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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
April 1, 2017

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How Often Do Autism and ADHD Co-Occur?
Generic Drugs Account for Nearly 80% of U.S. Prescriptions
Vitamin D Supplementation and Cancer Risk: Still No Clear Benefit
Possible Effects of 5α-Reductase Inhibitors on Mental Health
Does Pregnancy Affect Outcomes in Women with Breast Cancer?
How Did Lead Exposure Affect the Children of the '70s?
Should We Prescribe Light Therapy for Our Sleepy Parkinson Disease Patients?
How Should We Look for Atrial Fibrillation After Stroke?
Coronary Artery Calcium in Early Midlife Is Associated with Excess
  Coronary Heart Disease Risk

Mol Psychiatry 2017 Feb 28
How Often Do Autism and ADHD Co-Occur?
In a population-level study in Sweden, 48% of people with autism spectrum disorder had attention-deficit/hyperactivity disorder, and 17% of those with ADHD had ASD.
Some genes are associated with both attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). To learn more about the frequency of comorbidity and familial aggregation, researchers analyzed population-level data in Sweden involving 1.9 million people born between 1987 and 2006.
Only the combined type of ADHD was analyzed. There were 28,468 individuals (1.5%) with ASD diagnosed at age ≥1 year and 82,398 (4.3%) diagnosed at age ≥3 years with ADHD. Both disorders occurred more frequently in males. Overall, 48% of people with ASD had ADHD, and 17% of those with ADHD had ASD. Risk for ADHD was 22 times greater among those with ASD than among those without ASD. Having ASD but not intellectual disability significantly increased the risk for ADHD; the odds ratio was 26.1 without intellectual disability, but only 1.3 in people with both ASD and intellectual disability. Familial aggregation of ADHD was found among relatives of ASD cases (monozygotic twins: OR, 18; dizygotic twins: OR, 4; full siblings: OR, 5).
COMMENT: Establishing whether ADHD is present in people with ASD is important because ADHD is usually easily treatable. Alleviating attention and hyperactivity symptoms might increase the ability of patients to engage in treatments for autism. Practitioners should use the lowest effective dose of stimulants to avoid cognitive impairments that occur with higher doses (Science 1977; 198:1274). Low doses are also important because stimulants can lessen empathy and increase perseveration, which are already challenges for people with ASD
(J Child Adolesc Pharmacol 2017 Feb 16; [e-pub]).
CITATION(S): Ghirardi L et al. The familial co-aggregation of ASD and ADHD: A register-based cohort study. Mol Psychiatry 2017 Feb 28; [e-pub].
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Generic Drugs Account for Nearly 80% of U.S. Prescriptions
The U.S. is the biggest generic drugs market in the world, with nearly 80% of prescriptions in America written for generics, according to Research and Markets' "Analyzing the Generic Drugs Sector of the U.S. Pharmaceutical Industry 2017." Also covered in the report is an analysis of major industry players, such as Teva, Mylan, Sandoz, and Sanofi. 
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JAMA 2017 Mar 28; 317:1217
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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JAMA Intern Med 2017 Mar 20
Possible Effects of 5α-Reductase Inhibitors on Mental Health
These drugs were associated with modest excess risks for depression and suicide attempts.
Postmarketing surveillance has raised concerns that 5α-reductase inhibitors might increase risk for depression and suicide; the biologic plausibility of this association is supported by evidence that these drugs affect neuropeptides, testosterone, and other neurotransmitters. In this retrospective Canadian study, researchers identified about 93,000 older men (mean age, 75) who started new prescriptions for finasteride or dutasteride between 2003 and 2013; these men were matched by age, history of depression or suicidal thoughts, and other demographic and clinical variables with an equal number of men without such prescriptions. Data also were collected on suicide, new-onset depression, and self-harm (e.g., hospitalization or emergency department visits for suicide attempts) during continuous medication use plus 12 months after stopping.
At median follow-up of about 18 months, suicide rates were similar in both groups. Risk for self-harm was modestly but significantly elevated with active treatment compared with placebo (71 vs. 53 events per 100,000 person-years), as was risk for incident depression (767 vs. 530 events per 100,000 person-years). After 18 months, risk for self-harm faded and was no longer significant; risk for depression also faded but remained significant.
COMMENT: Retrospective cohort studies are messy, given the potential for unidentified confounders, and the differences in risk in this study are small, albeit statistically significant. These results might encourage clinicians to counsel patients about potential risks to mental health, but they're unlikely to discourage patients from using 5α-reductase inhibitors.
CITATION(S): Welk B et al. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med2017 Mar 20; [e-pub].
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JAMA Oncol 2017 Mar 9
Does Pregnancy Affect Outcomes in Women with Breast Cancer?
Pregnancy around the time of diagnosis or afterward did not affect 5-year survival.
One of the greatest dilemmas and sources of anxiety for young breast cancer survivors and their physicians relates to recommendations regarding pregnancy following a diagnosis of breast cancer. The notion that a flood of hormones associated with pregnancy will cause a recurrence of breast cancer is embedded in the thinking of many patients and physicians.
To better understand the effect of pregnancy on survival in women with breast cancer, Canadian investigators conducted a population-based retrospective cohort study involving more than 7500 women who received a diagnosis of breast cancer from 2003 through 2014.
At a mean follow-up of 5.2 years, 5-year overall survival (the primary outcome) was similar for women with no pregnancy (87.5%), women with a pregnancy 1 to 5 years before breast cancer diagnosis (85.3%), and women with pregnancy-associated breast cancer (11 months before diagnosis to 21 months after diagnosis; 82.1%). The 5-year survival rate for women who delivered 6 months or more after diagnosis was 96.7%. Among women with pregnancy-associated breast cancer, the youngest patients (<30 years) had a worse prognosis than older patients and were more likely to have higher-stage disease and ER-negative tumors.
COMMENT: These data provide assurance to young, premenopausal breast cancer survivors who wish to conceive following a diagnosis of breast cancer. In the group of survivors waiting until 6 months have passed from the diagnosis, there is no difference in survival compared with their counterparts who do not get pregnant.
CITATION(S): Iqbal J et al. Association of the timing of pregnancy with survival in women with breast cancer. JAMA Oncol 2017 Mar 9; [e-pub]. (http://dx.doi.org/10.1001/jamaoncol.2017.0248)
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JAMA 2017 Mar 28; 317:1244
How Did Lead Exposure Affect the Children of the '70s?
Greater childhood lead exposure was associated with lower adult IQ and socioeconomic status at age 38, though effects were small.
Lead exposure has been linked to lower IQ in children and adolescents, but effects later in life have not been studied on a large scale.
Researchers reported on 565 individuals from a 1972–73 New Zealand birth cohort whose blood lead level had been measured at age 11 years. At age 38 years, IQ was reassessed and socioeconomic status scored by job type using a standard national formula (range [low to high], 10 to 90). Adjustments were made for child and maternal IQ, as well as childhood socioeconomic status.
Blood lead levels ranged from 4 to 31 μg/dL, with a mean of 11 μg/dL. Forty-six percent of children had levels >10 μg/dL. After adjusting for potential covariates, every 5-μg/dL increase in blood lead level at age 11 was associated with a 1.61-point lower IQ score and a 1.79-unit lower socioeconomic status score at age 38. Blood lead level >10 μg/dL was associated with a 2.73-point lower mean adult IQ score and a 3.42-unit lower mean adult socioeconomic score compared with blood lead level ≤10 μg/dL. Forty percent of the association between childhood lead exposure and decline in socioeconomic status from childhood to adulthood was mediated by IQ decline.
COMMENT: Though these differences in IQ and socioeconomic status are small from the clinical perspective, the cumulative impact of childhood lead exposure could be significant, given the widespread exposure that occurred in the 1970s and '80s. We might question whether these results are relevant today, when broad lead exposure is less common, but the recent Flint water crisis and ongoing regional lead contamination (such as in Missouri, where I practice) show that we remain in a perilous situation regarding childhood lead toxicity. Vigilance, rather than complacency, must define our approach to public health policy and pediatric care through not only testing but also aggressive lead abatement strategies.
CITATION(S): Reuben A et al. Association of childhood blood lead levels with cognitive function and socioeconomic status at age 38 years and with IQ change and socioeconomic mobility between childhood and adulthood.JAMA 2017 Mar 28; 317:1244. (http://dx.doi.org/10.1001/jama.2017.1712)
Bellinger DC.Childhood lead exposure and adult outcomes. JAMA 2017 Mar 28; 317:1219.

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