Oral HPV Infection: Higher in Men, Transmitted by Sex

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

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 stabilized and optimally managed

 Sexual Activity and Specific Cardiovascular Conditions

 Coronary Artery Disease Recommendations
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 Disease Recommendations
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 valve interventions
 3. Sexual activity is not advised for patients with severe or significantly symptomatic valvular disease until their condition is stabilized and optimally managed

 Heart Failure Recommendations 
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 Disease Recommendation 
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 Cardiomyopathy Recommendations 
 2. Sexual activity should be deferred for patients with HCM who are severely symptomatic until their condition is stabilized

 Arrhythmias, Pacemakers, and ICDs Recommendations
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 atrial tachycardia 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 precipitate ventricular 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 Function Recommendation 
 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 Inhibitors Recommendations
 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 Medications Recommendation 
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 CVD Recommendation
1. Anxiety and depression regarding sexual activity should be assessed in patients with CVD

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

Milk Supplements Might Prevent Gout Flares

NEWS REFERENCE EDUCATION Medical News
Janis C. Kelly January 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

From Heartwire
 Michael O'Riordan January 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

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

What Clinicians and Patients Need to Know
JoAnn E. Manson, MD, DrPH 01/12/2012

 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=17 Related Link: Statins Associated With Significant Increase in Diabetes Risk

'Exergaming' Helps Older Adults Improve Cognitive Function

From Medscape Medical News > Neurology
 Allison Shelley January 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).

 Neuroplasticity Serge 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

From Medscape Education Clinical Briefs News Author: Emma Hitt, PhD CME Author: Charles P. Vega, MD CME Released: 01/11/2012; Clinical Context There 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 Perspective Cognitive 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 Debate According 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 Agenda In 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, Editorial Study Highlights Researchers 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 Implications Neurofibrillary 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?

From Heartwire Experts Debate in WSJ: Prescribe Statins for Primary Prevention? Michael O'Riordan January 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 Factors Just 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, JUPITER Blumenthal, 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

By KATIE MOISSE | ABC News – Tue, Jan 17, 2012 10:08 AM EST Sleeping 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

From Medscape Medical News > Oncology Zosia Chustecka January 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

Nexus How Doctors Die It’s Not Like the Rest of Us, But It Should Be by Ken Murray Years 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

From FDA Approvals > Medscape Medical News Megan Brooks January 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 Adults Pneumococcal 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

From Medscape Medical News Janis C. Kelly December 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; and exercise: 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.