Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.

A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.

Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.

In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.

Despite advances in the last decade, people with schizophrenia remain disabled by negative symptoms and function poorly in community settings. Until recently negative symptoms were neglected as a treatment target despite apparent recognition of their importance among clinicians.

To examine the impact of negative symptoms on psychosocial functioning in order to assess the importance of such symptoms as a potential treatment target.

295 community based participants with DSM4R schizophrenia were recruited in 11 different European centres and assessed using the following scales: PANSS, GAF, Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Recovery Scale in Schizophrenia (FRSS) and PsychoSocial Remission in Schizophrenia (PSRS). Relationships between and negative symptoms and functionality were examined using standard statistical approaches.

In this European cohort negative symptom scores were highly correlated with poor psychosocial functioning in participants living in the community. This significant trend occurred across different scales for measuring functional assessment.

The pharmacological treatment of schizophrenia appears rather becalmed at present. First and second generation antipsychotics appear to have similar efficacy for positive symptoms, different side effect profiles, but little impact on negative symptoms. This study shows a close relationship between negative symptoms and psychosocial functioning: high negative symptom scores are associated with poor functioning. This work supports the view that negative symptoms are a key target for drug development with significant potential benefit for the functioning of individuals. Drug development will increasingly focus on negative symptoms and develop effective adjunctive medication used with existing antipsychotics.

The effect of minor orthopaedic day surgery (MiODS) on patient's mood.

A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of General Anaesthesia (GA) were included. The Medical Outcomes Study-Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and postoperatively.

The mean physical component score of SF-36 before surgery was 45.3 (SD = ±10.1) and 8 weeks following surgery was 44.9 (SD = ±11.04) [n = 148, p = 0.51, 95%CI = (-1.03 -1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov = 69.44) corresponded to a correlation coefficient, r = 0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with χ2 (df = 1) = 0.86 for which p = 0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected.

MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.

Many patients with schizophrenia suffer from poor social functioning, with high levels of unemployment being one particular consequence. Negative symptoms tend to persist during periods of clinical stability and may have a detrimental effect on function. This paper aims to investigate the relationship between negative symptoms and ability to function.

The EGOFORS study measured negative symptoms in 295 schizophrenia patients in 11 European sites using the PANSS Negative Subscale and assessment scales for psychosocial function: Global Assessment of Functioning (GAF), Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Remission of General Schizophrenia (FROGS), Psychosocial Remission in Schizophrenia (PSRS) and Subjective Wellbeing under Neuroleptics (SWN). The relationships between the PANSS Negative Subscale and the functional scales were investigated, adjusting for differences between study sites. Being in work, duration of illness, age of onset and number of years of education were also investigated for a relationship with function.

There were strong, statistically significant correlations between PANSS Negative Subscale and all of the function scales (95% confidence intervals for the correlation coefficients: PSRS 0.77–0.91; FROGS 0.74–0.89; QLS 0.74–0.92; GAF 0.64–0.78; PSP 0.63–0.80) except the SWN. All of the functional scales except SWN were at least moderately related to one another. All of the items in each of the PANSS Negative Subscale and the function scales contributed to the relationships between them. Better functioning correlated strongly with participants being in work.

This study shows a strong and significant relationship between negative symptoms and psychosocial functioning. Given the impact of negative symptoms on psychosocial function, much more emphasis should be placed on developing effective treatments for negative symptoms, given that most patients with schizophrenia now live in community settings and require to function adequately to support their quality of life.

ll antipsychotics act via dopaminergic receptor antagonism. This pharmacology is shared by all first (FGA) & second (SGA) generation antipsychotics. We reviewed the efficacy & safety of all antipsychotics in clinical use for BMJ Clinical Evidence (Barry et al 2012).

Our paper summarises key results from this systematic review based on comprehensive literature search of the Medline, Embase, Cochrane Library, and other databases including safety information from the FDA and MHRA in UK. The main clinical questions of interest were: What is the efficacy of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? How effective are treatments for people with schizophrenia resistant to standard antipsychotic drugs?

We found 51 systematic reviews, RCTs, or observational studies that met our inclusion/quality criteria and performed GRADE analysis to assess quality of evidence. Key results are presented for efficacy & safety for: amisulpiride, chlorpromazine, clozapine, depot haloperidol, haloperidol, olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine, aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol, zuclopenthixol, depot zuclopenthixol, and clozapine.

The evidence for some ‘standard’ treatments is surprisingly weak. Up to 1/3 -1/2 of patients fail to respond to currently available antipsychotics, and all antipsychotics cause side effects in most people. This downbeat conclusion is not surprising, given clinical experience and the common mechanism of action of all antipsychotics. More efficacious antipsychotic medication will only be developed from understanding the biological pathogenesis of schizophrenia.Barry S, Gaughin T, and Hunter R. Schizophrenia. BMJ Clinical Evidence 13 July 2012.

http://clinicalevidence.bmj.com/x/systematic-review/1007/overview.html.

Extended brief interventions (EBIs) are effective in targeting alcohol misuse in the general population. However, little is known on the effects of EBI in adults with intellectual (also known as learning disabilities).

In this feasibility trial we compared EBI with usual care for alcohol misuse in adults with mild to moderate intellectual disability (ID).

The study took place in three community ID services in England. Participants aged 18–65 years with reported alcohol problems, a score > 8 on the alcohol use disorder identification test (AUDIT), and IQ < 70 (+/5% CI) were recruited and were randomly allocated to either EBI (5 weekly sessions and 1 follow-up at 8 weeks) and usual care or usual care alone. Research assessments took place at baseline, two and three months.

Thirty individuals were randomised (15 in each arm). In regard to harmful drinking, at baseline, all the participants exceeded the relevant threshold. At 8 weeks, the proportion of participants with harmful drinking decreased to 60% for both groups, at 12 weeks it was decreased by 66.7% and 46.7% for the intervention and the control group respectively. The unit cost for the delivery of EBI is £ 430.

Recruitment to this trial has been proven challenging as prevalence of alcohol misuse in the targeted population was lower than anticipated. EBI may provide an effective low intensity treatment for this population. Participants’ and carers’ feedback on their experience was overall positive.

The authors have not supplied their declaration of competing interest.

Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.

To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.

A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.

The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.

The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.

The authors have not supplied their declaration of competing interest.

Intravenous dextrose aids in the resolution of ketosis in dehydrated patients not tolerating oral glucose and is often recommended in this clinical scenario. Our aim was to determine whether the addition of dextrose to intravenous rehydration solutions results in decreased hospital admissions or other clinically important benefits among dehydrated children or adults.

MEDLINE, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched by a medical librarian from inception through November 2017. The inclusion criteria were randomized controlled trials comparing dextrose containing intravenous solutions with intravenous solutions without dextrose in patients being treated for dehydration, and not already hospitalized.

The database and bibliographies search identified 1,472 unique citations. Only two trials (N = 333) met the inclusion criteria. Both compared normal saline with solutions of dextrose in normal saline. There was no statistically significant difference in admission rates (relative risk = 0.83; 95% confidence interval = 0.62 to 1.10) or revisits (relative risk = 0.54; 95% confidence interval = 0.24 to 1.22). Heterogeneity was low (I2 = 0). No other outcome results were eligible for pooling, but neither study found differences in any clinical outcomes. No adverse events were reported in either trial.

The addition of dextrose to intravenous saline has not been shown to improve clinical outcomes in dehydrated children presenting to the emergency department with gastroenteritis, but the confidence intervals around the estimate of effect are wide and include the possibility of substantial benefit.