Chronic Inflammation May Mean Early Menopause

From Medscape Medical News Megan Brooks October 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

Medscape Medical News from the: Canadian Psychiatric Association (CPA) 61st Annual Conference Exercise a Viable Treatment Option for Mental Illness Absence of Guidelines Should Not Be a Barrier Caroline Cassels October 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 Properties Early 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 Endeavor Dr. 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

From Heartwire > Alerts, Approvals and Safety Changes > Alerts Michael O'Riordan October 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 Review In 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

From Medscape Medical News > Oncology Zosia Chustecka October 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 Guidelines The 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 Guidelines Similarly, 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

From CDC Expert Commentary Katherine Kolor, PhD, CGC Posted: 10/10/2011 Hello, 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 Options For 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 mutation To 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 Categories http://www.medscape.com/viewarticle/749018?src=mp&spon=17

Hypertension Linked to First-Trimester Birth Defects

From Medscape Medical News Ricki Lewis, PhD October 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

Medscape Medical News from:From Reuters Health Information Obesity 2011: The Obesity Society 29th Annual Scientific Meeting By Rob Goodier NEW 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."