Explaining Gender Differences in Non-fatal Suicidal Behaviour Among Adolescents

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

Losing Weight by Midlife Reduces CVD Risk

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

Chest X-Ray Screening Does Not Reduce Lung Cancer Mortality

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

Physical Activity Cuts Risk for Invasive Breast Cancer

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

PSA Screening: USPSTF Review

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

Testosterone May Not Treat ED

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

Chronic Inflammation May Mean Early Menopause

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."

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

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

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

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

Noncommunicable Diseases: More Than a Health Crisis

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

Vitamin Supplements Associated With Increased Risk for Death

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

Managing the Adverse Effects of Nonsteroidal Anti-inflammatory Drugs

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

Anti-Infective Agents in Periodontal Treatment

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

Peptic Ulcer Disease

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