Barriers to uptake of the hip fracture core outcome set: an international survey of 80 hip fracture trialists.

Background: Core outcome sets are an agreed recommendation to inform the selection of outcome measures in clinical trials. There has been low uptake of the 2014 hip fracture core outcome set. The reasons for this remain unclear. The aim of this study was to understand the reasons for the non-adoption and approaches to increase adoption of the hip fracture core outcome set. Methods: Randomised controlled trials from PubMed (2017–2019) and ClinicalTrials.gov (2015–2019) were identified. Corresponding authors for each identified trial (n = 302) were surveyed using five questions on awareness of the hip fracture core outcome set, reasons for non-adoption and approaches to increase adoption. Data were analysed descriptively using frequencies, mean values and standard deviations. Results: Fifty-four percent of the respondents (n = 43) were aware of the concept of core outcome set. Only 15% (n = 12) based the outcome measure selection on the 2014 hip fracture core outcome set. Key reasons for non-adoption included the following: authors being unaware and perceived inappropriateness to their trial design. Eighty-six percent (n = 69) of respondents agreed to the need for increased awareness of core outcome sets through research training, academic and clinical journal requirements, and funding or publication stipulations. Eighty-eight percent (n = 70) of respondents indicated the current core outcome set required revision to focus on trials investigating people with cognitive impairment, caregivers, rehabilitation, surgical interventions and anaesthetic trial designs. Conclusion: Barriers to the adoption of the hip fracture core outcome set centre on education, awareness of the core outcome sets and applicability to the breath of hip fracture trial designs. Further consideration should be made to address these, to improve the harmonisation of outcome measures across hip fracture trials

Does Basic Skills Education Work? Some Evidence from the National Adult Literacy Survey

No Abstract available

F-18-FDG and C-11-choline positron emission tomography in human esophago-gastric cancer : prediction of response to therapy

Peer reviewedPublisher PD

Nonpublication in the Eleventh Circuit: An Empirical Analysis

This Article examines the criteria used by the Eleventh Circuit Court of Appeals in determining whether or not a judicial opinion should be published. Through an empirical study and analysis, the authors conclude that the written rule governing publication offers little guidance to the judges and is often applied inconsistently within the circuit

Identifying individuals with intellectual disability who access mental health support and are at high risk for adverse clinical outcomes: cohort study

BACKGROUND: People with intellectual disability often experience aggressive challenging behaviour and mental health issues. It can be difficult to identify those who are at higher risk of adverse clinical outcomes when in clinical care. AIMS: To characterise potential subgroups in adults with intellectual disability referred to mental health services in those presenting with aggressive behaviour or common mental disorders (CMDs). METHOD: There were 836 adults (≥18 years) with intellectual disability and a record of aggressive challenging behaviour, and 205 patients with intellectual disability and CMDs, who were seen in specialist mental health services over a 5-year period. Cluster analysis was used to define patient characteristics associated with clinical outcome. RESULTS: Distinct patient groups with differentiated profiles were observed in people with intellectual disability displaying aggressive challenging behaviour, and in those presenting with CMDs. Characteristics of the aggressive behaviour group who experienced adverse outcomes included being <30 years old, being male, more mentions of aggression and agitation in their clinical record, a diagnosis of pervasive developmental disorder and prescription of psychotropic medication. Characteristics of the CMD cluster that experienced adverse clinical outcomes were being older, being a White male, having a mild intellectual disability and physical health concerns. CONCLUSIONS: People with intellectual disability who experience adverse clinical outcomes can be identified with a cluster analysis approach of common features, but differ by clinical presentation. This could be used not only to stratify this clinically heterogeneous population in terms of response to interventions, but also improve precision in the development of tailored interventions

Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

Objectives:To determine the relationship between falls and deficits in specific cognitive domains in older adults.Design:An analysis of the English Longitudinal Study of Ageing (ELSA) cohort.Setting:United Kingdom community-based.Participants:5197 community-dwelling older adults recruited to a prospective longitudinal cohort study.Measurements:Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models.Results:Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls.Conclusions:The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

Objective To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design Pragmatic, parallel group, cluster randomised controlled trial. Setting 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies

Aggressive challenging behaviour in adults with intellectual disability: an electronic register-based cohort study of clinical outcome and service use

Background: Aggressive challenging behavior in people with intellectual disability is a frequent reason for referral to secondary care services and is associated with direct harm, social exclusion, and criminal sanctions. Understanding the factors underlying aggressive challenging behavior and predictors of adverse clinical outcome is important in providing services and developing effective interventions. Methods: This was a retrospective total-population cohort study using electronic records linked with Hospital Episode Statistics data. Participants were adults with intellectual disability accessing secondary services at a large mental healthcare provider in London, United Kingdom, between 2014 and 2018. An adverse outcome was defined as at least one of the following: admission to a mental health hospital, Mental Health Act assessment, contact with a psychiatric crisis team or attendance at an emergency department. Results: There were 1,515 patient episodes related to 1,225 individuals, of which 1,019 episodes were reported as displaying aggressive challenging behavior. Increased episode length, being younger, psychotropic medication use, pervasive developmental disorder (PDD), more mentions of mood instability, agitation, and irritability, more contact with mental health professionals, and more mentions of social and/or home care package in-episode were all associated with increased odds of medium-high levels of aggression. Risk factors for an adverse clinical outcome in those who exhibited aggression included increased episode length, personality disorder, common mental disorder (CMD), more mentions of agitation in-episode, and contact with mental health professionals. PDD predicted better outcome. Conclusions: Routinely collected data confirm aggressive challenging behavior as a common concern in adults with intellectual disability who are referred for specialist support and highlight factors likely to signal an adverse outcome. Treatment targets may include optimizing management of CMDs and agitation

Stabilization of GABAA Receptors at Endocytic Zones Is Mediated by an AP2 Binding Motif within the GABAA Receptor β3 Subunit

The strength of synaptic inhibition can be controlled by the stability and endocytosis of surface and synaptic GABAA receptors (GABAARs), but the surface receptor dynamics that underpin GABAAR recruitment to dendritic endocytic zones (EZs) have not been investigated. Stabilization of GABAARs at EZs is likely to be regulated by receptor interactions with the clathrin-adaptor AP2, but the molecular determinants of these associations remain poorly understood. Moreover, although surface GABAAR downmodulation plays a key role in pathological disinhibition in conditions such as ischemia and epilepsy, whether this occurs in an AP2-dependent manner also remains unclear. Here we report the characterization of a novel motif containing three arginine residues (405RRR407) within the GABAAR β3-subunit intracellular domain (ICD), responsible for the interaction with AP2 and GABAAR internalization. When this motif is disrupted, binding to AP2 is abolished in vitro and in rat brain. Using single-particle tracking, we reveal that surface β3-subunit-containing GABAARs exhibit highly confined behavior at EZs, which is dependent on AP2 interactions via this motif. Reduced stabilization of mutant GABAARs at EZs correlates with their reduced endocytosis and increased steady-state levels at synapses. By imaging wild-type or mutant super-ecliptic pHluorin-tagged GABAARs in neurons, we also show that, under conditions of oxygen–glucose deprivation to mimic cerebral ischemia, GABAARs are depleted from synapses in dendrites, depending on the 405RRR407 motif. Thus, AP2 binding to an RRR motif in the GABAAR β3-subunit ICD regulates GABAAR residency time at EZs, steady- state synaptic receptor levels, and pathological loss of GABAARs from synapses during simulated ischemia

Climatic and Biogeochemical Effects of a Galactic Gamma-Ray Burst

It is likely that one or more gamma-ray bursts within our galaxy have strongly irradiated the Earth in the last Gy. This produces significant atmospheric ionization and dissociation, resulting in ozone depletion and DNA-damaging ultraviolet solar flux reaching the surface for up to a decade. Here we show the first detailed computation of two other significant effects. Visible opacity of NO2 is sufficient to reduce solar energy at the surface up to a few percent, with the greatest effect at the poles, which may be sufficient to initiate glaciation. Rainout of dilute nitric acid is could have been important for a burst nearer than our conservative nearest burst. These results support the hypothesis that the characteristics of the late Ordovician mass extinction are consistent with GRB initiation.Comment: 12 pages, 2 figures, in press at Geophysical Research Letters. Minor revisions, including details on falsifying the hypothesi