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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
April 29, 2017

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Aim at the Gut, Hit the Brain?
Negative Impact of Body Dissatisfaction Is Similar for Adolescent Boys and Girls
School Performance Decline in Childhood Predicts Injury Risk in Adolescence
More evidence that excessive Blood Pressure lowering can heighten Cardiovascular Risk
Moderate Alcohol Drinkers Experience Fewer Adverse Cardiovascular Outcomes
When Are Fluctuations in Weight Unhealthy?
Vitamin D Supplementation and Cancer Risk: Still No Clear Benefit

Biol Psychiatry 2017 Feb 24
Aim at the Gut, Hit the Brain?
An animal study shows that prebiotics ameliorate maladaptive stress responses.
Probiotics, which may improve overall functioning, are live organisms that alter the intestinal microbiome. In contrast, prebiotics are soluble nonliving fibers that stimulate beneficial intestinal bacteria. Investigators in Ireland studied whether the prebiotics fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) might be effective in animal models of anxiety and depression.
Mice were given 3 weeks of supplementation with GOS, FOS, GOS plus FOS, or water and then were exposed to chronic social and other forms of stress. Compared with water, the prebiotics, especially their combination, altered the types and number of intestinal bacteria, with higher cecal concentrations of short-chain fatty acids. Paralleling these changes, the prebiotics induced hippocampal BDNF and GABABreceptor genes and attenuated stress-induced production of the cytokines interleukin-6 and tumor necrosis factor alpha and of the primary stress hormone corticosterone. The prebiotics showed no effects on cognition, pain perception, and sociability, but GOS+FOS reduced anxiety- and depression-like behaviors in response to established stressful provocations of these behaviors.
COMMENT: The mechanisms by which the intestinal microbiome ameliorate maladaptive stress responses may involve actions on the autonomic nervous system that feed back to the central nervous system, reduced production of cytokines that alter brain function, and altered production of monoamine neurotransmitters and expression of neuroprotective genes. Because prebiotics are inert, they may be easier to use and more practical than probiotics in balancing the organismic stress response.
CITATION(S): Burokas A et al. Targeting the microbiota-gut-brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 2017 Feb 24; [e-pub].
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Adolesc Health 2017 Mar 25
Negative Impact of Body Dissatisfaction Is Similar for Adolescent Boys and Girls
Girls reported higher levels of body dissatisfaction than boys, but its effect on quality of life was comparable for both sexes.
Studies of the negative impact of body dissatisfaction have generally been limited to girls. Recognizing that body dissatisfaction is a growing concern among boys, investigators in Australia conducted a school-based survey to examine its effect on quality of life (QOL) among adolescent girls and boys.
Of 1749 students who completed surveys (79% response rate), 1666 (mean age 15.5 years, 531 boys) had complete data on measures of body dissatisfaction, eating disorder symptoms, quality of life, and self-reported height and weight (from which body-mass index [BMI] was calculated). Girls were on average were 8 months older than boys, but BMI did not differ significantly between sexes (mean, ~ 20.6 kg/m2). Girls reported significantly higher levels of body dissatisfaction than boys for each of 12 body features. The biggest differences were for legs, stomach and hips, and the smallest differences were for height, chest, and shoulders. Girls also reported more eating disorder symptoms and lower levels of both psychosocial and physical QOL. However, the strength of the association between body dissatisfaction and diminished physical and psychosocial QOL was equal for boys and girls, even after controlling for eating disorder symptoms.
COMMENT: While body dissatisfaction remains a greater concern for girls than boys, in boys it is often associated with use of anabolic steroids or other potentially risky nutritional supplements. Since boys may be reluctant to share body image concerns, clinicians should be attuned to comments suggesting body dissatisfaction is present and explore the adolescent's concerns with him.
Griffiths S et al. Sex differences in quality of life impairment associated with body dissatisfaction in adolescents. J Adolesc Health 2017 Mar 25; [e-pub].
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J Adolesc Health 2017 Apr 05; S1054-139X(17)30069-1
School Performance Decline in Childhood Predicts Injury Risk in Adolescence
Students whose academic performance fell off between 7 and 11 years of age had a 16% to 20% excess risk for an injury-related, primary-care visit during adolescence.
Education and good health are inextricably linked. To explore this association further, investigators in Wales examined the impact of childhood academic performance on risk for injuries during adolescence. The researchers linked data on more than 172,000 Welsh children registered with a general practitioner (from the Wales Electronic Cohort for Children) with educational records — including standardized assessments of achievement in language and math at ages 7 to 8 years and 10 to 11 years — as well as general-practitioner records and hospital-admissions and mortality data. A subset of students completed a health behavior survey between ages 11 and 16 years.
Analyses adjusted for free school meal eligibility showed that both boys and girls who achieved academically at age 7 to 8, but not at age 10 to 11, were 16% to 20% more likely than those who maintained achievement at both age points to have one or more injury-related visits to a general practitioner during adolescence (median follow-up after age 12, 2.5 years); students whose performance declined were also 30% more likely to have injuries severe enough to require one or more hospitalizations (risk was slightly higher for boys than girls). Among 400 students whose health behavior data could be linked with education records, alcohol use was reported significantly more often by those whose performance declined than by those with steady performance (70% vs. 55%).
COMMENT: This large population-based study clearly demonstrates the link between academic success and both relatively minor and serious health outcomes. The authors speculate that the health behavior data indicate that increased injury rates may be attributed to the adoption of risky behaviors by teens with declining school performance. In any case, monitoring educational achievement at primary care visits is a critical first step toward potentially reducing future health risks. The American Academy of Pediatrics Bright Futures Guidelines includes tools to help practitioners achieve that goal.
CITATION(S): Demmler JC et al. Educational attainment at age 10–11 years predicts health risk behaviors and injury risk during adolescence. J Adolesc Health 2017 Apr 05; S1054-139X(17)30069-1; [e-pub].
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Lancet 2017 Apr 5
More evidence that excessive Blood Pressure lowering can heighten Cardiovascular Risk
In two trials, achieved systolic BP <120 mm Hg was associated with greater CV-related and all-cause mortality.
Optimal target blood pressure (BP) for patients who are receiving antihypertensive therapy remains controversial; numerous studies have suggested that excessive BP lowering can increase risk for some adverse cardiovascular (CV) events. However, in the SPRINT trial, targeting a systolic BP of <120 mm Hg lowered the incidence of adverse CV events more than did less-aggressive treatment, although average achieved systolic BP actually remained slightly higher than 120 mm Hg (NEJM JW Gen Med Dec 15 2015 and N Engl J Med 2015; 373:2174). To elucidate further the relation between BP and adverse CV outcomes, researchers analyzed pooled data from 31,000 high-risk patients (age, ≥55; history of CV disease or diabetes with organ damage; 70% with hypertension) who were assigned to take ramipril, telmisartan, both, or neither for a median 56 months in two trials funded by the manufacturer of telmisartan. Outcomes included a composite endpoint (CV-related death, myocardial infarction, stroke, or hospitalization for heart failure), individual CV endpoints, and all-cause death.
Mean BP achieved on treatment was a stronger predictor of CV outcomes than was baseline BP or last recorded BP before an adverse CV event. For most outcomes, risk was lowest at mean achieved systolic and diastolic BPs of 120 to 140 mm Hg and 70 to 80 mm Hg, respectively. The composite outcome, CV-related death, heart failure hospitalization, and all-cause death all occurred significantly more commonly at lower systolic BPs, and all outcomes except stroke were more frequent at lower diastolic BPs.
COMMENT: Statistical adjustments could not completely eliminate the possibility of reverse causality in this observational study. Optimal BP targets might vary for preventing specific adverse CV outcomes, but, for most patients at high CV risk, targets of 120/70 to 140/80 mm Hg probably are safest and most effective.
CITATION(S): Böhm M et al. Achieved blood pressure and cardiovascular outcomes in high-risk patients: Results from ONTARGET and TRANSCEND trials. Lancet 2017 Apr 5; [e-pub].
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BMJ 2017 Mar 22; 356:j909
Moderate Alcohol Drinkers Experience Fewer Adverse Cardiovascular Outcomes
In a cohort study, both teetotalers and heavy drinkers had higher rates of many adverse CV events.
Prior studies have shown that both drinking no alcohol and heavy alcohol consumption are associated with higher risk for cardiovascular (CV) morbidity and mortality compared with moderate drinking — a “U-shaped” association. However, some of these studies categorized both never drinkers and former drinkers as nondrinkers — a methodological flaw that could have biased results, because former drinkers might have excess risk for CV disease. In this population-based U.K. cohort study, researchers assessed associations between specific categories of alcohol consumption and multiple adverse CV outcomes in almost 2 million adults without known CV disease at baseline.
During a median follow-up of 6 years, 115,000 participants received incident CV diagnoses. The following associations were noted in analyses adjusted for possible confounders (e.g., smoking):

COMMENT: This study supports the U-shaped relation between alcohol intake and CV disease. Both teetotalers and heavy drinkers had higher risks for various adverse CV outcomes than did moderate drinkers. Whether clinicians should endorse alcohol intake in the generally accepted moderate range (i.e., 1–2 drinks daily for men, and 1 drink daily for women) for carefully selected patients remains controversial.
CITATION(S): Bell S et al. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: Population based cohort study using linked health records. BMJ 2017 Mar 22; 356:j909.

Mukamal K and Lazo M.Alcohol and cardiovascular disease: Big data puts the link between moderate drinking and lower risk under the microscope. BMJ 2017 Mar 22; 356:j1340. (http://dx.doi.org/10.1136/bmj.j1340)

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N Engl J Med 2017 Apr6; 376:1332
When Are Fluctuations in Weight Unhealthy?
A post hoc analysis links weight fluctuations to risk for coronary events, but only in overweight or obese people.
Patients commonly receive advice about their body weight, and fluctuations in weight are a typical occurrence for many people as they cycle through various diets. To examine the relationship between weight fluctuations and risks for cardiovascular events, investigators in a manufacturer-funded study analyzed data on 9509 people from the Treating to New Targets (TNT) trial, which tested atorvastatin in patients with established coronary artery disease.
The authors defined body-weight fluctuations as intraindividual variability in weight between study visits, which occurred every 3 months in the first year and every 6 months thereafter. Mean baseline weight was 85 kg. During a median follow-up of 4.7 years, participants had a median of 12 weight measurements and a median body-weight variability of 1.8 kg.
With each increase in body-weight variability of one standard deviation (1.5–1.9 kg), the risk for any coronary event increased by 4%. Participants in the highest quintile of variability, compared with those in the lowest, had a 64% higher relative risk for any coronary event. The association was not significant for those with a normal weight. Mean weight was not significantly associated with coronary events in a model fully adjusting for demographics, comorbidities, and other factors.
COMMENT: This provocative, post hoc study of a trial population suggests that body-weight fluctuations over 5 years predict elevated risk in those who are overweight and obese — and mean weight itself does not predict events. These findings need further validation. The reason for them is not clear, and the relationship may not be causal. For now, however, the results bring into question the wisdom of interventions that may result in weight fluctuations.
CITATION(S): Bangalore S et al. Body-weight fluctuations and outcomes in coronary disease. N Engl J Med 2017 Apr6; 376:1332.
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JAMA 2017 Mar 28; 317:1234
Vitamin D Supplementation and Cancer Risk: Still No Clear Benefit
In women who received supplementation, a small decrease in cancer incidence did not quite reach significance.
Despite epidemiologic and biologic reasons to expect that vitamin D might prevent cancer, dietary supplementation studies have shown no benefit. Now, researchers randomized 2303 healthy postmenopausal women in Nebraska (mean age, 65; 99% non-Hispanic white; mean baseline serum 25-hydroxyvitamin D [25(OH)D], 33 ng/mL) to supplementation with vitamin D3 (2000 IU daily) and calcium (1500 mg daily) or placebo. All participants were asked to limit outside supplementation; actual mean daily amounts of outside supplementation plus dietary intake were about 900 IU (vitamin D3) and 1200 mg (calcium) in both groups.
Over 4 years, mean 25(OH)D levels increased to 44 ng/mL in the intervention group and remained constant in the placebo group. The overall incidence of new cancers was not significantly different in the intervention and placebo groups (3.9% vs. 5.6%; P=0.06). However, in a post hoc analysis of study years 2 through 4, the difference barely reached significance (3.2% vs. 4.9%; P=0.048).
COMMENT: It's not surprising that this trial did not add support for vitamin D in cancer prevention. Short-term supplementation with vitamin D (or calcium) later in life seems unlikely to significantly affect cancer incidence. Also, the participants' relatively high mean baseline 25(OH)D levels and substantial outside supplementation could have blunted any effect. Still, the findings after the first year are intriguing and should be revisited in light of a larger, longer-duration supplementation trial of vitamin D now under way.
CITATION(S): Lappe J et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: A randomized clinical trial. JAMA 2017 Mar 28; 317:1234. (http://jamanetwork.com/journals/jama/article-abstract/2613159)
Manson JE et al. Vitamin D, calcium, and cancer: Approaching daylight? JAMA 2017 Mar 28; 317:1217.

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