in Finland have been developing clinical expertise with music therapy in people with psychiatric disorders since the late 1960s, Dr. Erkkila explained.
"In Finland, depression has become a common reason for inability to work and affects 5% to 6.5% of the population. The usual treatment is medication plus psychiatric counseling. Psychotherapy is also effective, but verbal psychotherapy processing can be difficult or insufficient for some people," he said.
Music therapy offers an alternative and is another way to get in touch with emotions and develop relationships. Although it has been found to be effective in some studies, the methods of these studies have been "methodologically insufficient and lacking in clarity," Dr. Erkkilä said.

Strong Emotional Experience
In this study, Dr. Erkkilä sought to focus on the utility of music therapy in depressed people of working age, not only because of their socioeconomic importance, but also because research in this group is scarce.
He and his colleagues studied 79 people between 18 and 50 years old who had been diagnosed as having depression. They randomized 33 participants to receive 20 music therapy sessions in addition to their usual treatment for depression, which consisted of antidepressants, 5 to 6 individual psychotherapy sessions, and psychiatric counseling. The other 46 participants received standard treatment only and acted as the control group.
Music therapy consisted of one-on-one sessions with a music therapist, which consisted of free music making with drums and xylophone, as well as talking.
"The idea was to create free music based on the inner feelings of the client in a safe, trustworthy context and then to elaborate on these experiences verbally," Dr. Erkkilä explained.
"From experience, we knew that this kind of working is highly emotional and often leads to strong emotional experiences and insights connected to one's psychopathology."
After 3 months, the researchers found that the participants who received music therapy had showed greater improvement than those who received standard care only.

International Debate
For depression, the mean change from baseline in the Montgomery-Asberg Depression rating scale was −6.05 for the controls vs −10.70 for those in the music therapy group (mean difference, 4.65; 95% confidence interval [CI], 0.59 – 8.70; P = .03).
For anxiety, the mean change from baseline on the Hospital Anxiety and Depression Scale was −1.95 for the controls vs −3.77 for those in the music therapy group (mean difference, 1.82; 95% CI, 0.09 – 3.55; P = .04).
For general functioning, the mean change from baseline on the Global Assessment of Functioning scale was 6.92 for the controls vs 11.50 for the music therapy group (mean difference, −4.58; 95% CI, −8.93 to −0.24; P = .04).
The study also found that the treatment response was significantly better in the music therapy group than in the control group.
"There is an active, international debate on depression treatment which centers on whether the antidepressants are good enough forms of treatment or whether psychotherapy or other therapies are needed in addition to medication," Dr. Erkkilä said. "Our study strongly advocates the good effect of combination of medication and therapy. In addition, it strongly advocates the benefit of creative therapy methods, in particular music therapy, in the treatment of depression."
He added that the commitment to music therapy was high in the study.
"It has been noticed in previous music therapy studies as well, that in music therapy trials dropouts are more rare than in many other psychotherapy studies."
Still, the people who will probably benefit the most from the addition of music therapy are those "with natural capacity for symbolic thinking and creative functioning," he said.

High Levels of Engagement
Music stimulates the mind and triggers images, metaphors, and emotions that often are preconscious by nature, Dr. Erkkilä suggested.
"In other words, music is kind of an emotional language with a lot of abstract, unformed psychic ideas. It enriches communication, stimulates and even evokes speech, and through these qualities is an excellent way to deal with and consider mental problems that are emotional by nature. Making music is also a physical activity, thus enabling functioning and bodily communication."
UK researchers who commented on this study in an accompanying editorial state, "This is a high-quality randomized trial of music therapy specifically for depression and the results suggest that it can improve the mood and global functioning of people with this disorder."
Anna Maratos, MSc, of the London Foundation Trust, Mike J. Crawford, MD, of Imperial College London, and Simon Procter, MMT(NR), of the National Music Therapy Training Programme, Nordoff Robbins, United Kingdom, write that the playing of musical instruments with the musical therapists was important to the patients who received music therapy.
The editorialists suggest that this activity has 3 interlinked dimensions, which are aesthetic, physical, and relational.
"Above all, music making is social (and hence interpersonal), pleasurable, and meaningful: this may also be why randomised trials of music therapy have shown high levels of engagement with patient groups who are traditionally difficult to engage," they note.
Erkkila and colleagues "lay down a clear marker for the value of music therapy as part of the range of interventions available for the treatment of people with depression," they conclude.

Br J Psychiatry. 2011;199:132-139, 92-93. Abstract Editorial

An Update on Analgesics

2011-08-10T20:41:00.000-07:00

From British Journal of Anaesthesia

I. Power

Abstract

Recent introduction of new analgesics into the clinic is best described as a slow process with activity classified into two main areas: improving analgesic efficacy/potency and reducing side-effect profile. This review article describes some of the recent advances with an emphasis on use in the acute setting.
In this respect, opioids continue to be the mainstay (but not the only) analgesic and there have been important improvements in their clinical effect profile. For example, tapentadol has been introduced as a mixed opioid and norepinephrine uptake inhibitor which, unlike tramadol, does not require metabolic activation and does not suffer from isomer-dependent pharmacodynamics.
Opioid antagonists have received much attention recently either used alone, methylnaltrexone (s.c) or alvimopan (p.o), or in combination, Targinact (oxycodone/naloxone), and appear to be effective in reducing opioid side-effects such as those in the gastrointestinal tract. Other agents where there has been recent development include the use of gabapentin, methylxanthines, and local anaesthetics. An interesting area of translation of basic research is in the inhibition of breakdown of endogenous opioids with opiorphin, targeting of the endocannabinoid system, and the use of ampakines to obtund opioid-induced side-effects. It is clear that there is still much work to be done, but the need for highly efficacious analgesics with good side-effect profile remains.

Introduction

This article was written as part of Professor Jennifer Hunter's Festschrift entitled 'Anaesthesia and Critical Care in the 21st Century: The First Decade' which will be held in May 2011. I was asked to present an update on analgesics, mainly those used in the 'acute' setting that would give some idea of the advances we have made in alleviating pain after surgery or trauma. My consideration of this was rapidly fashioned by various articles published in the recent past, indicating that for the acute setting, progress in terms of the introduction of new drugs has been incredibly slow.
Woolf in an article about overcoming obstacles to developing new analgesics states that 'despite substantial financial investment by the pharmaceutical industry over several decades, there has been little progress in developing new efficacious and safe analgesics'. Woolf then indicates that this is leading some pharmaceutical companies to consider withdrawing from the acute pain relief market, and that the problem might be a lack of understanding of pain itself. Certainly, there does seem to be a lack of understanding of how to design studies to investigate acute pain relief. This is clearly shown by a recent article entitled 'Getting the pain you expect'.
The problem seems to be our design of studies in many ways, which allows us to accept placebos, 'nocebos' (that is, negative outcomes, see Tracey), and reappraisal effects in humans. Our clinical studies tend to neglect these and to set them aside and Quessyhas addressed this issue in an article entitled 'Where are the new analgesics?' and suggests an alternative approach to early phase analgesic trials using a multivariate input model. Certainly, trial design does seem to be a large part of the problem, but also the issue is that in addressing pain, we must also address safety and efficacy. This was very well demonstrated by the attempts to improve upon the safety profile of non-steroidal anti-inflammatory drugs where by selectively changing the action of drug molecules, the enzyme affected was influenced. The result was that efficacy was improved, but safety markedly affected, so that some of the drugs were withdrawn because of unexpected cardiovascular side-effects.
As a result, senior researchers are now asking the question 'what is this thing called pain?'There is no doubt that when we deal with pain after surgery or trauma, we are dealing with the various classifications proposed by Woolf which include nociceptive: associated with the detection of potentially tissue damaging stimuli; inflammatory: tissue damage; and pathological: damage to the nervous system (neuropathic).
Part of the problem with pain after surgery is that consent renders the patient open to accepting nociceptive damage and anaesthesia, while greatly minimizing and allowing invasive surgery has very little effect on the nociceptive process. Also, after surgery and trauma, these classifications become somewhat blurred as neuropathic pain can appear immediately after a surgical process. In looking for new analgesics that work in the acute setting, there is a problem of having to address many types of pain simultaneously, using the same compounds. We are indeed a long way from Tracey's postulation of making postoperative pain 'pleasant'.
However, Tracey's idea of arranging more suitable studies may well render an individualized approach to the problem of pain possible and produce safer and more effective analgesics.

Analgesia for acute pain relief still tends to be drawn from the traditional opiates, aspirin and the non-steroidal drugs, paracetamol, and local anaesthetics.
The opiates were in wide use as a natural product, and, for example, in the 15th century, 'the Soporific sponge' was mentioned where opium is mixed with various herbal products and then dried, so that the sponge could be warmed later and used for pain relief. 'Opium' was used widely in the 19th century and indeed quoted in the family doctor as 'the best medicine we possess'. In 1803, Serturner assimilated crystals from opium and named them 'morphine' after the Greek God of dreams, Morpheus. Morphine was delivered on the point of a lancet and washed into the wound, injections not yet being available. This moved on until Stein and colleaguesrealized that opioids were part of the physiology of the inflammatory, painful process and suggested that where tissue damage occurred, local anti-inflammatory analgesic opioids were released to aid the repair process.
Opioids have continued to be the mainstay of our armamentarium against pain based on new formulations, mixed preparations, novel norepinephrine inhibitors, and the use of opioid antagonists to address the thorny issue of opioid-related gut side-effects. Each of the evidence-based guidelines that exist about the relief of acute pain address the efficacy and safety in different ways, but the aim has been to improve on the efficacy of drugs like morphine and reduce its drastic side-effects, including nausea, gastrointestinal effects, and acute loss of the patent airway and hence hypoxia. Aspirin was introduced as an attempt to improve upon the palatability profile of the older sodium salicylate and the non-steroidals resulted from that in due time. Paracetamol was made available by an entirely different chemical process, but this routine drug taken by all of us seems to be one of the best analgesics that work from cradle to grave, although smitten by the dire side-effect of liver impairment upon overdose. New drugs such as tramadol and now tapentadol make use of the endogenous pain-modulating pathway that occurs in response to tissue damage, giving the pharmacological site of action for most of our presently used drugs.Opioids work at various sites of the pain pathway but are of course inherent to the modulation of pain physiologically. Non-steroidal anti-inflammatory drugs work at the site of tissue damage and in the central nervous system. The descending pathways from the brain down to the lower sensory pathways for pain depend on various substances, including enkephalins, endorphins, and norepinephrine that have been used for the production of analgesics. The introduction of tapentadol is an example of this. Therefore, attempts need to be made to improve efficacy and reduce side-effects in an individualized fashion. It may be that increased understanding of the genetic role of our pain physiology might allow us to do this and produce individualized approaches to tissue damage and pain, but again we are someway from that at present. One new possibility is the introduction of 'epigenetics in pain and analgesia', which might allow a personalized, individualized approach to pain and tissue damage.
The aim should be to stop viewing morphine, for example, as a two-faced God, Janus, that produces powerful analgesia that is blighted by common, serious, and sometimes life-threatening adverse effects.

for rest of article refer:
http://www.medscape.com/viewarticle/745129?src=mp&spon=17

WHO Guidelines for Drug-Resistant Tuberculosis Updated

2011-08-08T19:32:00.000-07:00

From Medscape Medical News

Nancy A. Melville

August 5, 2011 — New guidelines from the World Health Organization (WHO) on the management of drug-resistant tuberculosis (TB) offer the latest approaches for better control of the disease that claims millions of lives each year.
The guidelines, published online August 4 in the European Respiratory Journal, update recommendations from previous guidelines published in 2008 and are intended to help inform practitioners, particularly those in lower-income settings, of the very latest and most cost-effective standards of care for achieving optimal patient outcomes.
"The updated WHO program guidelines on [multidrug-resistant]-TB are an essential resource for healthcare professionals with a responsibility for TB patient care," stated Mario Raviglione, MD, director of the WHO Stop TB Department in a press release.
"WHO has produced this latest version to reflect important developments in TB, developments that will have a beneficial impact on clinical and operational outcomes."
The guidelines reflect the recommendations of a multidisciplinary panel of TB practitioners, public health professionals, representatives of professional societies, national TB control program staff, guideline methodologists, and other professionals.
Although there are no radical changes from the 2008 guidelines, the new guidelines include some important adjustments and provide the most updated information on issues such as diagnosis, treatment, and monitoring.
The guidelines feature 11 key recommendations for caregivers, including the following:

Wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone over conventional testing upon patient diagnosis with TB and before treatment initiation to allow for earlier identification of patients with drug-resistant TB. The approach is considered the most cost-effective, and administration of appropriate treatment as quickly as possible is recommended to avoid unnecessary deaths.
Monitoring patients with sputum smear microscopy and culture, rather than sputum smear microscopy alone, for multidrug-resistant TB (MDR-TB) to detect failure as early as possible during treatment. Users are advised to be aware of differences in the quality of the culture performance because a false-positive result could lead to an unnecessary continuation or modification of treatment and increased risk for toxicity.
The use of fluoroquinolones and ethionamide, with later-generation fluoroquinolone, rather than earlier-generation forms of the drug recommended for patients with MDR-TB.
A focus on cost-effective ambulatory models of care that treat patients outside of the hospital rather than hospitalizing them. In addition to reducing the risk for re-infection, the ambulatory care model reduces travel and social isolation for patients.
For patients with MDR-TB, the minimum duration of treatment has been extended by 2 months from previous guidelines to reflect research showing improved treatment success with the longer duration. Intensive treatment should therefore last at least 8 months, and for those who have not been treated with second-line drugs for TB in the past, treatment should extend to 20 months. The duration may be adjusted for some patients according to their clinical and bacteriologic response.
Early use of antiretroviral agents for HIV-infected patients with TB who are receiving second-line drug regimens, irrespective of CD4 cell-count, as early as possible (within the first 8 weeks) after initiation of anti-TB treatment.

Tuberculosis claimed as many as 1.7 million lives in 2009, not including those who died from the disease while affected by AIDS. An estimated 3% of new TB cases around the world are MDR-TB — major shortcomings in healthcare systems have led to increasing resistances to anti-TB drugs.
Evidence is said to be particularly lacking in pediatric MDR-TB, the best drug regimens for treatment with isoniazid resistance, extremely drug-resistant TB or non-MDR-TB polydrug resistance, and therapy for symptomatic relief from adverse reactions linked to second-line anti-TB drugs.
The guidelines therefore place a heavy emphasis on the need for more research, while striving to help improve understanding of critical issues, such as duration, composition, and management of treatment, particularly for patients with MDR-TB.
"The new evidence-based WHO guidelines are a milestone clinicians and public health specialists were waiting anxiously to guide their interventions," said Professor G.B. Migliori, head of the Respiratory Infections Assembly at the European Respiratory Society.
"They resulted from an unprecedented collaboration among the top global experts and national program managers who accepted to share data to inform the guidelines."

Eur Respir J. Published online August 4, 2011.

AHA/ASA Issue Scientific Statement on Vascular Dementia

2011-08-08T19:20:00.000-07:00

From Medscape Education Clinical Briefs

News Author: Megan Brooks
CME Author: Désirée Lie, MD, MSEd

07/28/2011

Clinical Context

According to the current study by Gorelick and colleagues, by 2025 there will be 1.2 billion persons worldwide who will be 60 years and older. Also, in persons 80 years and older — a fast-growing population in developed countries — approximately 20% experience difficulties in activities of daily living, with cognitive impairment increasing in prevalence with age.
In addition, risk markers for stroke are now understood to be risk markers for Alzheimer's disease and other cognitive impairments. Vascular cognitive impairment (VCI) is a cause of microvascular brain damage, and arterial stiffness and atherosclerotic changes may be common risk factors for VCI.
This statement from the American Heart Association (AHA) and the American Stroke Association (ASA) describes vascular contributions to cognitive impairment and provides recommendations for prevention, treatment, and future research.

Study Synopsis and Perspective

Vascular changes are "important" contributors to cognitive impairment and dementia and should be routinely addressed in clinical practice, according to a new scientific statement from the AHA and ASA.
The 42-page statement, "Vascular Contributions to Cognitive Impairment and Dementia," was published online July 21 in Stroke and will appear in the September print issue of the journal.
The American Academy of Neurology and the Alzheimer's Association have endorsed the statement. The Alzheimer's Association participated in its development.
In comments to Medscape Medical News, Philip B. Gorelick, MD, MPH, cochair of the writing group for the statement and director of the Center for Stroke Research at the University of Illinois College of Medicine at Chicago, said vascular factors "have long been thought to be an important contributor to cognitive decline and dementia in later life."
Still, they have not received as much attention as Alzheimer's disease, "which has been on the center stage of scientific inquiry," he added.

Introducing 'Vascular Cognitive Impairment'
Dr. Gorelick and the writing group systematically reviewed published studies, guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, offer recommendations for care.
"Over time and with careful study, vascular factors have been found to play a role in both vascular and so-called neurodegenerative forms of cognitive impairment such as Alzheimer disease," Dr. Gorelick said.
On the basis of the evidence, the writing group formally introduces the construct of "vascular cognitive impairment" (VCI). This, they say, captures "the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury — solely stroke — ranging from mild cognitive impairment through fully developed dementia.
"The neuropathology of cognitive impairment in later life is often a mixture of Alzheimer disease and microvascular brain damage," the study authors note, "which may overlap and synergize to heighten the risk of cognitive impairment."
In this regard, magnetic resonance imaging and other neuroimaging techniques "play an important role" in detecting and defining VCI, they advise.

What's Good for the Heart Is Good for the Brain
It is now "accepted," the team writes, that many of the traditional risk markers for heart disease and stroke are also risk markers for VCI and Alzheimer's disease.
"Stroke and heart disease are linked by a number of cardiovascular risk factors, such as hypertension, hypercholesterolemia, diet, tobacco exposure, and other factors," Dr. Gorelick explained.
"These vascular factors and others may play a causal role in the development of cognitive impairment and dementia in later life."
Carotid intimal-medial thickness and arterial stiffness are "emerging as markers of arterial aging and may serve as risk markers for VCI," the writing group points out.
Detection and control of the traditional risk factors for stroke and cardiovascular disease may help guard against VCI. "We encourage clinicians to use screening tools to detect cognitive impairment in their older patients and continue to treat vascular risks according to nationally- and regionally-accepted guidelines," the study authors write.
"At the very least," Dr. Gorelick said, screening for and treatment of vascular risk factors, including hypertension, hyperglycemia, and hypercholesterolemia, may reduce the occurrence of stroke and heart disease. "There may be an added benefit of prevention and treatment of vascular risk factors — the prevention of cognitive impairment and dementia in later life," he added.

Specifically, in persons at risk for VCI, the writing group concludes that

Smoking cessation is reasonable (Class IIa; Level of Evidence A);
Moderation of alcohol intake, weight control, and physical activity may be reasonable (all Class IIb; Level of Evidence B); and
Use of antioxidants and B vitamins is not useful, based on current evidence (Class III; Level of Evidence A).

For individuals with vascular dementia, they conclude that

Donepezil can be useful for cognitive enhancement (Class IIa; Level of Evidence A);
Galantamine can be beneficial for individuals with mixed Alzheimer disease/vascular dementia (Class IIa; Level of Evidence A); and
The benefits of rivastigmine and memantine are not well established in vascular dementia (Class IIb; Level of Evidence A).

The study authors also note that a Mediterranean-type dietary pattern has been associated with less cognitive decline in several studies and may be reasonable (Class IIb; Level of Evidence B).
Vitamin supplementation is not proven to improve cognitive function, even if homocysteine levels have been positively influenced, and its usefulness is not well established (Class IIb; Level of Evidence B). The effectiveness of antiaggregant therapy for VCI is not well established (Class IIb; Level of Evidence B).
Reached for comment, Thomas Russ, MD, PhD, from the University of Edinburgh, Scotland, said, "This is a clear outline of the difficulties surrounding the rather complicated overlap and interaction between vascular changes and the neuropathological changes of Alzheimer disease both resulting in cognitive impairment and dementia.
"The recommendations for prevention are a useful restatement of the current state of knowledge and a helpful reminder that we need to intervene sufficiently early in a condition which develops over the course of years and decades — ie, middle age," added Dr. Russ, who was not involved in the writing group.

Stroke. Published online July 21, 2011.

Antibiotic More Effective Than Cranberry Prophylaxis to Prevent UTI

2011-08-08T19:05:00.000-07:00

From Medscape Education Clinical Briefs

News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD

07/27/2011

Clinical Context

Among women, urinary tract infections (UTIs) are very common, with almost half of all women reporting at least 1 UTI sometime during their lifetime.
After an initial UTI, 20% to 30% of women have recurrence.
With more than 2 UTIs per year, low-dose antibiotic prophylaxis is often recommended.
Because of the increasing prevalence of uropathogens resistant to antimicrobial agents, it has stimulated interest in cranberries to prevent recurrent UTIs.
The aim of this study by Beerepoot and colleagues was to compare prophylaxis uses with either trimethoprim-sulfamethoxazole (TMP-SMX) or cranberry capsules for prevention of recurrent UTI.

Study Synopsis and Perspective

TMP-SMX is more effective than cranberry capsules for prevention of recurrent UTI in premenopausal women, according to the results of a double-blind, double-dummy non inferiority trial reported in the July 25 issue of the Archives of Internal Medicine.
"The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent ...UTIs," write Mariëlle A. J. Beerepoot, MD, from the Academic Medical Center in Amsterdam, the Netherlands, and colleagues.
"For premenopausal women with more than 2 UTIs per year, low-dose antibiotic prophylaxis is commonly recommended. However, this may lead to drug resistance not only of the causative microorganisms but also of the indigenous flora."
In this study, 221 premenopausal women with recurrent UTIs were randomly assigned to receive prophylaxis with TMP-SMX, 480 mg once daily, or cranberry capsules, 500 mg twice daily, for 12 months. The main study outcomes were the mean number of symptomatic UTIs during the 12-month period of prophylaxis, the proportion of women who had 1 or more symptomatic UTIs, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli.
Compared with the TMP-SMX group, the cranberry group had a higher mean number of patients with at least 1 symptomatic UTI after 12 months (4.0 vs 1.8; P = .02) and a higher proportion of patients with at least 1 symptomatic UTI (78.2% vs 71.1%). In the cranberry group, median time to the first symptomatic UTI was 4 months, compared with 8 months in the TMP-SMX group.
TMP-SMX resistance after 1 month was present in 23.7% of fecal and 28.1% of asymptomatic bacteriuria E coli isolates in the cranberry group, compared with 86.3% and 90.5%, respectively, in the TMP-SMX group.
Resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E coli isolates after 1 month were also increased in the TMP-SMX group. When TMP-SMX was discontinued, resistance returned to baseline levels after 3 months.
In the cranberry group, antibiotic resistance did not increase. Participants tolerated cranberries and TMP-SMX equally well.
"In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance," the study authors write.
Limitations of this study include high withdrawal rates, lack of microbiological confirmation of all recurrent UTIs, inability to confirm that all women took the cranberry prophylaxis, and unclear optimal dosage of cranberries.
"From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis and preferred either no or nonantibiotic prophylaxis," the study authors concluded. "In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness."
An invited commentary by Bill J. Gurley, PhD, from the University of Arkansas for Medical Sciences, Little Rock, notes that the comparison may not have been fair regarding dose and bioavailability of active ingredients.
"To date, few botanical dietary supplements have lived up to their claims as effective 'alternative' medicines, and until more is known about phytochemical disposition in humans, efficacy concerns will continue to plague these products," Dr. Gurley writes. "Uncertainty regarding mechanisms of action and adequate dosing regimens underscore many of these concerns. It would appear, however, that cranberry has the potential to dispel some of this uncertainty."

Arch Intern Med. 2011;171:1270-1278, 1279-1280.

Immunohistochemistry Not Effective in Early Breast Cancer Survival

2011-08-08T19:02:00.000-07:00

From Medscape Education Clinical Briefs

News Author: Nick Mulcahy
CME Author: Désirée Lie, MD, MSEd

08/01/2011;JAMA. 2011;306:385-393 and 436-437.

Study Highlights

The study involved 126 US centers between 1999 and 2003.
Included were women with clinical T1 to T2N0M0 invasive breast carcinoma planning to undergo breast-conserving therapy. These women were not pregnant and had a functional status score of 2 or less.
Excluded were those who required neoadjuvant therapy, those with prepectoral breast implants, women with concurrent bilateral disease, those with previous axillary dissection, and those with breast cancer not amenable to lumpectomy.
Bilateral bone marrow aspiration biopsy of the anterior iliac crest was performed immediately before SLN dissection and lumpectomy.
SLN dissection technique was left at the discretion of individual surgeons.
Whole-breast irradiation specified in the protocol excluded a third supraclavicular field.
Total dose for the breast was 45 to 50 Gy administered in tangential fields with coplanar posterior borders.
IHC for both SLN and bone marrow was performed at a central laboratory on H&E-negative SLNs.
Pathologists blinded to patient status assessed both specimens for occult metastases.
Of 5210 patients enrolled between 1999 and 2003, SLNs were identified in 5119 (98.3%).
69% of patients were older than 50 years, 83.3% had clinical stage I disease, and 80.1% had invasive ductal carcinoma.
Median duration of follow-up was 6.3 years, and median tumor size was 1.4 cm.
81.2% of patients had estrogen-receptor–positive tumors, and axillary lymph node dissection was performed in 107 (2.1%) with H&E-negative SLNs.
Of 5119 patients in whom an SLN specimen was identified, 1215 (23.7%) had nodes that were H&E-negative, and 3326 (85.2%) had specimens assessed by IHC.
Of those patients, 349 (10.5%) had occult metastases.
Of 3413 patients who underwent bone marrow biopsy, 104 (3.0%) had occult metastases by ICC.
Increasing tumor size was associated with SLN metastases but not with occult bone marrow metastases.
At follow-up of 6.3 years, there were 435 deaths and 376 women with disease recurrence.
Less than 10% of women had overdue follow-up.
The 5-year overall survival rate was 95.7% among women with immunohistochemical-negative SLNs and 95.1% among women with immunohistochemical-positive SLNs, with no significant difference in overall survival benefit (P = .64).
Rates of disease-free survival were 92.2% and 90.4%, respectively, for women with negative and positive occult SLN metastases, with no significant differences.
Immunochemically detected metastases in SLNs were not associated with overall survival or disease-free survival benefit.
Occult bone marrow metastases were positively associated with overall survival rate (mortality rates were 5.0% for ICC-negative bone marrow specimens and 9.9% for ICC-positive bone marrow specimens; P = .01).
Overall survival rates were 95.0% in women with ICC-negative bone marrow specimens and 90.1% in women with ICC-positive occult bone marrow metastases (P = .01).
The 5-year disease-free survival rates were 90.8% for ICC-negative occult bone marrow metastases and 86.7% for ICC-positive occult bone marrow metastases.
However, when multivariate analysis was applied, the difference in mortality was significant only for women older than 50 years and for those with a tumor size greater than 1.0 cm.
For the 2 groups, the unadjusted HR for overall survival benefit was 1.94, and the adjusted HR was 1.83.
Adjuvant systemic therapy did not affect the association between occult SLN or bone marrow metastases.
The authors concluded that among women with breast-conserving therapy for early-stage breast cancer, immunochemical evidence of SLN metastases was not useful in the prediction of overall survival benefit, but occult bone marrow metastases was associated with overall survival benefit.

Clinical Implications

In women with breast-conserving therapy for early-stage breast cancer, occult metastases in SLNs are not associated with overall survival or disease-free survival benefit.
In women with breast-conserving therapy for early-stage breast cancer, occult metastases in bone marrow are associated with overall survival benefit for women older than 50 years with a tumor size of 1.0 cm or greater.

Long-term Health Impacts of Hematopoietic Stem Cell Transplantation Inform Recommendations for Follow-up

2011-08-08T18:54:00.000-07:00

From Expert Review of Hematology

Smita Bhatia, MD, MPH

08/01/2011

Abstract

Advances in transplantation techniques and supportive care strategies have resulted in a significant improvement in survival of those who have undergone treatment.
However, hematopoietic stem-cell transplantation (HSCT) survivors are at risk of developing long-term complications, such as endocrinopathies, musculoskeletal disorders, cardiopulmonary compromise and subsequent malignancies.
These complications have a direct impact on the morbidity and mortality experienced by HSCT survivors. Two-thirds of HSCT survivors develop at least one chronic health condition; while a fifth develop severe or life-threatening conditions. HSCT patients who have survived for at least 5 years post-transplantation are at a fourfold to ninefold increased risk of late mortality for as long as 30 years from HSCT, producing an estimated 30% lower life expectancy compared with the general population.
The high burden of morbidity experienced by HSCT survivors makes it critically important that there is standardized follow-up of HSCT survivors at high risk for post-HSCT complications.
The Center for International Blood and Marrow Transplant Research/European Group for Blood and Marrow Transplantation/American Society for Blood and Marrow Transplantation and the Children’s Oncology Group long-term follow-up guidelines offer such standardized care. Future steps include wider dissemination and refinement of these guidelines.

Introduction

Hematopoietic stem-cell transplantation (HSCT) is an established curative option for a variety of hematological malignancies.
Advances in transplantation techniques and supportive care strategies have resulted in a significant improvement in survival: 70–80% of those who survive the first 2 years following HSCT are expected to become long-term survivors.
However, cure or control of the underlying disease is not accompanied by full restoration of health.
HSCT survivors are at risk of developing long-term complications, such as endocrinopathies, musculoskeletal disorders, cardiopulmonary compromise and subsequent malignancies (summarized inTable 1).
These complications have a direct impact on the morbidity and mortality experienced by HSCT survivors. The high burden of morbidity experienced by HSCT survivors forms the basis for standardized follow-up of HSCT survivors at high risk for post-HSCT complications.
This article summarizes the magnitude of risk of key long-term complications experienced by HSCT survivors, identifying those at increased risk for these complications owing to host characteristics and therapeutic exposures. The article also describes the current recommendations for follow-up, patterns of healthcare utilization by the HSCT survivors and adherence to these recommendations. Finally, the article identifies the need for future research efforts related to HSCT outcomes, identification of those at highest risk and refinement of the existing follow-up guidelines so that those at the highest risk are targeted.

http://www.medscape.org/viewarticle/747181

Autoimmune Myopathies: Autoantibodies, Phenotypes, and Pathogenesis: Statin-associated IMNM

2011-08-08T18:46:00.000-07:00

From Nature Reviews Nephrology

Andrew L. Mammen, MD, PhD Assistant Professor of Neurology and Medicine; Co-Director; Johns Hopkins Myositis Center, Baltimore, Maryland

06/08/2011;

Abstract

The different autoimmune myopathies—for example, dermatomyositis, polymyositis, and immune-mediated necrotizing myopathies (IMNM)—have unique muscle biopsy findings, but they also share specific clinical features, such as proximal muscle weakness and elevated serum levels of muscle enzymes.
Furthermore, around 60% of patients with autoimmune myopathy have been shown to have a myositis-specific autoantibody, each of which is associated with a distinct clinical phenotype.
The typical clinical presentations of the autoimmune myopathies are reviewed here, and the different myositis-specific autoantibodies, including the anti-synthetase antibodies, dermatomyositis-associated antibodies, and IMNM-associated antibodies, are discussed in detail.
This Review also focuses on a newly recognized form of IMNM that is associated with statin use and the production of autoantibodies that recognize 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the pharmacological target of statins.
The contribution of interferon signaling to the development of dermatomyositis and the potential link between malignancies and the initiation of autoimmune myopathies are also assessed.

Introduction

Autoimmune myopathies are a heterogeneous group of diseases, of which polymyositis and dermatomyositis are probably the best known.
These two entities share several clinical features, such as proximal muscle weakness that typically progresses over a period of weeks to months, and evidence of inflammation on muscle biopsy.
Immune-mediated necrotizing myopathies (IMNMs) probably represent a distinct form of autoimmune myopathy that is not associated with the same levels of inflammatory infiltrates as polymyositis or dermatomyositis on muscle biopsy.
Inclusion body myositis (IBM) is also a disorder considered by some authors to be a member of this group of diseases.Indeed, IBM muscle biopsies reveal inflammatory infiltrates similar to those found in poly-myositis, and patients with IBM have other evidence of immune system activation.
Nevertheless, patients with IBM, unlike those with dermatomyositis, polymyositis or IMNM, have a unique pattern of weakness and lack a sustained response to immunosuppression, which is the treatment of choice for patients with these conditions.Furthermore, pathological evidence suggests that IBM might actually be a myodegenerative disease that is associated with abnormal accumulation of amyloid-βand/or TAR DNA-binding protein 43, as seen in Alzheimer disease and amyotrophic lateral sclerosis, respectively.
Given that the primary role of the inflammatory response in IBM is currently under debate, this Review focuses primarily on the clinical presentation and pathogenesis of adult-onset polymyositis, dermatomyositis, and IMNM.
The association between distinct clinical phenotypes and autoantibodies is also reviewed.
Furthermore, evidence that statins may trigger a unique form of autoimmune muscle disease is discussed, along with data highlighting the involvement of interferon (IFN) signaling and malignancies in the initiation and maintenance of specific autoimmune myopathies.

Clinical Presentation

In 1975 and 1977, Bohan and Peter published a series of papers that established diagnostic criteria for dermatomyositis and polymyositis (Box 1).Although these criteria are imperfect, they are still widely used in both clinical and research settings, and provide a useful starting point for discussing the typical clinical features associated with autoimmune myopathy.

Proximal Muscle Weakness

The most common clinical feature associated with autoimmune myopathies is symmetrical proximal muscle weakness that progresses over a time period of weeks to months.
A patient with such a disease may complain that they have difficulty rising from chairs, climbing stairs, or washing their hair. In severe cases of autoimmune myopathy, oropharyngeal weakness can result in dysphagia and/or dysphonia; in such cases diaphragmatic weakness may also occur and require mechanical ventilation.
Although autoimmune myopathies are frequently characterized as 'painless weakness', some patients do have considerable myalgia; thus, the presence of muscle pain should not preclude a diagnosis of autoimmune myopathy.By contrast, muscle weakness slowly evolving over years, asymmetric or distal muscle weakness, facial weakness or scapular winging are rarely associated with autoimmune myopathies and should strongly suggest the possibility of an alternative diagnosis such as limb-girdle muscular dystrophy, or other non-immune-mediated muscle disease.

Electromyography

In patients with dermatomyositis or polymyositis, electromyography (EMG) of the affected muscle typically reveals short-duration, small-amplitude, polyphasic motor units. These motor units are also evident in other myopathic processes, including muscle disuse. In addition, patients with active autoimmune myopathy usually have features on EMG associated with 'irritable myopathy', such as spontaneous activity (fibrillation potentials and positive sharp waves) and/or complex repetitive discharges.Of note, in the experience of this reviewer, patients with partially treated dermatomyositis, polymyositis or steroid myopathy may have a non-irritable myopathy that lacks spontaneous activity on EMG.

Muscle Biopsy

In patients with suspected autoimmune muscle disease, a muscle biopsy can provide valuable diagnostic information. Muscle biopsy findings that were recognized by Bohan and Peter to be associated with autoimmune myopathies include: degenerating and/or necrotic myofibers, regenerating muscle fibers, atrophic muscle cells, and evidence of inflammatory exudates.These features are not, however, specific for immune-mediated myopathies, as they can also be found in patients with IBM and inflammatory muscular dystrophies, such as limb-girdle muscular dystrophy type 2B (also called dysferlinopathy).
Since Bohan and Peter published their classification scheme, biopsies from patients with dermatomyositis, polymyositis and IMNM have been shown to have unique pathological features, indicating that different pathophysiological mechanisms underlie these distinct diseases. As discussed in detail below, evidence of atrophic, degenerating or regenerating fibers within the perifascicular area is pathognomonic for dermatomyositis (Figure 1).By contrast, muscle biopsies from patients with polymyositis are characterized by the presence of cytotoxic T cells surrounding and invading non-necrotic myofibers (Figure 1b).
Muscle biopsies from patients with IMNM typically show marked myofiber necrosis, degeneration and regeneration, and few, if any, inflammatory cells are usually seen in muscle biopsies from these patients (Figure 1d).
Since toxic myopathies, endocrine-associated myopathies, paraneoplastic myopathies, and muscular dystrophies can also be associated with necrotic myofibers on muscle biopsy, the presence of myositis-specific autoantibodies (MSAs, see below) can help differentiate between these diseases and disorders that have an immune-mediated pathology.
When specific features of dermatomyositis, polymyositis or IMNM are absent, non-immune-mediated muscle diseases should always be considered as an alternative diagnosis. Moreover, features on muscle biopsies that are clearly characteristic of other muscle diseases, such as rimmed-vacuoles (as seen in IBM) or increased accumulation of glycogen (as seen in acid maltase deficiency), should suggest that the patient does not have dermatomyositis, polymyositis or IMNM.

(Enlarge Image)

Figure 1. Muscle Biopsies From Patients With Polymyositis, Dermatomyositis or Immune-mediated Necrotic Myopathy. a | A typical muscle fascicle from a normal muscle biopsy specimen includes myofibers of uniform size. b | The presence of lymphocytes (the small blue cells in this hematoxylin and eosin stain) surrounding and invading muscle fibers is a characteristic feature of polymyositis muscle biopsies, whereas c | perifascicular atrophy is typically seen in muscle biopsies from patients with dermatomyositis. d | Degenerating, necrotic and regenerating muscle fibers are a characteristic feature of muscle biopsies from patients with immune-mediated necrotic myopathy.

Elevated Muscle Enzymes

Elevated serum levels of muscle enzymes such as creatine kinase, aldolase, aspartate transaminase and/or alanine transaminase are present in at least 90% of patients with autoimmune myopathy. Although elevated levels of creatine kinase are believed to be the most sensitive and specific marker of muscle damage, patients with autoimmune myopathies can present with elevated serum aldolase levels without an accompanying increase in serum creatine kinase levels.
In 2009, a series of 12 patients with elevated serum aldolase levels but normal levels of creatine kinase was studied in detail.This analysis showed that many of these patients had muscle pain (92%) as well as arthralgias (75%) and interstitial lung disease (42%); only 50% of the patients had muscle weakness on examination.
Muscle biopsies showed that fragmentation of perimysial connective tissue and elevated acid phosphatase cellularity was prominent in those patients with selectively high serum aldolase levels. Furthermore, a few of the patients with high levels of serum aldolase were shown to have perifascicular atrophy on muscle biopsy, or skin rashes suggestive of dermatomyositis.
Importantly, all patients responded to corticosteroid therapy. Taken together, these findings indicate that in patients with muscle discomfort and normal serum levels of creatine kinase, measuring serum aldolase levels might help identify patients with a steroid-responsive autoimmune myopathy.
In patients with autoimmune myopathy, identifying whether elevated serum levels of transaminases are the result of muscle or liver disease can be challenging, particularly in those patients taking potentially hepatotoxic medications, such as methotrexate or azathioprine. However, as the liver enzyme γ-glutamyl transpeptidase (GGT) is not released by damaged muscle fibers,elevated serum levels of GGT should suggest the possibility of concurrent liver damage.

MRI

Although not included in the Bohan and Peter criteria, MRI might help identify and, thus, aid the management of patients with autoimmune myopathy. On short tau inversion recovery (STIR) imaging, increased signal intensity within muscle tissue is consistent with the presence of muscle necrosis, degeneration, and/or inflammation (Figure 2).As a result, this finding has been incorporated into contemporary diagnostic criteria for autoimmune myopathies.

(Enlarge Image)

Figure 2. Thigh MRI From a Patient With Dermatomyositis. a | In T1-weighted images, fat is bright and muscle is dark. b | In short tau inversion recovery sequences, normal muscle is dark and inflamed muscle is bright. Long arrows indicate the inflamed left vastus lateralis muscle. Short arrows highlight the left biceps femoris muscle; the bright rim around this muscle is consistent with fascial inflammation.

MRI can also identify when chronic muscle damage has resulted in fatty replacement of skeletal muscle (Figure 2); in my experience, muscles that have been extensively replaced by fatty tissue are unlikely to improve with immunosuppressive therapy. Since autoimmune myopathies can result in 'patchy' muscle involvement,and considering that 'blind' muscle biopsies have a substantial false-negative rate of at least 12%,some authors have suggested that MRI-guided muscle biopsies might improve diagnostic accuracy. In one small study, five of 11 patients with polymyositis who underwent blind biopsies were falsely identified as not having this disorder. By contrast, only one of 14 patients with polymyositis who had an MRI-guided biopsy had a false-negative result.
A study of patients with autoimmune myopathy (polymyositis or dermatomyositis) has revealed that inflammatory cells are abundant in areas with high-intensity STIR signal on MRI; however, inflammatory cells, albeit fewer in number, were also shown to be present in areas deemed not to be affected on MRI. The same investigators also found that MRI signal intensity decreased in patients with dermatomyositis or polymyositis after treatment had been initiated;this finding suggests that MRI could help the treating clinician to assess a clinical response. Nevertheless, further studies are required before the utility of MRI in informing decision-making relating to the treatment of autoimmune myopathies is known.

Dermatomyositis Rash

Characteristic cutaneous features often help the treating clinician to differentiate patients with dermatomyositis from those with polymyositis or IMNM.Purplish discoloration around the eyes known as a heliotrope rash and/or an erythematous rash over the extensor surfaces of the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints referred to as Gottron papules (Figure 3) are both features of dermatomyositis. In fact, the heliotrope rash and Gottron papules are the only two cutaneous findings that are specific for this disorder. Indeed, patients with these features who lack muscle involvement are referred to as having 'amyopathic' dermatomyositis.

(Enlarge Image)

Figure 3. Gottron Papules. In a patient with dermatomyositis, Gottron papules—pathognomonic cutaneous manifestations of dermatomyositis—are evident on the extensor surfaces of the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints.

Although less specific than the cutaneous features mentioned above, patients with dermatomyositis might also present with skin atrophy, dyspigmentation, and telangectasias on the upper back (the 'shawl sign') or the upper chest (the 'V-sign').Changes in the nail beds, including periungual telangiectasias and cuticular hypertrophy, might be seen in patients with dermatomyositis, but these cutaneous features are also commonly found in patients with scleroderma. Of note, dermatomyositis rashes can be exacerbated by exposure to ultraviolet light.When performed, skin biopsies taken from patients with this condition frequently show inflammatory cells at the dermoepidermal junctionor around small blood vessels in the dermis;however, these pathological findings may also be seen in patients with lupus erythematosus. Finally, patients with dermatomyositis may develop painful subcutaneous calcifications, although these calcifications are most commonly found in juvenile cases.

Overlap Syndromes

Patients with autoimmune myopathy can present with, or develop, an overlap autoimmune rheumatic disease such as scleroderma, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, or mixed connective disease.
Thus, patients with autoimmune myopathy can have typical features of the coexisting rheumatic disease; for example, dryness of the eyes and mouth (Sjögren syndrome) or kidney involvement (systemic lupus erythematosus), as well as symptoms associated with immune-mediated muscle disease.
The frequency with which autoimmune muscle disease occurs in the context of other rheumatic diseases has not been well-defined. For example, in the case of scleroderma, skeletal muscle involvement has been reported to occur in 16-93% of patients, depending on the diagnostic criteria used to classify the condition.
Patients with autoimmune myopathies, especially those with dermatomyositis or polymyositis, might also present with cardiological symptoms including conduction defects, arrhythmias, and reduced ejection fractionsFurthermore, interstitial lung disease (ILD) occurs in a substantial number of patients with dermatomyositis or polymyositis. This condition is typically thought to occur in 5-46% of patients with either of these conditions,and the incidence of pulmonary symptoms seems to depend on the clinical setting and the criteria used to determine pulmonary involvement. In one study, when abnormalities on high-resolution CT and/or pulmonary function tests were used to diagnose ILD (even in the absence of symptoms), 11 of 17 (65%) patients with dermatomyositis or polymyositis were shown to have ILD.Importantly, ILD most often occurs in the context of anti-Jo-1 or one of the other antisynthetase autoantibodies (see below).

Autoantibodies

Since Bohan and Peter's diagnostic criteria for dermatomyositis and polymyositis were developed, it has become clear that patients with autoimmune myopathies frequently have autoantibodies. Myositis-associated auto-antibodies (for example, anti-Ro and anti-La) are associated with both immune-mediated myopathies and other connective tissue disorders and will not be discussed further here. By contrast, each MSA is associated with a unique clinical phenotype, and these autoantibodies are found almost exclusively in patients with immune-mediated myopathy or antisynthetase syndrome. New autoantibodies are continually being identified and, to date, around 60-80% of patients with autoimmune myopathy seem to have at least one MSA.In fact, several classification schemes have proposed that the presence of MSAs be included in inclusion criteria for dermatomyositis and polymyositis.Interestingly, with the exception of anti-155/140, MSAs are associated with a decreased risk of malignancy.The individual MSAs are discussed in detail below.

Statin-associated IMNM

Musculoskeletal symptoms such as myalgia and cramp are quite common in patients taking statins (9-20%), but they are usually mild.
By contrast, rhabdomyolysis is a well-known severe adverse event associated with statin use. Fortunately, however, this adverse event occurs rarely in patients taking this medication, at a rate of around 0.4 per 10,000 patient years.
In most cases, statin-associated muscle complaints improve when the treatment is discontinued, and complete recovery can be expected within a few weeks or months after discontinuation of the drug.
Nevertheless, over the past two decades, numerous case reports have indicated that statins might cause dermatomyositis or polymyositis in some patients, and the identification of inflammatory cells in muscle biopsies taken from these patients supports this hypothesis.
Several compelling studies have also shown that patients can develop IMNMs after taking statins.
In one case series, eight patients were shown to develop myopathy while taking statins, and in some cases the myopathy persisted or even progressed despite discontinuation of the medication.
In fact, seven of the eight patients only improved on initiation of immunosuppressive therapy. Seven of the eight cases had numerous necrotic and regenerating fibers on muscle biopsy, indicating that they might have had statin-associated IMNM. In five cases, marked inflammation on muscle biopsy was absent, indicating that these patients did not have clinical features associated with dermatomyositis or polymyositis. In all eight cases, major histocompatibility complex class I (MHC-I) expression was present in non-necrotic muscle fibers; this finding is a characteristic feature of immune-mediated muscle diseases, and is not seen in patients with other forms of muscle disease such as the muscular dystrophies
In a second case series, 24 patients were identified who had progressive proximal muscle weakness after starting statins, which progressed even after these medications were discontinued.These patients had elevated serum creatine kinase levels, and muscle biopsies revealed marked myofiber necrosis and regeneration in the absence of prominent lymphocytic infiltrates, consistent with a necrotizing myopathy. The patients' symptoms improved with immunosuppressive medications; however, over 50% of the patients worsened when immunosuppressive therapy was tapered. This series also demonstrated that the prevalence of statin exposure was markedly higher in patients with IMNM than in control patients with dermatomyositis, polymyositis or IBM.
Taking a different approach, researchers at Johns Hopkins University (including myself) have identified novel autoantibodies that recognize 200 kDa and 100 kDa proteins in 16 of 26 patients who presented to our department with a necrotizing myopathy. No other autoantibodies or alternative diagnoses were identified in these patients.The patients who expressed these novel antibodies had proximal muscle weakness and high serum levels of creatine kinase, and responded to immunosuppressive therapy—clinical symptoms worsened in many of the patients when immunosuppressive treatment was tapered. Analysis of muscle biopsies taken from these patients revealed that 75% of the cases had abnormal capillary morphologies, 50% had evidence of MAC deposition on non-necrotic muscle cells, and 50% had MHC-I expression in non-necrotic myofibers.Of note, 63% of the patients who had these novel antibodies had been exposed to statins before developing myopathy. Furthermore, compared with age-matched control patients with myopathy, the prevalence of statin use in patients with anti-200/100 autoantibodies (83%) was significantly higher than in patients with dermatomyositis (25%), polymyositis (37%) or IBM (34%).
In a follow-up study, we identified the autoantigen recognized by the anti-200/100 autoantibody as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)—the pharmacological target of statins.
Statins are known to dramatically upregulate HMGCR protein levels; thus, in some patients, increased HMGCR expression could trigger anti-HMGCR autoimmunity. Why some statin-naive patients with IMNM also develop anti-HMGCR autoantibodies remains to be determined.
Of note, elevated HMGCR expression is required for muscle differentiation in vitro.We have shown that in muscle biopsy specimens, regenerating human muscle fibers also express high levels of HMGCR.This finding suggests that after statin medications are discontinued, high levels of HMGCR expression in regenerating muscle tissue might continue to drive the autoimmune response.
Together, the studies mentioned above strongly suggest that an environmental factor—statin medication—is associated with a distinct form of autoimmune necrotizing myopathy that is characterized by the production of anti-HMGCR autoantibodies.
Since associations between environmental factors and the development of sustained autoimmunity are rare, this distinct form of autoimmune necrotizing myopathy might prove to be a model system for studying this phenomenon.
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http://www.medscape.org/viewarticle/743647_4

Urine Dipstick Protein Test Detects Silent Kidney Disease

2011-08-05T22:00:00.000-07:00

From Medscape Medical News

Laurie Barclay, MD

August 4, 2011 — An inexpensive urine dipstick test can help screen for asymptomatic kidney disease, according to the results of a community-based, prospective cohort study reported online July 29 in the Journal of the American Society of Nephrology.
"We showed that routine inexpensive urine dipstick screening in a population with and without risk factors will allow primary clinicians to follow fewer patients with serial monitoring to identify those with rapid kidney function decline [RKFD] that will potentially benefit from earlier referral and therapeutic intervention," said lead author William F. Clark, MD, from the University of Western Ontario and London Health Sciences Centre in London, Canada, in a news release.
Although RKFD is associated with cardiovascular morbidity and mortality, serial evaluation of estimated glomerular filtration rate (eGFR) is not cost effective as screening in the general population. The investigators therefore assessed the predictive value of albuminuria and 3 thresholds of dipstick proteinuria to detect RKFD, defined as an annual decline from baseline eGFR of 5% or more.
The study cohort consisted of 2574 community-dwelling participants with follow-up for median duration of 7 years. Median change in eGFR was −0.78 mL/minute/1.73 m²/year, and RKFD developed in 8.5% of patients. Advancement to a new stage of chronic kidney disease (CKD) occurred in 64.7% of participants with RKFD and in 19.0% of those without RKFD.
Compared with albuminuria, a dipstick protein level of at least 1 g/L was a better predictor of RKFD.
If all participants (2.5% of the total cohort) who screened positive for a dipstick protein value of at least 1 g/L at baseline were monitored with serial eGFR, 1 of every 2.6 participants would have RKFD. Following this strategy for screening would correctly identify the 90.8% of patients who progressed to RFKD, would falsely label 1.5% as having RKFD, and would miss 7.7% of those in whom RKFD ultimately would develop.
"Among those with risk factors (cardiovascular disease, age >60, diabetes, or hypertension), the probability of identifying RKFD from serial eGFR measurements increased from 13 to 44% after incorporating dipstick protein (≥1g/L threshold)," the study authors write. "In summary, inexpensive screening with urine dipstick should allow primary care physicians to follow fewer patients with serial eGFR assessment but still identify those with rapid decline of kidney function."
Limitations of this study include possible selection bias.
"At the population level, this screening strategy may enable more appropriate targeting of resources," the study authors conclude. "However, future research must assess the effect and cost-effectiveness of different follow-up strategies in independent cohorts."

J Am Soc Nephrol. Published online July 29, 2011.

No Clear Benefit for Tight Blood Glucose Control in T2DM

2011-08-05T21:58:00.000-07:00

From Medscape Medical News

Laurie Barclay, MD

August 4, 2011 — Intensive glycemic control has no clear benefit vs conventional glycemic control for patients with type 2 diabetes, according to the results of a Cochrane systematic review reported online August 1 in the Cochrane Database of Systematic Reviews.
"Targeting the intensive levels means that many patients have to cope with complex and time consuming treatment," said lead author Bianca Hemmingsen, from the Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital in Copenhagen, Denmark, in a news release. "On top of this, they have the fear that their blood glucose might drop too low.... With the numbers of people in the world with type 2 diabetes increasing, it is important that we work out the best way of helping them to manage their blood glucose levels."
To compare outcomes when targeting intensive vs conventional glycemic control in patients with type 2 diabetes, the reviewers searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL (until December 2010) for randomized clinical trials comparing prespecified glycemic control targets in adults with type 2 diabetes. Determination of the risk for bias and data extraction was performed independently by 2 reviewers. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to compare dichotomous outcomes.
The reviewers identified 20 trials in which a total of 16,106 adults with type 2 diabetes were randomly assigned to intensive glycemic control and 13,880 to conventional glycemic control. In each of the included trials, there were 20 to 11,140 participants, mean age 62.1 years, and the intervention lasted from 3 days to 12.5 years.
Mortality risk was not significantly different between the intensive and conventional glycemic control groups. For all-cause mortality, the RR was 1.01 (95% CI, 0.90 - 1.13; 29,731 participants, 18 trials), and for cardiovascular mortality, the RR was 1.06 (95% CI, 0.90 - 1.26; 29,731 participants, 18 trials). Using trial sequential analysis (TSA), the investigators demonstrated that a 10% reduction in RR could be refuted for all-cause mortality.
With use of a random-effects model, there was no significant effect of targeting intensive glycemic control on the risk for nonfatal myocardial infarction. However, in the fixed-effect model, there was a 14% reduction in risk (RR, 0.86; 95% CI, 0.78 - 0.96; P = .006; 29,174 participants, 12 trials).
Targeting intensive glycemic control was associated with a lower risk for amputation (RR, 0.64; 95% CI, 0.43 - 0.95; P = .03; n = 6960; 8 trials), a composite microvascular outcome (RR, 0.89; 95% CI, 0.83 - 0.95; P = .0006; n = 25,760; 4 trials), retinopathy (RR, 0.79; 95% CI, 0.68 - 0.92; P =.002; n = 10,986, 8 trials), retinal photocoagulation (RR, 0.77; 95% CI, 0.61 - 0.97; P = .03; n = 11,142; 7 trials), and nephropathy (RR, 0.78; 95% CI, 0.61 - 0.99; P = .04; n = 27,929; 9 trials).

Although targeting intensive glycemic control was associated with increased risks for mild and severe hypoglycemia, there was substantial heterogeneity among trials. In a subgroup analysis of trials studying glycemic control only in usual-care settings, there was a significant benefit of targeting intensive glycemic control for nonfatal myocardial infarction, but TSA showed that more trials are needed.

"The included trials did not show significant differences for all-cause mortality and cardiovascular mortality when targeting intensive glycaemic control compared with conventional glycaemic control," the review authors write. "Targeting intensive glycaemic control reduced the risk of microvascular complications while increasing the risk of hypoglycaemia. Furthermore, intensive glycaemic control might reduce the risk of non-fatal myocardial infarction in trials exclusively dealing with glycaemic control in usual care settings."

Cochrane Database Syst Rev. 2011;6:CD008143.

FDA Warns Against Repeat, High-Dose Fluconazole in Early Pregnancy

2011-08-05T20:16:00.000-07:00

From Medscape Medical News >

Megan Brooks

August 3, 2011 — The US Food and Drug Administration (FDA) warned today that chronic use of fluconazole (Diflucan, Pfizer) in high doses (400 - 800 mg/day) during the first trimester of pregnancy may be associated with certain birth defects in infants.
The risk does not appear to be associated with a single, low dose of fluconazole (150 mg) used to treat vaginal candidiasis (yeast infection), the agency emphasizes.
According to the agency, "a few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in utero to high-dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester."
"The features seen in these infants include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. These effects are similar to those seen in animal studies," the agency notes.
Four of the case reports involved maternal use of chronic high-dose intravenous fluconazole for coccidioidal meningitis, and 1 report involved an HIV-positive mother who received chronic high-dose oral fluconazole for vaginal candidiasis.
Cases associated with high-dose fluconazole use all shared some characteristics with the autosomal recessive genetic disorder known as Antley-Bixler syndrome, the FDA notes. This combination of congenital anomalies occurs rarely in the general population and is similar to anomalies seen in animals following in utero fluconazole exposure.

Category Change
On the basis of available information, the FDA has changed the pregnancy category for fluconazole indications (other than vaginal candidiasis) from category C to category D.
"Pregnancy category D means there is positive evidence of human fetal risk based on human data but the potential benefits from use of the drug in pregnant women with serious or life-threatening conditions may be acceptable despite its risks," the FDA explains.
The pregnancy category for a single, low dose of fluconazole has not changed and remains category C.
The FDA recommends that healthcare professionals counsel patients if the drug is used during pregnancy or if a patient becomes pregnant while taking the drug. "If a patient uses fluconazole during pregnancy, the patient should be informed of the potential risk to the fetus," the agency says.

More information on the alert is available on the FDA Web site.
Adverse events related to this product can also be communicated to MedWatch, the FDA's adverse event and reporting program, by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

FDA Sunscreen Guidelines -- The Key Changes

2011-08-03T22:21:00.000-07:00

From Medscape Internal Medicine > Medicine Matters

Sandra A. Fryhofer, MD

Posted: 07/22/2011

Hello. I'm Dr. Sandra Fryhofer. Welcome to Medicine Matters. The topic: the new US Food and Drug Administration (FDA) guidelines for rating and labeling sunscreens.Here's why it matters.
Skin cancer is the most common cancer affecting adults in the United States, but there are ways to diminish the sun's danger. The new gold standard for sunscreens is broad spectrum protection from products that block both ultraviolet (UV)B, the burning rays, and UVA, the rays that cause aging and wrinkles.
The sun protection factor (SPF) number rating system for UV protection will still be used, but the highest rating allowed will now be 50+. Sunscreens with an SPF of 70 or more are history. Only products with an SPF of 15 or higher will be able to claim protection from sunburn, skin cancer, and aging. Note, however, that, dermatologists prefer an SPF of at least 30.
Sunscreen products can now only claim to be water-resistant. They can no longer be labeled as waterproof or sweat-proof. Even with water-resistant sunscreens, check to be sure that the application works for 40 or 80 minutes. Because these labeling rules are new, products with the older labels are still available.
Consumer Reports provides a list of products already tested for UVA protection.
You can also check the list of active ingredients on the label.
Of note, zinc oxide and titanium dioxide offer protection against both UVA and UVB.
Be sure to apply sunscreen liberally and reapply it often, especially after swimming.
And remember, a wet t-shirt has an SPF of 0, and there's no such thing as a safe tan.

A–Z of Nutritional Supplements for Athletes

2011-08-03T22:13:00.000-07:00

From British Journal of Sports Medicine

Dietary Supplements, Sports Nutrition Foods and Ergogenic Aids for Health and Performance—Part 22

H Geyer; H Braun; L M Burke; S J Stear; L M Castell

References

Introductory Remarks

Practitioners who work with elite athletes know that the pressure and considerable rewards involved with success provide a high level of motivation to look for any safe and legal strategy that might enhance performance, even by small margins.
Dietary supplements operate in this space, whether they promise a large performance boost or just create the fear that an athlete cannot afford to miss out on what everyone else is using.
It is often tempting to overlook the lack of evidence to support the claims made about a supplement on the basis that the stakes are higher for elite athletes; therefore the cost:benefit ratio favours experimentation in the absence of clear proof.
Over the past decade, however, we have become aware that the cost of getting it wrong has also escalated for elite athletes.
A new hazard related to supplement use has emerged: inadvertent ingestion of substances that are banned under the antidoping codes in place in elite sport, but present in supplement products.
In some cases, the level of the presence, or contamination, of banned substances in supplements presents a health hazard for all consumers.
In some cases, the concentration may be too small to achieve any health or performance effect but large enough to record an infringement for athletes who submit to doping tests.
Newspapers, the internet and Courts of Arbitration in Sport now bear stories of dedicated athletes whose careers have been or are being jeopardised because of the ingestion of a banned substance via a dietary supplement.
This problem was first brought to scientific recognition by Hans Geyer and his colleagues from the Centre for Preventive Doping Research in Cologne. The following article provides an update of a recent review by this team.

Non-Steroidal Anti-Inflammatory Drug Use and Risk of Atrial Fibrillation or Flutter

2011-08-03T21:28:00.000-07:00

From British Medical Journal

Population Based Case-Control Study

Morten Schmidt; Christian F Christiansen; Frank Mehnert; Kenneth J Rothman; Henrik Toft Sørensen

Authors and Disclosures

Objectives To examine the risk of atrial fibrillation or flutter associated with use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase (COX) 2 inhibitors.
Design Population based case-control study using data from medical databases.
Setting Northern Denmark (population 1.7 million).
Participants 32 602 patients with a first inpatient or outpatient hospital diagnosis of atrial fibrillation or flutter between 1999 and 2008; 325 918 age matched and sex matched controls based on risk-set sampling.
Main outcome measures Exposure to NSAID use at the time of admission (current use) or before (recent use). Current use was further classified as new use (first ever prescription redemption within 60 days before diagnosis date) or long term use. We used conditional logistic regression to compute odds ratios as unbiased estimates of the incidence rate ratios.
Results 2925 cases (9%) and 21 871 controls (7%) were current users of either non-selective NSAIDs or COX 2 inhibitors. Compared with no use, the incidence rate ratio associating current drug use with atrial fibrillation or flutter was 1.33 (95% confidence interval 1.26 to 1.41) for non-selective NSAIDs and 1.50 (1.42 to 1.59) for COX 2 inhibitors. Adjustments for age, sex, and risk factors for atrial fibrillation or flutter reduced the incidence rate ratio to 1.17 (1.10 to 1.24) for non-selective NSAIDs and 1.27 (1.20 to 1.34) for COX 2 inhibitors. Among new users, the adjusted incidence rate ratio was 1.46 (1.33 to 1.62) for non-selective NSAIDs and 1.71 (1.56 to 1.88) for COX 2 inhibitors. Results for individual NSAIDs were similar.
Conclusions Use of non-aspirin NSAIDs was associated with an increased risk of atrial fibrillation or flutter. Compared with non-users, the association was strongest for new users, with a 40-70% increase in relative risk (lowest for non-selective NSAIDs and highest for COX 2 inhibitors). Our study thus adds evidence that atrial fibrillation or flutter needs to be added to the cardiovascular risks to be considered when prescribing NSAIDs.

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammatory conditions and pain.
By inhibiting cyclo-oxygenase (COX)-1 mediated production of prostaglandins,non-selective NSAIDs are known to cause gastrointestinal toxicityand a variety of nephrotoxic syndromes.
An alternative is selective COX 2 inhibitors, available in the form of older or newer agents.
The newer COX 2 inhibitors, introduced into clinical practice in 1998, were developed as NSAIDs with an improved gastrointestinal side effect profile.
The cardiovascular safety of all marketed newer COX 2 inhibitors requires thorough evaluation in view of the increased cardiovascularand renal risk reported for several of these drugs.

Atrial fibrillation is the most common rhythm disorder observed in clinical practice. It more than doubles in prevalence during each advancing decade of life, from 0.5% at age 50-59 years to above 10% at age 80-89 years.It is associated with increased mortality and morbidity, mainly due to haemodynamic impairments that exacerbate or even cause heart failure,and a threefold to fourfold increased risk of thromboembolic stroke.

Use of NSAIDs may increase the risk of atrial fibrillation through its adverse renal effects—for example, fluid retention, electrolyte disturbances, and blood pressure destabilisation —but the evidence for such effects is limited. Although no original research has been published on COX 2 inhibitors and atrial fibrillation, a meta-analysis summarised data from 114 clinical trials and found that rofecoxib was associated with an increased risk of cardiac arrhythmias (relative risk 2.90, 95% confidence interval 1.07 to 7.88).
Because the meta-analysis included only 286 incident arrhythmias, precision was low and risk of arrhythmia subtypes such as atrial fibrillation could not be examined. Recently, traditional NSAIDs (that is, non-selective NSAIDs and older COX 2 inhibitors) have been associated with increased risk of chronic atrial fibrillation (incidence rate ratio 1.44, 1.08 to 1.91).
Any confirmed association between use of NSAIDs and atrial fibrillation would have major clinical and public health implications. Older people are of special concern because the prevalence of use of NSAIDs and the incidence of atrial fibrillation increase with age.
To address the limitations of the existing literature, we conducted a large population based case-control study examining whether and to what extent use of NSAIDs increases the risk of atrial fibrillation or flutter.

Midlife CV Risk Linked to Brain Atrophy, Cognitive Decline

2011-08-03T21:14:00.000-07:00

From Medscape Medical News > Neurology

Pauline Anderson

August 2, 2011 — Cardiovascular risk factors, such as hypertension, diabetes, and obesity, in midlife are associated with an increase in the rate of brain changes linked to dementia just 10 years down the road, a new study has found.
For example, the study showed that being hypertensive at about 54 years of age was a significant predictor of white matter hyperintensity volume (WMHV) progression and worsening performance in executive function at about 61 years of age.
The study results should be a "wake-up call" not to take midlife hypertension lightly, said lead study author Charles DeCarli, MD, Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento.
"We should be very, very clear about the insidious impact of hypertension and be more wary about just saying, 'Your blood pressure is 140 over 90; that's no big deal, we'll just watch it,'" he said. "That's a common mistake."
The study was published in the August 2 issue of Neurology.
The analysis included 1352 subjects from the offspring cohort of the Framingham Heart Study, a community-based, prospective study initiated in 1949. Researchers assessed vascular risk factors (hypertension, systolic blood pressure, diabetes, smoking, hypercholesterolemia, obesity, and waist to hip ratio [WHR]) in these offspring at a mean age of 54 years, 7 to 10 years before they first underwent neuropsychological testing and volumetric brain magnetic resonance imaging.
The study found that all measures of change in brain structure and cognitive function were more marked with increasing age. APOE ε4 carriers had a more rapid decline in logical memory performance compared with noncarriers.

Insidious Impact of Hypertension
Hypertension and increasing systolic blood pressure in midlife were associated with a more rapid increase in WMHV (both P < .001), even after adjusting for interim stroke, hypertension, and systolic blood pressure.
It's not surprising that the study linked hypertension to brain aging; what was a surprise was that this association starts so early in life, said Dr. DeCarli. This is especially important to know because a quarter of middle-aged Americans has hypertension. In this study, hypertension affected 26.5% of study subjects, making it one of the "big players" when it comes to brain aging, he said.
The study found that diabetes was significantly associated with a greater annual increase in temporal horn volume (THV), a surrogate marker of accelerated hippocampal atrophy (P = .017).
Midlife obesity, which affected 22.6% of study subjects, was associated with increasing WHR with marked decrease in total brain volume (TBV), whereas smoking (15.0% of subjects) was associated with a greater annual increase in THV and decrease in TBV and also predicted an increased risk for prominent change in THV, TBV, and WMHV.

Cognitive Decline
For cognitive decline, both hypertension and systolic blood pressure were associated with a more marked decline in Trail-Making Test B-A performance (P = .012 and .002, respectively). These associations were unaltered after adjusting for baseline cognitive performance.
Midlife obesity, too, was associated with rapid decline in executive function. There was only a trend toward an association of midlife diabetes with decline in executive function, but the study's power was limited because of the small number of diabetic patients (only 5% had diabetes).
Vascular risk factors are highly correlated with each other, making it difficult to tease out individual mechanisms, but the study authors speculated that hypertension could increase small vessel disease load, leading to an accelerated rate of WMHV progression and decline in executive function. Diabetes could have a neurodegenerative effect that accelerates hippocampal atrophy, and smoking could lead to both vascular and neurodegenerative lesions, they said.
Although the study didn't uncover a significant association between midlife vascular risk factors and decline in memory, it did suggest at least an indirect association because it found effects of most risk factors on structural brain measures, said the study authors.

'Walking Train Wrecks'
Having vascular risk factors in middle age means "you're not at the top of your game" as you move into your 70s and 80s, when Alzheimer's disease begins to be an issue, said Dr. DeCarli.
"People get to age 80 and they've got these brain injuries from the hypertension they've had for 50 years; they might have had a stroke or a heart attack, and maybe their kidneys aren't working," he said. "They're walking train wrecks."
Dr. DeCarli pointed out that vascular risk factors are additive, "so if you have all of these things, you're in much worse shape," he said.
The study suggests that vascular risk factors in midlife should be targeted for primary prevention trials of dementia, said the study authors. Identifying these risk factors in middle-aged people could be useful in screening those who may be at risk for dementia and encouraging them to make crucial lifestyle changes, added Dr. DeCarli.

Important Supporting Role
Reached by email for a comment, David Knopman, MD, professor of neurology at the Mayo Clinic in Rochester, Minnesota, and a member of the American Academy of Neurology, said the study is "scientifically valid and informative."
The results are important because they show that cardiovascular risk factors influence brain integrity relatively early in life, said Dr. Knopman. "Although the results do not challenge the view that Alzheimer pathology is still the dominant one in late-life dementia, the current results emphasize that vascular risk factors play an important supporting role."
But the results, he said, will probably not change clinical practice. "After all, it is no mystery that attention to vascular risk factors in midlife is critically important from a cardiovascular point of view, so that adding a neurological reason shouldn't make a very, very compelling story more so."

Neurology. 2011;77:461-468.

First Study to Quantify Benefits of Exercise on CHD Risk

2011-08-03T21:07:00.000-07:00

From Heartwire

Lisa Nainggolan

August 2, 2011 (Boston, Massachusetts) — The first meta-analysis to specifically examine the dose-response relationship between physical activity and risk reduction for coronary heart disease (CHD) has found that those engaging in the equivalent of 150 minutes of moderate-intensity exercise per week--the basic minimum as recommended by 2008 US federal guidelines--had a 14% lower CHD risk, and those who achieved 300 minutes per week had a 20% lower risk of CHD, compared with those who were sedentary.

Dr Jacob Sattelmair (Harvard School of Public Health, Boston, MA) and colleagues report their findings online August 1, 2011 in Circulation.
"Although it is well-established that physical activity helps prevent CHD, a lot of the literature compares active vs inactive individuals or qualitative concepts, such as 'high,' 'medium,' and 'low' amounts of exercise," Sattelmair explained to heartwire .
"We wanted to look at studies done recently that assessed physical activity quantitatively. Generally, the 'industry-standard' quote is that if you are physically active, you will lower your CHD risk by 20% to 30%. We wanted to see, if you follow the US federal guidelines, what does that mean? What are the risk reductions for CHD?

The conclusion is that even a little bit of physical activity is beneficial and more is better, but the biggest bang for your buck happens at the lower end of the spectrum.

The majority of the population in the US is inactive, so if you start by doing something, that's a great first step, and you'll start to realize the benefits. If you're doing nothing, you don't have to start by running a marathon to see the benefit; even walking briskly for 15 minutes a day was associated with a significant reduction in CHD risk," he observes. This is, he says, in line with the US guidelines, which encourage any amount of activity for those unable to meet the minimum recommended.
Findings Support US Federal Physical-Activity Guidelines
Sattelmair and colleagues included in their review 26 studies published in English since 1995, nine of which allowed for quantitative estimates of leisure-time physical activity. The researchers performed initial analyses comparing high and low physical activity, which included all 26 studies, and the findings were similar to those of the primary analysis, which included only the nine studies.

As well as the 14% and 20% CHD risk reduction observed with the minimum and advanced recommended amounts of exercise, the researchers found that those who were physically active at levels lower than the minimum recommended also had a significantly lower risk of CHD, compared with those who did nothing.
So although meeting the basic guideline "is associated with a lower risk reduction than that which is generally ascribed to being physically active, meeting the advanced guideline--300 minutes of moderate-intensity exercise per week--is associated with a risk reduction that is pretty much in line with the benefit that has generally been ascribed to physical activity," he notes.

And those who engaged in more than the advanced amount of exercise saw additional benefits--those able to participate in 750 minutes per week of moderate intensity exercise (five times the minimum recommended amount) had around a 25% reduction in risk of CHD, Sattelmair said.

The researchers also found that the cardiovascular benefits of exercise appeared to be stronger in women than in men but say they don't have any plausible explanation for this finding.
And there were insufficient data to examine the effect of age at baseline or race on the relationship between physical activity and CHD risk.
Nevertheless, "These findings provide quantitative data that support the 2008 US physical-activity guidelines," they say, and indicate that the most benefit for CHD risk occurs at the lower end of the activity spectrum--ie, very modest, achievable levels of physical activity.
Future studies that quantitatively assess the dose-response relation between leisure-time physical activity and CHD risk will help clarify the upper end of the dose-response curve, they note, "and enable additional quantitative evaluations in future reviews, such as exploring potential differences by age and race."