Search

Parental elaborative reminiscing supports young children's autobiographical memory, narrative, and socioemotional skills.This study is an adolescent follow-up of a reminiscing intervention in which 115 primary-caregiver mothers of toddlers were randomly assigned to a control group (n = 59) or to receive training in elaborative reminiscing (n = 56) for the next year.At age 15, 93 of the now-adolescents (81%) were invited to narrate a turning point in their lives and to report on their personality traits and well-being. Turning-point narratives were coded for causal coherence (connections between past events and present self) and thematic coherence (elaboration and resolutions).Adolescents whose mothers were in the intervention group told more causally coherent turning-point narratives and reported fewer emotional problems than control participants, covarying for baseline measures and personality traits.Maternal elaborative reminiscing in early childhood appears to have long-term benefits for adolescents' causal coherence in turning-point narratives and well-being.

BACKGROUND: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity.METHODS: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection.FINDINGS: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 [Relative Risk (RR) = 0.42 (95%CI: 0.34-0.52), P < 0.001], WHO outcome score >5 [RR = 0.33 (95%CI: 0.21-0.50), P < 0.001], and to have had a LOS > 3 days [RR = 0.84 (95%CI: 0.76-0.92), P < 0.001]. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity.INTERPRETATION: We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease.FUNDING: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

BACKGROUND: Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed effectiveness against other more clinically robust indices of COVID-19 severity.METHODS: A prospective single-centre test-negative design case-control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay [LOS] >3 days, WHO COVID Score >5 and supplementary oxygen FiO2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence.FINDINGS: 935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% [95% confidence interval 76.2%-87.2%] against hospitalisation following Delta infection, 63.3% [26.9-81.8%], 58.5% [24.8-77.3%], and 51.5% [16.7-72.1%] against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% [5.9-49.3%], with sensitivity analyses ranging from 28.8-72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% [20.6-76.5%], 58.8% [31.2-75.8%], and 41.5% [-0.4-66.3%], respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% [16.8-66.6%].INTERPRETATION: BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease.FUNDING: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

STEM education programs are often formulated with a "hands-on activities" focus across a wide array of topics from robotics to rockets to ecology. Traditionally, the impact of these programs is based on surveys of youth on program-specific experiences or the youths’ interest and impressions of science in general. In this manuscript, we offer a new approach to analyzing science programming design and youth participant impact. The conceptual framework discussed here concentrates on the organization and analysis of common learning activities and instructional strategies. We establish instrument validity and reliability through an analysis of validity threats and pilot study results. We conclude by using this instrument in an example analysis of a STEM education program.

Background Dysarthria after stroke is when speech intelligibility is impaired, and this occurs in half of all stroke survivors. Dysarthria often leads to social isolation, poor psychological well-being and can prevent return to work and social lives. Currently, a variety of outcome measures are used in clinical research and practice when monitoring recovery for people who have dysarthria. When research studies use different measures, it is impossible to compare results from trials and delays our understanding of effective clinical treatments. The aim of this study is to develop a core outcome set (COS) to agree what aspects of speech recovery should be measured for dysarthria after stroke (COS-Speech) in research and clinical practice. Methods The COS-Speech study will include five steps: (1) development of a long list of possible outcome domains of speech that should be measured to guide the survey; (2) recruitment to the COS-Speech study of three key stakeholder groups in the UK and Australia: stroke survivors, communication researchers and speech and language therapists/pathologists; (3) two rounds of the Delphi survey process; (4) a consensus meeting to agree the speech outcomes to be measured and a follow-up consensus meeting to match existing instruments/measures (from parallel systematic review) to the agreed COS-Speech; (5) dissemination of COS-Speech. Discussion There is currently no COS for dysarthria after stroke for research trials or clinical practice. The findings from this research study will be a minimum COS, for use in all dysarthria research studies and clinical practice looking at post-stroke recovery of speech. These findings will be widely disseminated using professional and patient networks, research and clinical forums as well as using a variety of academic papers, videos, accessible writing such as blogs and links on social media. Trial registration COS-Speech is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, October 2021 https://www.comet-initiative.org/Studies/Details/1959. In addition, “A systematic review of the psychometric properties and clinical utility of instruments measuring dysarthria after stroke” will inform the consensus meeting to match measures to COS-Speech. The protocol for the systematic reviews registered with the International Prospective Register of Systematic Reviews. PROSPERO registration number: CRD42022302998.

Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood.Cohort study.Ninety subjects with uveitis including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulointerstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy controls were enrolled, predominantly at Oregon HealthScience University. RNA-Seq data generated from peripheral, whole blood identified 19,859 unique transcripts. We analyzed gene expression pathways via Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). We validated our list of upregulated genes by comparison to a previously published study on peripheral blood gene expression among 50 subjects with diverse forms of uveitis.Both the Kyoto Encyclopedia of Genes and Genomes and GO analysis identified multiple shared pathways or GO terms with a P value of.0001. Almost all pathways related to the immune response and/or response to an infection. A total of 119 individual transcripts were upregulated by at least 1.5-fold and false discovery rate.05, and 61 were downregulated by similar criteria. Comparing mRNA from our study with a false discovery rate.05 and the prior report, we identified 10 common gene transcripts: ICAM1, IL15RA, IL15, IRF1, IL10RB, GSK3A, TYK2, MEF2A, MEF2B, and MEF2D.Many forms of uveitis share overlapping mechanisms. These data support the concept that a single therapeutic approach could benefit diverse forms of this disease.

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010–2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area. A total of 126 patients were included, with a median distance between the patient’s home and the IF center of 17.5 km (IQR 10.9–39.1; maximum 317.4 km). A total of 28 (22%) patients experienced at least one HPN-related complication, the most common being a central venous catheter (CVC) occlusion and electrolyte abnormalities. The catheter-related bloodstream infection (CRBSI) rate was 0.49/1000 catheter days. The CVC type, administration of concomitant chemotherapy via a distinct CVC lumen separate from PN, venting gastrostomy and distance between the patient’s home and the IF center were not associated with CRBSI or mechanical CVC complications. A total of 82 (65.1%) patients were readmitted while on HPN, but only 7 (8.5%) of these readmissions were HPN-related. A total of 44 (34.9%) patients died at home, 41 (32.5%) at a hospice and 41 (32.5%) in a hospital. In conclusion, this study demonstrates that a centralized approach to IF care can provide HPN to patients over a large geographical area while maintaining low HPN-related complications that are comparable to patients requiring HPN for benign conditions and low hospital readmission rates.

This protocol focuses on measuring the microscope's lateral and axial resolution, essential for reporting size measurements of near-resolution limit objects or distances between them. Here resolution is expressed as the Full Width at Half Maximum (FWHM) of a measured Point Spread Function (PSF) of sub-resolution size beads. PSF is highly related to objective quality and condition, but also depends strongly upon other parameters ranging from sample preparation to signal detection. Monitoring PSF over time will identify possible aberrations in the system (e.g., damaged, unclean objective, defective or not adapted oil, etc.). We define test sample preparation, image acquisition, and data analysis protocols for point scanning and spinning disk confocal microscopes.

AimsClinical guidelines recommend testing both germline and tumour DNA for BRCA1/2 pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour BRCA1/2 PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline BRCA1/2 PVs.MethodsAn observational study that included all tumour BRCA1/2 PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumour BRCA1/2 PVs were compared with PVs recorded in a prospectively gathered pan-cancer germline BRCA1/2 (gBRCA) testing database for the same geographical region (gBRCA1 PVs=910 and gBRCA2 PVs=922). Tumour BRCA1/2 PVs were categorised as common (≥1%), uncommon (ResultsOne hundred and thirteen tumour BRCA1/2 PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCA and somatic BRCA1/2 (sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test pBRCA PVs were detected in non-familial cases. All tumour BRCA1/2 PVs with a variant allele frequency (VAF) BRCA1/2 PVs were present (common=31, uncommon=25) in the gBRCA testing database, while 89% of somatic-tumour BRCA1/2 PVs were absent (n=39).ConclusionsWe predict the likelihood of a tumour BRCA1/2 PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality.

PURPOSE: To test the hypothesis that idiopathic uveitis can be categorized into subtypes based on gene expression from blood. DESIGN: Case control study METHODS: We applied RNA-Seq to peripheral blood from patients with uveitis associated with one of four systemic diseases, including axial spondyloarthritis (n=17), sarcoidosis (n=13), inflammatory bowel disease (n=12), tubulo-interstitial nephritis with uveitis (n=10), or idiopathic uveitis (n=38) as well as 18 healthy controls evaluated predominantly at Oregon Health & Science University. A high dimensional negative binomial regression model implemented in the edgeR R package compared each disease group against the controls. The 20 most distinctive genes for each diagnosis were extracted. Out of 80 genes, there were 75 unique genes. A classification algorithm was developed by fitting a gradient boosting tree with 5-fold cross-validation. mRNA from subjects with idiopathic uveitis was analyzed to see if any fit clinically and by gene expression pattern with one of the diagnosable entities. RESULTS: For uveitis associated with a diagnosable systemic disease, gene expression profiling achieved an overall accuracy of 85% (balanced average of sensitivity plus specificity, p-value < 0.001). Although the majority of patients with idiopathic uveitis presumably have none of these four associated systemic diseases, gene expression profiles helped to reclassify 11 of 38 subjects. CONCLUSIONS: Peripheral blood gene expression profiling is a potential adjunct in accurate differential diagnosis of the cause of uveitis. Validation of these results and characterization of the gene expression profile from additional discrete diagnoses could enhance the value of these observations.

Clinical guidelines recommend testing both germline and tumour DNA forAn observational study that included all tumourOne hundred and thirteen tumourWe predict the likelihood of a tumour

This study presents the evaluation of ability-based methods extended to keyboard generation for alternative communication in people with dexterity impairments due to motor disabilities. Our approach characterizes user-specific cursor control abilities from a multidirectional point-select task to configure letters on a virtual keyboard based on estimated time, distance, and direction of movement. These methods were evaluated in three individuals with motor disabilities against a generically optimized keyboard and the ubiquitous QWERTY keyboard. We highlight key observations relating to the heterogeneity of the manifestation of motor disabilities, perceived importance of communication technology, and quantitative improvements in communication performance when characterizing an individual's movement abilities to design personalized AAC interfaces.

The objective of this review was to synthesise studies which address the views of healthcare professionals (HCPs) towards patients with functional neurological disorder (FND).An interpretive systematised review was conducted. Seven databases were searched using a comprehensive search strategy (MEDLINE, EMBASE, AMED, CINAHL, PsychINFO, ProQuest Nursing and Allied Health, and Scopus). Qualitative studies and those using survey methods were included. An inductive approach to thematic analysis was used to identify concepts from the data and to synthesise the results.The views of 2769 HCPs were represented in 11 included articles. The overarching theme across the articles was uncertainty: about making the diagnosis of FND, about professional roles, and about optimum management. Fear was also a common theme: of saying the wrong thing, of offending patients, or of breaking the therapeutic relationship.If all HCPs felt uncertain about how to manage patients with FND and avoided them by passing them on to another discipline, then a "vicious cycle" is formed in which patients are passed from one professional to another but without receiving clear, honest information, or effective treatment. HCPs would benefit from increased training on FND and clear clinical pathways to alleviate feelings of uncertainty.Implications for rehabilitationEvidence-based or, at the very least, consensus-based multi-disciplinary care pathways for the assessment and treatment of patients with functional neurological disorder are required to improve equitability of services.Training packages for healthcare professionals need to be developed, evaluated and implemented in order to improve confidence of making and explaining the diagnosis and to reduce stigma of functional neurological disorders.Improved input for patients with functional neurological disorder is likely to occur if healthcare professionals are open, honest and use effective communication skills, both with their patients and fellow healthcare professionals.

Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics. Eras included: Period 1 (20% risk threshold for testing): between January 2007 and May 2013; Period 2 (10% risk threshold for testing): between June 2013 and October 2017 and; Period 3 (mainstream testing): between November 2017 and November 2019. A total of 1081 women underwent germline BRCA1/2 testing between January 2007 and November 2019 and 222 (20.5%) were found to have a PV. The monthly testing rate increased by 3.3-fold and 2.5-fold between Periods 1–2 and Periods 2–3, respectively. A similar incidence of germline BRCA1/2 PVs were detected in Period 2 (17.2%) and Period 3 (18.5%). Uptake of cascade testing from first-degree relatives was significantly lower in those women undergoing mainstream testing compared with those tested in regional genetics clinics (31.6% versus 47.3%, P = 0.038). Mainstream testing allows timely detection of germline BRCA1/2 status to select patients for PARP inhibitors, but shortfalls in the uptake of cascade testing in first-degree relatives requires optimisation to broaden benefits within families.

Background: Stroke causes communication impairments but we lack the real-world population-level data needed to inform inpatient and community services. Objectives: To establish prevalence of aphasia and dysarthria within inpatient stroke survivors, describe those affected, the amount of therapy they receive and their outcomes. Methods: Secondary analysis of data from the Sentinel Stroke National Audit Programme including inpatient stroke survivors after 72 hours, with completed National Institute of Health Stroke Scale data (communication items), excluding those already discharged, not conscious or with incomplete data. Results: 64% of the 88,974 stroke survivors meeting our criteria were communication impaired: 28% had both aphasia and dysarthria, 24% had dysarthria only and 12% had aphasia only. Those in the older age range and with more severe stroke were more likely to have a communication impairment and had a worse outcome than those without communication impairment. Subgroups with communication impairment received an average of 10 minutes of speech and language therapy for communication and/or dysphagia per day of stay. Conclusions: Communication impairment is common during the inpatient phase of stroke care yet average therapy provision is below the recommended levels and is likely to include dysphagia assessment and intervention. Dysarthria is reported as more prevalent than aphasia at this early stage, although this is not necessarily diagnosed by a speech and language therapist. The most common presentation is to have a combination of aphasia and dysarthria for which there is limited clinical guidance.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. Significance: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion–positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype. See related video: https://vimeo.com/438254885 See related commentary by Szulzewsky and Cimino, p. 904. This article is highlighted in the In This Issue feature, p. 890

Introduction Research with adults and older adolescents has found that people exhibiting higher narrative coherence in life stories also report higher psychological wellbeing; however, this link has not been investigated longitudinally. The current study investigated concurrent and longitudinal relationships in mid-adolescence between narrative coherence (causal and thematic coherence) of turning point narratives and psychopathology (depressive symptoms and rumination) and psychological wellbeing (life satisfaction). Hypothesis one was that in concurrent analyses, narrative coherence would be negatively associated with psychopathology and positively associated with wellbeing. Hypothesis two was that higher narrative coherence would predict lower psychopathology and greater wellbeing over time. Method A sample of 132 adolescents (ages 14–18 years) wrote a narrative about a turning point event in their life and completed psychopathology and psychological wellbeing measures twice, approximately one year apart. Results Partial correlations on concurrent data showed that only causal coherence was associated with lower psychopathology and higher wellbeing. Longitudinal regressions showed that causal coherence predicted higher wellbeing one year later. Conclusions These findings suggest that causal coherence in life stories may play a causal role in increased life satisfaction over time for adolescents. Experimental research is required to further investigate this possibility.

Background Many patients referred with a provisional diagnosis of cancer of unknown primary (pCUP) present with presumed metastatic disease to the liver. Due to the lack of definitive histological markers, intrahepatic cholangiocarcinoma (iCCA) may be overlooked. This study assessed the frequency of iCCA within a pCUP cohort. Methods A single UK cancer-center study of sequential patients referred with pCUP from January 2017 to April 2020. Baseline diagnostic imaging was reviewed independently by a radiologist and oncologist; those with radiological features of iCCA (dominant liver lesion, capsular retraction) were identified. Results Of 228 patients referred with pCUP, 72 (32%) had malignancy involving the liver. 24/72 patients had radiological features consistent with iCCA; they were predominantly female (75%) with an average age of 63 years and 63% had an ECOG PS ≤ 2. The median overall survival (OS) of the iCCA group and the remaining liver-involved CUP group were similar (OS 4.1 vs 4.4 months, p-value = 0.805). Patients, where a primary diagnosis was subsequently determined, had better OS (10.2 months, p-values: iCCA = 0.0279: cCUP = 0.0230). Conclusions In this study, 34% of patients with liver-involved pCUP, fulfilled the radiological criteria for an iCCA diagnosis. Consideration of an iCCA diagnosis in patients with CUP could improve timely diagnosis, molecular characterisation and treatment.

People with spatial neglect have difficulty attending to one side of space, which can affect their ability to carry out many everyday tasks and reduce independence. We examined the evidence for any type of nonpharmacological intervention.1MethodsWe searched for randomized controlled trials of any nonpharmacological intervention versus any control specifically aimed at spatial neglect, searching 6 databases including MEDLINE, Embase, CINAHL, and international trials registers in October 2020. Review authors independently assessed risk of bias of included trials and extracted data and assessed the quality of evidence for each outcome using the Grading of Recommendations, Assessment, Development and Evaluations approach. We categorized interventions into 8 broad types through iterative discussion. Our primary outcome was longer term functional ability in activities of daily living (ADL), that is, ≥1 month after the end of intervention.Main ResultsWe included 65 small randomized controlled trials (1951 participants); 43 provided data for meta-analyses. All included people with stroke, one included 3 participants with nonstroke brain injury, and only 7 included participants with left brain damage. All evidence is very low quality, with very low certainty. There were only 2 low risk of bias trials and no adequately powered definitive trials. None reported patient involvement in design or reporting. Outcome measurement focused on cognitive tests and short-term effects; 58 of 65 trials measured ADL using different methods and 16 measured it longer term. Other meaningful outcomes were rarely reported.Four intervention types measured our primary outcome:Visual interventions (training eye movements or scanning): 17 trials (n=398). No evidence of effect on ADL from visual interventions (2 trials, 55 participants; standardized mean difference, −0.04 [95% CI, −0.57 to 0.49]).Noninvasive brain stimulation: 17 trials (n=467). No evidence of effect on ADL from noninvasive brain stimulation (3 trials, 92 participants; standardized mean difference, 0.35 [95% CI, −0.08 to 0.77]).Body awareness (increasing awareness of affected side): 12 trials (n=447). Very low certainty evidence suggesting possible benefit on ADL from body awareness interventions (5 trials, 125 participants; standardized mean difference, 0.61 [95% CI, 0.24–0.97]).Prism adaptation training: 8 trials (n=257). No evidence of effect on ADL from prism adaptation (2 trials, 39 participants; standardized mean difference, −0.29 [95% CI, −0.93 to 0.35]).Four intervention types did not provide data on longer term ADL: electrical stimulation, 8 trials (n=270); mental function (increasing mental processing skills), 7 trials (n=170); movement (of the arm/body), 6 trials (n=220); and acupuncture, 2 trials (n=104).DiscussionDespite 65 trials (1951 participants), evidence of benefit/risk of nonpharmacological intervention to improve longer term functional ability remains very uncertain due to study quality. No rehabilitation approach can be supported or refuted over any other based on current evidence.Implications for Clinical Practice and Future ResearchNo strategy for neglect rehabilitation has been researched through fully powered randomized controlled trials. One way to improve the quality of research is by involving patients in trial design and management. Clinicians should continue to follow national clinical guidelines and are strongly encouraged to participate in trials.AcknowledgmentsThis article is based on a Cochrane Review published in The Cochrane Library 2021, Issue 7, doi: 10.1002/14651858.CD003586.pub4/full (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review. This review was supported by the Cochrane Stroke Review Group.Sources of FundingNational Institute for Health Research (NIHR) Development and Skills Enhancement Award, United Kingdom: funded Verity Longley; The Stroke Association, United Kingdom: part-funded Audrey Bowen and Christine Hazelton; NIHR NETSCC Incentive Award, United Kingdom: awarded to Audrey Bowen for the update.

BackgroundPeople with spatial neglect after stroke or other brain injury have difficulty attending to one side of space. Various rehabilitation interventions have been used, but evidence of their benefit is unclear.ObjectivesThe main objective was to determine the effects of non‐pharmacological interventions for people with spatial neglect after stroke and other adult‐acquired non‐progressive brain injury.Search methodsWe searched the Cochrane Stroke Group Trials Register (last searched October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; last searched October 2020), MEDLINE (1966 to October 2020), Embase (1980 to October 2020), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1983 to October 2020), and PsycINFO (1974 to October 2020). We also searched ongoing trials registers and screened reference lists.Selection criteriaWe included randomised controlled trials (RCTs) of any non‐pharmacological intervention specifically aimed at spatial neglect. We excluded studies of general rehabilitation and studies with mixed participant groups, unless separate neglect data were available.Data collection and analysisWe used standard Cochrane methods. Review authors categorised the interventions into eight broad types deemed to be applicable to clinical practice through iterative discussion: visual interventions, prism adaptation, body awareness interventions, mental function interventions, movement interventions, non‐invasive brain stimulation, electrical stimulation, and acupuncture. We assessed the quality of evidence for each outcome using the GRADE approach.Main resultsWe included 65 RCTs with 1951 participants, all of which included people with spatial neglect following stroke. Most studies measured outcomes using standardised neglect assessments. Fifty‐one studies measured effects on ADL immediately after completion of the intervention period; only 16 reported persisting effects on ADL (our primary outcome). One study (30 participants) reported discharge destination, and one (24 participants) reported depression. No studies reported falls, balance, or quality of life. Only two studies were judged to be entirely at low risk of bias, and all were small, with fewer than 50 participants per group. We found no definitive (phase 3) clinical trials. None of the studies reported any patient or public involvement.Visual interventions versus any control: evidence is very uncertain about the effects of visual interventions for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 55 participants) (standardised mean difference (SMD) ‐0.04, 95% confidence interval (CI) ‐0.57 to 0.49); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments.Prism adaptation versus any control: evidence is very uncertain about the effects of prism adaptation for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 39 participants) (SMD ‐0.29, 95% CI ‐0.93 to 0.35); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments.Body awareness interventions versus any control: evidence is very uncertain about the effects of body awareness interventions for spatial neglect based on measures of persisting functional ability in ADL (5 studies, 125 participants) (SMD 0.61, 95% CI 0.24 to 0.97); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events.Mental function interventions versus any control: we found no trials of mental function interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of mental function interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments.Movement interventions versus any control: we found no trials of movement interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of body awareness interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments.Non‐invasive brain stimulation (NIBS) versus any control: evidence is very uncertain about the effects of NIBS on spatial neglect based on measures of persisting functional ability in ADL (3 studies, 92 participants) (SMD 0.35, 95% CI ‐0.08 to 0.77); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events.Electrical stimulation versus any control: we found no trials of electrical stimulation for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of electrical stimulation on spatial neglect based on immediate neglect assessments.Acupuncture versus any control: we found no trials of acupuncture for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of acupuncture on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments.Authors' conclusionsThe effectiveness of non‐pharmacological interventions for spatial neglect in improving functional ability in ADL and increasing independence remains unproven. Many strategies have been proposed to aid rehabilitation of spatial neglect, but none has yet been sufficiently researched through high‐quality fully powered randomised trials to establish potential or adverse effects. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. As recommended by a number of national clinical guidelines, clinicians should continue to provide rehabilitation for neglect that enables people to meet their rehabilitation goals. Clinicians and stroke survivors should have the opportunity, and are strongly encouraged, to participate in research. Future studies need to have appropriate high‐quality methodological design, delivery, and reporting to enable appraisal and interpretation of results. Future studies also must evaluate outcomes of importance to patients, such as persisting functional ability in ADL. One way to improve the quality of research is to involve people with experience with the condition in designing and running trials.

Anterior uveitis is the most common anatomic subset of uveitis. We used fluorescence activated cell sorting to characterize T cell cytokine expression in stimulated T cell subsets from patients with HLA B27-associated acute anterior uveitis (AAU) (n=4) compared to healthy controls (n= 14) or subjects with axial spondyloarthritis (n=6). Positive findings among subjects with AAU included a statistically significant increase in stimulated granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, and IL-22 synthesized by CD8 cells, a trend for stimulated ILC (innate lymphoid cells)-3 cells to synthesize more IL-22 (p=0.07), and stimulated MAIT (mucosa associated innate lymphoid cells)-like cells that express the T cell receptor V alpha 7.2 to express IL-17A, IL-17F, and IL-22 in a greater percentage of cells relative to controls. IL-17F, GM-CSF, and IL-22 represent potentially novel targets in AAU. Our report is arguably the first to implicate IL-17F or ILC-3 and MAIT cells in the pathogenesis of AAU.

Background The purpose of this article is to describe neonatal intensive care unit clinician perceptions of a continuous predictive analytics technology and how those perceptions influenced clinician adoption. Adopting and integrating new technology into care is notoriously slow and difficult; realizing expected gains remain a challenge. Methods Semistructured interviews from a cross-section of neonatal physicians (n = 14) and nurses (n = 8) from a single U.S. medical center were collected 18 months following the conclusion of the predictive monitoring technology randomized control trial. Following qualitative descriptive analysis, innovation attributes from Diffusion of Innovation Theory-guided thematic development. Results Results suggest that the combination of physical location as well as lack of integration into work flow or methods of using data in care decisionmaking may have delayed clinicians from routinely paying attention to the data. Once data were routinely collected, documented, and reported during patient rounds and patient handoffs, clinicians came to view data as another vital sign. Through clinicians' observation of senior physicians and nurses, and ongoing dialogue about data trends and patient status, clinicians learned how to integrate these data in care decision making (e.g., differential diagnosis) and came to value the technology as beneficial to care delivery. Discussion The use of newly created predictive technologies that provide early warning of illness may require implementation strategies that acknowledge the risk–benefit of treatment clinicians must balance and take advantage of existing clinician training methods.

IntroductionPoly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic BRCA1/2 variant. Consequently, the demand for germline BRCA1/2 testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline BRCA1/2 variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification.MethodsA cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germline BRCA1/2 testing by next-generation sequencing and multiplex ligation-dependent probe amplification.ResultsFive hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenic BRCA1/2 variant. The prevalence of pathogenic BRCA1/2 variants was >10% in women diagnosed with ovarian cancer earlier than 60 years of age (21%) and those diagnosed later than 60 years of age with a family history of breast and/or ovarian cancer (17%) or a medical history of breast cancer (34%). The prevalence of pathogenic BRCA1/2 variants was also >10% in women with a Manchester BRCA Score of ≥15 points (14%).DiscussionOur study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ≥15 points are associated with a >10% prevalence of germline pathogenic BRCA1/2 variants in epithelial ovarian cancer.