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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
July 16, 2016

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Early Bedtime in Preschool Years might Prevent Obesity in Adolescence
Being Modestly Overweight linked to Increased All-Cause Mortality Risk
Interview: Medical Marijuana’s Effect on Medicare Prescriptions
Synthetic Cannabinoid Poisonings on the Rise in U.S.
How the Microbiome might promote Metabolic Syndrome and Obesity
The DASH Diet and Risk for Metabolic Syndrome in Children
Racial Differences in End-of-Life Care Among Patients with Metastatic Cancer
AHA Provides Comprehensive List of Drugs that could lead to Heart Failure
Hair Today, Gone Tomorrow
The President Reviews the Lessons of the Affordable Care Act
New Treatment Approved for Dry Eye Disease
For Pelvic Organ Prolapse, POP in a Pessary?
Tai Chi might be as Effective as Physical Therapy for Knee Osteoarthritis

Early Bedtime in Preschool Years might Prevent Obesity in Adolescence
By Christine Judge, Edited by André Sofair, MD, MPH
Putting preschoolers to bed early is associated with lower risk for adolescent obesity, suggests a Journal of Pediatrics study.
Nearly 1000 U.S. children were enrolled in a prospective cohort study at birth. Bedtime was reported by mothers when children were of preschool age, and body-mass index was assessed at age 15 years.
At a mean age of 4.7 years, 25% of children had bedtimes at or before 8 p.m, 50% between 8–9 p.m., and 25% after 9 p.m. After adjustment for maternal sensitivity (determined by observations of mother-child play interactions) and other factors, risk for adolescent obesity was reduced by half in children going to bed at or before 8 p.m., compared with those going to bed after 9 p.m. Nonwhite race/ethnicity, lower socioeconomic status, and lower maternal education were associated with later bedtimes.
The authors conclude, “Pediatricians should encourage parents to establish a routine of early bedtimes for young children and support parents in their efforts to overcome the barriers they face in implementing this routine.”
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Being Modestly Overweight linked to Increased All-Cause Mortality Risk
By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Being even modestly overweight is associated with increased mortality risk, according to a large meta-analysis in the Lancet. The finding calls into question prior research suggesting that a slightly elevated body-mass index might be protective.
Researchers examined individual participant data from 189 studies comprising nearly four million adults who had never smoked, had no known chronic conditions at baseline, and survived beyond 5 years of follow-up. Participants were from North America, Europe, Australia, and East Asia.
Overall, roughly 386,000 participants died. All-cause mortality was lowest at a BMI of 20.0–24.9 (normal weight) and then increased significantly and linearly beginning at a BMI of 25.0–27.4 (hazard ratio, 1.07). BMIs below 20.0 also posed increased risk. The findings were consistent across geographic regions, and associations between higher BMIs and mortality were greater in younger than older participants and in men than in women.
The authors write, "These findings suggest that if the overweight and obese population had WHO-defined normal levels of BMI, the proportion of premature deaths that could be avoided would be about one in five in North America."
Dr. Harlan Krumholz of NEJM Journal Watch Cardiology commented: "What I really want to know is not average risk, but who has the most risk, if any, among those who are modestly overweight. Meanwhile, as a physician, my greatest emphasis regarding weight loss will remain on those with marked elevation of BMI, those with the highest risk."
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Interview: Medical Marijuana’s Effect on Medicare Prescriptions
By the Editors of The Journal Watch
Clinical Conversations interviews a co-author of last week's Health Affairs study, which offered "strong indirect evidence that medical marijuana has been replacing 'standard' drugs in states where it is legal." Listen in at the link below.
Clinical Conversations podcast (running time, ~15 min.) (Free)
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Synthetic Cannabinoid Poisonings on the Rise in U.S.
By Cara Adler, Edited by André Sofair, MD, MPH
Acute intoxication from use of synthetic cannabinoids (such as K2 and Spice) increased across the U.S. from 2010 to 2015, according to anMMWR analysis of cases from the Toxicology Investigators Consortium (ToxIC).
During that period, 456 patients were treated for synthetic cannabinoid intoxication at 50 ToxIC sites. Three deaths were recorded. Synthetic cannabinoids were the sole toxic exposure in about 60% of patients. Nervous system symptoms were most common, including agitation, coma, and toxic psychosis. Nearly 60% of patients received specific toxicologic treatments; the others were monitored with standard supportive care.
From 2010 to 2015, the greatest increase in cases occurred in the Northeast, largely in New York City.
The authors note that synthetic cannabinoids are 2 to 100 times more potent than cannabis, and there is currently no antidote for them. They call for targeted prevention and education about the "potentially life-threatening consequences of synthetic cannabinoid use."
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Nature 2016 Jun 9; 534:213
How the Microbiome might promote Metabolic Syndrome and Obesity
Acetate might be the pivotal molecule.
Certain phyla of gut bacteria are more common in patients with metabolic syndrome, obesity, or both (NEJM JW Gen Med Nov 15 2013 and Nature 2013; 500:541). A series of experiments in rats provides strong evidence for metabolic and physiologic mechanisms that explain this correlation.
Consistent with previous study results, relatively large numbers of Firmicutes and small numbers of Bacteroidetes in the rats' feces led to glucose intolerance and obesity. This bacterial milieu was associated with a high concentration of the short-chain fatty acid, acetate, in the gut. High-fat diets promoted this bacterial milieu and increased production of acetate. As acetate travelled through the blood to the brain (or was administered into the ventricular system of the brain), it stimulated the parasympathetic nervous system to increase pancreatic β-cell production of insulin in response to glucose and also to increase production of ghrelin (the “appetite hormone”) in the stomach. Increased caloric intake by the rats, combined with increased circulating insulin, led to weight gain. Eliminating gut bacteria with antibiotics, or interrupting parasympathetic signals to the gut through vagotomy or atropine, eliminated glucose intolerance and weight gain.
COMMENT: If the results of these rat studies prove to be applicable to humans, three new targets for preventing metabolic syndrome and obesity have been identified: modification of the gut microbiome, lowering acetate production in the gut, and parasympathetic blockade.
CITATION(S): Perry RJ et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature2016 Jun 9; 534:213.
Trajkovski M and Wollheim CB.Microbial signals to the brain control weight. Nature 2016 Jun 9;534:185.
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J Pediatr 2016 Jul; 174:178
The DASH Diet and Risk for Metabolic Syndrome in Children
After an average of 3.6 years on a DASH diet, children and adolescents with good adherence had a 64% reduced risk for metabolic syndrome.
The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to be effective in reducing risks for a number of lifestyle-associated health disorders. In a prospective cohort study, researchers examined the association between degree of adherence to a DASH diet and risk for developing metabolic syndrome (MetS) among 424 healthy Iranian children and adolescents aged 6 to 18 years.
MetS was defined as having three or more of the following: waist circumference ≥90th percentile for age, systolic and diastolic blood pressures ≥90th percentile, fasting glucose ≥100 mg/dL, fasting triglycerides ≥110 mg/dL, and high-density lipoprotein cholesterol <40 m/dL. The DASH diet features high intake of whole grains, fruits, vegetables, legumes, and nuts; moderate intake of low-fat dairy; and low intake of sweets and red meats. Children with MetS at study onset were excluded. Researchers ranked the cohort by quartile of DASH diet adherence.
Mean follow-up was 3.6 years. DASH adherence was associated with greater intake of potassium, calcium, magnesium, and carbohydrates and reduced intake of sodium. After adjustment for potential confounders, including energy intake, body-mass index, physical activity, and family history of diabetes, the risk for developing MetS was reduced by 64% in the top quartile of DASH adherence compared with the lowest quartile. Waist circumference, fasting glucose, and hypertension were inversely associated with DASH adherence.
COMMENT: The DASH diet is great for many disorders and was associated with reduced risk for MetS in this population of children and adolescents. A fascinating finding was the reduction in waist circumference, which was independent of physical activity and caloric intake. Pediatricians should consider recommending DASH diet components for children who are overweight or have a strong family history of type II diabetes.
CITATION(S): Asghari G et al. Dietary Approaches to Stop Hypertension (DASH) dietary pattern is associated with reduced incidence of metabolic syndrome in children and adolescents. J Pediatr 2016 Jul; 174:178.

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J Clin Oncol 2016 Jul 1; 34:2265
Racial Differences in End-of-Life Care among Patients with Metastatic Cancer
Compared with white patients, black patients were more likely to receive intensive medical intervention and to overestimate their life expectancy.
Two studies provide complementary insights on racial differences in end-of-life medical care in the U.S.
Researchers linked national cancer-registry and Medicare data to examine end-of-life interventions in 883 women (age, ≥65; 85% white, 15% black) who had stage IV disease at initial presentation with breast cancer and who died between 2007 and 2012. Black women, compared with white women, were less likely to use hospice (60% vs. 71%), less likely to receive antidepressants or medications for insomnia, more likely to die in the hospital (36% vs. 22%), and more likely to either be admitted to an intensive care unit or have more than one hospitalization or emergency department visit during the last 30 days of life (40% vs. 29%).
Another study involved 229 patients (86% white, 14% black) with metastatic cancer and physician-estimated life expectancy of <6 months. Patients were asked to estimate their life expectancies and to indicate the source of their estimates. All patients died during the study's observation period. White patients were significantly more likely than black patients (43% vs. 13%) to give estimates that fell within 12 months of actual survival. Fully 65% of black patients (vs. 22% of white patients) overestimated their survival by at least 5 years. Black patients' estimates came from personal beliefs (65%) or religious beliefs (35%), whereas white patients' estimates came mostly from personal beliefs (72%) or information from physicians (21%).
COMMENT: The higher intensity of medical care near the end of life among black cancer patients seems to fit with their overestimates of life expectancy (compared with white patients' estimates). These studies weren't designed to determine specific reasons for their findings, but black patients' mistrust of the medical establishment — an outgrowth of a history of discrimination — is a plausible factor mentioned by the authors of the life-expectancy study.
CITATION(S): Check DK et al. Investigation of racial disparities in early supportive medication use and end-of-life care among Medicare beneficiaries with stage IV breast cancer. J Clin Oncol 2016 Jul 1; 34:2265.

Trevino KM et al. Accuracy of advanced cancer patients' life expectancy estimates: The role of race and source of life expectancy information. Cancer 2016 Jun 15; 122:1905. (http://dx.doi.org/10.1002/cncr.30001)
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AHA Provides Comprehensive List of Drugs that could Lead to Heart Failure
By Kelly Young
Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
The American Heart Association has published an exhaustive list of prescription drugs from many classes that may lead to or worsen heart failure.
Some of the drugs that may exacerbate existing myocardial dysfunction include nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, metformin, dronedarone, verapamil, tricyclic antidepressants, and itraconazole. Some that could cause direct myocardial toxicity include appetite suppressants, clozapine, docetaxel, and stimulants.
The document, published in Circulation, also provides a list of prescription drugs that are high in sodium, as well as lists of complementary and alternative treatments that may increase risk in patients with heart failure.
The AHA recommends that clinicians perform a thorough medication reconciliation at each clinical encounter and ask patients about the dose and frequency of all prescription, over-the-counter, and complementary-alternative medications.

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JAMA Dermatol 2016 Jun 29
Hair Today, Gone Tomorrow
Predominant reasons why U.S. women remove their pubic hair.
Pubic hair removal is increasingly common among U.S. women but carries risk for injury. To assess the prevalence of and reasons for this practice, investigators surveyed a nationally representative sample of 3316 U.S. women.
Some 84% of respondents said they had removed some or all pubic hair at least once in their lives; such women were more likely to be younger, white, and better educated. Specific grooming habits varied, with 62% reporting having removed all pubic hair at least once. The most commonly cited reasons for hair removal were hygiene (59%) and appearance (32%); 56% removed hair in preparation for sex, and 40% before visits with their clinicians. Almost half of women who pursued this activity stated that their partner also did so.
COMMENT: The high rate of pubic hair removal among young white women mirrors my observations in clinic; still, I'm surprised that the primary motivation among these respondents is hygiene, and that the practice is common in preparation for a visit to a clinician. These reasons probably reflect the view that going “au naturel” is perceived as a lack of cleanliness. As the authors point out, media images and pornography increasingly reinforce the bare pubis as a norm. Given that pubic hair removal has no clear health benefits (aside from lowering risk for pubic lice) — and that some women experience rashes or local infections as a result — clinicians can reassure their patients that cleanliness and absence of pubic hair are not connected.
CITATION(S):Rowen TS et al. Pubic hair grooming prevalence and motivation among women in the United States.JAMA Dermatol 2016 Jun 29; [e-pub]. (http://dx.doi.org/10.1001/jamadermatol.2016.2154)
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The President Reviews the Lessons of the Affordable Care Act
By Joe Elia, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
President Barack Obama presents his analysis of the Affordable Care Act (ACA) in JAMA, which also contains several editorials on the future of U.S. health care.
Obama points to the decline in uninsured — from 16% when the ACA was signed into law in 2010 to 9% in 2015 — as unprecedented since the passage of Medicare and Medicaid in 1965. Since ACA's existence, the number of uninsured dropped from 49 million to 29 million. Expanded coverage, he observes, has also decreased both the number of people reporting "fair" or "poor" health and the burden of medical debt.
He calls for the expansion of Medicaid in the 19 states that have yet to do so, and he advocates for more competition in the medical marketplace, notably for reconsideration of a "public plan" to compete with insurers in states where competition is limited.
His lessons? Change is difficult; special interests like drug companies "pose a continued obstacle to change"; and "pragmatism in both legislation and implementation" is important
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MM: The acquisition cost of this drug is close to $500 monthly for 60 unit dose packets.
New Treatment Approved for Dry Eye Disease
By Kristin J. Kelley, Edited by David G. Fairchild, MD, MPH, and 
Lorenzo Di Francesco, MD, FACP, FHM
The FDA has approved the first lymphocyte function-associated antigen 1 (LFA-1) antagonist for treating dry eye disease. Lifitegrast ophthalmic solution (marketed as Xiidra) is indicated for patients 17 years and older — the drug has not been tested for pediatric patients because they typically don’t experience the condition.
In four trials made up of mostly (76%) female patients, groups were randomized to twice-daily treatment with either lifitegrast eye drops or placebo. Patients who got the lifitegrast eye drops saw greater improvement in symptoms of eye dryness than did those treated with placebo.
The drug's most common adverse reactions are blurred vision, dysgeusia, and eye discomfort and irritation.
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Obstet Gynecol 2016 Jun 6
For Pelvic Organ Prolapse, POP in a Pessary?
Randomized trial suggests adding a pessary is more effective than pelvic floor exercises alone.
Pelvic organ prolapse (POP) is likely to become even more common as the population ages. In a trial of vaginal pessary use, researchers enrolled 276 women (mean age, 63; median parity, 3) with symptomatic POP awaiting surgery at an academic urogynecology service in Hong Kong. All received training in pelvic floor exercises, then were randomized to these exercises alone (control) or with placement of a ring pessary. The primary outcome was changes in POP symptoms and quality of life at 12 months based on questionnaire responses.
Among women who received pessaries, fitting was successful in 66% and pessary use was ongoing at 12 months in 60%. Vaginal bleeding and discharge were more common in the pessary group, but this difference did not achieve statistical significance. Although improvements in POP symptoms and quality of life were seen in both groups, these improvements were significantly greater among women with pessaries. However, more women in the pessary group (63% vs. 47%; P=0.02) opted to proceed with surgery after the study.
COMMENT: This is the first randomized trial to assess the addition of pessary management to pelvic floor exercises for POP. The high ongoing use of pessaries at 12 months among participants is striking, and perhaps reflects a patient population that tends to follow clinicians' instructions. Although I was disappointed that almost two thirds of women who received pessaries ultimately opted for POP surgery, this probably reflects the fact that the entire study population was drawn from patients already awaiting such surgery. Finally, the authors imply that pessary replacement every 6 months is acceptable. My experience suggests that malodorous vaginal leukorrhea — as well as mucosal erosions — often accompany such infrequent pessary changes. For many pessary types, the recommendation is to remove and clean the pessary every 1 or 2 weeks, leave it out overnight, and reinsert it the next morning.
CITATION(S): Cheung RYK et al. Vaginal pessary in women with symptomatic pelvic organ prolapse: A randomized controlled trial. Obstet Gynecol 2016 Jun 6; [e-pub]. (http://journals.lww.com/greenjournal/Abstract/publishahead/
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Ann Intern Med 2016 May 17
Tai Chi might be as Effective as Physical Therapy for Knee Osteoarthritis
Pain scores between groups were similar at 12 weeks and 1 year.
Researchers from Tufts have reported that tai chi is more effective than no treatment among patients with rheumatoid arthritis, fibromyalgia, or knee osteoarthritis (OA; Arthritis Rheum 2009; 61:1545). Now, this research group has conducted a randomized trial to compare standard physical therapy and tai chi in 204 patients with knee OA. Tai chi sessions were 60 minutes twice weekly for 12 weeks; physical therapy sessions were 30 minutes twice weekly for 6 weeks, with close phone monitoring for another 6 weeks. Assessors were blinded to treatment assignments.
At 12, 24, and 52 weeks, mean pain scores (as measured on the WOMAC scale) had improved similarly in both groups, and outcomes in the two groups were similar for most secondary measures (i.e., physical function, medication use, and overall quality of life). However, the tai chi group showed statistically superior improvement in the secondary measures of depression and the physical component of a quality-of-life measure at 12 weeks.
COMMENT: This paper adds to the growing literature that supports noninvasive therapies for patients with knee OA. Tai chi was as effective as physical therapy, but the tai chi intervention was longer than the physical therapy intervention, and no untreated or “usual-care” group was included for comparison. In any event, more nonsurgical treatment options for OA patients are welcome.
CITATION(S):Wang C et al. Comparative effectiveness of tai chi versus physical therapy for knee osteoarthritis: A randomized trial. Ann Intern Med 2016 May 17; [e-pub]. (http://dx.doi.org/10.7326/M15-2143)
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