Adherence with NICE guidance on lifestyle advice for people with schizophrenia: a survey

Background Substantial weight gain is common in people taking antipsychotics. NICE recommends these patients are offered physical health screening and intervention. The STEPWISE trial is currently evaluating a lifestyle education programme in addition to usual care. However, it is difficult to define what constitutes “usual care”. Aims To define “usual care” for lifestyle management in people with schizophrenia, schizoaffective disorder and first episode psychosis in STEPWISE study sites. Method Ten NHS Mental Health Trusts participated in a bespoke survey based on NICE guidance. Results Eight trusts reported offering lifestyle education programmes. Nine Trusts reported offering smoking cessation support. Reported recording of biomedical measures varied. Conclusions No consistent lifestyle education programme is currently offered across UK NHS Mental Health Trusts. The survey benchmarks ‘usual care’ for the STEPWISE study on which changes can be measured

Recruitment of older adults to three preventative lifestyle improvement studies

YesBackground: Recruiting isolated older adults to clinical trials is complex, time-consuming and difficult. Previous studies have suggested querying existing databases to identify appropriate potential participants. We aim to compare recruitment techniques (general practitioner (GP) mail-outs, community engagement and clinician referrals) used in three randomised controlled trial (RCT) studies assessing the feasibility or effectiveness of two preventative interventions in isolated older adults (the Lifestyle Matters and Putting Life In Years interventions). Methods: During the three studies (the Lifestyle Matters feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data were collected about how participants were recruited. The number of letters sent by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we qualitatively interviewed participants and intervention facilitators at 6 months post randomisation to seek their thoughts on the recruitment process. Results: Referrals were planned to be the main source of recruitment in the Lifestyle Matters feasibility study, but due to a lack of engagement from district nurses, community engagement was the main source of recruitment. District nurse referrals and community engagement were also utilised in the Lifestyle Matters and Putting Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were the main source of recruitment in both the RCTs, but of those contacted, recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters intervention questioned whether the most appropriate individuals had been recruited. Participants recommended that direct contact with health professionals would be the most beneficial way to recruit. Conclusions: Recruitment to the Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the same intervention. Direct district nurse referrals were not effective at recruiting participants. The majority of participants were recruited via GP mail-outs, which may have led to isolated individuals not being recruited to the trials. Further research is required into alternative recruitment techniques, including respondent-driven sampling plus mechanisms which will promote health care professionals to recruit vulnerable populations to research.The Lifestyle Matters RCT was funded by the Medical Research Council (grant number G1001406); Sheffield Health and Social Research Consortium; National Institute for Health Research Public Health Research programme (project number 09/ 3004/01

Tools for analysis and conditional deletion of subsets of sensory neurons [version 1; peer review: 4 approved]

Background: Somatosensation depends on primary sensory neurons of the trigeminal and dorsal root ganglia (DRG). Transcriptional profiling of mouse DRG sensory neurons has defined at least 18 distinct neuronal cell types. Using an advillin promoter, we have generated a transgenic mouse line that only expresses diphtheria toxin A (DTA) in sensory neurons in the presence of Cre recombinase. This has allowed us to ablate specific neuronal subsets within the DRG using a range of established and novel Cre lines that encompass all sets of sensory neurons. // Methods: A floxed-tdTomato-stop-DTA bacterial artificial chromosome (BAC) transgenic reporter line (AdvDTA) under the control of the mouse advillin DRG promoter was generated. The line was first validated using a Nav1.8Cre and then crossed to CGRPCreER (Calca), ThCreERT2, Tmem45bCre, Tmem233Cre, Ntng1Cre and TrkBCreER (Ntrk2) lines. Pain behavioural assays included Hargreaves’, hot plate, Randall-Selitto, cold plantar, partial sciatic nerve ligation and formalin tests. // Results: Motor activity, as assessed by the rotarod test, was normal for all lines tested. Noxious mechanosensation was significantly reduced when either Nav1.8 positive neurons or Tmem45b positive neurons were ablated whilst acute heat pain was unaffected. In contrast, noxious mechanosensation was normal following ablation of CGRP-positive neurons but acute heat pain thresholds were significantly elevated and a reduction in nocifensive responses was observed in the second phase of the formalin test. Ablation of TrkB-positive neurons led to significant deficits in mechanical hypersensitivity in the partial sciatic nerve ligation neuropathic pain model. // Conclusions: Ablation of specific DRG neuronal subsets using the AdvDTA line will be a useful resource for further functional characterization of somatosensory processing, neuro-immune interactions and chronic pain disorders

Understanding suicidality in Pacific adolescents in New Zealand using network analysis

Introduction: Pacific adolescents in New Zealand (NZ) are three to four times more likely than NZ European adolescents to report suicide attempts and have higher rates of suicidal plans. Suicidal thoughts, plans, and attempts, termed suicidality in this study, result from a complex dynamic interplay of factors, which emerging methodologies like network analysis aim to capture. Methods: This study used cross-sectional network analysis to model the relationships between suicidality, self-harm, and individual depression symptoms, whilst conditioning on a multi-dimensional set of variables relevant to suicidality. A series of network models were fitted to data from a community sample of New Zealand-born Pacific adolescents (n = 550; 51% male; Mean age (SD) = 17 (0.35)). Results: Self-harm and the depression symptom measuring pessimism had the strongest associations with suicidality, followed by symptoms related to having a negative self-image about looks and sadness. Nonsymptom risk factors for self-harm and suicidality differed markedly. Conclusions: Depression symptoms varied widely in terms of their contribution to suicidality, highlighting the valuable information gained from analysing depression at the symptom-item level. Reducing the sources of pessimism and building self-esteem presented as potential targets for alleviating suicidality amongst Pacific adolescents in New Zealand. Suicide prevention strategies need to include risk factors for self-harm

Depression, anxiety and worry in young Pacific adults in New Zealand during the COVID-19 pandemic

Objective: To measure symptoms of anxiety, depression and hopelessness in a sample of young Pacific adults living in Auckland, New Zealand during the 2020/2021 COVID-19 pandemic and identify protective factors. Methods: Participants were 267 Pacific adults (58% female) who completed a survey online. Analyses included descriptive statistics, correlations, linear regression and symptom network analysis. Results: Around 25% of the sample scored in the range for moderate to severe anxiety and 10% for moderate to severe depression on standard measures. Almost 40% indicated that they found the first lockdown very stressful and 55% noted that some members of their family found it stressful. Only 16% worried about COVID-19 and their future quite a bit or constantly, while another 25% worried sometimes. Self-compassion and Pacific Identity had moderate, negative correlations, and Worry about COVID-19 had weak positive correlations, with anxiety, depression, hopelessness and perceived stress. Conclusion: These results suggest that, while the prevalence of depression and anxiety are quite high among this population, fostering ethnic identity and self-compassion in Pacific children and adolescents might protect against developing depression and anxiety

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Combined Effects of Rotation and Age Spreads on Extended Main-Sequence Turn Offs

The extended main-sequence turn offs (eMSTOs) of several young to intermediate age clusters are examined in the Magellanic Clouds and the Milky Way. We explore the effects of extended star formation (eSF) and a range of stellar rotation rates on the behavior of the color–magnitude diagram, paying particular attention to the MSTO. We create synthetic stellar populations based on MESA stellar models to simulate observed Hubble Space Telescope and Gaia star cluster data. We model the effect of rotation as a nonparametric distribution, allowing for maximum flexibility. In our models the slow rotators comprise the blueward, and fast rotators the redward portion of the eMSTO. We simulate data under three scenarios: nonrotating eSF, a range of rotation rates with a single age, and a combination of age and rotation effects. We find that two of the five clusters (the youngest and oldest) favor an age spread, but these also achieve the overall worst fits of all clusters. The other three clusters show comparable statistical evidence between rotation and an age spread. In all five cases, a rotation-rate distribution alone is capable of qualitatively matching the observed eMSTO structure. In future work, we aim to compare our predicted $V\sin i$ with observations in order to better constrain the physics related to stellar rotation