An in-depth analysis of head-on crash severity and fatalities in Ghana.

Head-on collisions are often linked to more serious injuries compared to other types of crashes, due to the intense impact they cause. In low- and middle-income countries, these collisions frequently involve high occupancy public transportation vehicles, leading to higher fatality rates per crash. Given the high risk of injury and potential for multiple casualties, this study delves into the factors influencing the outcomes of head-on crashes and the number of fatalities in Ghana. The study analyzed six years of historical head-on collision data from Ghana and developed two models to address the issue. The injury-severity analysis was performed using a random parameter multinomial logit with heterogeneity in means and variances approach and aimed to identify the factors that have a significant impact on the severity of injuries sustained in head-on collisions, while the random parameters negative binomial fatality count model was designed to examine the factors that contribute to the number of fatalities in these crashes in the country. Results showed that head-on collisions with drivers over 65, buses, motorcycles, and those between 25 and 65 years of age were more likely to result in fatalities. Speeding and vehicle malfunctions were also found to be significant contributing factors to fatal head-on collisions. Head-on crashes involving minibuses and incidents where the driver was attempting to overtake another vehicle were found to be more likely to result in a higher number of fatalities. The results of this study uncover an intriguing interaction between human-related elements and socioeconomic factors, which pose obstacles to the Government's endeavor to upgrade the major highways in the country. Additionally, the increasing need for transportation has led to the presence of vehicles on the roads that may not meet safety standards. Consequently, it is no surprise that several of the study's findings align with expectations. Nevertheless, within the specific context of Ghana, these findings furnish compelling data-driven evidence supporting the adoption and implementation of the safe systems approach as a means to tackle fatal head-on collisions in the country.

Supporting Medical Student Scholarship: A Novel Case Report Elective to Teach the Writing and Publishing Process.

PROBLEM: Successful residency placement requires medical students to pursue activities beyond formal education, including showing their commitment to the specialty. Case reports are a common publication pursued by medical students, which provide trainees with opportunities to show commitment to the specialty, broaden their clinical and scholarly knowledge, improve their ability to find and interpret literature, and gain faculty mentorship. However, case reports can be intimidating to trainees with limited exposure to medical writing and publishing. The authors describe a case report elective designed specifically for medical students. APPROACH: Since 2018, Western Michigan University Homer Stryker M.D. School of Medicine has offered a week-long medical student elective designed to teach the process of writing and publishing a case report. Students wrote a first draft of a case report during the elective. Students could pursue publication, including revisions and journal submission, after the elective. An optional, anonymous survey was sent to students who participated in the elective to evaluate their experience with the elective, motivations for taking the elective, and perceived outcomes. OUTCOMES: Between 2018 and 2021, the elective was taken by 41 second-year medical students. Five scholarship outcomes of the elective were measured, including conference presentations (35, 85% of students) and publications (20, 49% of students). Students who completed the survey (n = 26) indicated the elective was very valuable with an average score of 85 ± 15.6 (range: minimally valuable [0] to extremely valuable [100]). NEXT STEPS: Next steps for this elective will be to allocate more faculty time to this curriculum promoting both education and scholarship at the institution, and to curate a list of journals to ease the publication process. Overall, student experiences with this case report elective were positive. This report aims to provide a framework for other schools to implement similar courses for their preclinical students.

Early-stage economic analysis of research-based comprehensive genomic sequencing for advanced cancer care.

Genomic research is driving discovery for future population benefit. Limited evidence exists on immediate patient and health system impacts of research participation. This study uses real-world data and quasi-experimental matching to examine early-stage cost and health impacts of research-based genomic sequencing. British Columbia's Personalized OncoGenomics (POG) single-arm program applies whole genome and transcriptome analysis (WGTA) to characterize genomic landscapes in advanced cancers. Our cohort includes POG patients enrolled between 2014 and 2015 and 1:1 genetic algorithm-matched usual care controls. We undertake a cost consequence analysis and estimate 1-year effects of WGTA on patient management, patient survival, and health system costs reported in 2015 Canadian dollars. WGTA costs are imputed and forecast using system of equations modeling. We use Kaplan-Meier survival analysis to explore survival differences and inverse probability of censoring weighted linear regression to estimate mean 1-year survival times and costs. Non-parametric bootstrapping simulates sampling distributions and enables scenario analysis, revealing drivers of incremental costs, survival, and net monetary benefit for assumed willingness to pay thresholds. We identified 230 POG patients and 230 matched controls for cohort inclusion. The mean period cost of research-funded WGTA was $26,211 (SD: $14,191). Sequencing costs declined rapidly, with WGTA forecasts hitting $13,741 in 2021. The incremental healthcare system effect (non-research expenditures) was $5203 (95% CI: 75, 10,424) compared to usual care. No overall survival differences were observed, but outcome heterogeneity was present. POG patients receiving WGTA-informed treatment experienced incremental survival gains of 2.49 months (95% CI: 1.32, 3.64). Future cost consequences became favorable as WGTA cost drivers declined and WGTA-informed treatment rates improved to 60%. Our study demonstrates the ability of real-world data to support evaluations of only-in-research health technologies. We identify situations where precision oncology research initiatives may produce survival benefit at a cost that is within healthcare systems' willingness to pay. This economic evidence informs the early-stage healthcare impacts of precision oncology research.

Clinical and cost outcomes following genomics-informed treatment for advanced cancers.

BACKGROUND: Single-arm trials are common in precision oncology. Owing to the lack of randomized counterfactual, resultant data are not amenable to comparative outcomes analyses. Difference-in-difference (DID) methods present an opportunity to generate causal estimates of time-varying treatment outcomes. Using DID, our study estimates within-cohort effects of genomics-informed treatment versus standard care on clinical and cost outcomes. METHODS: We focus on adults with advanced cancers enrolled in the single-arm BC Cancer Personalized OncoGenomics program between 2012 and 2017. All individuals had a minimum of 1-year follow up. Logistic regression explored baseline differences across patients who received a genomics-informed treatment versus a standard care treatment after genomic sequencing. DID estimated the incremental effects of genomics-informed treatment on time to treatment discontinuation (TTD), time to next treatment (TTNT), and costs. TTD and TTNT correlate with improved response and survival. RESULTS: Our study cohort included 346 patients, of whom 140 (40%) received genomics-informed treatment after sequencing and 206 (60%) received standard care treatment. No significant differences in baseline characteristics were detected across treatment groups. DID estimated that the incremental effect of genomics-informed versus standard care treatment was 102 days (95% CI: 35, 167) on TTD, 91 days (95% CI: -9, 175) on TTNT, and CAD$91,098 (95% CI: $46,848, $176,598) on costs. Effects were most pronounced in gastrointestinal cancer patients. CONCLUSIONS: Genomics-informed treatment had a statistically significant effect on TTD compared to standard care treatment, but at increased treatment costs. Within-cohort evidence generated through this single-arm study informs the early-stage comparative effectiveness of precision oncology.

An approach to rapid characterization of DMD copy number variants for prenatal risk assessment.

Prenatal detection of structural variants of uncertain significance, including copy number variants (CNV), challenges genetic counseling, and creates ambiguity for expectant parents. In Duchenne muscular dystrophy, variant classification and phenotypic severity of CNVs are currently assessed by familial segregation, prediction of the effect on the reading frame, and precedent data. Delineation of pathogenicity by familial segregation is limited by time and suitable family members, whereas analytical tools can rapidly delineate potential consequences of variants. We identified a duplication of uncertain significance encompassing a portion of the dystrophin gene (DMD) in an unaffected mother and her male fetus. Using long-read whole genome sequencing and alignment of short reads, we rapidly defined the precise breakpoints of this variant in DMD and could provide timely counseling. The benign nature of the variant was substantiated, more slowly, by familial segregation to a healthy maternal uncle. We find long-read whole genome sequencing of clinical utility in a prenatal setting for accurate and rapid characterization of structural variants, specifically a duplication involving DMD.

Comparing cost of intravenous infusion and subcutaneous biologics in COVID-19 pandemic care pathways for rheumatoid arthritis and inflammatory bowel disease: A brief UK stakeholder survey.

OBJECTIVES: One important group of people at higher risk from the SARS-CoV-2(COVID-19) pandemic are those with autoimmune conditions including rheumatoid arthritis/inflammatory bowel disease. To minimise infection risk, many people have been switched from intravenous to subcutaneous biologics including biosimilars. DESIGN: The survey was designed to understand comparative economic issues related to the intravenous infusion vs subcutaneous biologic administration routes for infliximab. The survey focused on direct cost drivers/indirect cost drivers. Acquisition costs of medicines were not included due to data not being available publicly. Wider policy implications linked to the pandemic were also explored. SETTING/PARTICIPANTS: Semistructured single telephone interviews were carried out with twenty key stakeholders across the National Health Service(NHS) from 35 clinical/42 pharmacy/28 commissioning roles. The interviews were undertaken virtually during April 2020. From interview (n = 20) results, a simple cost analysis was developed plus a qualitative analysis of reports on wider policy/patient impacts. RESULTS: Key findings included evidence of significant variation in local infusion tariffs UK wide, with interviewees reporting that not all actual costs incurred are captured in published tariff costs. A cost analysis showed administration costs 50% lower in the subcutaneous compared to infusion routes, with most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times/reduced risk of COVID-19 infection plus reduced patient 'out of pocket' costs. However, this was to some extent offset by increased pressure on home-care and community/primary care services. CONCLUSIONS: Switching from infusion to subcutaneous routes is currently driven by the COVID-19 pandemic in many services. A case for biologics (infusion vs subcutaneous) must be made on accurate real-world economic analysis. In an analysis of direct/indirect costs, excluding medicine acquisition costs, subcutaneous administration appears to be the more cost saving option for many patients even without the benefit of industry funded home-care. What's known One important group of people at high risk in COVID-19 pandemic are those with autoimmune conditions, including those with rheumatoid arthritis and inflammatory bowel disease. Depending on the complexity of their condition, some of the patients in this group may be receiving intravenous biologic infusion therapy which under normal circumstances is administered within a hospital or day hospital setting. The National Institute for Health and Care Excellence has published new guidance to ensure that patients having intravenous treatment are assessed for possible switching to the same treatment in subcutaneous form. What's new A cost analysis showed that administration costs for subcutananous routes are 50% lower than for infusion routes, with most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times and reduced risk of COVID-19 infection, along with reduced patient costs. Cost savings were partly offset by increased pressure on home-care and community/primary care services.

A web-based, peer-supported self-management intervention to reduce distress in relatives of people with psychosis or bipolar disorder: the REACT RCT.

BACKGROUND: Relatives caring for people with severe mental health problems find information and emotional support hard to access. Online support for self-management offers a potential solution. OBJECTIVE: The objective was to determine the clinical effectiveness and cost-effectiveness of an online supported self-management tool for relatives: the Relatives' Education And Coping Toolkit (REACT). DESIGN AND SETTING: This was a primarily online (UK), single-blind, randomised controlled trial, comparing REACT plus a resource directory and treatment as usual with the resource directory and treatment as usual only, by measuring user distress and other well-being measures at baseline and at 12 and 24 weeks. PARTICIPANTS: A total of 800 relatives of people with severe mental health problems across the UK took part; relatives who were aged ≥ 16 years, were experiencing high levels of distress, had access to the internet and were actively seeking help were recruited. INTERVENTION: REACT comprised 12 psychoeducation modules, peer support through a group forum, confidential messaging and a comprehensive resource directory of national support. Trained relatives moderated the forum and responded to messages. MAIN OUTCOME MEASURE: The main outcome was the level of participants' distress, as measured by the General Health Questionnaire-28 items. RESULTS: Various online and offline strategies, including social media, directed potential participants to the website. Participants were randomised to one of two arms: REACT plus the resource directory (n = 399) or the resource directory only (n = 401). Retention at 24 weeks was 75% (REACT arm, n = 292; resource directory-only arm, n = 307). The mean scores for the General Health Questionnaire-28 items reduced substantially across both arms over 24 weeks, from 40.2 (standard deviation 14.3) to 30.5 (standard deviation 15.6), with no significant difference between arms (mean difference -1.39, 95% confidence interval -3.60 to 0.83; p = 0.22). At 12 weeks, the General Health Questionnaire-28 items scores were lower in the REACT arm than in the resource directory-only arm (-2.08, 95% confidence interval -4.14 to -0.03; p = 0.027), but this finding is likely to be of limited clinical significance. Accounting for missing data, which were associated with higher distress in the REACT arm (0.33, 95% confidence interval -0.27 to 0.93; p = 0.279), in a longitudinal model, there was no significant difference between arms over 24 weeks (-0.56, 95% confidence interval -2.34 to 1.22; p = 0.51). REACT cost £142.95 per participant to design and deliver (£62.27 for delivery only), compared with £0.84 for the resource directory only. A health economic analysis of NHS, health and Personal Social Services outcomes found that REACT has higher costs (£286.77), slightly better General Health Questionnaire-28 items scores (incremental General Health Questionnaire-28 items score adjusted for baseline, age and gender: -1.152, 95% confidence interval -3.370 to 1.065) and slightly lower quality-adjusted life-year gains than the resource directory only; none of these differences was statistically significant. The median time spent online was 50.8 minutes (interquartile range 12.4-172.1 minutes) for REACT, with no significant association with outcome. Participants reported finding REACT a safe, confidential environment (96%) and reported feeling supported by the forum (89%) and the REACT supporters (86%). No serious adverse events were reported. LIMITATIONS: The sample comprised predominantly white British females, 25% of participants were lost to follow-up and dropout in the REACT arm was not random. CONCLUSIONS: An online self-management support toolkit with a moderated group forum is acceptable to relatives and, compared with face-to-face programmes, offers inexpensive, safe delivery of National Institute for Health and Care Excellence-recommended support to engage relatives as peers in care delivery. However, currently, REACT plus the resource directory is no more effective at reducing relatives' distress than the resource directory only. FUTURE WORK: Further research in improving the effectiveness of online carer support interventions is required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72019945. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 32. See the NIHR Journals Library website for further project information.

Relatives of people with severe mental health problems need better access to information and emotional support. The Relatives' Education And Coping Toolkit (REACT) is a website designed to do this. It includes lots of information presented in text and video, an online forum for relatives to share knowledge and experience, a messaging system where they can ask questions in confidence and a comprehensive directory of contact details for national organisations offering relevant support. Trained relatives support the forum and messaging. In the UK, we recruited 800 relatives of people with severe mental health problems: all were aged ≥ 16 years, had high levels of distress, had access to the internet and wanted help. We divided them into two equal groups: one group received REACT (including the resource directory), whereas the other group received the resource directory only. To ensure that there were no differences between groups at the start, relatives were allocated to the two groups randomly, so they had an equal chance of being in either group. We followed up with both groups at 12 and 24 weeks, and received data from approximately three-quarters of the participants. This trial found that REACT was acceptable, safe and inexpensive to deliver (£62.27 per relative), compared with face-to-face interventions, and that relatives using it felt well supported. However, once we accounted for missing data (relatives who dropped out of the trial or did not complete the follow-up questionnaires), there were no significant differences between the groups. There was no evidence that REACT increased relatives' quality of life or saved money for the NHS.

An internet-delivered self-management programme for bipolar disorder in mental health services in Ireland: Results and learnings from a feasibility trial.

Bipolar disorder (BD) is a chronic condition that requires continued care. Psychological interventions are recommended by clinical guidelines but there are treatment barriers that prevent patients to access these services. Internet-delivered self-management interventions are promising alternatives to improve treatment accessibility in patients with BD. Several studies indicate that these interventions are acceptable and beneficial for patients with BD, but no studies have been conducted in routine care settings. This trial aimed to examine the feasibility, acceptability, and preliminary efficacy of implementing an internet-delivered, clinician-supported intervention for BD as an adjunct to treatment as usual at two secondary-care services in Ireland. This study used an uncontrolled design with mixed-methods evaluation. Feasibility and acceptability were assessed in terms of recruitment, use of the intervention, and satisfaction from both clinicians and patients' perspectives. Personal recovery, quality of life, and severity of symptoms were measured at baseline and post-intervention. Fifteen patients signed consent and used the programme for 10 weeks. Usage of the intervention was adequate with high frequency of tool usage. There was a significant improvement in patients' sense of personal recovery (z = 2.38, p = .017). The intervention was found acceptable and easy-to-use; however, implementation barriers will need to be overcome for scaling the intervention. This is the first study testing the feasibility of a digital intervention for patients with BD in public mental health services in Ireland. More research is needed in order to increase the understanding of how to promote the integration and the uptake of digital interventions for individuals with BD.

National survey and analysis of barriers to the utilisation of the 2005 mental capacity act by people with bipolar disorder in England and Wales.

Background: The Mental Capacity Act (2005) (MCA) provides a legal framework for advance planning for both health and welfare in England and Wales for people if they lose mental capacity, for example, through mania or severe depression.Aims: To determine the proportion of people with bipolar disorder (BD) who utilise advance planning, their experience of using it and barriers to its implementation.Methods: National survey of people with clinical diagnosis of BD of their knowledge, use and experience of the MCA. Thematically analysed qualitative interviews with maximum variance sample of people with BD.Results: A total of 544 respondents with BD participated in the survey; 18 in the qualitative study. 403 (74.1%) believed making plans about their personal welfare if they lost capacity to be very important. A total of 199 (36.6%) participants knew about the MCA. A total 54 (10%), 62 (11%) and 21 (4%) participants made advanced decisions to refuse treatment, advance statements and lasting power of attorney, respectively. Barriers included not understanding its different forms, unrealistic expectations and advance plans ignored by services.Conclusion: In BD, the demand for advance plans about welfare with loss of capacity was high, but utilisation of the MCA was low with barriers at service user, clinician and organisation levels.

Qualitative investigation of relatives' and service users' experience of mental healthcare for suicidal behaviour in bipolar disorder.

OBJECTIVE: People with bipolar disorder are known to be at high risk of engaging in suicidal behaviours, and those who die by suicide have often been in recent contact with mental health services. The objective of this study was to explore suicidal behaviour in bipolar disorder and how this is monitored and managed by mental health services. AIMS: To identify themes within relatives' and service users' accounts of mental healthcare, related to management and prevention of suicidal behaviour in bipolar disorder. DESIGN: Thematic analysis of 22 semistructured interviews. PARTICIPANTS: Participants were aged 18 years or over, fluent in written and spoken English, and either had bipolar disorder with a history of suicidal behaviour, or were relatives of people with bipolar disorder who had died by suicide. SETTING: England, UK. PRIMARY OUTCOME: Themes identified from participants' accounts of mental healthcare for suicidal behaviours in bipolar disorder. RESULTS: Two main themes were identified. 'Access to care' was characterised by a series or cycle of potential barriers to care (eg, gate-keepers, lack of an accurate diagnosis) which had the potential to increase risk of suicidal behaviour if failure to access care continued over time. 'Problems with communication' captured the importance of maintaining open routes of communication between all parties involved in care to ensure successful monitoring and management of suicidal behaviours in bipolar disorder. CONCLUSIONS: Mental health services need to be accessible and respond rapidly to people with suicidal behaviour in bipolar disorder. Open communication and inclusion of relatives in care, where appropriate, could help closer monitoring of changes in symptoms that indicate increased risk.

Impact of improved low-density lipoprotein cholesterol assessment on guideline classification in the modern treatment era-Results from a racially diverse Brazilian cross-sectional study.

BACKGROUND: The Martin/Hopkins low-density lipoprotein cholesterol equation (LDL-CN) was previously demonstrated as more accurate than Friedewald LDL-C estimation (LDL-CF) in a North American database not able to take race into account. OBJECTIVES: We hypothesized that LDL-CN would be more accurate than LDL-CF and correlate better with LDL particle number (LDL-P) in a racially diverse Brazilian cohort. METHODS: We performed a cross-sectional analysis of 4897 participants in the Brazilian Longitudinal Study of Adult Health, assessing LDL-CF and LDL-CN accuracy via overlap with ultracentrifugation-based measurement among clinical guideline LDL-C categories as well as mg/dL and percent error differences. We analyzed by triglyceride categories and correlated LDL-C estimation with LDL-P. RESULTS: LDL-CN demonstrated improved accuracy at 70 to <100 and <70 mg/dL (P < .001), with large errors ≥20 mg/dL about 9 times more frequent in LDL-CF at LDL-C <70 mg/dL, mainly due to underestimation. Among individuals with LDL-C <70 mg/dL and triglycerides ≥150 mg/dL, 65% vs 100% of ultracentrifugation-based low-density lipoprotein cholesterol calculation fell within appropriate categories of estimated LDL-CF and LDL-CN, respectively (P < .001). Similar results were observed when analyzed for age, sex, and race. Participants at LDL-C <70 and 70 to <100 mg/dL with discordantly elevated LDL-CN vs LDL-CF had a 58.5% and 41.5% higher LDL-P than those with concordance (P < .0001), respectively. CONCLUSIONS: In a diverse Brazilian cohort, LDL-CN was more accurate than LDL-CF at low LDL-C and high triglycerides. LDL-CN may avoid underestimation of LDL-C and better reflect atherogenic lipid burden in low particle size, high particle count states.

Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study.

Aims: Relatively little is known about the health outcomes associated with very low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) mainly because of the small numbers of individuals with such extreme values included in clinical trials. We, therefore, investigated the association between low and very low HDL-C concentration at baseline and incident all-cause-mortality, death from malignant disease (i.e. cancer), and with fatal or non-fatal incident coronary heart disease (CHD) in individuals from the Reasons for Geographical And Racial Differences in Stroke (REGARDS) study. Methods and results: Analysis was based on 21 751 participants from the REGARDS study who were free of CHD, other cardiovascular disease, and cancer at baseline and were categorized by baseline HDL-C into <30 mg/dL (very low), 30-<40 mg/dL (low), and ≥40 mg/dL (reference). A series of incremental Cox proportional hazards models were employed to assess the association between the HDL-C categories and outcomes. Statistical analysis was performed using both complete case methods and multiple imputations with chained equations. After adjustment for age, race, and sex, the hazard ratios (HRs) comparing the lowest and highest HDL-C categories were 1.48 [95% confidence interval (CI) 1.28-1.73] for all-cause mortality, 1.35 (95% CI 1.03-1.77) for cancer-specific mortality and 1.39 (95% CI 0.99-1.96) for incident CHD. These associations became non-significant in models adjusting for demographics, cardiovascular risk factors, and treatment for dyslipidaemia. We found evidence for an HDL paradox, whereby low HDL (30-<40 mg/dL) was associated with reduced risk of incident CHD in black participants in a fully adjusted complete case model (HR 0.63; 95% CI 0.46-0.88) and after multiple imputation analyses (HR 0.76; 95% CI 0.58-0.98). HDL-C (<30 mg/dL) was significantly associated with poorer outcomes in women for all outcomes, especially with respect to cancer mortality (HR 2.31; 95% CI 1.28-4.16) in a fully adjusted complete case model, replicated using multiple imputation (HR 1.81; 95% CI 1.03-3.20). Conclusion: Low HDL-C was associated with reduced risk of incident CHD in black participants suggesting a potential HDL paradox for incident CHD. Very low HDL-C in women was significantly associated with cancer mortality in a fully adjusted complete case model.

The clinical and cost effectiveness of adapted dialectical behaviour therapy (DBT) for bipolar mood instability in primary care (ThrIVe-B programme): a feasibility study.

BACKGROUND: In bipolar spectrum disorder, some individuals experience ongoing, frequent fluctuations in mood outside of affective episodes. There are currently no evidence-based psychological interventions designed to address this. This feasibility study is a phase II evaluation of a dialectical behavioural therapy-informed approach (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). It seeks to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. METHODS/DESIGN: Patients will be randomised 1:1 to either treatment as usual only (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points will be at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point for the candidate primary outcome measures. We aim to recruit 48 individuals meeting diagnostic criteria for a bipolar spectrum disorder and reporting frequent mood swings outside of acute episodes, through primary and secondary care services and self-referral. To evaluate feasibility and acceptability, we will examine recruitment and retention rates, completion rates for study measures and feedback from participants on their experience of study participation and therapy. DISCUSSION: Proceeding to a definitive trial will be indicated if the following criteria are met: (1) trial participation does not lead to serious negative consequences for our participants; (2) any serious concerns about the acceptability and feasibility of the trial procedures can be rectified prior to a definitive trial; (3) follow-up data at 9 months are available for at least 60% of participants; (4) at least 60% of patients in the ThrIVe-B arm complete treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN54234300 . Registered on 20 July 2017.

Web-based intervention to improve quality of life in late stage bipolar disorder (ORBIT): randomised controlled trial protocol.

BACKGROUND: The primary objective of this randomised controlled trial (RCT) is to establish the effectiveness of a novel online quality of life (QoL) intervention tailored for people with late stage (≥ 10 episodes) bipolar disorder (BD) compared with psychoeducation. Relative to early stage individuals, this late stage group may not benefit as much from existing psychosocial treatments. The intervention is a guided self-help, mindfulness based intervention (MBI) developed in consultation with consumers, designed specifically for web-based delivery, with email coaching support. METHODS/DESIGN: This international RCT will involve a comparison of the effectiveness and cost-effectiveness of two 5-week adjunctive online self-management interventions: Mindfulness for Bipolar 2.0 and an active control (Psychoeducation for Bipolar). A total of 300 participants will be recruited primarily via social media channels. Main inclusion criteria are: a diagnosis of BD (confirmed via a phone-administered structured diagnostic interview), no current mood episode, history of 10 or more mood episodes, no current psychotic features or active suicidality, under the care of a medical practitioner. Block randomisation will be used for allocation to the interventions, and participants will retain access to the program for 6 months. Evaluations will be conducted at pre- and post- treatment, and at 3- and 6- months follow-up. The primary outcome measure will be the Brief Quality of Life in Bipolar Disorder Scale (Brief QoL.BD), collected immediately post-intervention at 5 weeks (T1). Secondary measures include BD-related symptoms (mania, depression, anxiety, stress), time to first relapse, functioning, sleep quality, social rhythm stability and resource use. Measurements will be collected online and via telephone assessments at baseline (T0), 5 weeks (T1), three months (T2) and six months (T3). Candidate moderators (diagnosis, anxiety or substance comorbidities, demographics and current treatments) will be investigated as will putative therapeutic mechanisms including mindfulness, emotion regulation and self-compassion. A cost-effectiveness analysis will be conducted. Acceptability and any unwanted events (including adverse treatment reactions) will be documented and explored. DISCUSSION: This definitive trial will test the effectiveness and cost-effectiveness of a novel QoL focused, mindfulness based, online guided self-help intervention for late stage BD, and investigate its putative mechanisms of therapeutic action. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03197974 . Registered 23 June 2017.

Impact of Novel Low-Density Lipoprotein-Cholesterol Assessment on the Utility of Secondary Non-High-Density Lipoprotein-C and Apolipoprotein B Targets in Selected Worldwide Dyslipidemia Guidelines.

BACKGROUND: Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). After considering 2 LDL-C estimates that differ in accuracy, we examined: (1) how frequently non-HDL-C guideline targets could change management; and (2) the utility of apoB targets after meeting LDL-C and non-HDL-C targets. METHODS: We analyzed 2518 adults representative of the US population from the 2011 to 2012 National Health and Nutrition Examination Survey and 126 092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features, including coronary artery disease, diabetes mellitus, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-C <70 and <100 mg/dL using Friedewald estimation (LDL-CF) and a novel, more accurate method (LDL-CN). Next, we examined those not meeting non-HDL-C (<100, <130 mg/dL) and apoB (<80, <100 mg/dL) guideline targets. In those meeting dual LDL-C and non-HDL-C targets (<70 and <100 mg/dL, respectively, or <100 and <130 mg/dL, respectively), we determined the proportion of individuals who did not meet guideline apoB targets (<80 or <100 mg/dL). RESULTS: A total of 7% to 9% and 31% to 36% of individuals had LDL-C <70 and <100 mg/dL, respectively. Among those with LDL-CF<70 mg/dL, 14% to 15% had non-HDL-C ≥100 mg/dL, and 7% to 8% had apoB ≥80 mg/dL. Among those with LDL-CF<100 mg/dL, 8% to 10% had non-HDL-C ≥130 mg/dL and 2% to 3% had apoB ≥100 mg/dL. In comparison, among those with LDL-CN<70 or 100 mg/dL, only ≈2% and ≈1% of individuals, respectively, had non-HDL-C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ≈0% to 3% of individuals with LDL-CN<70 mg/dL had non-HDL-C ≥100 mg/dL or apoB ≥80 mg/dL compared with 13% to 38% and 9% to 25%, respectively, in those with LDL-CF<70 mg/dL. With LDL-CF or LDL-CN<70 mg/dL and non-HDL-C <100 mg/dL, 0% to 1% had apoB ≥80 mg/dL. Among all dual LDL-CF or LDL-CN<100 mg/dL and non-HDL-C <130 mg/dL individuals, 0% to 0.4% had apoB ≥100 mg/dL. These findings were robust to sex, fasting status, and lipid-lowering therapy status. CONCLUSIONS: After more accurately estimating LDL-C, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary artery disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.

Fasting or Non-fasting Lipids for Atherosclerotic Cardiovascular Disease Risk Assessment and Treatment?

PURPOSE OF REVIEW: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD); however, lipid testing for risk assessment and treatment surveillance has been underutilized. Several factors likely account for this, including the common practice of measuring lipid levels in the fasting state, which often necessitates that patients return for an additional visit. In this review, we evaluate potential advantages and cautions associated with measuring lipids in the non-fasting state. RECENT FINDINGS: There is similar performance with the use of either fasting or non-fasting total cholesterol and HDL cholesterol in ASCVD risk assessment. Observational studies demonstrate that in comparison to fasting levels, non-fasting triglycerides are approximately 20% higher on average, although the magnitude of difference is subject to substantial inter-patient variability. Higher triglycerides can lead to the under-estimation of low-density lipoprotein cholesterol (LDL-C) by approximately 10 mg/dL or more when calculated using the Friedewald equation. This is especially clinically relevant at low LDL-C levels, although a novel validated algorithm for LDL-C estimation largely overcomes this limitation. Non-fasting lipid assessment is reasonable in many clinical circumstances given that ASCVD risk prediction is similar using fasting or non-fasting lipid values and because LDL-C can be accurately estimated using modern methods. Allowing the option for non-fasting lipid assessment can reduce a barrier to lipid testing and can facilitate a more convenient assessment of ASCVD risk with the ultimate potential effect of reducing the global burden of ASCVD. However, certain patients such as those with severe hypertriglyceridemias or high-risk patients being treated to low LDL-C levels may still need fasting lipid panels performed for precise diagnosis and to standardize therapeutic monitoring.

Multilevel analysis of the role of human factors in regional disparities in crash outcomes.

A growing body of research has examined the disparities in road traffic safety among population groups and geographic regions. These studies reveal disparities in crash outcomes between people and regions with different socioeconomic characteristics. A critical aspect of the road traffic crash epidemic that has received limited attention is the influence of local characteristics on human elements that increase the risk of getting into a crash. This paper applies multilevel logistic regression modeling techniques to investigate the influence of driver residential factors on driver behaviors in an attempt to explain the area-based differences in the severity of road crashes across the State of Alabama. Specifically, the paper reports the effects of characteristics attributable to drivers and the geographic regions they reside on the likelihood of a crash resulting in serious injuries. Model estimation revealed that driver residence (postal code or region) accounted for about 7.3% of the variability in the probability of a driver getting into a serious injury crash, regardless of driver characteristics. The results also reveal disparities in serious injury crash rate as well as significant proportions of serious injury crashes involving no seatbelt usage, driving under influence (DUI), unemployed drivers, young drivers, distracted driving, and African American drivers among some regions. The average credit scores, average commute times, and populations of driver postal codes are shown to be significant predictors for risk of severe injury crashes. This approach to traffic crash analysis presented can serve as the foundation for evidence-based policies and also guide the implementation of targeted countermeasures.

Users' experiences of an online intervention for bipolar disorder: important lessons for design and evaluation.

BACKGROUND: The evidence base for digital interventions for physical and mental health, including severe and enduring mental health difficulties, is increasing. In a feasibility trial, web-based Enhanced Relapse Prevention (ERPonline) for bipolar disorder demonstrated high recruitment and retention rates. Relative to participants in the waitlist control group, those who received ERPonline showed increased monitoring for early warning signs of relapse and had developed more positive illness models. OBJECTIVE: To understand users' motivations and barriers for taking part in an online/telephone-based trial, and for engagement with ERPonline. METHODS: Participants from the trial who had been allocated to receive ERPonline were purposively sampled to participate in telephone-based, in-depth qualitative interviews about their experiences. Interviews (n=19) were analysed using framework analysis to identify themes relevant to study aims. FINDINGS: Participants took part due to the convenient, flexible and rewarding aspects of the trial design, as well as a desire to improve the mental health of themselves and others. Barriers included extensive assessments, practical difficulties and mood. ERPonline was was generally considered to be accessible, relevant and straightforward, but there were individual preferences regarding design, content and who it was for. Several participants reported positive changes, but there was a sense that digital interventions should not replace routine care. CONCLUSIONS: There are a number of barriers and facilitators to consider when evaluating and implementing digital interventions. Individual preferences and human contact were key factors for both trial design and engagement with an online intervention. CLINICAL IMPLICATIONS: Digital interventions should be co-produced, personalised, interactive and embedded as one component in a broader package of care. TRIAL REGISTRATION NUMBER: ISRCTN56908625; Post-results.

Protocol for an online randomised controlled trial to evaluate the clinical and cost-effectiveness of a peer-supported self-management intervention for relatives of people with psychosis or bipolar disorder: Relatives Education And Coping Toolkit (REACT).

INTRODUCTION: Despite clinical guidelines recommendations, many relatives of people with psychosis or bipolar disorder do not currently receive the support they need. Online information and support may offer a solution. METHODS AND ANALYSIS: This single-blind, parallel, online randomised controlled trial will determine clinical and cost-effectiveness of the Relatives Education And Coping Toolkit (REACT) (including an online resource directory (RD)), compared with RD only, for relatives of people with psychosis or bipolar disorder. Both groups continue to receive treatment as usual. Independent, web-based variable, block, individual randomisation will be used across 666 relatives. Primary outcome is distress at 24 weeks (measured by General Health Questionnaire; GHQ-28) compared between groups using analysis of covariance, adjusting for baseline score. Secondary clinical outcomes are carer well-being and support. Cost-effectiveness analysis will determine cost of a significant unit change (three-point reduction) in the GHQ-28. Costs include offering and supporting the intervention in the REACT arm, relevant healthcare care costs including health professional contacts, medications prescribed and time off (or ability to) work for the relative. Cost utility analysis will be calculated as the marginal cost of changes in quality-adjusted life years, based on EuroQol. We will explore relatives' beliefs, perceived coping and amount of REACT toolkit use as possible outcome mediators. We have embedded two methodological substudies in the protocol to determine the relative effectiveness of a low-value (£10) versus higher value (£20) incentive, and an unconditional versus conditional incentive, on improving follow-up rates. ETHICS AND DISSEMINATION: The trial has ethical approval from Lancaster National Research Ethics Service (NRES)Committee (15/NW/0732) and is overseen by an independent Data Monitoring and Ethics Committee and Trial Steering Committee. Protocol version 1.5 was approved on 9 January 2017. All updates to protocols are uploaded to the National Institute for Health Research (NIHR) Journals Library. A full statistical analysis plan is available at https://figshare.com/account/home#/projects/19975. Publications will be in peer-reviewed journals (open access wherever possible). Requests for access to the data at the end of the study will be reviewed and granted where appropriate by the Trial Management Group. TRIAL REGISTRATION NUMBER: ISRCTN72019945, pre-results.

Feasibility randomised controlled trial of Recovery-focused Cognitive Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA): study protocol.

INTRODUCTION: Bipolar disorder is a severe and chronic mental health problem that persists into older adulthood. The number of people living with this condition is set to rise as the UK experiences a rapid ageing of its population. To date, there has been very little research or service development with respect to psychological therapies for this group of people. METHODS AND ANALYSIS: A parallel two-arm randomised controlled trial comparing a 14-session, 6-month Recovery-focused Cognitive-Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA) plus treatment as usual (TAU) versus TAU alone. Participants will be recruited in the North-West of England via primary and secondary mental health services and through self-referral. The primary objective of the study is to evaluate the feasibility and acceptability of RfCBT-OA; therefore, a formal power calculation is not appropriate. It has been estimated that randomising 25 participants per group will be sufficient to be able to reliably determine the primary feasibility outcomes (eg, recruitment and retention rates), in line with recommendations for sample sizes for feasibility/pilot trials. Participants in both arms will complete assessments at baseline and then every 3 months, over the 12-month follow-up period. We will gain an estimate of the likely effect size of RfCBT-OA on a range of clinical outcomes and estimate parameters needed to determine the appropriate sample size for a definitive, larger trial to evaluate the effectiveness and cost-effectiveness of RfCBT-OA. Data analysis is discussed further in the Analysis section in the main paper. ETHICS AND DISSEMINATION: This protocol was approved by the UK National Health Service (NHS) Ethics Committee process (REC ref: 15/NW/0330). The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and local, participating NHS trusts. TRIAL REGISTRATION NUMBER: ISRCTN13875321; Pre-results.