Shared genetic architecture underlying sleep and weight in children.

Meta-analyses suggest shorter sleep as a risk factor for obesity in children. The prevailing hypothesis is that shorter sleep causes obesity by impacting homeostatic processes. Sleep duration and adiposity are both heritable, and the association may reflect shared genetic aetiology. We examined the association between a body mass index (BMI) genetic risk score (GRS) and objectively-measured total sleep time (TST) in a cohort of Norwegian children (enrolled at age four in 2007-2008) using cross-sectional data at age six. The analytical sample included 452 six-year old children with complete genotype and phenotype data. The outcome was actigraphic total sleep time (TST) measured at age six years. Genetic risk of obesity was inferred using a 32-single nucleotide polymorphism (SNP) weighted GRS of BMI. Covariates were BMI-Standard deviation scores (SDS) (which takes into account age and sex) and, in a sensitivity analysis socioeconomic status. Analyses consisted of Pearson's correlations and linear regressions. In our sample, 54% of participants were male; mean (SD) TST, age and BMI were 9.6 (0.8) hours, 6.0 (0.2) years and 15.3 (1.2) kg/m2, respectively. BMI and TST were not correlated, r = -0.003, p = 0.946. However, the BMI GRS was associated with TST after adjusting for BMI-SDS, standardised β = -0.11; 95% confidence interval (CI) = -0.22, -0.01. To our knowledge, this is the first study to establish a relationship between genetic risk of obesity and objective sleep duration in children. Findings suggest some shared genetic aetiology underlying these traits. Future research could identify the common biological pathways through which common genes predispose to both shorter sleep and increased risk of obesity

Citation analysis of the scientific publications of Britton Chance in ISI citation indexes

Britton Chance was a pioneer in many scientific fields such as enzymatic reaction kinetics, bioenergetics, metabolism, in vivo NMR, and biophotonics. As an engineer, physical chemist, physicist, physiologist, biophysicist, biochemist, innovator and educator, he had worked in diversified fields over extended periods between 1926 until his death in 2010, at the age of 97. In order to illustrate his scientific career and great impact on research from a new perspective, we employ scientometric analysis tools to analyze the publications of Britton Chance with data downloaded from the ISI Citation Indexes in April 2013. We included articles, reviews and proceeding papers but excluded meeting abstracts. In total, we obtained 1023 publication records with 1236 authors in 266 journals with 17,114 citations from 1945 to 2013. We show the annual publications and citations that Britton Chance received from 1945 to 2013, and generate HistCite maps on the basis of the global citations (GCS) and local (self) citations (LCS) to show the citation relationships among the top-30 publications of Britton Chance. Metabolism and the development of physical methods to probe it appear to be the connecting thread of the lifelong research of Britton Chance. Furthermore, we generate the journal map and co-authorship map to show the broad scope of research topics and collaborators and the high impacts of the scientific oeuvre of Britton Chance ranging from physics, engineering, chemistry and biology to medicine

Distribution of cells responsive to 5-HT6 receptor antagonist-induced hypophagia

Open Access funded by Medical Research CouncilPeer reviewedPublisher PD

5-HT obesity medication efficacy via POMC activation is maintained during aging

Peer reviewedPublisher PD

Medication adherence and community pharmacy: A review of education, policy and research in England

Objective: The objective of this narrative review was to identify and describe the current policy, education and research related to community pharmacy and medication adherence in England. Methods: Medline, Embase, International Pharmaceutical Abstracts and Pharmline were used to search for relevant research articles. Current policy documents were identified via the websites of the Department of Health in England, the Royal Pharmaceutical Society of Great Britain, the National Pharmacy Association, the Pharmaceutical Services Negotiating Committee and NHS Employers. All pharmacy schools in England were contacted to obtain information about the adherence-related courses they provide to undergraduate and postgraduate pharmacy students. Results: National policies and guidelines in England are conducive to an increasing role for community pharmacists to support patients with medication adherence. Many pharmacy schools cover the issue of adherence in their undergraduate and postgraduate courses. Research in this area has tested the effectiveness of pharmacists providing adherence support in the form of compliance aids, education, involvement in discharge planning, and tailored interventions. Conclusion: In community pharmacy in England, current policy and funding arrangements suggest there is great scope for pharmacists to support patients with medication adherence. Further research is necessary to identify the most useful, cost-effective and sustainable approach in practice

Medikamentengabe und Psychotherapie

Psychopharmakotherapie ist ein möglicher Baustein in der multimodalen Behandlung kinder- und jugendpsychiatrischer Störungsbilder. Diese simple Aussage ist unumstritten. Dennoch haben im klinischen Alltag sowohl Eltern als auch Psychotherapeuten häufig erhebliche Bedenken, einem Kind ein Psychopharmakon zu verabreichen. Neben angemessenen Bedenken zu potenziellen Wechselwirkungen zwischen psychopharmakotherapie und Psychotherapie oder Unsicherheiten zu Wirkungen und Nebenwirkungen eines Psychopharmakons trifft man immer wieder auf Vorurteile und sehr prinzipielle Bedenken. Der eher psychotherapeutisch Arbeitende mag die Psychopharmakotherapie für zu kurz gegriffen, biologistisch, Abhängigkeit erzeugend oder mechanistisch halten, während der eher psychopharmakologisch Arbeitende die Psychotherapie für weniger wirksam, überflüssig, verschwendete Lebenszeit oder schädlich halten mag. In einem derartigen Klima ist weder die Entscheidung für ein Psychopharmakon noch das Reflektieren über die Wechselwirkungen zwischen Psychopharmakotherapie und Psychotherapie im Verlauf möglich. Dieser kleine Aufsatz erhebt keinen Anspruch auf eine vollständige Betrachtung, insbesondere ist er keine Übersicht zu Stoffgruppen, Wirkungen und Nebenwirkungen, sondern soll mit einigen Gedanken und klinischen Beispielen zur Reflexion über das Thema >>Medikamentengabe im Kontext der Psychotherapie<< einladen

5-HT2C Receptor Agonist Anorectic Efficacy Potentiated by 5-HT1B Receptor Agonist Coapplication: An Effect Mediated via Increased Proportion of Pro-Opiomelanocortin Neurons Activated

An essential component of the neural network regulating ingestive behavior is the brain 5-hydroxytryptamine2C receptor (5-HT2CR), agonists of which suppress food intake and were recently approved for obesity treatment by the US Food and Drug Administration. 5-HT2CR-regulated appetite is mediated primarily through activation of hypothalamic arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons, which are also disinhibited through a 5-HT1BR-mediated suppression of local inhibitory inputs. Here we investigated whether 5-HT2CR agonist anorectic potency could be significantly enhanced by coadministration of a 5-HT1BR agonist and whether this was associated with augmented POMC neuron activation on the population and/or single-cell level. The combined administration of subanorectic concentrations of 5-HT2CR and 5-HT1BR agonists produced a 45% reduction in food intake and significantly greater in vivo ARC neuron activation in mice. The chemical phenotype of activated ARC neurons was assessed by monitoring agonist-induced cellular activity via calcium imaging in mouse POMC-EGFP brain slices, which revealed that combined agonists activated significantly more POMC neurons (46%) compared with either drug alone (~25% each). Single-cell electrophysiological analysis demonstrated that 5-HT2CR/5-HT1BR agonist coadministration did not significantly potentiate the firing frequency of individual ARC POMC-EGFP cells compared with agonists alone. These data indicate a functional heterogeneity ofARCPOMCneurons by revealing distinct subpopulations of POMC cells activated by 5-HT2CRs and disinhibited by 5-HT1BRs. Therefore, coadministration of a 5-HT1BR agonist potentiates the anorectic efficacy of 5-HT2CR compounds by increasing the number, but not the magnitude, of activated ARC POMC neurons and is of therapeutic relevance to obesity treatment. © 2013 the authors

Measuring the severity of prescribing errors: a systematic review.

Prescribing errors are common. It has been suggested that the severity as well as the frequency of errors should be assessed when measuring prescribing error rates. This would provide more clinically relevant information, and allow more complete evaluation of the effectiveness of interventions designed to reduce errors

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation