Available data although limited in terms of number of studies are consistent in demonstrating that CLZ is effective and generally safe in the treatment of refractory EOS provided patients are regularly monitored.

SummaryBackgroundIntensive community treatment to reduce dependency on adolescent psychiatric inpatient care is recommended in guidelines but has not been assessed in a randomised controlled trial in the UK. We designed a supported discharge service (SDS) provided by an intensive community treatment team and compared outcomes with usual care.MethodsEligible patients for this randomised controlled trial were younger than 18 years and had been admitted for psychiatric inpatient care in the South London and Maudsley NHS Foundation Trust. Patients were assigned 1:1 to either the SDS or to usual care by use of a computer-generated pseudorandom code with random permuted blocks of varying sizes. The primary outcome was number of inpatient bed-days, change in Strengths and Difficulties Questionnaire (SDQ) scores, and change in Children's Global Assessment Scale (CGAS) scores at 6 months, assessed by intention to treat. Cost-effectiveness was explored with acceptability curves based on CGAS scores and quality-adjusted life-years (QALYs) calculated from the three-level EuroQol measure of health-related quality of life (EQ-5D-3L), taking a health and social care perspective. This study is registered with the ISRCTN Registry, number ISRCTN82129964.FindingsHospital use at 6 months was significantly lower in the SDS group than in the usual care group (unadjusted median 34 IQR 17–63 vs 50 days, 19–125, p=0·04). The ratio of mean total inpatient days for usual care to SDS was 1·67 (95% CI 1·02–2·81, p=0·04), which decreased to 1·65 (0·99–2·77, p=0·057) when adjusted for differences in hospital use before randomisation. Scores for SDQ and CGAS did not differ between groups. The cost-effectiveness acceptability curve based on QALYs showed that the probability of SDS being cost-effective compared with usual care was around 60% with a willingness-to-pay threshold of £20 000–30 000 per QALY, and that based on CGAS showed at least 58% probability of SDS being cost-effective compared with usual care irrespective of willingness to pay. We recorded no adverse events attributable to SDS or usual care.InterpretationSDS provided by an intensive community treatment team reduced bed usage at 6 months' follow-up but had no effect on functional status and symptoms of mental health disorders compared with usual care. The possibility of preventing admissions, particularly through features such as reduced self-harm and improved reintegration into school, with intensive community treatment should be investigated in future studies.FundingSouth London and Maudsley NHS Trust.

Objective: Hormesis, the biological and toxicological concept that small quantities have opposite effects from large quantities, is reviewed with emphasis on its relevance to nutrition. Results: Hormetic and other dose-response relationships are categorized, depicted, and discussed. Evidence for nutritional hormesis is presented for essential vitamin and mineral nutrients, dietary restriction, alcohol (ethanol), natural dietary and some synthetic pesticides, some herbicides, and acrylamide. Some of the different hormetic mechanisms that have been proposed are reviewed. Conclusions:The credence and relevance of hormesis to nutrition are considered to be established. The roles of hormesis in nutritional research and in formulating nutritional guidelines are discussed.

Background Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity. Methods We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted “features” [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources. Results Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum. Conclusions This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder.

I address and explain the increased risk of adverse effects from nutrients by using the paradigm of hormesis, the biological and toxicological concept that small quantities have opposite effects from large quantities. To provide necessary background, I categorize, depict, discuss, and contrast hormetic and other dose-response relations. I review some of the different hormetic mechanisms that others have proposed. I then use the hormetic paradigm to explain adverse effects from essential nutrients, including vitamin D. The hormesis paradigm could be useful to nutritional scientists in their consideration of nutritional adverse effects.

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