Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies.

Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event

Study protocol : the empirical investigation of methods to correct for measurement error in biobanks with dietary assessment

Peer reviewedPublisher PD

Arsenic Exposure in Pregnancy Increases the Risk of Lower Respiratory Tract Infection and Diarrhea during Infancy in Bangladesh

BACKGROUND: Previous studies have reported associations between prenatal arsenic exposure and increased risk of infant mortality. An increase in infectious diseases has been proposed as the underlying cause of these associations, but there is no epidemiologic research to support the hypothesis. OBJECTIVE: We evaluated the association between arsenic exposure in pregnancy and morbidity during infancy. METHODS: This prospective population-based cohort study included 1,552 live-born infants of women enrolled during 2002-2004 in Matlab, Bangladesh. Arsenic exposure was assessed by the concentrations of metabolites of inorganic arsenic in maternal urine samples collected at gestational weeks 8 and 30. Information on symptoms of lower respiratory tract infection (LRTI) and diarrhea in infants was collected by 7-day recalls at monthly home visits. RESULTS: In total, 115,850 person-days of observation were contributed by the infants during a 12-month follow-up period. The estimated risk of LRTI and severe LRTI increased by 69% [adjusted relative risk (RR) = 1.69; 95% confidence interval (CI), 1.36-2.09)] and 54% (RR = 1.54; 95% CI, 1.21-1.97), respectively, for infants of mothers with urinary arsenic concentrations in the highest quintile (average of arsenic concentrations measured in early and late gestation, 262-977 µg/L) relative to those with exposure in the lowest quintile (< 39 µg/L). The corresponding figure for diarrhea was 20% (RR = 1.20; 95% CI, 1.01-1.43). CONCLUSIONS: Arsenic exposure during pregnancy was associated with increased morbidity in infectious diseases during infancy. Taken together with the previous evidence of adverse effects on health, the findings strongly emphasize the need to reduce arsenic exposure via drinking water

The status of clinical trials: Cause for concern

<p>Abstract</p> <p>Background</p> <p>Americans see clinical research as important, with over 15 million American residents participating in NIH-sponsored studies in 2008 and growing yearly.</p> <p>Methods</p> <p>Documents reporting NIH supported Clinical Research projects were reviewed.</p> <p>Results</p> <p>When compared with other studies, the number of interventional Phase III and Phase IV trials have decreased from 20% to 4.4% from 1994-2008.</p> <p>Conclusions</p> <p>This finding most likely has occurred for several reasons. One reason is that the physician lacks an infrastructure for designing and carrying out trials. This lack is because of an absence of a coordinated effort to train clinical trialists. It is clear that the Nation needs a more purposeful approach to developing and maintaining the infrastructure for designing and conducting clinical trials. Building it de novo trial by trial is profoundly inefficient, to say nothing about time consuming and error prone.</p

Examining the impact of health research facilitated by small peer-reviewed research operating grants in a women's and children's health centre

Abstract Background There has been limited research on the impact of research funding for small, institutional grants. The IWK Health Centre, a children and women's hospital in Maritime Canada, provides small amounts (up to $15,000) of research funding for staff and trainees at all levels of experience through its Research Operating Grants. These grants are rigorously peer-reviewed. To evaluate the impact of these grants, an assessment was completed of several different areas of impact. Findings An online questionnaire was sent to 64 Principal Investigators and Co-Investigators from Research Operating Grants awarded from 2004 to 2006. The questionnaire was designed to assess five areas of potential impact: (1) research, (2) policy, (3) practice, (4) society and (5) personal. Research impact reported by participants included publications (72%), presentations (82%) and knowledge transfer beyond the traditional formats (51%). Practice impact was reported by 67% of participants, policy impact by 15% and societal impact by 18%. All participants reported personal impact. Conclusions Small research grants yield similar impacts to relatively large research grants. Regardless of the total amount of research funds awarded, rigorously peer-reviewed research projects have the potential for significant impact at the level of knowledge transfer and changes in clinical practice and policy. Additional findings in the present research indicate that small awards have the potential to have significant impact on the individual grant holder across a variety of capacity building variables. These personal impacts are particularly noteworthy in the context of developing the research programs of novice researchers.</p

A novel online food recall checklist for use in an undergraduate student population : a comparison with diet diaries

Peer reviewedPublisher PD

Volunteering in the care of people with severe mental illness: a systematic review

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