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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
June 17, 2017

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A Blood Pressure–Lowering Diet Might Also Lower Gout Risk
Chronic Pain Might Hasten Cognitive Decline in Older Adults
Sodium Content of Packaged Foods and Beverages Is on the Decline
Can Omega-3 Supplementation Prevent or Treat Neuropathy in Type 1 Diabetes?
Early-Onset Hypertension Confers Greater Cardiovascular Risk than
  Late-Onset Hypertension
Does Antidepressant Use During Pregnancy Raise Risk for ADHD in Offspring?
Do Mothers' Eating Disorders Affect Their Newborns and Infants?
Teens with ADHD Get Licenses Later and Have More Motor Vehicle Crashes
The Downsides of Short-Term Corticosteroids

BMJ 2017 May 9; 357:j1794
A Blood Pressure–Lowering Diet Might Also Lower Gout Risk
A DASH-like diet limits purine intake and has uricosuric effects.
The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure and lowers uric acid levels in people with hyperuricemia. However, whether the DASH diet — rich in fruits, vegetables, whole grains, and low-fat dairy products and low in sodium, sweetened beverages, and red and processed meats — lowers risk for gout is unclear. Researchers used data from the Health Professionals Follow-Up Study to examine associations between the DASH diet and risk for gout in 44,000 men without gout at baseline who completed food frequency questionnaires periodically. Diets were scored based on their similarity to the DASH diet or a “typical Western diet” (e.g., high in red and processed meats, French fries, refined grains, and sweets).
During 26 years of follow-up, more than 1700 participants developed gout. Adjusted for multiple variables (including diuretic use and alcohol intake), risk for gout was lower in the highest DASH diet quintile than in the lowest quintile (relative risk, 0.68). Conversely, gout risk was higher in the highest Western diet quintile than in the lowest (RR, 1.42).
COMMENT: In this study, a DASH-like diet was associated with lower risk for gout; the opposite was noted with the Western diet. Although residual confounding is possible, these results are biologically plausible: The DASH diet limits purine intake and has uricosuric effects, potentially resulting in lower blood uric acid levels.
CITATION(S): Rai SK et al. The dietary approaches to stop hypertension (DASH) diet, Western diet, and risk of gout in men: Prospective cohort study. BMJ 2017 May 9; 357:j1794. (http://dx.doi.org/10.1136/bmj.j1794)

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JAMA Intern Med 2017 Jun 5
Chronic Pain Might Hasten Cognitive Decline in Older Adults
Persistent moderate-to-severe pain was associated with about a 2% increase in absolute risk for developing dementia.
One quarter to one third of older adults have chronic pain, and cross-sectional studies have shown associations between chronic pain and cognitive decline. In this study, researchers used data from a national health and retirement study to explore the longitudinal relation between chronic pain and subsequent cognitive decline in about 10,000 older adults (median age, 73; mostly white women). Participants were assessed every 2 years for pain and cognitive function, and those who reported moderate-to-severe pain at baseline and at 2 years — about 11% of participants — were considered to have persistent pain; those with less or no pain served as the control group. Baseline prevalence of arthritis and depression was higher in the persistent-pain group than in controls (91% vs. 60%).
At median follow-up of about 10 years, cognitive decline was greater in the persistent-pain group than in controls. In analyses adjusted for a wide range of demographic and clinical factors (but not for medications such as opioids or psychotropic drugs), risk for developing dementia was significantly higher in persistent-pain patients than in controls (about 22% vs. 20%). Risk for having difficulty managing medications or finances was also about 2 percentage points higher in persistent-pain patients.
COMMENT: This association between persistent pain and cognitive decline might represent yet another good reason for developing more effective ways to control chronic pain in older adults. The authors note plausible explanations for their observations, including attentional impairment and subsequent memory dysfunction. However, an important limitation of this study is the absence of adjustment for patients' use of medications with central nervous system side effects. Those effects (and not the pain itself) might have contributed to the study's findings.
CITATION(S): Whitlock EL et al. Association between persistent pain and memory decline and dementia in a longitudinal cohort of elders. JAMA Intern Med 2017 Jun 5; [e-pub].
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JAMA Intern Med 2017 Jun 5
Sodium Content of Packaged Foods and Beverages Is on the Decline
During the past 15 years, the decline was about 400 mg daily per person.
Most people in the U.S. consume more sodium than guidelines recommend, due in part to the sodium content of store-bought packaged foods. Researchers used a national database of household packaged food purchases from 2000 through 2014 to evaluate purchasing habits and the associated sodium content of packaged foods and beverages in about 170,000 households; household members used a barcode scanner to identify specific purchased foods and beverages, each of which was then linked to nutritional label data for nearly 1.5 million products. Whether foods actually were consumed was not assessed.
The amount of sodium acquired from purchased packaged foods, beverages, and table salt declined from about 2400 to 2000 mg daily per person from 2000 through 2014. The decline came mostly from decreases in the sodium content of packaged foods rather than decreases in the amount of foods purchased, but most packaged foods still exceeded optimal sodium density levels (≤1.1 mg/kcal). Most of the remainder of the decline came from a decrease in table salt purchases.
COMMENT: Lowering the sodium content of packaged foods is a positive step toward reducing sodium consumption, and might reflect consumer education and purchasing pressure on manufacturers. However, the sodium density of most packaged foods still is high. Also, this study was not designed to assess individual sodium intake, particularly with regard to restaurant food and other away-from-home sources.
CITATION(S): Poti JM et al. Sodium reduction in US households' packaged food and beverage purchases, 2000 to 2014. JAMA Intern Med 2017 Jun 5; [e-pub].
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Neurology 2017 May 17
Can Omega-3 Supplementation Prevent or Treat Neuropathy in Type 1 Diabetes?
Supplementation with omega-3 is associated with growth of corneal nerve fiber length in patients with type 1 diabetes and neuropathy.
About half of patients with diabetes mellitus develop sensorimotor polyneuropathy. Current treatment targets vascular changes, but there is good evidence that neuronal changes take place before or in conjunction with vascular abnormalities. Intensive blood glucose control in type 1 diabetes mellitus has been shown to decrease the incidence of diabetic sensorimotor polyneuropathy and slow the progression of nerve injury.
For this single-arm, open-label pilot trial, researchers recruited 40 participants (53% female) with type 1 diabetes mellitus and a Toronto Clinical Neuropathy score of ≥1. Participants took 10 mg daily of seal oil omega-3 polyunsaturated fatty acids (ω-3PUFA) for 12 months. The investigators hypothesized that omega-3 supplementation could stop the progression of diabetic sensorimotor polyneuropathy. The primary outcome of this study was the change in corneal nerve fiber length (CNFL) and sensory and nerve conduction measures as secondary outcomes.
Among 4 participants who completed 4 months of supplementation and 32 who completed the 12-month protocol, CNFL increased by 29.2% ± 45.9% (from 8.3 ± 2.9 mm/mm2 to10.1 ± 3.7 mm/mm2).
COMMENT: The authors of this study conclude that omega-3 supplementation increases CNFL in patients with type 1 diabetes and neuropathy. Nerve conduction study findings did not change. This is a Class IV evidence study; additional clinical trials are needed before we can recommend use of this supplement in clinical practice.
CITATION(S): Lewis EJH et al. Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month pilot trial. Neurology 2017 May 17; [e-pub].
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BMJ 2017 May 12; 357:j1949
Early-Onset Hypertension Confers Greater Cardiovascular Risk than Late-Onset Hypertension
Early-onset hypertension also is associated with excess hypertension risk in offspring.
Whether early-onset hypertension confers more cardiovascular (CV) risk than does late-onset hypertension is unclear. In this study, investigators used data from 3600 community-dwelling participants in the Framingham Heart Study to determine whether early-onset, compared with late-onset, hypertension is associated with CV-related death. Risk for CV-related death was significantly higher among those with early-onset hypertension (age, <45) than among those without hypertension (odds ratio, 2.19). Notably, as age of hypertension onset rose, risk fell: For example, onset at age ≥65 conferred an OR of 1.47 for CV-related death.
In another analysis, the researchers examined associations between hypertension in first-generation Framingham participants and hypertension in their offspring. Having parents with early-onset hypertension (defined as age, <55) was associated with excess incidence of hypertension, compared with having nonhypertensive parents (adjusted hazard ratio, 2.0 if 1 parent; 3.5 if both parents). In contrast, late-onset hypertension was not associated with excess incidence in offspring.
COMMENT: In this study, the earlier the hypertension onset, the higher the risk for CV-related death — presumably owing to hypertension's cumulative effects. The authors believe these results probably aren't confounded by antihypertensive drug therapy, given that treatment was uncommon and the drugs had limited efficacy during the first 40 years of the study. In addition, early-onset, but not late-onset, hypertension was associated with development of hypertension in offspring — suggestive of a genetic effect. Clinicians should consider age of hypertension onset and its effects on CV risk, and should advise patients with early-onset hypertension to have their children monitored for developing hypertension.
CITATION(S): Niiranen TJ et al. Heritability and risks associated with early onset hypertension: Multigenerational, prospective analysis in the Framingham Heart Study. BMJ 2017 May 12; 357:j1949.

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BMJ 2017 May 31; 357:j2350
Does Antidepressant Use During Pregnancy Raise Risk for ADHD in Offspring?
Maternal psychiatric disease and family factors all contribute to the observed association between antidepressant use and attention-deficit/hyperactivity disorder.
Placebo-controlled, randomized studies of the effects of maternal antidepressant use on offspring neurodevelopment aren't feasible, so epidemiologic studies remain the most useful approach to investigating potential associations. In a cohort study of 190,618 children in Hong Kong, 1252 had mothers who had received prenatal antidepressants. Incidence of attention-deficit/hyperactivity disorder (ADHD) was assessed ≥6 years after birth.
A total of 5659 children had ADHD diagnoses or received treatment for the disorder. Gestational antidepressant use was associated with excess risk for ADHD in offspring (crude hazard ratio, 2.26; P<0.01). Pregnant women with psychiatric disease who did not use antidepressants also had excess risk for offspring with ADHD (HR, 1.96; P<0.01). In a post hoc matched analysis of siblings prenatally exposed or unexposed to an antidepressant, in utero antidepressant exposure had no significant effect on risk for ADHD (adjusted HR, 0.54; P=0.30).
COMMENT: Although a significant association may exist between maternal antidepressant use and abnormal neurodevelopment in offspring, this association is likely confounded by a direct effect of maternal psychiatric problems and family conditions. Despite being limited by modest statistical power, the matched sibling analysis showed no direct effect of maternal prenatal antidepressant use on ADHD risk in offspring. Similarly, a recent analysis of maternal antidepressant use and autism spectrum disorder in offspring showed no significant association among siblings exposed and unexposed in utero to antidepressants (NEJM JW Womens Health Jun 2017 and JAMA 2017; 317:1544). Clinicians should continue to prescribe antidepressants to pregnant women based on their individual needs.
CITATION(S): Man KKC et al. Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: Population based cohort study. BMJ 2017 May 31; 357:j2350.

Pedersen LH et al. The safety of antidepressants in pregnancy: Maternal antidepressants are implicated in ADHD, but so is maternal depression. BMJ 2017 May 31; 357:j2544. 

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J Child Psychol Psychiatry 2017 Apr 28
Do Mothers' Eating Disorders Affect Their Newborns and Infants?
Infants of eating-disordered mothers had various autonomic, language, and motor impairments during their first year of life.
Maternal nutrition is known to be important for healthy babies. To learn about the effects of mothers' eating disorders (EDs) on their children during the first year of life, researchers recruited 37 women with active EDs, 39 women with past EDs, and 61 healthy controls during their first or second trimester (mothers were in their early 30s).
Data at 8 days postpartum were available on newborns of 15 women with active EDs, 20 with past EDs, and 28 healthy controls. Compared with infants in the control group, those in the active-ED group showed autonomic instability. At 1 year postpartum (active-ED group, 18 infants; past-ED group, 19; control group, 28), infants in the past-ED group had impaired language and motor development compared with those in the control group. Statistical models controlled for maternal age, education, child's sex, birthweight, depression, and anxiety but not for maternal body-mass index, weight gain during pregnancy, or birthweight for gestational age.
COMMENT: This small investigation did not control for many factors that could have influenced outcomes (e.g., weight gain during pregnancy; NEJM JW Gen Med Nov 15 2007 and Obstet Gynecol 2007; 110:745). Still, the findings are consistent with studies showing adverse effects of maternal malnutrition, which can extend across generations (e.g., after the Dutch famine during World War II).
Eating-disordered patients are usually women before or during their childbearing years. These patients can be difficult to engage in treatment and often have considerable denial about their medical condition. Perhaps, educating these young women about potential risks to their babies posed by their eating disorders would increase motivation for treatment.
CITATION(S):Barona M et al. Neurobehavioural and cognitive development in infants born to mothers with eating disorders. J Child Psychol Psychiatry 2017 Apr 28; [e-pub].
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JAMA Pediatr 2017 Jun 12
Teens with ADHD Get Licenses Later and Have More Motor Vehicle Crashes
Findings support informing patients and parents of crash risk and offering practical steps to reduce it.
Previous studies documenting a link between attention-deficit/hyperactivity disorder (ADHD) and motor vehicle crash risk are limited by self-report of accidents, small sample size, or inclusion of only male participants. To further study this association, researchers linked electronic health records with New Jersey state traffic safety database records for approximately 18,000 adolescents (2500 with ADHD) receiving primary care within one hospital system.
Adjusting for important confounders including race/ethnicity, insurance, income, seizure disorder, disruptive behavior disorder, and prescription of ADHD medications, researchers conducted survival analyses to examine time to licensure and first motor vehicle crash. Compared with patients without ADHD, licensure rates were lower in both females and males with ADHD, but this difference diminished by age 19 years in males. Crashes occurred sooner and more frequently in both males and females with ADHD (hazard ratio, 1.36), regardless of whether they had recently been prescribed stimulants or their length of driving experience.
COMMENT: This study is the first to use state traffic databases to document links between ADHD and crash risk, and findings support current practices of informing families of this heightened risk and offering commonsense steps to reduce it — such as avoiding nighttime driving, use of mobile devices in the car, or transporting friends. Although ADHD medication did not lower crash risk in this study, it has been protective in prior studies. As the authors acknowledge, patients might have received stimulant prescriptions from providers outside the single hospital system, which could mask a protective association.
CITATION(S): Curry AE et al. Motor vehicle crash risk among adolescents and young adults with attention-deficit/hyperactivity disorder. JAMA Pediatr 2017 Jun 12; [e-pub].
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BMJ 2017 Apr 12; 357:j1415
The Downsides of Short-Term Corticosteroids
Oral use for <30 days was associated with excess risk for sepsis, venous thromboembolism, and fracture.
Although the adverse effects of long-term corticosteroids are clear, relatively little is known about short-term use. In this retrospective U.S. study, researchers used a nationwide commercial insurance claims dataset to determine the incidence of three adverse effects (sepsis, venous thromboembolism, and fracture) associated with oral corticosteroid use for <30 days by >1.5 million adults (age range, 18–64; mean age, 45) continuously enrolled from 2012 through 2014.
In all, 21% of participants received at least one short-term prescription for an oral corticosteroid (median duration, 6 days; median prednisone equivalent dose, 20 mg daily). Nearly half (47%) of patients received a 6-day “dosepack” of methylprednisolone. Respiratory tract infections and disorders, spinal conditions, and allergies accounted for 56% of prescriptions. In users compared with nonusers, incidence rates for sepsis (1.8 vs. 1.0 per 1000 person-years), venous thromboembolism (VTE; 4.6 vs. 2.4), and fracture (21.4 vs. 14.3) were significantly higher regardless of age. In a self-controlled case series, risks for sepsis (incidence rate ratio, 5.3), VTE (IRR, 3.3), and fracture (IRR, 1.9) were significantly higher during the 5 to 30 days after the prescription date than the 5 to 180 days before the prescription date.
COMMENT: An astonishing one in five commercially insured adults received a short course of oral corticosteroid therapy during this 3-year study period. Although the absolute excess risk for sepsis, VTE, and fracture associated with short-term corticosteroid use was low, the cumulative number of affected people was not trivial; widespread use of short-term oral corticosteroids thus has substantial public health implications. Clinicians should not administer short-term oral corticosteroids for conditions in which such agents are ineffective. For conditions in which corticosteroids might provide transient symptom relief but are not essential, clinicians should think twice before prescribing these drugs.
CITATION(S): Waljee AK et al. Short term use of oral corticosteroids and related harms among adults in the United States: Population based cohort study. BMJ 2017 Apr 12; 357:j1415.

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