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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
November 21, 2015

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Obesity Epidemic Not Abating in U.S.
Physical Fitness in Late Adolescence Predicts Future Cardiovascular Outcomes
Another Study of the Statin–Diabetes Relation
Bright-Light Therapy Alleviates Nonseasonal Depression
Inhaled Corticosteroids Are Associated with Pneumonia in COPD Patients
PSA Screening for Prostate Cancer Declined from 2007 to 2013
SSRIs, Benzodiazepines, and Early Postnatal Development
FDA Approves First Genetically Engineered Animal for Human Consumption
Sildenafil Enhances Insulin Sensitivity in Patients with Prediabetes
Vaccine-Refusing Families: What Do Physicians Do?
Dangerous Antibiotic-Resistance Gene Identified in China — Implications "Enormous"
Don't Rely on Peripheral Thermometers to Accurately Estimate Temperature
Drinking Coffee Tied to Lower Relative Mortality Risk

Obesity Epidemic Not Abating in U.S.
By Kelly Young, Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH
Nearly 38% of U.S. adults are obese, and the prevalence has been increasing in recent years — but not significantly so — according to new CDC data.
Researchers used data from the National Health and Nutrition Examination Survey from 2011 to 2014. They found that during this period, the prevalence of obesity was still higher for women than for men (38% vs. 34%) and for non-Hispanic blacks and Hispanics, relative to other ethnic groups.
In 1999 to 2000, 31% of U.S. adults were obese. By 2009 to 2010, the figure increased to 36%, and it inched to 38% in 2013 to 2014, but the difference between these recent years was not statistically significant.
The obesity prevalence for youth aged 2 to 19 years held steady at 17%, with prevalence increasing with age
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BMJ 2015 Sep 16; 351:h4543
Physical Fitness in Late Adolescence Predicts Future Cardiovascular Outcomes
Exercise capacity and muscle strength at age 18 predict mid-life cardiovascular events in a 26-year follow-up study.
Exercise capacity and muscle strength in adulthood predict later cardiovascular outcomes; however, whether exercise capacity and muscle strength in late adolescence are predictive of cardiovascular risk in mid-life is unknown. To assess effects on vascular diseases and arrhythmias, investigators performed a prospective follow-up study of 1.1 million men examined at mandatory military conscription in Sweden between 1972 and 1995 (median baseline age, 18; median follow-up, 26 years). An ergometer bicycle test and handgrip strength were used to estimate maximum exercise capacity and muscle strength, respectively.
During follow-up, 26,088 vascular disease events and 17,312 arrhythmia events occurred. Exercise capacity was inversely associated with risk for vascular disease overall and all of its subgroups (ischemic heart disease, heart failure, stroke, and cardiovascular death), with the association driven mostly by lower risk for heart failure and cardiovascular death. Exercise capacity had a U-shaped association with risk for arrhythmia overall and specifically with bradyarrhythmia risk and was directly associated with risk for atrial fibrillation. Greater muscle strength was associated with lower arrhythmia risk. The combination of high exercise capacity and high muscle strength was associated with significant reductions in vascular events (hazard ratio, 0.67) and arrhythmia (HR, 0.92) compared with the combination of low exercise capacity and low muscle strength.
COMMENT: Increasing evidence suggests that the path to your cardiovascular destiny is laid down at a young age. For example, dietary patterns in adolescence can affect future cardiovascular events. This study confirms that exercise capacity and muscle strength in late adolescence affect future cardiovascular events. Rates of serious cardiovascular events and cardiovascular deaths were lower with greater exercise capacity and muscle strength. Although arrhythmia (primarily atrial fibrillation and bradyarrhythmia) was linked to higher exercise capacity, the authors note that the health benefits were “not outweighed by higher risk of arrhythmia.”
Strengths of this study are its very large sample size, long follow-up, and detailed data. A limitation is that the cohort evaluated was restricted to male military registrants. The authors note that “equivalent data for women are needed.”
CITATION(S):Andersen K et al. Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: Cohort study. BMJ 2015 Sep 16; 351:h4543.

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J Gen Intern Med 2015 Nov; 30:1599
Another Study of the Statin–Diabetes Relation
In a cohort study of relatively healthy people, diabetes developed in 31% of statin users and in 19% of nonusers.
Much of the data on the association between statin therapy and new-onset diabetes has been generated from high-risk populations. In this retrospective cohort study, researchers examined this association in a relatively healthy population of patients enrolled in the Tricare healthcare program for U.S. military families.
The researchers compared 3351 nondiabetic statin users and 3351 nonusers with no history of cardiovascular, pulmonary, renal, rheumatologic, or psychiatric disorders. Patients in these two groups were matched closely on numerous demographic and clinical variables through propensity-scoring. During a 7-year follow-up, the proportion of patients who developed diabetes was significantly higher among statin users than nonusers (30.9% vs. 19.4%). Users of high-intensity statins were more likely to develop diabetes than were users of moderate- or low-intensity statins.
COMMENT: The magnitude of reported excess risk for diabetes among statin users has varied considerably, depending on study methodology (randomized trial vs. cohort study), duration of statin use, and characteristics of the studied populations. However, this finding seems to be consistent and should be considered in decision-making about statin use, especially in primary-prevention populations. But an important issue that hasn't been discussed widely and, to my knowledge, hasn't been investigated adequately is whether statin-related diabetes is reversible when the statin is stopped.
CITATION(S):Mansi I et al. Statins and new-onset diabetes mellitus and diabetic complications: A retrospective cohort study of US healthy adults. J Gen Intern Med 2015 Nov; 30:1599.
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Bright-Light Therapy Alleviates Nonseasonal Depression
By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Bright-light therapy can improve depression symptoms that are not related to seasonal affective disorder, according to a randomized, double-blind trial in JAMA Psychiatry.
Some 120 adults in Canada with nonseasonal major depression were assigned to one of four treatments for 8 weeks: light monotherapy (use of a fluorescent light box for 30 minutes each morning, plus a placebo pill), fluoxetine monotherapy (20 mg/day, plus use of an inactive ion generator as sham light therapy), combination therapy, or sham plus placebo.
At the end of treatment, light therapy — alone or combined with fluoxetine — was associated with significant improvements in depression symptoms relative to sham-placebo. In particular, the mean change in a 60-point depression score was 16.9 with combination therapy, 13.4 with light monotherapy, 8.8 with fluoxetine monotherapy, and 6.5 with sham-placebo.
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Chest 2015 Nov; 148:1177
Inhaled Corticosteroids Are Associated with Pneumonia in COPD Patients
In a case-control study, discontinuing ICS in patients with chronic obstructive pulmonary disease lowered relative risk for pneumonia.
Chronic obstructive pulmonary disease (COPD) guidelines recommend adding inhaled corticosteroids (ICS) when patients continue to have exacerbations while taking long-acting bronchodilators. However, ICS use in COPD patients is associated with excess risk for pneumonia and, in some studies, patients who discontinue their ICS exhibit little or no deterioration. Researchers performed a case-control study using the Canadian national healthcare database to determine if withdrawal of ICS in COPD patients leads to a shorter time to first severe pneumonia (i.e., causing death or hospitalization).
More than 100,000 COPD patients who received ICS were followed for a mean 4.9 years; 14,000 severe pneumonia events occurred, and each case was matched on several parameters to as many as 10 nonpneumonia controls. Risk was highest in patients who received fluticasone. Patients who stopped taking ICS were 37% less likely to contract pneumonia than those who continued to take ICS. The discontinuation effect was evident in the first month, but excess risk still was evident for 4 months after ICS was discontinued.
COMMENT: As many as 85% of COPD patients are treated with ICS, which suggests that these drugs are overused in patients who probably could be managed with long-acting bronchodilators alone. The benefit of ICS is greatest among patients with COPD/asthma overlap syndrome. Other patients should only be started on ICS if exacerbations continue despite adequate long-acting bronchodilator therapy; once patients are stable, we should consider discontinuing ICS.
CITATION(S):Suissa S et al. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest 2015 Nov; 148:1177.

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JAMA 2015 Nov 17; 314:2054
PSA Screening for Prostate Cancer Declined from 2007 to 2013
But the clinical effect, good or bad, is unknown.
The U.S. Preventive Services Task Force recommended against prostate cancer screening with prostate specific antigen (PSA) in men 75 years and older in 2008, and then extended that recommendation to all men in 2012 (NEJM JW Gen Med Jul 1 2012 and Ann Intern Med 2012; 157:120). In two studies, researchers looked at the effect of those recommendations on screening and cancer diagnosis.
In the first study, investigators used national health behavior and cancer surveillance databases to compare screening rates and prostate cancer diagnoses for 2005, 2008, 2010, and 2013. In adjusted analyses, screening rates increased for both middle-aged (age range, 50–74) and older (age, ≥75) men from 2005 to 2008; screening rates declined from 2008 to 2013. The absolute rates of screening in 2013 for the younger and older subgroups were 30% and 36%, respectively. Annual prostate cancer incidence increased from 2005 to 2007 and then declined steadily from 593 cases per 100,000 men in 2007 to 416 per 100,000 in 2012.
Using national data, researchers illustrate a decline in prostate cancer incidence that closely parallels the 2008 U.S. Preventive Services Task Force (USPTF) recommendations to curtail PSA screening in elderly men and the 2012 recommendations to curtail it in all men. In 2005, the incidence rate was 535 per 100,000 men aged 50 and older; in 2010, it dropped to 505; and in 2012, to 416. Screening rates during that period decreased from roughly 37% to 31%.
In the second study, the same national health behavior database was used to identify roughly 5000 middle-aged and older men in each study year (2000, 2005, 2010, and 2013). PSA screening rates were 34% in 2000 and 2005, 36% in 2010, and 31% in 2013. The 2013 decline was driven by lower screening rates in men younger than 75, particularly those younger than 55 (23% in 2010 vs. 18% in 2013) and those who were 60 to 64 (45% in 2010 vs. 35% in 2013).
COMMENT: An editorialist used data from a European screening study (NEJM JW Gen Med Sep 15 2014 and Lancet 2014 Aug 7; [e-pub]) to calculate that about 1200 additional U.S. men might die annually of prostate cancer because of the lower screening rate, but he acknowledges that such a calculation depends on many assumptions. Calculating how much morbidity and mortality is prevented by avoiding unnecessary follow-up and treatment of indolent cancers is much more difficult, but equally important. These unresolvable controversies continue to perplex both patients and physicians.
CITATION(S):Jemal A et al. Prostate cancer incidence and PSA testing patterns in relation to USPSTF screening recommendations. JAMA 2015 Nov 17; 314:2054. (http://dx.doi.org/10.1001/jama.2015.14905)

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Am J Psychiatry 2015 Oct 30
SSRIs, Benzodiazepines, and Early Postnatal Development
Neonatal effects of maternal drug therapy persisted longer than 1 week and were not prevented by stopping medication during late pregnancy.
Neonatal adaptation syndrome (characterized by tremors, irritability, and respiratory distress) has been reported in up to 30% of newborns prenatally exposed to selective serotonin reuptake inhibitors (SSRIs). In a prospective cohort study involving 184 women (mean age, 28) and their healthy, singleton infants born at ≥37 weeks' gestation, investigators examined neurobehavioral development during the first postnatal month after in utero exposure to SSRIs (52 pregnancies), SSRIs plus benzodiazepines (10 pregnancies), untreated unipolar depression (56 pregnancies), or no psychiatric disorder (66 pregnancies). Infants were assessed on postnatal days 2, 4, 7, 14, and 30.
Compared with the no-exposure group, SSRI-exposed infants had lower quality of movement, more hypotonia, more stress-abstinence signs in the central nervous system (CNS), and higher arousal and lower self-regulation scores at day 14. All three clinical groups showed poorer habituation and attention at day 30. No differences were seen in infants with SSRI exposure through delivery versus those whose mothers discontinued SSRIs before the last month of pregnancy. Benzodiazepine exposure was associated with significantly higher rates of maternal comorbid anxiety disorders and, in newborns, the poorest movement quality and highest number of CNS stress-abstinence signs.
COMMENT: This study suggests that neonatal symptoms in SSRI-exposed infants persist longer than the first postnatal week and are not prevented by discontinuing SSRIs during the last month of pregnancy. Whether in utero SSRI exposure has even longer-term neurodevelopmental effects requires further study. The findings in infants exposed to SSRIs plus benzodiazepines are difficult to interpret, given the small group size and presence of comorbid maternal anxiety disorders. At least for now, clinicians should avoid stopping SSRIs at the end of pregnancy (especially given the risk for postpartum depression), avoid polypharmacy whenever possible, and continue to weigh carefully the risks and benefits of SSRI treatment during pregnancy.
CITATION(S):Salisbury AL et al. The roles of maternal depression, serotonin reuptake inhibitor treatment, and concomitant benzodiazepine use on infant neurobehavioral functioning over the first postnatal month. Am J Psychiatry 2015 Oct 30; [e-pub]. (http://dx.doi.org/10.1176/appi.ajp.2015.14080989)
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FDA Approves First Genetically Engineered Animal for Human Consumption
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
The FDA approved on Thursday the AquAdvantage Salmon, the first genetically engineered (GE) animal to be used for food. This version of Atlantic salmon grows faster than non-GE farm-raised Atlantic salmon.
On the basis of "a comprehensive analysis of the scientific evidence," the FDA has determined that "food from AquAdvantage Salmon is as safe to eat and as nutritious as food from other non-GE Atlantic salmon and that there are no biologically relevant differences in the nutritional profile of AquAdvantage Salmon compared to that of other farm-raised Atlantic salmon." In addition, the recombinant DNA construct that speeds the fish's growth is safe for the salmon itself.
AquAdvantage Salmon does not require any special labeling, the FDA says, because its nutritional profile does not differ from that of non-GE salmon.
The GE salmon may be raised only in land-based hatchery tanks in two facilities in Canada and Panama, the FDA notes.
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Sildenafil Enhances Insulin Sensitivity in Patients with Prediabetes
By Cara Adler, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Chronic inhibition of phosphodiesterase 5 via three months of treatment with sildenafil (Revatio) improves tissue insulin sensitivity in individuals at high-risk for diabetes, according to a small, randomized controlled trial in the Journal of Clinical Endocrinology & Metabolism.
Fifty-one overweight patients with prediabetes were assigned to treatment with sildenafil (25 mg three times per day) or placebo for 3 months. Twenty-one patients in each group completed the study and were included in the analysis.
After 3 months, the insulin sensitivity index was significantly higher with sildenafil than placebo. In addition, the urine albumin-to-creatinine ratio decreased significantly in the sildenafil group — whereas it increased in the placebo group — and this effect persisted 3 months after treatment ended. Sildenafil treatment had no effect on glucose-stimulated insulin secretion.
Whether long-term treatment can prevent diabetes in high-risk individuals requires further study, conclude the authors.
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Pediatrics 2015 Nov 2
Vaccine-Refusing Families: What Do Physicians Do?
More than 20% of pediatricians dismiss these families from their practices.
The number of families who decline some or all vaccinations is growing, and healthcare providers must make decisions about continuing to care for these families. The American Academy of Pediatrics does not endorse dismissing nonvaccinating families, but this practice is thought to be relatively common and was reported to be as high as 39% in one study (NEJM JW Pediatr Adolesc Med Feb 2006 and Arch Pediatr Adolesc Med 2005; 159:929).
To determine how often parents refuse vaccinations for their children and how often physicians dismiss nonvaccinating families from their practices, investigators surveyed a random sample of 400 U.S. pediatricians and family physicians during a 6-month period in 2012. The researchers also sought to better understand how physician characteristics and state exemption laws affect decisions about dismissing families.
Overall, 83% of respondents (88% of pediatricians and 76% of family physicians) encountered families that refused vaccines, and 14% (21% of pediatricians and 4% of family physicians) dismissed these families from their practices. Dismissal rates were significantly higher in states that do not allow philosophic exemptions for vaccinations than in those that do (34% vs. 9%); dismissal rates were also higher in states where it is more difficult to obtain exemptions. Physicians in private practice were more likely than those in community, hospital, HMO, or managed-care settings to dismiss nonvaccinating families.
COMMENT: Physicians often encounter families who refuse some or all vaccines, and they face the difficult task of trying to convince them to vaccinate their children. When physicians dismiss these families from their practices, they lose the opportunity to continue this important conversation. Whether eliminating all but medical exemptions would increase vaccination rates remains to be seen, but it may make these conversations easier.
CITATION(S): O'Leary ST et al. Characteristics of physicians who dismiss families for refusing vaccines. Pediatrics 2015 Nov 2; [e-pub].
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Dangerous Antibiotic-Resistance Gene Identified in China —
Implications "Enormous"

By Joe Elia, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Polymyxin resistance, possibly caused by extensive use of colistin in meat production, has emerged in China, according to a study in theLancet Infectious Diseases.
The resistance factor, called MCR-1, is carried on a plasmid (a small, extrachromosomal piece of DNA in bacteria) and could be transferred between strains of E. coli. It has also occurred in other enterobacteria, including Klebsiella and Pseudomonas.
Samples of meat sold at retail in China showed an increased prevalence of the factor between 2011 and 2014. Sixteen hospitalized people also tested positive for MCR-1.
Commentators say that "the implications of this finding are enormous," warning that MCR-1 "will seriously limit the lifespan of the polymyxins as the backbone of regimens against multiply resistant Gram-negative bacilli."
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Don't Rely on Peripheral Thermometers to Accurately Estimate Temperature
By Jenni Whalen, Edited by David G. Fairchild, MD, MPH
Peripheral thermometers do not accurately estimate body temperature, suggests a meta-analysis from the Annals of Internal Medicine.
Researchers reviewed data from roughly 8700 patients in 75 prospective studies that compared peripheral thermometers (tympanic membrane, temporal artery, axillary, or oral) with central thermometers (pulmonary artery catheter, urinary bladder, esophageal, or rectal).
Peripheral thermometers were less accurate than central thermometers. Sensitivity for fever detection was low for peripheral thermometers (64%), although high-quality data were not available for all thermometer types. The authors note that during fever or hypothermia, peripheral thermometers may differ from actual body temperature by 1 to 2 degrees.
They conclude that peripheral thermometers "should not be used when accurate measurement of body temperature will influence clinical decisions... Rectal thermometers could be used for most of these patients, and bladder thermometers could be used for those requiring a bladder catheter. When a central thermometer is best avoided (for example, in patients with neutropenia) or impractical, electronic oral thermometers (for use in adults) or tympanic membrane thermometers (for use in adults and children) that are calibrated before use seem to be the best alternative."
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Drinking Coffee Tied to Lower Relative Mortality Risk
By Kelly Young, Edited by David G. Fairchild, MD, MPH
Coffee consumption is associated with reduced mortality risk, suggests an observational study in Circulation.
The analysis included nearly 210,000 U.S. health professionals free of cancer and cardiovascular disease at baseline. Participants completed food-frequency questionnaires at baseline and every 4 years thereafter. Roughly 32,000 died during 4.7 million person-years of follow-up.
Participants who drank one to five cups of coffee (decaf or regular) daily had slightly lower risk for all-cause mortality than nondrinkers (hazard ratios, 0.91–0.95). For heavier coffee drinkers, there was no association. When the analysis was limited to people who never smoked, there was an inverse linear relationship between coffee consumption and all-cause mortality, with those drinking over five cups daily having the lowest risk (HR, 0.88). Among never smokers, coffee appeared protective against mortality related to cardiovascular and neurological diseases and suicide.
The authors conclude: "Results from this and previous studies indicate that coffee consumption can be incorporated into a healthy lifestyle."

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