Measuring Substance-Related Disorders Using Canadian Administrative Health Databanks: Interprovincial Comparisons of Recorded Diagnostic Rates, Incidence Proportions and Mortality Rate Ratios.

CONTEXT: Assessing temporal changes in the recorded diagnostic rates, incidence proportions, and health outcomes of substance-related disorders (SRD) can inform public health policymakers in reducing harms associated with alcohol and other drugs. OBJECTIVE: To report the annual and cumulative recorded diagnostic rates and incidence proportions of SRD, as well as mortality rate ratios (MRRs) by cause of death among this group in Canada, according to their province of residence. METHODS: Analyses were performed on linked administrative health databases (AHD; physician claims, hospitalizations, and vital statistics) in five Canadian provinces (Alberta, Manitoba, Ontario, Québec, and Nova Scotia). Canadians 12 years and older and registered for their provincial healthcare coverage were included. The International Classification of Diseases (ICD-9 or ICD-10 codes) was used for case identification of SRD from April 2001 to March 2018. RESULTS: During the study period, the annual recorded SRD diagnostic rates increased in Alberta (2001-2002: 8.0‰; 2017-2018: 12.8‰), Ontario (2001-2002: 11.5‰; 2017-2018: 14.4‰), and Nova Scotia (2001-2002: 6.4‰; 2017-2018: 12.7‰), but remained stable in Manitoba (2001-2002: 5.5‰; 2017-2018: 5.4‰) and Québec (2001-2002 and 2017-2018: 7.5‰). Cumulative recorded SRD diagnostic rates increased steadily for all provinces. Recorded incidence proportions increased significantly in Alberta (2001-2002: 4.5‰; 2017-2018: 5.0‰) and Nova Scotia (2001-2002: 3.3‰; 2017-2018: 3.8‰), but significantly decreased in Ontario (2001-2002: 6.2‰; 2017-2018: 4.7‰), Québec (2001-2002: 4.1‰; 2017-2018: 3.2‰) and Manitoba (2001-2002: 2.7‰; 2017-2018: 2.0‰). For almost all causes of death, a higher MRR was found among individuals with recorded SRD than in the general population. The causes of death in 2015-2016 with the highest MRR for SRD individuals were SRD, suicide, and non-suicide trauma in Alberta, Ontario, Manitoba, and Québec. DISCUSSION: Linked AHD covering almost the entire population can be useful to monitor the medical service trends of SRD and, therefore, guide health services planning in Canadian provinces.

Assessment of technical errors and validation processes in economic models submitted by the company for NICE technology appraisals.

BACKGROUND: Economic models play a central role in the decision-making process of the National Institute for Health and Care Excellence (NICE). Inadequate validation methods allow for errors to be included in economic models. These errors may alter the final recommendations and have a significant impact on outcomes for stakeholders. OBJECTIVE: To describe the patterns of technical errors found in NICE submissions and to provide an insight into the validation exercises carried out by the companies prior to submission. METHODS: All forty-one single technology appraisals (STAs) completed in 2017 by NICE were reviewed and all were on medicines. The frequency of errors and information on their type, magnitude, and impact was extracted from publicly available NICE documentation along with the details of model validation methods used. RESULTS: Two STAs (5 percent) had no reported errors, nineteen (46 percent) had between one and four errors, sixteen (39 percent) had between five and nine errors, and four (10 percent) had more than ten errors. The most common errors were transcription errors (29 percent), logic errors (29 percent), and computational errors (25 percent). All STAs went through at least one type of validation. Moreover, errors that were notable enough were reported in the final appraisal document (FAD) in eight (20 percent) of the STAs assessed but each of these eight STAs received positive recommendations. CONCLUSIONS: Technical errors are common in the economic models submitted to NICE. Some errors were considered important enough to be reported in the FAD. Improvements are needed in the model development process to ensure technical errors are kept to a minimum.

Alternatives to custodial remand for women in the criminal justice system: A multi-sector approach.

Throughout the world, women involved in criminal justice systems often present with substantial needs and vulnerabilities. Diverting vulnerable people away from prison is government policy in England and Wales, but full psychiatric and social assessments are expensive and hard to access. A screening and quick response initiative - alternatives to custodial remand for women (ACRW) - was implemented across three areas of London (West, South and East) to supplement existing court liaison and diversion services, to assess the feasibility of a supplementary custodial remand service as part of a women's specialist service pathway in the criminal justice system in England. Three mental health trusts and two voluntary sector providers offered this service enhancement - a screening and service link provision in three London boroughs between 2012 and 2014. We conducted a service evaluation using routinely collected service use record data. The service made 809 contacts, of whom 104 had contact on multiple occasions. Many were identified as at risk of self-harm (46%) or had histories of hospital admission for mental disorder (36%), but few were referred either to the liaison and diversion service or specialist mental health services. The largest group of referrals was to women's community services outside the health service (e.g. counselling, domestic violence or sexual abuse services). 180 women had dependent children and 22 were pregnant, increasing the urgency to find non-custodial alternatives. As well as confirming high levels of need amongst women entering the criminal justice system, this evaluation confirms the feasibility of working across sectors in this field, providing an extra layer of service that can complement existing liaison and diversion service provision. The service was responsive and most women using it were kept out of custody. Research is now required to understand the appropriateness of the referrals, the extent to which women follow them through and the impact on their mental health and desistance from offending.

Mental health in the criminal justice system: A pathways approach to service and research design.

BACKGROUND: Care pathway approaches were introduced into health care in the 1980s and have become standard international practice. They are now being introduced more specifically for health care in the criminal justice system. Care pathway delivery has the theoretical advantage of encouraging a whole-systems approach for health and social care within the criminal justice system, but how well is it supported by empirical evidence? AIMS: The aim of this study is to review the nature and extent of evidence streams supporting health care delivery within interagency pathway developments since 2000. METHOD: We used an exploratory narrative method to review the nature and extent of evidence streams supporting health care delivery within interagency pathway developments since 2000. The available literature was reviewed using a keyword search approach with three databases: PubMed, Medline, and Google Scholar. FINDINGS: Research in this field has covered police custody, courts, prisons, and the wider community, but there is little that follows the entire career through all these elements of offender placement. Main themes in the research to date, regardless of where the research was conducted, have been counting the disorder or the need, development and evaluation of screening tools, and evaluation of clinical intervention styles. Most evidence to date is simply observational, although the possibility of conducting randomised controlled trials of interventions within parts of the criminal justice system, especially prisons, is now well established. CONCLUSIONS: Access to health care while passing through the criminal justice system is essential because of the disproportionately high rates of mental disorder among offenders, and the concept of structured pathways to ensure this theoretically satisfying, but as yet empirically unsupported. Further, substantial cuts in services, generally following government economies, are largely unresearched. Considerable investment in new possibilities, driven by both pressure groups and government, tend to be informed by good will and theory rather than hard evidence and are often not evaluated even after introduction. This must change.

Exposure to Traumatic Events and the Experience of Burnout, Compassion Fatigue and Compassion Satisfaction among Prison Mental Health Staff: An Exploratory Survey.

Psychiatric morbidity is high in the prison population and prisoners with mental health problems present with complex needs. Working within the stressful prison environment and exposure to traumatic events may make prison mental health staff and correctional officers vulnerable to burnout, compassion fatigue, and reduced compassion satisfaction. This issue has not previously been explored in the prison setting. In this exploratory study, 36 mental health professionals and correctional officers were recruited from a prison in England and completed a series of questionnaires on their demographic and professional characteristics, exposure to traumatic events, support from managers and colleagues and on levels of burnout, compassion fatigue, and compassion satisfaction. Staff had high levels of exposure to traumatic events and the level of support provided by managers and colleagues was mixed. The majority of staff were not at high risk of burnout, compassion fatigue and reduced compassion satisfaction but higher levels of burnout, compassion fatigue and reduced compassion satisfaction were found to be associated with a range of factors including staff characteristics, exposure to traumatic events, and working environment. These findings should be interpreted with the small sample size and limited power in mind and larger surveys of staff working in prison mental health settings are needed to confirm these results across a wider number of sites but nonetheless this study highlights the need for providers to consider staff's exposure to traumatic events and to promote supportive working environments.

Prison Mental Health In-reach: The Effect of Open Referral Pathways.

In England and Wales, mental health in-reach teams manage high levels of mental disorder in prisons, but problems with reception screening and referral triage have been identified. As one potential solution, we examined the effect of an open referral pathway upon one in-reach team by evaluating its referrals and caseload across two time periods (in 2008 and 2011). There was a doubling of team referrals (from 101 to 203) with significantly improved identification of people with no mental health history. There was further evidence for a lowering of thresholds for referral and assessment, an approach that can be seen as helpful within a system that is known to under-identify mental health problems. Despite limitations, this evaluation offers some evidence for the effectiveness of open referral systems. It also raises questions about the potential effects of liaison and diversion services that are presently being piloted for national introduction.

Key successes and challenges in providing mental health care in an urban male remand prison: a qualitative study.

PURPOSE: This study aimed to describe the workings of an urban male remand prison mental health service exploring the key challenges and successes, levels of integration and collaboration with other services. METHOD: A purposive sampling was used to recruit key prison and healthcare professionals for in-depth interviews. A thematic analysis was used to analyse transcripts based on an initial coding frame of several predefined themes. Other key themes were also identified. RESULTS: Twenty-eight interviews were conducted. Prisoners referred to the service had complex, sometimes acute mental illness requiring specialist assessment and treatment. Key successes of the in-reach service included the introduction of an open referral system, locating a mental health nurse at reception to screen all new prisoners and a zoning system to prioritise urgent or non-urgent cases. Achieving an integrated system of healthcare was challenging because of the numerous internal and external services operating across the prison, a highly transient population, limited time and space to deliver services and difficulties with providing inpatient care (e.g., establishing the criteria for admission and managing patient flow). Collaborative working between prison and healthcare staff was required to enable best care for prisoners. CONCLUSIONS: The prison mental health in-reach service worked well in assessing and prioritising those who required specialist mental health care. Although the challenges of working within the prison context limited what the in-reach team could achieve. Further work was needed to improve the unit environment and how best to target and deliver inpatient care within the prison.

Anti-stigma interventions in low-income and middle-income countries: a systematic review.

Background: Stigma exacerbates power imbalances and societal disparities, significantly impacting diverse identities and health conditions, particularly for low and middle-income countries (LMICs). Though crucial for dismantling harmful stereotypes, and enhancing healthcare utilisation, existing research on anti-stigma interventions is limited with its condition-focused approach. We aimed to thoroughly evaluate peer-reviewed and non-peer-reviewed literature for a comprehensive review of anti-stigma interventions for diverse identities and all health conditions in LMICs. Methods: This review systematically explored peer-reviewed and non-peer-reviewed literature, in ten electronic databases up to January 30, 2024, covering all anti-stigma interventions across various stigmatised identities and health conditions in LMICs. Quality assessment for this systematic review was conducted as per Cochrane Collaboration's suggested inclusions. The review was registered with PROSPERO (Registration: 2017 CRD42017064283). Findings: Systematic synthesis of the 192 included studies highlights regional imbalances, while providing valuable insights on robustness and reliability of anti-stigma research. Most studies used quasi-experimental design, and most centred on HIV/AIDS or mental health related stigma, with very little work on other issues. Certain high-population LMICs had no/little representation. Interpretation: The interventions targeted diverse segments of populations and consequently yielded a multitude of stigma-related outcomes. However, despite the heterogeneity of studies, most reported positive outcomes underscoring the effectiveness of existing interventions to reduce stigma. Funding: This study is supported by the UK Medical Research Council Indigo Partnership (MR/R023697/1) award.

A non-randomised controlled trial of the R&R2MHP cognitive skills program in high risk male offenders with severe mental illness.

BACKGROUND: The growing popularity of offending behavior programs has led to the interest of whether such programs are effective with mentally disordered offenders. This study aimed to evaluate the effectiveness of the Reasoning and Rehabilitation program adapted for offenders with severe mental illness (R&R2 MHP). METHODS: A sample of 59 adult high risk males detained in a high secure hospital completed questionnaires at baseline and post treatment to assess violent attitudes, anger, coping processes and social problem-solving. An informant measure of social and psychological functioning, including disruptive behavior, was completed by staff at the same time. The data of 30 patients who participated in the group condition were compared using intention to treat analysis with 29 controls who received treatment as usual. RESULTS: 80% of group participants completed the program. In contrast to controls, significant medium-large treatment effects were found at outcome on self-reported measures of violent attitudes, social problem-solving and coping processes. Improvements were endorsed by informant ratings of disruptive behavior, social and psychological functioning. CONCLUSIONS: The R&R2MHP had a comparatively low dropout rate and was effective in a sample of high risk mentally disordered offenders requiring detention in high security. Future research should use a randomized controlled design. TRIAL REGISTRATION: Current Controlled Trials ACTRN12613000216718.

Diagnostics and treatments of COVID-19: two-year update to a living systematic review of economic evaluations.

Objectives: As the initial crisis of the COVID-19 pandemic recedes, healthcare decision makers are likely to want to make rational evidence-guided choices between the many interventions now available. We sought to update a systematic review to provide an up-to-date summary of the cost-effectiveness evidence regarding tests for SARS-CoV-2 and treatments for COVID-19. Methods: Key databases, including MEDLINE, EconLit and Embase, were searched on 3 July 2023, 2 years on from the first iteration of this review in July 2021. We also examined health technology assessment (HTA) reports and the citations of included studies and reviews. Peer-reviewed studies reporting full health economic evaluations of tests or treatments in English were included. Studies were quality assessed using an established checklist, and those with very serious limitations were excluded. Data from included studies were extracted into predefined tables. Results: The database search identified 8,287 unique records, of which 54 full texts were reviewed, 28 proceeded for quality assessment, and 15 were included. Three further studies were included through HTA sources and citation checking. Of the 18 studies ultimately included, 17 evaluated treatments including corticosteroids, antivirals and immunotherapies. In most studies, the comparator was standard care. Two studies in lower-income settings evaluated the cost effectiveness of rapid antigen tests and critical care provision. There were 17 modelling analyses and 1 trial-based evaluation. Conclusion: A large number of economic evaluations of interventions for COVID-19 have been published since July 2021. Their findings can help decision makers to prioritise between competing interventions, such as the repurposed antivirals and immunotherapies now available to treat COVID-19. However, some evidence gaps remain present, including head-to-head analyses, disease-specific utility values, and consideration of different disease variants. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021272219], identifier [PROSPERO 2021 CRD42021272219].

Evaluation of parent and youth experiences in advisory groups as part of a mental healthcare clinical trial: protocol for a mixed-method study.

INTRODUCTION: Patient engagement in healthcare research is a necessity to ensure that research objectives align with priorities, outcomes and needs of the population under study, and to facilitate ease of implementation and adoption of findings. In clinical trials, there is an increasing focus on patient engagement during the planning and conduct of clinical trials due to the potential for ethical and methodological benefits. As patient engagement in clinical trials increases, there is a need to evaluate the approaches of these activities to contribute evidence on what is most appropriate and successful. The purpose of this study is to evaluate patient engagement processes and the activities of patient partners during and after a paediatric mental healthcare trial. METHODS AND ANALYSIS: Using a mixed-methods study design, we will evaluate patient partners' engagement activities across set time-points during the trial and after trial completion. In this study, the term 'patient partner' is inclusive of two groups of people with lived experience: (1) caregivers (parents, formal/informal caregivers and family), and (2) youth (aged 15-24 years). Engagement will be evaluated using the participant and project questionnaires of the Public and Patient Engagement Evaluation Tool (PPEET), followed sequentially by semi-structured interviews. Quantitative data from the PPEET questionnaire will be analysed and reported using descriptive statistics. Data from open-ended questions from the PPEET questionnaires and semi-structured interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Approval from Athabasca University Research Ethics Board will be obtained for this project. Findings will be disseminated at both academic and public venues whether in-person or online, and using platforms that are caregiver and youth friendly. TRIAL REGISTRATION NUMBER: NCT04902391.

Frailty inclusive care in acute and community-based settings: a systematic review protocol.

BACKGROUND: Frailty is a known risk factor for an array of adverse outcomes including more frequent and prolonged health services use and high health care costs. Aging of the population has implications for care provision across the care continuum, particularly for people living with frailty. Despite known risks associated with frailty, there has been limited research on care pathways that address the needs of persons living with frailty. Our study aims to review and examine, in a rigorous way, the quality of evidence for multi-component interventions and care pathways focused on frailty. METHODS: A comprehensive electronic search strategy will be used to identify studies that evaluate multi-component interventions or care pathways for persons living with frailty. The search strategy will include terms for frailty, multi-component interventions, effectiveness, and cost effectiveness applied to the following databases: MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews. An adapted search for Google Scholar and gray literature databases will also be used. References of included studies will be hand-searched for additional citations of frailty-inclusive care. Known experts and corresponding authors of identified articles will be contacted by email to identify further eligible studies. Risk of bias will be assessed using the Effective Public Health Practice Project Quality Assessment tool. Data will be extracted from eligible studies and it is anticipated that narrative analysis will be used. If studies with sufficient homogeneity are found, then pooled effects will be reported using meta-analysis. DISCUSSION: This review will appraise the evidence currently available on multi-component frailty interventions. Results will inform on clinical pathway development for people living with frailty across the care continuum and will guide future research to address gaps in the literature and areas in need of further development. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020166733.

Vasodilator Myocardial Perfusion Cardiac Magnetic Resonance Imaging Is Superior to Dobutamine Stress Echocardiography in the Detection of Relevant Coronary Artery Stenosis: A Systematic Review and Meta-Analysis on Their Diagnostic Accuracy.

Objectives: Guideline recommendations for patients with either a high or a low risk of obstructive coronary artery disease (CAD) are clear. However, the evidence for initial risk stratification in patients with an intermediate risk of CAD is still unclear, despite the availability of multiple non-invasive assessment strategies. The aim of this study was to synthesize the evidence for this population to provide more informed recommendations. Background: A meta-analysis was performed to systematically assess the diagnostic accuracy of vasodilator myocardial perfusion cardiovascular magnetic resonance imaging (pCMR) and dobutamine stress echocardiography (DSE) for the detection of relevant CAD. In contrast to previous work, this meta-analysis follows rigorous selection criteria in regards to the risk stratification and a narrowly prespecified definition of their invasive reference tests, resulting in unprecedentedly informative results for this reference group. Data Collection and Analysis: From the 5,634 studies identified, 1,306 relevant articles were selected after title screening and further abstract screening left 865 studies for full-text review. Of these, 47 studies fulfilled all inclusion criteria resulting in a total sample size of 4,742 patients. Results: pCMR studies showed a superior sensitivity [0.88 (95% confidence interval (CI): 0.85-0.90) vs. 0.72 (95% CI: 0.61-0.81)], diagnostic odds ratio (DOR) [38 (95% CI: 29-49) vs. 20 (95% CI: 9-46)] and an augmented post-test probability [negative likelihood ratio (LR) of 0.14 (95% CI: 0.12-0.18) vs. 0.31 (95% CI: 0.21, 0.46)] as compared to DSE. Specificity was statistically indifferent [0.84 (95% CI: 0.81-0.87) vs. 0.89 (95% CI: 0.83-0.93)]. Conclusion: The results of this systematic review and meta-analysis suggest that pCMR has a superior diagnostic test accuracy for relevant CAD compared to DSE. In patients with intermediate risk of CAD only pCMR can reliably rule out relevant stenosis. In this risk cohort, pCMR can be offered for initial risk stratification and guidance of further invasive treatment as it also rules in relevant CAD.

A novel preference-informed complementary trial (PICT) design for clinical trial research influenced by strong patient preferences.

BACKGROUND: Patients and their families often have preferences for medical care that relate to wider considerations beyond the clinical effectiveness of the proposed interventions. Traditionally, these preferences have not been adequately considered in research. Research questions where patients and families have strong preferences may not be appropriate for traditional randomized controlled trials (RCTs) due to threats to internal and external validity, as there may be high levels of drop-out and non-adherence or recruitment of a sample that is not representative of the treatment population. Several preference-informed designs have been developed to address problems with traditional RCTs, but these designs have their own limitations and may not be suitable for many research questions where strong preferences and opinions are present. METHODS: In this paper, we propose a novel and innovative preference-informed complementary trial (PICT) design which addresses key weaknesses with both traditional RCTs and available preference-informed designs. In the PICT design, complementary trials would be operated within a single study, and patients and/or families would be given the opportunity to choose between a trial with all treatment options available and a trial with treatment options that exclude the option which is subject to strong preferences. This approach would allow those with strong preferences to take part in research and would improve external validity through recruiting more representative populations and internal validity. Here we discuss the strengths and limitations of the PICT design and considerations for analysis and present a motivating example for the design based on the use of opioids for pain management for children with musculoskeletal injuries. CONCLUSIONS: PICTs provide a novel and innovative design for clinical trials with more than two arms, which can address problems with existing preference-informed trial designs and enhance the ability of researchers to reflect shared decision-making in research as well as improving the validity of trials of topics with strong preferences.

Optimizing Physician Payment Models to Address Health System Priorities: Perspectives from Specialist Physicians.

OBJECTIVE: Despite well-documented data on the mixed impact of physician payment models, there is limited evidence on how to enhance existing payment model designs. This study examines the approaches to optimizing payment models from the perspective of specialist physicians to better support patient and physician experience and other health system objectives. METHOD: Semi-structured interviews were conducted with 32 specialist physicians across Alberta, Canada. Data from the interviews were analyzed using a framework approach. RESULTS: Respondents emphasized the need to incentivize physicians with the right blend of financial and non-financial incentives, including physician wellness. Respondents also highlighted the need for physician involvement and accountability to optimize the value of physician payment models. CONCLUSION: To optimize physician payment models, it may be useful to include a blend of financial and non-financial incentives with clear accountability measures as this may better align physician practice with health system priorities.

Factors that influence specialist physician preferences for fee-for-service and salary-based payment models: A qualitative study.

Most physicians across the world are paid through fee-for-service. However, there is increased interest in alternative payment models such as salary, capitation, episode-based payment, pay-for-performance, and strategic blends of these models. Such models may be more aligned with broad health policy goals such as fiscal sustainability, delivery of high-quality care, and physician and patient well-being. Despite this, there is limited research on physicians' preferences for different models and a disproportionate focus on differences in income over other issues such as physician autonomy and purpose. Using qualitative interviews with 32 specialist physicians in Alberta, Canada, we examined factors that influence preferences for fee-for-service (FFS) and salary-based payment models. Our findings suggest that a series of factors relating to (1) physician characteristics, (2) payment model characteristics, and (3) professional interests influence preferences. Within these themes, flexibility, autonomy, and compatibility with academic roles were highlighted. To encourage physicians to select a specific payment model, the model must appeal to them in terms of income potential as well as non-monetary values. These findings can support constructive discussions about the merits of different payment models and can assist policy makers in considering the impact of payment reform.

Differences between homeless and non-homeless people in a matched sample referred for mental health reasons in police custody.

INTRODUCTION: Homelessness has risen across high-income countries in the last decade, and in the United Kingdom, there has been a drastic increase in people living on the streets. Due to these increases, policy responses from public services are required to address the needs of this group. The risk factors for homelessness and conditions that this group live in mean they are at elevated risk of both mental health problems and contact with the criminal justice system. Despite this, there is little previous research on the homeless in police custody. METHODS: Our study used a matched sample of homeless (n = 77) and non-homeless (n = 77) individuals to examine whether there were different needs across this group and whether the responses of a criminal justice mental health service differ for this group. This study is a secondary data analysis of a more extensive study. RESULTS: Homeless and non-homeless detainees referred to the mental health service were broadly similar. However, differences in some variables show that homeless detainees had higher rates and frequency of substance misuse as well as some suggestion of more acute immediate need. Onward referrals were lower for homeless people, and it is not clear why this is the case. In addition, for those referred contact with services over time was reduced compared to the non-homeless group. DISCUSSION: Our findings indicate that mental health services in police custody may need adaptations to ensure homeless individuals' higher level of need is addressed and that they receive appropriate care both during and after detention. Further quantitative and qualitative research is needed to confirm why responses differ and to assess what can be done to address this issue.

Non-steroidal or opioid analgesia use for children with musculoskeletal injuries (the No OUCH study): statistical analysis plan.

BACKGROUND: Pediatric musculoskeletal injuries cause moderate to severe pain, which should ideally be addressed upon arrival to the emergency department (ED). Despite extensive research in ED-based pediatric pain treatment, recent studies confirm that pain management in this setting remains suboptimal. The No OUCH study consist of two complementary, randomized, placebo-controlled trials that will run simultaneously for patients presenting to the ED with an acute limb injury and a self-reported pain score of at least 5/10, measured via a verbal numerical rating scale (vNRS). Caregiver/parent choice will determine whether patients are randomized to the two-arm or three-arm trial. In the two-arm trial, patients will be randomized to receive either ibuprofen alone or ibuprofen in combination with acetaminophen. In the three-arm trial, patients can also be randomized to a third arm where they would receive ibuprofen in combination with hydromorphone. This article details the statistical analysis plan for the No OUCH study and was submitted before the trial outcomes were available for analysis. METHODS/DESIGN: The primary endpoint of the No OUCH study is self-reported pain at 60 min, recorded using a vNRS. The principal safety outcome is the presence of any adverse event related to study drug administration. Secondary effectiveness endpoints include pain measurements using the Faces Pain Scale-Revised and the visual analog scale, time to effective analgesia, requirement of a rescue analgesic, missed fractures, and observed pain reduction using different definitions of successful analgesia. Secondary safety outcomes include sedation measured using the Ramsay Sedation Score and serious adverse events. Finally, the No OUCH study investigates the reasons given by the caregiver for selecting the two-arm (Non-Opioid) or three-arm (Opioid) trial, caregiver satisfaction, physician preferences for analgesics, and caregiver comfort with at-home pain management. DISCUSSION: The No OUCH study will inform the relative effectiveness of acetaminophen and hydromorphone, in combination with ibuprofen, and ibuprofen alone as analgesic agents for patients presenting to the ED with an acute musculoskeletal injury. The data from these trials will be analyzed in accordance with this statistical analysis plan. This will reduce the risk of producing data-driven results and bias in our reported outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03767933 . Registered on December 7, 2018.

A pragmatic randomized controlled trial of multi-dose oral ondansetron for pediatric gastroenteritis (the DOSE-AGE study): statistical analysis plan.

BACKGROUND: Acute gastroenteritis is a leading cause of emergency department visits and hospitalizations among children in North America. Oral-rehydration therapy is recommended for children with mild-to-moderate dehydration, but children who present with vomiting are frequently offered intravenous rehydration in the emergency department (ED). Recent studies have demonstrated that the anti-emetic ondansetron can reduce vomiting, intravenous rehydration, and hospitalization when administered in the ED to children with dehydration. However, there is little evidence of additional benefit from prescribing ondansetron beyond the initial ED dose. Moreover, repeat dosing may increase the frequency of diarrhea. Despite the lack of evidence and potential adverse side effects, many physicians across North America provide multiple doses of ondansetron to be taken following ED disposition. Thus, the Multi-Dose Oral Ondansetron for Pediatric Gastroenteritis (DOSE-AGE) trial will evaluate the effectiveness of prescribing multiple doses of ondansetron to treat acute gastroenteritis-associated vomiting. This article specifies the statistical analysis plan (SAP) for the DOSE-AGE trial and was submitted before the outcomes of the study were available for analysis. METHODS/DESIGN: The DOSE-AGE study is a phase III, 6-center, placebo-controlled, double-blind, parallel design randomized controlled trial designed to determine whether participants who are prescribed multiple doses of oral ondansetron to administer, as needed, following their ED visit have a lower incidence of experiencing moderate-to-severe gastroenteritis, as measured by the Modified Vesikari Scale score, compared with a placebo. To assess safety, the DOSE-AGE trial will investigate the frequency and maximum number of diarrheal episodes following ED disposition, and the occurrence of palpitations, pre-syncope/syncope, chest pain, arrhythmias, and serious adverse events. For the secondary outcomes, the DOSE-AGE trial will investigate the individual elements of the Modified Vesikari Scale score and caregiver satisfaction with the therapy. DISCUSSION: The DOSE-AGE trial will provide evidence on the effectiveness of multiple doses of oral ondansetron, taken as needed, following an initial ED dose in children with acute gastroenteritis-associated vomiting. The data from the DOSE-AGE trial will be analyzed using this SAP. This will reduce the risk of producing data-driven results and bias in our reported outcomes. The DOSE-AGE study was registered on ClinicalTrials.gov on February 22, 2019. TRIAL REGISTRATION: ClinicalTrials.gov NCT03851835 . Registered on 22 February 2019.