Building Healthy Adults Starts in Childhood

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

Does the Cranberry Beat Antibiotics for Recurrent UTIs?

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

DHEA Hormone May Help Women Through Menopause

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

French Breast Implant Fears Spread Around World

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

Acetaminophen: Repeated Use of Slightly Too Much Can Be Fatal

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

Pomegranate Juice Lowers Cardiovascular Risk Factors

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

Statins Can Make Asthma Worse

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