• FDA Expands Approval of Ranibizumab to Diabetic Macular Edema
• Hypertension Not Clear
• A Closer Look at Chemotherapy for Breast Cancer During Pregnancy
• Different Blood Types, Different Coronary Risks?
• Honey Helps Kids with Nocturnal Cough
• Judge Says State of Georgia to Pay for Makena Rather than Compounded 17P
• Researchers Say Drug Pipeline 'Crisis' a Ploy
• Micron-Scale Swimming Robots Could Deliver Drugs and Carry Cargo Using Simple Motion
• Pseudomonas aeruginosa and Cystic Fibrosis — The Estradiol Connection
• Weight Loss for Overweight Cancer Patients: Benefits Aplenty
• Sedentary Behavior Is Linked to Shorter Life Expectancy
• Consequences of Physical Inactivity Are Comparable to Those of Smoking or Obesity
• The Epley Maneuver on YouTube for Vertigo
• No Benefit from Early Aspirin After TPA for Ischemic Stroke
• Chemical in Antibacterial Soap Linked to Muscle Weakness in Animal Studies
• Diabetes Is Associated with Diminished Sexual Satisfaction in Women
• What's the Optimal HbA1c Level in Elders?
• When Breast-Conserving Surgery Doesn't Work the First Time
• N-Acetylcysteine for Cannabis Dependence in Teens
• Two Fluoroquinolones Associated with Hospitalization for Liver Injury
• States of Obesity: From Mississippi to Colorado
• Lactulose and Probiotics Are Effective in Preventing Recurrent Hepatic Encephalopathy
• Soldiers’ Smarts Linked to Omega-3s
• Cost-Effectiveness of Strategies to Reduce Sudden Death in Young Athletes
• Metronidazole for TB?
• Diabetes in Normal-Weight Patients Associated with Higher Mortality Risk
• CDC: All Baby Boomers Should Undergo One-Time Screening for Hepatitis C
MM: This drug has the same mechanism of action and is in the same class as the much less expensive product, Avastin®. Therefore there is no reason to think that Avastin® will not be as useful for this indication as Lucentis® is. The difference is that the drug company, Genentech will not spend the money to do the research to get this added indication for Avastin® since there is no financial incentive to do so. By the way, Lucentis® is more than 100 times the price per dose of Avastin®, both drugs are used as a maintenance therapy that is repeated every 6 weeks to retain vision and Medicare will pay for either treatment. That is why as consumers, clinicians and/or tax payers we should be aware of this news. With the increasing cost of health care and mandatory health coverage, it is imperative that we not further bankrupt the system and that we look for vuiable alternatives that are both clinically effective and cost effective.
FDA Expands Approval of Ranibizumab to Diabetic Macular Edema
The FDA approved on Friday the once-monthly injectable ranibizumab (marketed as Lucentis) for treating diabetic macular edema. Ranibizumab is a monoclonal antibody fragment (Fab) with antiangiogenic properties.
In two trials of 759 patients, 34% to 45% of those treated monthly for 2 years with ranibizumab injections (0.3 mg) gained at least three lines of vision on an eye chart, compared with 12% to 18% of those who didn't receive injections. The most common side effects included conjunctival hemorrhage, eye pain, floaters, and increased intraocular pressure.
In 2006, ranibizumab was approved for wet age-related macular degeneration. It is also approved for macular edema due to retinal vein occlusion.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315130.htm
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Hypertension Not Clear
The benefits of treating patients with mildly elevated blood pressure who are free of cardiovascular disease are unclear, according to a Cochrane review. These findings conflict with current hypertension treatment guidelines in the U.S., Canada, and Europe.
Researchers analyzed data from nearly 9000 participants in four trials and found no obvious benefit of drug treatment in patients with mild hypertension (systolic BP, 140 to 159 mm Hg and/or diastolic BP, 90 to 99 mm Hg) in terms of total mortality or cardiovascular events at 5 years' follow-up. They did, however, see an increased likelihood of drug withdrawal due to adverse effects (relative risk, 4.8).
http://click.jwatch.org/cts/click?q=227%3B67717454%3BBXBc8dPGlL2CnOyyeZEO6KhpxMi
VofsFBPvpFNMNxVI%3D
http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf
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A Closer Look at Chemotherapy for Breast Cancer During Pregnancy
Infants exposed in utero to chemotherapy have more adverse events than those whose mothers delay treatment until after delivery, but such complications are not clinically important, researchers conclude in the Lancet Oncology.
The study included 400 women diagnosed with early breast cancer during pregnancy, about half of whom received chemotherapy. None received chemotherapy in the first trimester.
Chemotherapy was associated with lower birth weight and an increase in obstetric complications (17% of treated women vs. 9% of the untreated) and neonatal events (31 vs. 7 events). However, the researchers say these outcomes were "not clinically significant" and were "most likely related to premature delivery." Birth defects, Apgar scores, and blood disorders did not differ between the groups.
The authors conclude that if their results "are substantiated by other studies, breast cancer during pregnancy could be treated as it is in non-pregnant women without putting fetal and maternal outcome at substantially increased risk."
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70261-9/abstract
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Different Blood Types, Different Coronary Risks?
People with non-O blood types are at higher risk for developing coronary heart disease, according to a study in Arteriosclerosis, Thrombosis, and Vascular Biology.
Using data from both the Nurses' Health Study and the Health Professionals Follow-up Study (together comprising almost 90,000 participants), researchers found a significant increase in the hazard ratio for coronary disease among those with type AB blood (HR, 1.23), B (1.15), and A (1.08), relative to those with type O blood. They estimate that over 6% of coronary disease is attributable to the presence of a non-O blood group. The association was not modified by the presence of other known risk factors, such as smoking or diabetes.
The authors speculate higher levels of some clotting factors in people with non-O blood types may partially explain the association.
http://atvb.ahajournals.org/content/early/2012/08/14/ATVBAHA.112.248757.abstract
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Pediatrics 2012 Aug 6
Honey Helps Kids with Nocturnal Cough
Honey is worth a try in children older than 1 year.
In children with nighttime cough, honey appears to offer symptom relief and improve sleep quality, according to a study funded, in part, by the Honey Board of Israel. Nearly 300 children aged 1 to 5 years who presented to Israeli pediatric clinics with upper respiratory infections were randomized to a single, 10 g dose of honey (eucalyptus, citrus, or labiatae) or placebo within 30 minutes of bedtime. Their parents completed questionnaires before randomization and then the day after treatment.
Compared with baseline, cough symptoms and sleep quality improved significantly with honey and with placebo. However, improvements were greater in the honey groups. Adverse events did not differ among groups. The researchers speculate that an interaction between fibers that control cough and those that taste sweetness may produce an antitussive effect. They conclude, "In light of this study, honey can be considered an effective and safe treatment [for nocturnal cough] of children >1 year of age."
Comment: Although this study was industry-sponsored, it improves upon a 2007 study of buckwheat honey by including a placebo control and various types of honey (JW Pediatr Adolesc Med Feb 20 2008). Further, unlike the previous study, no adverse effects (e.g., hyperactivity and insomnia) were noted. Because placebo was also effective, one could argue that the difference between honey and placebo might not be clinically significant. But for parents searching for something to help relieve frequent cough and sleepless nights owing to upper respiratory infections, honey is worth a try. This recommendation must always be accompanied by a warning to avoid over-the-counter cough preparations in young children and to never give honey to children younger than 1 year because of the risk for botulism.
— Cornelius W. Van Niel, MD Originally published in Physician's First Watch Aug 7, 2012
Published in Journal Watch Pediatrics and Adolescent Medicine August 15, 2012
Citation(s): Cohen HA et al. Effect of honey on nocturnal cough and sleep quality: A double-blind, randomized, placebo-controlled study. Pediatrics 2012 Aug 6; [e-pub ahead of print].
(http://dx.doi.org/10.1542/peds.2011-3075)
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Judge Says State of Georgia to Pay for Makena Rather than Compounded 17P
U.S. District Judge Charles Pannell granted a victory to K-V Pharmaceutical Co. by ordering the state of Georgia to provide Medicaid coverage for their pricey drug, Makena. State officials had argued that readily available compounded 17P costs far less and has no major safety issues. They accused K-V of seeking a court order that would let the company gouge taxpayers and consumers, as the compounded drug costs up to $20 per injection and K-V has said it has agreements for Makena's use in other states for rebated rates of less than $300 per injection.
Pannell said the key difference is that Makena has FDA approval and the compounded drug does not. "Because the court finds that the FDA drug approval process means something," Pannell wrote, the state has an "upside-down policy" because it is covering a drug that is not FDA-approved and not covering one that is. Pannell also ordered K-V to post a bond to cover the cost difference between Medicaid coverage of Makena and the compounded drug, in case his ruling is overturned on appeal.
http://www.ajc.com/news/atlanta/judge-orders-drug-for-1496467.html
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Researchers Say Drug Pipeline 'Crisis' a Ploy
Two researchers have charged that if development of innovative new drugs is lagging, it's largely because the pharmaceutical industry would rather spend its money on protecting the franchises built around existing products.
Financially, the two researchers state that the resources that drug companies devote to discovering new products pale in comparison to their spending on marketing, and on research aimed at tweaking their current drugs, argued Donald W. Light, PhD, of the University of Medicine and Dentistry of New Jersey in Cherry Hill, New Jersey, and Joel R. Lexchin, MD, of York University in Toronto.
Drug firms have long argued that the cost of bringing new drugs to market has become extraordinarily expensive, now averaging an estimated $1.3 billion per new chemical entity (NCE) approved. However, the researchers contend that these arguments are mostly bogus, founded on phony statistics. They have calculated that, far from spending $1.3 billion to develop each successful NCE, drug companies often shell out less than $100 million.
Of the $1.3 billion average figure, "half...comes from estimating how much profit would have been made if the money had been invested in an index fund of pharmaceutical companies that increased in value 11% a year, compounded over 15 years," (J Health Econ 2003; 22: 151-185). Half of the remainder is actually paid by taxpayers in the form of deductions and credits. They state that such companies' actual average expenditure is only about $330 million.
http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/34103
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Micron-Scale Swimming Robots Could Deliver Drugs and Carry Cargo
Using Simple Motion
A team of researchers at the Georgia Institute of Technology has used complex computational models to design swimming micro-robots that could overcome challenges to carry cargo and navigate in response to stimuli such as light. These simple micro-swimmers could rely on volume changes in unique hydrogels to move tiny flaps that will propel the robots. The micro-devices could be used in drug delivery, lab-on-a-chip microfluidic systems-and even as micro-construction robots working in swarms. These simple micro-robots were described July 23 in the online advance edition of the journal Soft Matter, published by the Royal Society of Chemistry in the United Kingdom.
http://www.fiercedrugdelivery.com/press-releases/micron-scale-swimming-robots-could-deliver-drugs-carry-cargo-using-simple-m?utm_medium=nl&utm_source=internal
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MM: This data seems to endorse the use of Bio-Identical Progesterone for use in patients with CF. The balancing of the estrogens with the use of progesterone would be the factor that would benefit women with CF.
N Engl J Med 2012 May 24; 366:1978.
Pseudomonas aeruginosa and Cystic Fibrosis — The Estradiol Connection
Estradiol and its metabolite estriol induce mucoid conversion of P. aeruginosa, thus increasing disease exacerbations in women with cystic fibrosis.
Mucoid conversion of Pseudomonas aeruginosa is associated with infective exacerbations in patients with cystic fibrosis (CF). Among CF patients, women acquire this pathogen — and experience mucoid conversion — earlier than men. Investigators recently examined the effect of estradiol and its metabolite estriol on P. aeruginosa isolates and the effect of estradiol on infective disease exacerbations in women with CF. The study was conducted in Ireland, which has the highest incidence and carrier rate of CF worldwide.
In vitro experiments demonstrated that estradiol and estriol induced the production of alginate (which is responsible for the mucoid phenotype) in a well-known laboratory strain of P. aeruginosa (PA01) that is initially nonmucoid, as well as in nonmucoid clinical isolates from patients with and without CF. Mucoid expression was linked to a frameshift mutation in mucA, the principal gene controlling alginate biosynthesis. In related experiments, estriol was detected in estradiol-treated, immortalized bronchial epithelial cells from patients with and without CF and in bronchoalveolar-lavage fluid from CF patients.
In vivo work showed a link between CF exacerbations and women's estradiol levels. The number of exacerbations increased significantly during the follicular phase of the menstrual cycle, when estradiol levels peak. Analysis of data from the Cystic Fibrosis Registry of Ireland revealed decreased need for antibiotics (a surrogate marker for number of CF exacerbations) in women receiving oral contraceptives. Because the progestin component of oral contraceptives suppresses ovarian estradiol production, estradiol levels are low in women using oral contraceptives.
Comment: Findings from this investigation introduce many of us to the concept of "microbial endocrinology." We now have at least one plausible explanation for the clinical observation of greater CF disease severity in women than in men. This work has sparked interest in further evaluating the role of oral contraceptives in reducing infective exacerbations in women with CF.
— Larry M. Baddour, MD Published in Journal Watch Infectious Diseases May 23, 2012
Citation(s):Chotirmall SH et al. Effect of estrogen on Pseudomonas mucoidy and exacerbations in cystic fibrosis. N Engl J Med 2012 May 24; 366:1978.
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J Clin Oncol 2012 Jul 1; 30:2354
Weight Loss for Overweight Cancer Patients: Benefits Aplenty
Diet and exercise interventions resulted in better maintenance of functional status and reductions in levels of hormones associated with postmenopausal breast cancer.
Obesity has many detrimental health implications, including excess risk for postmenopausal breast cancer and functional decline in cancer survivors. Lifestyle interventions with diet and exercise to reduce weight have been shown to lower risk for cancer and cancer recurrence and to decrease functional decline in older cancer survivors. However, the reproducibility, durability, and real-life adoption of such interventions have been questioned. Two studies address these concerns.
In the initial Reach Out to Enhance Wellness (RENEW) study, investigators assessed the effectiveness of a diet and exercise intervention in 641 sedentary, overweight patients (age, >65; body mass index, 25–40) who were long-term (
5-year) survivors of breast, prostate, or colorectal cancer (JAMA 2009; 301:1883). They found that those who participated in the 1-year telephone-based intervention achieved favorable changes in physical activity and dietary behaviors, modest weight loss, and less decline in functional status compared with wait-listed controls.
Now, the RENEW investigators update results for the original participants at 2 years (1 year after intervention ended) and report outcomes for controls who participated in the intervention for 1 year after a 1-year delay. In the original intervention group, no significant relapse in diet quality, body-mass index (BMI), or physical activity occurred, although an increase in functional decline was noted. In the delayed-intervention group, improvements in all endpoints were observed, similar to those achieved by the original intervention group. These data speak to the durability of this intervention and the ability of participants to adopt these lifestyle changes after the intervention ends.
In the Nutrition and Exercise for Women (NEW) trial, researchers evaluated the effect of diet and exercise interventions on 439 sedentary, overweight, postmenopausal women (mean age, 58; mean BMI, 30.9). Patients were randomized to a reduced-calorie diet, moderate to vigorous aerobic exercise, combined diet and exercise, or no diet or exercise intervention (controls). The objective was to determine whether the interventions could modify sex hormones that are linked to the risk for developing postmenopausal breast cancer.
Weight loss achieved by a reduced-calorie diet with or without exercise produced significant reductions in serum concentrations of estrone (the primary endpoint), estradiol, free estradiol, and free testosterone, while increasing sex hormone–binding globulin concentrations. Androstenedione concentrations were similar among patients in the intervention groups and controls.
Comment: These reports suggest that older, obese patients with or without cancer who focus on weight loss in a sustainable way can reap many benefits, including maintenance of functional status (a surrogate for independence) and reduction in levels of hormones that have been implicated in the development of postmenopausal breast cancer.
— William J. Gradishar, MD Published in Journal Watch Oncology and Hematology August 7, 2012
Citation(s): Demark-Wahnefried W et al. Reach out to enhance wellness home-based diet-exercise intervention promotes reproducible and sustainable long-term improvements in health behaviors, body weight, and physical functioning in older, overweight/obese cancer survivors. J Clin Oncol 2012 Jul 1; 30:2354.
http://www.ncbi.nlm.nih.gov/pubmed/22614994?dopt=Abstract
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BMJ Open 2012 Jul 9; 2:e000828
Sedentary Behavior Is Linked to Shorter Life Expectancy
Sitting daily for <3 hours and watching TV for <2 hours extends life expectancy by an estimated 1 to 2 years.
Adverse effects of sedentary behaviors on health outcomes are well known, but what are the effects on life expectancy? Investigators used data from five prospective cohort studies and from the National Health and Nutrition Examination Survey (NHANES) to estimate the effect of sitting and television viewing on life expectancy at birth in the U.S. population.
The pooled relative risks for all-cause mortality associated with sitting for 3 to 5 hours or for 
6 hours daily were 18% and 45% higher, respectively, than that for sitting <3 hours daily. Watching television for 2 to 3.9 hours or 
4 hours daily conferred similar excess risk (compared with watching TV for <2 hours daily). The health burden (or population-attributable fraction) determined from the pooled relative risks and prevalence of sedentary behaviors obtained from NHANES data indicated that estimated gains in life expectancy at birth in the U.S. population were 2 years for sitting <3 hours daily and 1.4 years for watching TV <2 hours daily.
Comment: In this analysis, sedentary people, on average, lived 1 to 2 years less than active people. However, given the study design, the analysis does not prove a cause-and-effect relation. Nevertheless, the results are biologically plausible, and individual patients should be advised to avoid sedentary behaviors.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine August 7, 2012
Citation(s): Katzmarzyk PT and Lee I-M. Sedentary behavior and life expectancy in the USA: A cause-deleted life table analysis. BMJ Open 2012 Jul 9; 2:e000828.
(http://dx.doi.org/10.1136/bmjopen-2012-000828)
http://www.ncbi.nlm.nih.gov/pubmed/22777603?dopt=Abstract
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Lancet 2012 Jul 21; 380:219
Consequences of Physical Inactivity Are Comparable to Those of Smoking or Obesity
A quantitative analysis of adverse effects highlights the need for societal and public-health initiatives to increase physical activity.
In anticipation of the Olympic games in London, members of a research group assembled by The Lancet quantified the effect of physical inactivity on major noncommunicable diseases (coronary heart disease, type 2 diabetes, and breast and colon cancers). To estimate how much disease could be prevented if physical inactivity were reduced or eliminated, the researchers used conservative assumptions to calculate population attributable fractions associated with physical inactivity for each disease by country. They also performed life-table analysis to estimate improvement in population-wide life expectancy.
Worldwide estimates of the burden of disease attributable to physical inactivity were as follows (median; see figure for distribution by region):
- Coronary heart disease, 6%
- Type 2 diabetes, 7%
- Breast cancer, 10%
- Colon cancer, 10%
Inactivity accounted for an estimated 9% (range, 5.1%–12.5%) of premature mortality, or more than 5.3 million of 57 million worldwide deaths in 2008. The authors estimated that a decrease in inactivity of 10% would prevent more than 533,000 deaths — and a decrease of 25% would prevent 3 million deaths — each year. The elimination of physical inactivity would result in an estimated increase in the world population's life expectancy of 0.68 years (range, 0.41–0.95).
Comment: According to these findings, the adverse effects of physical inactivity approximate those of smoking or obesity, and a decrease in — or removal of —this behavior could substantially improve health worldwide. As editorialists note, knowledge of the relationship between human health and physical activity is ancient, but these compelling epidemiological data could trigger a social revolution to promote a more active physical and mental life.
— Beat J. Meyer, MD Published in Journal Watch Cardiology August 15, 2012
Citation(s): Lee I-M et al. Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy. Lancet 2012 Jul 21; 380:219.
http://www.ncbi.nlm.nih.gov/pubmed/22818936?dopt=Abstract
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Neurology 2012 Jul 24; 79:376
The Epley Maneuver on YouTube for Vertigo
Many video depictions of this treatment for benign paroxysmal positional vertigo are available; some are inaccurate.
Canalith repositioning maneuvers (e.g., the Epley maneuver) are treatments of choice for patients with benign paroxysmal positional vertigo (BPPV); these maneuvers can be performed under clinician supervision or at home. Recognizing that patients frequently search the Internet for medical information ("consulting Dr. Google"), researchers sought to determine the accuracy of 33 video demonstrations of the Epley maneuver that were posted on the YouTube website.
The most popular video, with more than 1 million hits, was produced by the American Academy of Neurology (AAN) but was uploaded to YouTube by a patient. Twelve videos depicted one or more aspects of the Epley maneuver inaccurately. The authors noted that the videos generally do not discuss distinctions between BPPV and other causes of dizziness and thus might be used incorrectly by dizzy patients who don't have BPPV.
Comment: Primary care clinicians probably underuse canalith repositioning maneuvers; I've seen many BPPV patients who have been prescribed daily meclizine — an inappropriate intervention for symptoms that occur briefly and intermittently. Various resources, including UpToDate, offer illustrations of the Epley maneuver that can be printed out for patients. The video referenced above also can be accessed as part of an AAN practice parameter on BPPV
(Neurology 2008; 70:2067; click on "videos," and select "video 4").
— Allan S. Brett, MD Published in Journal Watch General Medicine August 7, 2012
Citation(s): Kerber KA et al. A prescription for the Epley maneuver: www.youtube.com? Neurology 2012 Jul 24; 79:376.
(http://dx.doi.org/10.1212/WNL.0b013e3182604533)
http://www.ncbi.nlm.nih.gov/pubmed/22826542?dopt=Abstract
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Lancet 2012 Jun 28
No Benefit from Early Aspirin After TPA for Ischemic Stroke
In a randomized trial, intravenous aspirin did not improve outcomes, and possibly increased intracranial hemorrhage risk, when given within 90 minutes after TPA.
Tissue plasminogen activator (TPA) is an imperfect therapy for acute ischemic stroke, because it often fails to recanalize blocked vessels or prevent reocclusion after initial recanalization. Observational data suggest that patients already on antiplatelet therapy may have more recanalization and better outcomes after TPA, but current guidelines recommend withholding aspirin for 24 hours after TPA administration.
To better assess the effect of aspirin therapy on thrombolysis results, investigators performed a multicenter, randomized, open-label trial of 300 mg of intravenous aspirin given within 90 minutes after intravenous TPA administration for acute ischemic stroke ("early aspirin"). Patients who had taken antiplatelet or anticoagulant drugs within 5 days before presentation were excluded. Patients and treating physicians were aware of treatment assignments, but outcome assessors were blinded. Follow-up computed tomography (CT) was mandated only for cases of neurological deterioration (defined as an increase of 
4 points in the NIH Stroke Scale score). All patients received oral antiplatelet therapy 24 hours after TPA administration.
The trial was stopped after enrollment of 642 patients out of a target of 800. A good outcome (modified Rankin Scale score of 
2 at 3 months) occurred in 54.0% of patients who received early aspirin versus 57.2% of those who did not, a nonsignificant difference. Symptomatic intracranial hemorrhage was documented significantly more often in the early-aspirin group (relative risk, 3.14).
Comment: As the authors note, the increased risk for intracranial hemorrhage seen with early aspirin use in this study may be a result of bias from lack of blinding, because treating physicians were probably more likely to order follow-up CT for transient neurological fluctuations in patients who received early aspirin than for those who did not. Nevertheless, these results convincingly show that routine aspirin therapy started early after TPA administration does not improve outcomes. This finding supports current guideline recommendations to withhold antiplatelet therapy for 24 hours after TPA for acute ischemic stroke.
— Hooman Kamel, MD Published in Journal Watch Neurology July 24, 2012
Citation(s): Zinkstok SM and Roos YB. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: A randomised controlled trial. Lancet 2012 Jun 28; [e-pub ahead of print].
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Chemical in Antibacterial Soap Linked to Muscle Weakness in Animal Studies
Patients may ask about reports that a chemical commonly used in antibacterial soaps and hand sanitizers may cause muscle weakness. The chemical — triclosan — is associated with impaired muscle function in vitro as well as in mice and minnows, according to study in the Proceedings of the National Academy of Sciences.
The FDA in 2010 said that similar studies warranted "further review."
http://www.pnas.org/content/early/2012/08/08/1211314109.abstract
http://www.latimes.com/health/boostershots/la-heb-triclosan-antibacterial-soap-20120813,0,6929564.story
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Obstet Gynecol 2012 Aug; 120:331.
Diabetes Is Associated with Diminished Sexual Satisfaction in Women
Diabetes negatively affects sexual function differently in women than it does in men.
Although diabetes is a strong risk factor for erectile dysfunction in men (JW Gen Med Feb 24 2006), the effects of this disease on women's sexual functioning are poorly understood. Investigators analyzed data from the Kaiser Reproductive Risks of Incontinence Study to assess sexual function in a cross-sectional cohort of ethnically diverse women (age range, 40–80) who completed self-administered questionnaires. Sexual activity was defined as "any activity that is arousing to you, including masturbation."
Of the 2270 participants (mean age, 55), 139 (6%) had insulin-treated diabetes and 347 (15%) had noninsulin-treated diabetes. Overall, 807 (36%) reported no sexual activity during the preceding 3 months. Neither sexual desire nor sexual activity differed by diabetic status, but satisfaction with sex did. Analysis adjusted for factors such as body-mass index showed that, compared with nondiabetic women, those with insulin-treated diabetes were more than twice as likely to report diminished sexual satisfaction (adjusted odds ratio, 2.0), and those with noninsulin-treated diabetes were almost one-and-a-half times as likely to report low sexual satisfaction (OR, 1.4). Among sexually active women, those with insulin-treated diabetes were more likely than nondiabetic women to report problems with vaginal lubrication (OR, 2.4) and difficulty achieving orgasm (OR, 1.8). Moreover, insulin-treated diabetic women were more likely to report that their health limited their sexual activity "quite a bit" or "extremely" (OR, 2.3).
Comment: Although this cross-sectional study did not include longitudinal follow-up, the data suggest that diabetic women, like diabetic men, experience sexual dysfunction, but the nature of their complaints differs. The extent to which these findings are mediated by organic factors, psychogenic factors, or both has not been well defined.
— Robert W. Rebar, MD Published in Journal Watch Women's Health August 9, 2012
Citation(s): Copeland KL et al. Diabetes mellitus and sexual function in middle-aged and older women. Obstet Gynecol 2012 Aug; 120:331.
http://www.ncbi.nlm.nih.gov/pubmed/22825093?dopt=Abstract
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J Am Geriatr Soc 2012 Jul; 60:1215
What's the Optimal HbA1c Level in Elders?
In an observational study, glycosylated hemoglobin between 8% and 9% was best.
Experienced clinicians have long recognized that tight glycemic control can be perilous in frail older patients with type 2 diabetes. Now, an observational study addresses that concern. Researchers in San Francisco studied 367 community-dwelling, older patients (mean age, 80) with diabetes who participated in a comprehensive adult day-care program and were unable to live independently. Glycosylated hemoglobin (HbA1c) levels were measured at baseline, and functional decline and death were tracked during 2 years of follow-up (during which, average HbA1c levels didn't change much).
Analyses were adjusted for potentially confounding variables. Compared with patients in the reference category (HbA1c levels, 7%–8%), patients whose HbA1c levels were between 8% and 9% had a significantly lower incidence of functional decline or death (relative risk, 0.88), and those with HbA1c levels <7% had a nearly significant higher incidence of functional decline or death. Overall, the relation between HbA1c level and functional decline or death was somewhat U-shaped, with the best outcomes among patients in the 8% to 9% range. These basic patterns were noted both among patients who took only oral antidiabetic drugs and those who took insulin.
Comment: This observational study is subject to residual confounding, but it suggests that an HbA1c target in the 8% to 9% range is reasonable for older patients with diabetes who are unable to live independently. The findings support a recent guideline in which less-tight glycemic control is acceptable in older adults with long-standing diabetes
(JW Gen Med Jul 24 2012).
— Allan S. Brett, MD Published in Journal Watch General Medicine August 9, 2012
Citation(s): Yau CK et al. Glycosylated hemoglobin and functional decline in community-dwelling nursing home–eligible elderly adults with diabetes mellitus. J Am Geriatr Soc 2012 Jul; 60:1215.
(http://dx.doi.org/10.1111/j.1532-5415.2012.04041.x)
http://www.ncbi.nlm.nih.gov/pubmed/22702660?dopt=Abstract
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BMJ 2012 Jul 12; 345:e4505
When Breast-Conserving Surgery Doesn't Work the First Time
In England, one in five women with breast cancer who had breast-conserving surgery required reoperation.
For women with invasive breast cancer, breast-conserving surgery plus radiotherapy yields survival rates similar to those achieved with mastectomy alone. However, breast-conserving surgery necessitates reoperation if the malignancy has been excised inadequately — and reoperation can lead to emotional distress, delays in adjuvant treatment, higher costs, and poorer cosmetic outcomes. Investigators in England analyzed national data to determine likelihood of, and factors associated with, reoperation after breast-conserving surgery.
Of 96,000 women who underwent primary breast cancer surgery, 55,000 underwent breast-conserving surgery. Of these, 83% had invasive disease, 12% had in situ disease, and 5% had both. Within 3 months after breast-conserving surgery, 11,000 women (20%) underwent reoperation (either additional breast-conserving surgery or mastectomy). Women with carcinoma in situ were significantly more likely to require reoperation than were women without in situ disease (30% vs. 18%). Reoperation also was significantly more likely in women younger than 50 than in older women.
Comment: In this study, one in five women with breast cancer who underwent breast-conserving surgery required reoperation. The authors' explanation for the higher rate of reoperation with carcinoma in situ (30%) is that these tumors are harder to localize preoperatively and often are multifocal. These findings should be helpful in guiding treatment decisions in women with breast cancer who are considering breast-conserving surgery.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine August 14, 2012
Citation(s): Jeevan R et al. Reoperation rates after breast conserving surgery for breast cancer among women in England: Retrospective study of hospital episode statistics. BMJ 2012 Jul 12; 345:e4505.
(http://dx.doi.org/10.1136/bmj.e4505)
http://www.ncbi.nlm.nih.gov/pubmed/22791786?dopt=Abstract
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Am J Psychiatry 2012 Jun 16
N-Acetylcysteine for Cannabis Dependence in Teens
After 8 weeks, N-acetylcysteine added to contingency management and cessation counseling proved modestly effective in reducing cannabis-positive urine results.
In animal models, chronic administration of the antioxidant N-acetylcysteine (NAC), a prodrug of the amino acid cysteine, normalized drug-induced pathology and reduced drug seeking. These investigators conducted a double-blind, randomized, placebo-controlled, 8-week trial of NAC (1200 mg twice daily) in 116 treatment-seeking, cannabis-dependent adolescents.
Abstinence was determined by weekly urine cannabinoid tests during treatment. Participants had no concurrent substance dependence aside from nicotine. All received weekly 10-minute cessation counseling sessions and twice-weekly contingency management, which paid for adherence and clean test results ($5 initially, escalating for additional progress).
Participants receiving NAC had significantly more negative urine cannabinoid results during treatment than placebo recipients (odds ratio, 2.4; negative urine tests throughout the study: NAC group, 40.9%; placebo group, 27.2%). The number needed to treat (NNT) for NAC was 7.3 during treatment and 11.6 at the 4-week follow-up (at which point the percentage of clean urine results fell for both groups). NAC and placebo groups showed no significant differences on secondary measures of effectiveness.
Comment: The study may have been underpowered to adequately examine the secondary measures; future studies using larger populations treated for longer may show added benefit. N-acetylcysteine, available over the counter, may prove to be an attractive addition to contingency-based treatments due to its easy accessibility, low price, and good safety profile, but no data currently suggest that NAC is suitable as a stand-alone treatment. The authors note that the NNTs reported here are comparable to those found for many accepted addiction-targeted pharmacotherapies. Although treatment for cannabis dependence still has a long way to go, pharmacological approaches (see JW Psychiatry Jul 2 2012) are being actively pursued.
— Joel Yager, MD Published in Journal Watch Psychiatry July 2, 2012
Citation(s): Gray KM et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry 2012 Jun 16; [e-pub ahead of print].
(http://dx.doi.org/10.1176/appi.ajp.2012.12010055)
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Two Fluoroquinolones Associated with Hospitalization for Liver Injury
Use of the common antibiotics moxifloxacin and levofloxacin among older patients is associated with increased likelihood of acute liver injury, according to a case-control study in the Canadian Medical Association Journal.
Researchers examined the use of five broad-spectrum antibiotics (moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil, and clarithromycin) in adults over age 65 free of liver disease. Nearly 150 patients who were hospitalized for liver injury within a month after receiving one of the antibiotics were matched to 1400 control recipients who were not hospitalized.
Moxifloxacin and levofloxacin were associated with roughly a doubling of risk for hospitalization, relative to clarithromycin. Ciprofloxacin and cefuroxime did not increase the risk.
Citing the low rate of hepatotoxicity found, commentators advise that "one should still choose the antibiotic most likely to cover the infection and worry less about the liver."
http://www.cmaj.ca/content/early/2012/08/13/cmaj.111823.full.pdf+html
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MM: It’s interesting that Mississippi had the highest incidence of obesity in the nation as their state law also prohihits physicians from writing for HCG for use as a weight loss product. Louisiana shares this same legal statute.
States of Obesity: From Mississippi to Colorado
Mississippi had the highest prevalence of obesity in 2011, at 34.9%, according to the latest data from the CDC's Behavioral Risk Factor Surveillance System.
Overall, 12 states exceeded the 30% rate, including Alabama, Arkansas, Indiana, Kentucky, and Louisiana. Colorado had the lowest obesity prevalence, at 20.7%.
htp://www.cdc.gov/obesity/data/adult.html
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MM: This is a wonderful study that demonstrates the benefits of a pre-biotic (Lactulose) and a probiotic. I would have liked to have seen an additional group; one that included a probiotic with a prebiotic to determine if a synergistic effect would have been present in this use.
Am J Gastroenterol 2012 Jul; 107:1043
Lactulose and Probiotics Are Effective in Preventing Recurrent Hepatic Encephalopathy
Both treatments were significantly more effective than placebo.
Hepatic encephalopathy (HE) is a common complication of hepatic cirrhosis. Lactulose has been effective in treating patients with acute or recurrent HE, but data supporting its use are lacking. Probiotics might also be beneficial for these patients, by altering gut flora to reduce ammonia production, although few studies have evaluated probiotics in this setting.
Now, investigators have conducted an open-label, randomized, controlled trial to evaluate the efficacy of lactulose and probiotics in 235 consecutive cirrhotic patients at a single hospital in India who had recovered from HE and had not received any HE medication. Patients were randomized to lactulose (30 mL 3 times daily), probiotics (1 capsule containing 112.5 billion viable lyophilized bacteria 3 times daily), or placebo. The primary endpoint was development of overt HE, according to West Haven criteria.
During 12-month follow-up, recurrent HE developed in more patients receiving placebo (37) than lactulose (18; P=0.001) or probiotics (22; P=0.02). Rates of hospitalization and death from causes other than HE were similar among the three groups.
Comment: Although unblinded, this study was large and well executed. It demonstrated that lactulose and probiotics are similarly effective in secondary prophylaxis of HE. Whether all probiotics would be as effective is unclear, but we now potentially have other therapeutic options for preventing recurrent HE in addition to rifaximin plus lactulose
(JW Gastroenterol Mar 24 2010).
— Atif Zaman, MD, MPH Published in Journal Watch Gastroenterology August 10, 2012
Citation(s): Agrawal A et al. Secondary prophylaxis of hepatic encephalopathy in cirrhosis: An open-label, randomized controlled trial of lactulose, probiotics, and no therapy. Am J Gastroenterol 2012 Jul; 107:1043.
http://www.ncbi.nlm.nih.gov/pubmed/22710579?dopt=Abstract
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http://www.imakenews.com/eletra/mod_print_view.cfm?this_id=2497259&u=
vitalchoiceseafood&show_issue_date=F&issue_id=000605448&lid=blqNskM&uid=b1h1R7NC
Soldiers’ Smarts Linked to Omega-3s
Brain tests among male soldiers link low omega-3 blood levels to poor thinking and decision capacities
by Craig Weatherby
The U.S military is finally getting serious about omega-3 research, thanks largely to a campaign by two concerned scientists. Captain Joe Hibbeln, M.D. – a psychiatrist at the National Institutes of Health – and fatty acids expert William Lands, Ph.D., rank among the world’s leading omega-3 researchers. Back in 2009, they organized a conference called Nutritional Armor for the War Fighter, that put omega-3s on the military’s radar screen … see “Soldiers and Omega-3s: Pentagon Pitched on Benefits”. Their project to get more omega-3s into military diets was advanced by a landmark study published last year by Dr. Hibbeln and his colleagues.
Dr. Hibbeln’s team compared omega-3 blood levels in 800 troops who’d committed suicide with those of 800 randomly selected service members, who were matched with the suicide cases by age, sex, and rank. All 1,600 service members had low omega-3 levels, but the lowest levels of omega-3 DHA – the omega-3s proven critical to brain functions and mood health – were more likely to be found among the 800 who’d taken their own lives. The risk of suicide death was 14 percent higher for every “standard deviation” of lower DHA percentage. (See “Soldiers' Suicide Risk Linked to Omega-3 Lack”.)
To prove that this apparent link between low omega-3 levels and suicide risk was more than a mere statistical correlation, they called for well-designed clinical trials to prove a cause-effect relationship. That wish starting becoming reality when one attendee at the Nutritional Armor conference – Lt. Colonel Daniel Johnston, M.D. – initiated a clinical trial among Iraq-based soldiers … see “Soldiers' Omega-3 Test Targets Suicide Risk”. The results of that study – titled “Effects of Omega-3 EPA/DHA for Soldiers at Risk for Mood Disorders” – have not yet been published. In the meantime, Dr. Johnston – Medical Director for the U.S. Army Comprehensive Soldier Fitness Program – has just published a study that provides more evidence of the brain benefits of omega-3s to military personnel.
Army study links omega-3 levels to thinking and decision-making
Dr Johnston and his co-workers studied 78 male personnel from two U.S. military camps, picking men who met all of the study’s inclusion/exclusion criteria (Johnston DT et al. 2012). Their ages ranged from 20 to 54 years (average age of 31.4 years). The majority (68) were white males, with four African-Americans, one Asian, and five Hispanics. Their occupational specialties varied, as did the level of education, with over 60 percent having at least some college classes and only five percent having not completed high school.
Blood samples were taken and used to measure the “Omega-3 Index” … a measure of the percent of omega-3 fatty acids in red blood cells that’s also part of our Vital Omega-3 and 6 HUFA Test™. (At least eight percent of the fatty acids on your cell membranes should be omega-3s in order to enable optimal cardiovascular health.) The participants underwent a series of psycho-social and computerized neuro-cognitive tests.
Confirming Dr. Hibbeln’s previous finding, the participants’ average omega-3 index (3.5 percent) was significantly lower than the average level (4.5 percent) found in non-military Americans of the same ages. As Dr. Johnston’s team wrote, “This relatively low Omega-3 Index [3.5%], given the deployment setting and likely low content of omega-3 fatty acids in the rations, is perhaps not surprising.” (Johnston DT et al. 2012)
The researchers compared the soldiers’ omega-3 levels to their performance on the mental tests, with important results:
- No link was found between the participants' omega-3 levels and their scores for anxiety, depression, or sleep.
- Lower omega-3 levels were strongly linked to poor cognitive flexibility and executive (decision-making) functioning … particularly in the 81 percent of participants who reported having poor sleep.
- Participants with poor sleep quality but above-average omega-3 levels seemed to have a “resilience to fatigue” and higher cognitive flexibility and executive function scores, compared with their sleepy peers who had lower omega-3 levels.
Due to the nature of the study, these results are inconclusive, and must be confirmed by a rigorous clinical trial testing the effects of omega-3 supplements in soldiers. As noted above, Dr. Johnston’s team has already performed such a trial. The results of this randomized, placebo-controlled study are being analyzed and should be published in a peer-reviewed journal later this year.
Dr. Johnston’s group came to the obvious conclusion: “On the basis of our findings and other research, educating Service members to choose foods high in omega-3s and raising the EPA and DHA levels in rations should be considered for general health promotion and possible performance optimization.” (Johnston DT et al. 2012)
We owe our military folks nothing less than the best possible nutrition to help maintain and optimize their mental health and performance.
Sources: ClinicalTrials.gov. Effects of Omega-3 EPA/DHA for Soldiers at Risk for Mood Disorders. Accessed at http://clinicaltrials.gov/ct2/show/NCT01216982. Johnston DT, Deuster PA, Harris WS, Macrae H, Dretsch MN. Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U.S. Service members. Nutr Neurosci. 2012 Jun 28. [Epub ahead of print]. von Schacky C, Harris WS. Cardiovascular risk and the omega-3 index. J Cardiovasc Med (Hagerstown). 2007 Sep;8 Suppl 1:S46-9. Review.
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Pediatrics 2012 Aug; 130:e380.
Cost-Effectiveness of Strategies to Reduce Sudden Death in Young Athletes
A strategy based on ECG results alone with cardiology referral only for athletes with abnormal results is cost-effective.
Some experts believe that routine screening of all athletes with electrocardiogram (ECG) before athletic participation will avert many cases of sudden cardiac death (SCD), but others caution that evidence for the cost-effectiveness and feasibility of this approach is lacking. National Institute of Health investigators used mathematical modeling to compare the following three strategies to reduce SCD in young athletes:
1) History and physical exam, with cardiology referral and ECG for athletes with suspicious findings (current practice)
2) History and physical exam, with ECG for athletes with negative history and physical, and direct cardiology referral for athletes with positive history, physical, or ECG
3) History, physical, and ECG for all athletes, with cardiology referral only for those with ECG abnormalities
The modeling factored in the effect of false-positive (e.g., unnecessary restriction from sports) or false-negative (preventable deaths) results, the effect of reclassification of false positives on subsequent testing, the sensitivity and specificity of ECG and cardiology evaluations, the cost of tests, the relative risk for SCD in athletes with undetected cardiac problems (base assumption, 2.5 cases per 1000 persons), and the prevalence of heart disease in the general population (base assumption, 1 case per 1000 persons).
Compared with current practice, strategy 2 added US$117 per athlete screened, averted 131 additional deaths ($900,000 per case), and cost $68,800 per quality-adjusted life year (QALY). Strategy 3 averted 127 deaths ($600,000 per case) and cost $37,700 per QALY. Strategy 2 drops below the generally accepted cost-effectiveness cutoff of $50,000 per QALY if the true prevalence of heart disease is 1.45 cases per 1000 or if the relative risk for death in athletes compared to nonathletes is 3.0. Strategy 3 rises above the $50,000 threshold if the prevalence of disease is only 0.75 cases per 1000 or if the relative risk for death in athletes falls below 2.1. The cost-effectiveness of each strategy was highly sensitive to the specificity of ECG and cardiology evaluations, with small changes in the false-positive rate (3%–5%) affecting the model outcomes.
Comment: A randomized, controlled trial of ECG testing in athletes is unlikely. This economic model suggests that augmenting history and physical with ECG for athletes with negative findings and cardiology referral for those with positive findings on history, exam, or ECG (strategy 2) is not cost-effective, primarily because of the high rate of false-positive results associated with the history, physical, and ECG. You may wonder, then, why the authors retained the history and physical in strategy 3. They argue (and I agree) that even if we only use ECG findings to determine which athletes require further evaluation, the history and physical exam provide benefits beyond screening for sudden cardiac death, including opportunities to deliver adolescent preventive services (e.g., immunizations, counseling about healthy behaviors, and risk reduction counseling as indicated).
— Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine August 1, 2012
Citation(s): Schoenbaum M et al. Economic evaluation of strategies to reduce sudden cardiac death in young athletes. Pediatrics 2012 Aug; 130:e380.
(http://dx.doi.org/10.1542/peds.2011-3241)
http://www.ncbi.nlm.nih.gov/pubmed/22753553?dopt=Abstract
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Proc Natl Acad Sci U S A 2012 Jul 23
Metronidazole for TB?
A 2-month metronidazole regimen was as effective as a 6-month isoniazid regimen in a macaque model of latent TB.
One concern in developing treatment regimens for tuberculosis (TB) is the need to target microorganisms in various growth states and microenvironments. Noting recent work showing that metronidazole was active against Mycobacterium tuberculosis in vitro under hypoxic conditions and additional findings that caseous granulomas are relatively hypoxic, a multinational team of investigators sought to determine whether metronidazole might be effective for treating TB.
The researchers used a cynomolgus macaque model in which animals with latent TB received no treatment, isoniazid (INH) alone for 6 months, or either metronidazole alone or INH plus rifampin for 2 months. The macaques then received 5 weeks of anti–tumor necrosis factor therapy to induce reactivation before being euthanized.
On necropsy, evidence of TB reactivation was seen in 9 of 11 untreated macaques, but was not seen in macaques treated with INH (n=5), INH/rifampin (n=7), or metronidazole (n=10). Parallel studies of treatment of active TB in macaques suggest more-rapid clearance of Mycobacterium tuberculosis with INH/rifampin/metronidazole than with INH/rifampin, but the sample size was too small for the results to be definitive.
Comment: These findings are intriguing and support a potential role for metronidazole in treating TB. The results are clearly limited by small sample size — a factor explained by the substantial cost of the animal model. A clinical trial assessing metronidazole in the treatment of multidrug-resistant TB is now under way.
— Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases August 8, 2012
Citation(s): Lin PL et al. Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques. Proc Natl Acad Sci U S A 2012 Jul 23; [e-pub ahead of print].
(http://dx.doi.org/10.1073/pnas.1121497109)
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Diabetes in Normal-Weight Patients Associated with Higher Mortality Risk
People who are at a normal weight when they develop diabetes have higher rates of mortality than those who are overweight or obese when diagnosed, according to an analysis of five cohort studies in JAMA.
The studies included 2500 adults over age 40 with incident diabetes; roughly 10% were normal weight. During 27,000 person-years of follow-up, adjusted hazard ratios among normal-weight patients were significantly increased for total mortality (2.08) and noncardiovascular mortality (2.32), compared with the overweight and obese group. Cardiovascular mortality was also elevated (1.52), but not significantly so.
The mechanism for the paradoxical increase is unknown and may, according to editorialists, lie in a phenotype characterized as "metabolically obese normal weight."
http://jama.jamanetwork.com/article.aspx?articleid=1309174
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CDC: All Baby Boomers Should Undergo One-Time Screening for Hepatitis C
The CDC is recommending one-time testing for hepatitis C in patients born between 1945 and 1965, regardless of the patients' risk for hepatitis, according to finalized guidelines published in MMWR.
Patients who test positive for hepatitis C should receive alcohol screening, and intervention if necessary, as well as referral for treatment of hepatitis C and any related conditions.
A CDC review found that hepatitis C mortality increased significantly from 1999 to 2007. Nearly three quarters of these deaths occurred in baby boomers. In addition, an NHANES study found a 3.25% prevalence in this age group.
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm?s_cid=rr6104a1_w
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