Predicting first-episode psychosis patients who will never relapse over 10 years.

BACKGROUND: Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode. METHOD: Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning. RESULTS: Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders. CONCLUSIONS: Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP

A reporting tool for practice guidelines in healthcare: the RIGHT Statement

The quality of reporting of practice guidelines is often poor and there is no widely accepted guidance or standards for the reporting of practice guidelines in healthcare. An international working group (the RIGHT working group) was therefore established to address this gap. The group followed an existing framework for developing health research reporting guidelines and the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach. We developed a checklist and an explanation and elaboration document. The RIGHT checklist includes 22 items that we consider essential for good reporting of practice guidelines. These items encompass basic information (items 1-4), background (items 5-9), evidence (items 10-12), recommendations (items 13-15), review and quality assurance (items 16-17), funding and declaration and management of interests (items 18-19), and other information (items 20-22). The RIGHT checklist can assist developers when reporting their guidelines, support journal editors and peer reviewers when considering guideline reports, and help healthcare practitioners understand and implement a guideline

Experimental Inoculation of Juvenile Rhesus Macaques with Primate Enteric Caliciviruses

Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV)-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes.Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Phototherapy for treating pressure ulcers

[[abstract]]Background A pressure ulcer is defined as "an area of localized injury to the skin and/or underlying tissue, usually over a bony prominence, as a result of pressure, or pressure in combination with shear". The use of phototherapy ‐ that is, light (or laser) used as an adjuvant, non‐surgical intervention, with the aim of having a therapeutic effect on healing ‐ has increased recently. Objectives To determine the effects of phototherapy on the healing of pressure ulcers. Search methods In January 2014, we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid EMBASE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); and EBSCO CINAHL. We did not restrict the search by language or publication date. Selection criteria Randomised controlled trials (RCTs) comparing the effects of phototherapy (in addition to standard treatment) with sham phototherapy (in addition to standard treatment), another type of phototherapy (in addition to standard treatment) or standard or conventional treatment alone. Data collection and analysis Two review authors assessed studies for relevance and design according to the selection criteria, extracted data and evaluated study quality. The authors made attempts to obtain missing data by contacting study authors. Disagreement was resolved by consensus and discussion with a third review author. Main results We identified seven RCTs involving 403 participants. All the trials were at unclear risk of bias. Trials compared the use of phototherapy with standard care only (six trials) or sham phototherapy (one trial). Only one of the trials included a third arm in which another type of phototherapy was applied. Overall, there was insufficient evidence to determine the relative effects of phototherapy for healing pressure ulcers. Time to complete healing was reported in three studies. Two studies showed the ultraviolet (UV) treated group had a shorter mean time to complete healing than the control group (mean difference ‐2.13 weeks (95% CI ‐3.53 to ‐0.72, P value 0.003)). One study reported that the laser group had a longer mean time to complete healing than the control group (mean difference 5.77 weeks; 95% CI ‐0.25 to 11.79). However, this result should be interpreted with caution, as these were small studies and the findings may have been due to chance. Three studies reported proportions of ulcers healed with a variety of results. One study reported a different outcome measure, and the other two studies had different treatment durations. These variations did not allow us to pool the studies and draw any conclusions as to whether phototherapy is effective or not. Adverse effects were reported in only two studies that compared phototherapy with control; the risk ratio for adverse events was imprecise. One study reported risk ratio (RR) 0.72 (95%CI 0.18 to 2.80). However, another study reported RR 0.89 (95% CI: 0.71 to 1.12) based on the number of events in each group, rather than the number of people with events. Among five studies reporting the rate of change in ulcer area, three studies found no statistically significant difference between the two groups. Pooling was not undertaken because of differences in outcome measures reported. The results were based on data from trials with unclear risk of bias for which generation of the randomisation sequence, concealment allocation and blinding of outcome assessors were unclear. No studies reported on quality of life, length of hospital stay, pain or cost. Authors' conclusions We are very uncertain as to the effects of phototherapy in treating pressure ulcers. The quality of evidence is very low due to the unclear risk of bias and small number of trials available for analysis. The possibility of benefit or harm of this treatment cannot be ruled out. Further research is recommended

Long-term effects of discontinuation from antipsychotic maintenance following first-episode schizophrenia and related disorders: a 10 year follow-up of a randomised, double-blind trial.

BACKGROUND: The long-term consequences of discontinuing antipsychotic medication after successful treatment of first-episode psychosis are not well studied. We assess the relation between early maintenance therapy decisions in first-episode psychosis and the subsequent clinical outcome at 10 years. METHODS: This is a 10 year follow-up study, spanning Sept 5, 2003, to Dec 30, 2014, of a randomised, double-blind trial in seven centres in Hong Kong in which 178 patients with first-episode psychosis with full positive symptom resolution after at least 1 year of antipsychotic treatment were given maintenance treatment (n=89; oral quetiapine 400 mg daily) or early treatment discontinuation (n=89; placebo) for 12 months. After the trial, patients received naturalistic treatment. Overall this cohort of patients will have received about 3 years of treatment before entering the follow-up phase of the study: about 2 years of maintenance treatment before study entry and 1 year of treatment in the trial. The primary outcome of this follow-up was the proportion of patients in each group (including those for whom direct follow-up was not available) with good or poor long-term clinical outcomes at 10 years, with poor outcome defined as a composite of persistent psychotic symptoms, a requirement for clozapine treatment, or death by suicide. The randomised trial was registered with ClinicalTrials.gov, number NCT00334035, and the follow-up study was registered with ClinicalTrials.gov, number NCT01926340. FINDINGS: Poor 10 year clinical outcome occurred in 35 (39%) of 89 patients in the discontinuation group and 19 (21%) of 89 patients in the maintenance treatment group (risk ratio 1·84, 95% CI 1·15-2·96; p=0·012). Suicide was the only serious adverse event that occurred in the follow-up phase (four [4%] patients in the early discontinuation group vs two [2%] in the maintenance group). INTERPRETATION: In patients with first-episode psychosis with a full initial response to treatment, medication continuation for at least the first 3 years after starting treatment decreases the risk of relapse and poor long-term clinical outcome. FUNDING: Food and Health Bureau, Research Grants Council of Hong Kong, and AstraZeneca

Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain

Blood–brain barrier dysfunction occurs in ageing and in neurodegenerative diseases. Here, the authors use scRNA-seq to identify transcriptomic changes in endothelial cell subtypes in the aged mouse brain, some of which may generalize to human and can be reversed by treatment with a GLP-1R agonist