Translated and culturally adapted internet-delivered cognitive therapy for social anxiety disorder in Japanese clinical settings: study protocol for a randomised controlled trial.

BACKGROUND: Cognitive therapy for social anxiety disorder (CT-SAD) has extensive empirical support and is recommended in several national guidelines. However, ensuring access to evidence-based psychological therapies such as CT-SAD remains a global challenge. An internet-delivered version of this treatment protocol (iCT-SAD) has recently been developed in the UK as a way to overcome this challenge, demonstrating comparable outcomes to face-to-face CT-SAD whilst requiring less therapist time per client. Initial findings also suggest its cross-cultural transferability, but the previous studies in other cultural settings used the English language programme and only included English-fluent participants as a second language. It is not yet known what outcomes can be achieved once the programme has been translated and adapted for a different cultural context. Therefore, this trial aims to evaluate the clinical efficacy of Japanese iCT-SAD when combined with treatment as usual (TAU) in clients with SAD. METHODS: This two-arm, parallel-group, superiority randomised controlled trial will recruit 60 Japanese participants with SAD, randomly assigning them to either Japanese iCT-SAD + TAU or TAU alone at a ratio of 1:1. The primary outcome measure is the self-report Liebowitz Social Anxiety Scale, and secondary.outcomes include other measures of social anxiety symptoms and processes, general mood and functioning, and response to treatment. We will also assess treatment acceptability and gather participant feedback. Assessments will take place at baseline (week 0), mid-treatment (week 8), and post-treatment (week 15), with a further 3-month follow-up (week 27) for the iCT-SAD + TAU arm. The primary analyses will be conducted on an intent-to-treat basis, comparing the primary and secondary outcome measures between groups using linear mixed-effect models, along with additional mediation analysis. DISCUSSION: Investigating the efficacy of translated and culturally adapted iCT-SAD in different cultural contexts is an important step in evaluating the global reach of internet interventions. This trial will provide valuable insights into the effects of iCT-SAD combined with usual care, and how this treatment could be delivered in routine clinical settings in Japan. TRIAL REGISTRATION: International Standard Randomized Controlled Trials (ISRCTN), ISRCTN82859645, registered on January 19, 2024. UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052702, registered on November 6, 2023.

Data wobbles in hidradenitis suppurativa clinical trials and potential contributing factors: a retrospective review.

Background: In some hidradenitis suppurativa (HS) clinical trial study arms, there is an unexpected decline in efficacy between the penultimate visit and the prespecified primary endpoint week, which we have termed a "wobble." Objective: We aimed to establish how often study arms in HS programs wobble. Methods: In a retrospective review, we identified HS clinical trials listed on ClinicalTrials.gov testing systemic, nonantibiotic medications that utilized Hidradenitis Suppurativa Clinical Response (HiSCR) as an outcome measure. We identified study arms demonstrating greater improvement in a visit prior to the primary endpoint week. Baseline subject characteristics were compared between studies with HiSCR wobble and no HiSCR wobble. Results: A total of 21 studies (randomized control trial [RCT], n = 14; open-label, n = 7) with 35 study drug arms (RCT, n = 27; open-label, n = 8) and 14 placebo arms were identified. HiSCR wobble occurred significantly more often in RCT compared to open-label study drug arms (11/27 [40.7%] vs 0/8 [0%]). In RCT study arms with HiSCR wobble, baseline draining fistula counts were significantly lower (2.3 vs 3.2), and numerically fewer Hurley stage 3 patients (33.2% vs 42.5%), lower weighted total abscess and nodule counts (12.1 vs 12.6), lower weighted dermatology life quality index scores (12.5 vs 14.5), and a higher proportion of female patients (63.9% vs 58.3%) were observed. Limitations: Include low number of HS clinical trials and insufficient data reported in many studies to assess for wobble, degree of wobble, and to compare all baseline characteristics. Conclusion: Nonlinear improvement in study arm response occurs in some HS RCTs. Potential contributing factors include a higher proportion of less severe patients at baseline and more female patients.

Effectiveness of in-group versus individually administered pain neuroscience education on clinical and psychosocial outcomes in patients with chronic low back pain: randomized controlled study protocol.

Objective: (1) This trial will compare the clinical and psychosocial effectiveness of in-group and individually pain neuroscience education (PNE) in patients with chronic low back pain (CLBP). In addition, (2) the influence of social determinants of health on post-treatment results will be analyzed. Methods: A three-arm randomized controlled trial will be conducted. Sixty-nine participants with CLBP will be recruited in a 1:1:1 ratio. Participants, assessor, and statistician will be blinded to group assignment. The PNE intervention will be adapted to the context of the participants. An experimental group (n = 33) will receive PNE in an in-group modality, the other experimental group (n = 33) will receive PNE in an individually modality and the control group (n = 33) will continue with usual care. Additionally, participants will be encouraged to stay active by walking for 20-30 min 3-5 times per week and will be taught an exercise to improve transversus abdominis activation (bracing or abdominal following). The outcome measures will be fear avoidance and beliefs, pressure pain threshold, pain self-efficacy, catastrophizing, pain intensity, and treatment expectation. Outcome measures will be collected at one-week before intervention, immediately post-intervention, and four-weeks post-intervention. Conclusion: The innovative approach of PNE oriented to fear beliefs proposed in this study could broaden the application strategies of this educational therapeutic modality. Impact. Contextualized PNE delivered by physical therapist could be essential to achieve a good cost-effectiveness ratio of this intervention to improve the clinical condition of people with CLBP.

Efficacy of Shenglin decoction in preventing acute severe lymphocytopenia in patients with non-small cell lung cancer undergoing concurrent chemoradiotherapy: a study protocol for a randomized controlled trial.

Background: Definitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL. Methods: This prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms. Discussion: This study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT. Trial Registration: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2300071788, https://www.chictr.org.cn/).

Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.

Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD. Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project. Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors. Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review - identifying impact of PPIE on project outputs. Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research.

Efficacy of heel lifts for mid-portion Achilles tendinopathy (the LIFT trial): study protocol for a randomised controlled trial.

BACKGROUND: Mid-portion Achilles tendinopathy is a common condition, characterised by localised Achilles tendon load-related pain and dysfunction. Numerous non-surgical treatments have been proposed for the treatment of this condition, but many of these treatments have a poor or non-existent evidence base. Heel lifts have also been advocated as a treatment for Achilles tendinopathy, but the efficacy and mechanism of action of this intervention is unclear. This proposal describes a randomised controlled trial comparing the effectiveness of heel lifts versus sham heel lifts for reducing pain associated with mid-portion Achilles tendinopathy, with an embedded biomechanical analysis. METHODS: One hundred and eight men and women aged 18 to 65 years with mid-portion Achilles tendinopathy (who satisfy the inclusion and exclusion criteria) will be recruited. Participants will be randomised, using the website Sealed Envelope, to either a control group (sham heel lifts) or an experimental group (heel lifts). Both groups will be provided with education regarding acceptable pain levels to ensure all participants receive some form of treatment. The participants will be instructed to use their allocated intervention for at least 8 h every day for 12 weeks. The primary outcome measure will be pain intensity (numerical rating scale) at its worst over the previous week. The secondary outcome measures will be additional measures of Achilles tendon pain and disability, participant-perceived global ratings of change, function, level of physical activity and health-related quality of life. Data will be collected at baseline and the primary endpoint (week 12). Data will be analysed using the intention-to-treat principle. In addition, the acute kinetic and kinematic effects of the interventions will be examined at baseline in a subpopulation of the participants (n = 40) while walking and running using three-dimensional motion analysis. DISCUSSION: The LIFT trial (efficacy of heeL lIfts For mid-portion Achilles Tendinopathy) will be the first randomised trial to compare the efficacy of heel lifts to a sham intervention in reducing pain and disability in people with Achilles tendinopathy. The biomechanical analysis will provide useful insights into the mechanism of action of heel lifts. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12623000627651 . Registered 7 June 2023.

Examining the Effectiveness of Interactive Webtoons for Premature Birth Prevention: Protocol for a Randomized Controlled Trial.

BACKGROUND: Premature birth poses significant health challenges globally, impacting infants, families, and society. Despite recognition of its contributing factors, efforts to reduce its incidence have seen limited success. A notable gap exists in the awareness among women of childbearing age (WCA) regarding both the risks of premature birth and the preventative measures they can take. Research suggests that enhancing health beliefs and self-management efficacy in WCA could foster preventive health behaviors. Interactive webtoons offer an innovative, cost-effective avenue for delivering engaging, accessible health education aimed at preventing premature birth. OBJECTIVE: This protocol describes a randomized controlled trial to assess the effectiveness and feasibility of a novel, self-guided, web-based intervention-Pregnancy Story I Didn't Know in Interactive Webtoon Series (PSIDK-iWebtoons)-designed to enhance self-management efficacy and promote behaviors preventing premature birth in WCA. METHODS: Using an explanatory sequential mixed methods design, this study first conducts a quantitative analysis followed by a qualitative inquiry to evaluate outcomes and feasibility. Participants are randomly assigned to 2 groups: one accessing the PSIDK-iWebtoons and the other receiving Pregnancy Story I Didn't Know in Text-Based Information (PSIDK-Texts) over 3 weeks. We measure primary efficacy through the self-management self-efficacy scale for premature birth prevention (PBP), alongside secondary outcomes including perceptions of susceptibility, severity, benefits, and barriers based on the health belief model for PBP and PBP intention. Additional participant-reported outcomes are assessed at baseline, the postintervention time point, and the 4-week follow-up. The feasibility of the intervention is assessed after the end of the 3-week intervention period. Outcome analysis uses repeated measures ANOVA for quantitative data, while qualitative data are explored through content analysis of interviews with 30 participants. RESULTS: The study received funding in June 2021 and institutional review board approval in October 2023. Both the PSIDK-iWebtoons and PSIDK-Texts interventions have been developed and pilot-tested from July to November 2023, with the main phase of quantitative data collection running from November 2023 to March 2024. Qualitative data collection commenced in February 2024 and will conclude in May 2024. Ongoing analyses include process evaluation and data interpretation. CONCLUSIONS: This trial will lay foundational insights into the nexus of interactive web-based interventions and the improvement of knowledge and practices related to PBP among WCA. By demonstrating the efficacy and feasibility of a web-based, interactive educational tool, this study will contribute essential evidence to the discourse on accessible and scientifically robust digital platforms. Positive findings will underscore the importance of such interventions in fostering preventive health behaviors, thereby supporting community-wide efforts to mitigate the risk of premature births through informed self-management practices. TRIAL REGISTRATION: Korea Disease Control and Prevention Agency (KDCA) KCT0008931; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=25857. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58326.

Contextual Factors-Enriched Standard Care on mechanical neck pain (ContextualizAR trial): Protocol for a randomised controlled trial.

BACKGROUND: Understanding the influence of contextual factors (CFs) on interventions for mechanical neck pain (MNP) is essential for evidence-based practice in physical therapy. However, the specific effects and synergies of combining different CFs remain unclear. OBJECTIVE: The primary purpose of this study will be to determine if a CFs-Enriched Standard Care (SC) approach is an effective treatment for MNP in terms of reducing pain and improving function. METHODS: This will be an assessor-blinded, 2-group (1:1) randomised clinical trial (RCT) aiming to enrol 94 participants with neck pain persisting for more than 4 weeks. Both groups will undergo 4 weeks of SC twice weekly, following established clinical practice guidelines. In the intervention group, CFs will be enhanced, encompassing the physical, psychological, and social elements inherent in the clinical encounter, based on existing evidence. The primary outcomes will encompass changes in pain and disability after 4 weeks of treatment, with a follow-up reassessment at week 12 post-treatment. Secondary outcomes will include changes in Active Range of Motion, Global Rating of Change, and Satisfaction with treatment. The change between groups after treatment and at the 12-week follow-up will be reported for all outcomes, considering the difference from scores recorded at baseline. RESULTS: We hypothesise that a 4-week CFs-Enriched SC approach will be superior to SC alone in terms of patient-reported disability and pain, with measurements conducted using the Northwick Park Neck Pain Questionnaire and the Numeric Pain Rating Scale, respectively. CONCLUSION: This RCT rigorously assesses the effect of purposeful manipulation of CFs during MNP treatment. By elucidating the role of these factors, our findings have the potential to significantly refine clinical practice in managing MNP, thereby enhancing patient care, and advancing the fields of physical therapy and rehabilitation.

Enhancing reporting through structure: a before and after study on the effectiveness of SPIRIT-based templates to improve the completeness of reporting of randomized controlled trial protocols.

BACKGROUND: Despite the improvements in the completeness of reporting of randomized trial protocols after the publication of the Standard Protocol Items: Recommendations for Interventional Trial (SPIRIT) guidelines, many items remain poorly reported. This study aimed to assess the effectiveness of using SPIRIT-tailored templates for trial protocols to improve the completeness of reporting of the protocols that master's students write as part of their master's theses. METHODS: Before and after experimental study performed at the University Master's Degree in Orthopaedic Manual Physiotherapy of the Universitat Internacional de Catalunya (Barcelona, Spain). While students in the post-intervention period were instructed to use a trial protocol template that was tailored to SPIRIT, students in the pre-intervention period did not use the template. PRIMARY OUTCOME: Difference between the pre- and post-intervention periods in the mean number of adequately reported items (0-10 scale). The outcomes were evaluated independently and in duplicate by two blinded assessors. Students and their supervisors were not aware that they were part of a research project. For the statistical analysis, we used a generalized linear regression model (dependent variable: number of adequately reported items in the protocol; independent variables: intervention period, call, language). RESULTS: Thirty-four trial protocols were included (17, pre-intervention; 17, post-intervention). Protocols produced during the post-intervention period (mean: 8.24; SD: 1.52) were more completely reported than those produced during the pre-intervention period (mean: 6.35; SD: 1.80); adjusted difference: 1.79 (95% CI: 0.58 to 3.00). CONCLUSIONS: SPIRIT-based templates could be used to improve the completeness of reporting of randomized trial protocols.

Educational nutritional intervention to prevent loss of health-related quality of life among older adults after a surgical treatment: design of a randomised controlled trial.

BACKGROUND: Disease-related malnutrition after a hospital stay has major consequences for older adults, the healthcare system and society. This study aims to develop and test the effectiveness of an educational video to prevent loss of health-related quality of life among live-at-home older adults after surgical treatment in a hospital. METHOD: This randomised controlled trial will occur at a regional hospital in Norway. Participants will be live-at-home adults aged 65 years and older. They will be recruited from three different surgical departments after a surgical procedure. Individuals with a body mass index below 24 and a home address in one of nine selected municipalities will be eligible for inclusion. Participants will be randomly assigned to either the intervention group or the control group. Those assigned to the intervention group will obtain access to a 6-min educational video 5 days after being discharged from the hospital. The control group will not obtain access to the video. The primary outcome will be health-related quality of life using the Norwegian Rand 36-Item Short Form Health Survey. Furthermore, we will measure body composition, number of readmissions and nutritional knowledge at inclusion and 3-month follow-up. DISCUSSION: This randomised controlled trial is expected to provide insight into whether an educational video can improve the nutritional status of older adults following a surgical procedure and discharge from the hospital. The findings will be useful for assessing how videos offering nutritional advice to older adults who have undergone a surgical procedure can improve their health-related quality of life, reduce loss of function, prevent readmission to hospital and reduce healthcare costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05950373. Registered on 11 July 2023.

A protocol for stakeholder engagement in deliver-EE: A pragmatic randomized comparative effectiveness trial evaluating effects of meal delivery on the ability of homebound older adults to remain in the community.

BACKGROUND: Few clinical trials include a detailed protocol for stakeholder engagement in the design and execution of the clinical trial. Deliver-EE is a pragmatic clinical trial to assess how different types of home-delivered meals can affect older adults' health and well-being. We present the protocol for stakeholder engagement in this national, multi-site trial and initial findings from our efforts. METHODS: Twenty-nine participants were recruited to two stakeholder advisory panels. The "Lived Experience Perspectives" panel is defined as the clients, caregivers, and meal delivery drivers with first-hand knowledge and lived experiences with meal delivery. The "System Perspectives" panel is defined as representatives from the larger financial, clinical, regulatory, and operational environments in which meal delivery to homebound older adults operate. Together, these two groups holistically represent interested parties that coordinate the interdependent elements of meal delivery to homebound older adults in order to: 1) inform our understanding of what matters most to older adults, their families, and the larger health and social care systems; 2) provide strategies to overcome challenges conducting the study; 3) enhance dissemination and uptake of study findings; and 4) identify opportunities for future research. RESULTS: Although stakeholder partners share a common goal of using home-delivered meals as a method to improve outcomes for homebound older adults, individuals have different goals for participating as advisors in this research. CONCLUSIONS: Understanding what individual stakeholders hope to gain from their participation is critical in designing an effective engagement protocol and critical for meaningful and rigorous stakeholder engagement in clinical trials.

Preventing smoking initiation in adolescents living in vulnerable socioeconomic conditions: Study protocol of the KickAsh!-intervention.

AIMS: Adolescents living in vulnerable socioeconomic conditions are confronted with tobacco-related health disparities. As school-based interventions appear to be less effective among these youngsters, other approaches are necessary. One promising avenue is youth social work settings that offer sport and recreational activities (SR-settings). SR-settings have been examined as a levering context for health promotion, but evidence regarding smoking prevention is currently lacking. METHODS: This study describes the protocol of a non-randomised cluster controlled trial evaluating a smoking prevention intervention for adolescents. At least 24 SR-settings are needed for the intervention and control group. A mixed-method design will be used. Quantitative measures will be used to assess effectiveness, involving validated questionnaires on smoking initiation behaviour and influencing factors (i.e. attitude, self-efficacy, social influence and risk perception). In addition, feasibility will be assessed with regard to intervention fidelity, dose and reach. Data will be collected at baseline, three and nine months following the intervention. To gain deeper understanding on the impact and underlying processes of the intervention, we will conduct qualitative interviews with users (adolescents) and implementers (youth workers within the SR-settings) of the intervention. CONCLUSIONS: Conducting this trial will offer novel insights into the effectiveness of a smoking prevention intervention designed for adolescents living in vulnerable socioeconomic conditions. A mixed-method design will enable to measure impact, implementation and underlying processes of the intervention. Overall, this design will enhance our understanding on the suitability of SR-settings as contexts for smoking prevention initiatives targeting hard-to-reach youth. This trial is registered on Clinicaltrials.gov: NCT05920772.

Healthy food delivery for type 2 diabetes management in rural clinics' patients: A comparative effectiveness randomized controlled trial protocol.

BACKGROUND: Rural populations experience a higher prevalence of both food insecurity and type 2 diabetes mellitus (T2DM) than metropolitan populations and face many challenges in accessing resources essential to optimal T2DM self-management. This study aims to address these challenges by delivering a T2DM-appropriate food box and recipes directly to rural participants' homes. METHODS: This is a comparative effectiveness randomized controlled trial including 400 English- or Spanish-speaking rural adult participants with T2DM (HbA1c ≥6.5%) experiencing food insecurity. Participants are randomly assigned to a 3-month Healthy Food Delivery Intervention (HFDI) plus one 60-min virtual consultation with a diabetes educator or consultation only. The HFDI includes a weekly food box delivery with recipes. Data are collected at pre-intervention, 3-months (post-intervention), 9-months, and 15-months. The primary outcome is change in HbA1c, with secondary measures including diet quality (Healthy Eating Index-2015, calculated from one 24-h dietary recall at each data collection time point), cardio-metabolic risk factors (i.e., blood pressure, lipids, body mass index, glucose), and patient-centered outcomes (e.g., T2DM self-efficacy, T2DM-related distress). Process evaluation data (e.g., successful food box deliveries, diabetes educator consultation attendance, intervention satisfaction) are collected during and post-intervention (3-months). A cost-effectiveness analysis based on traditional cost per quality-adjusted life year gain thresholds will be conducted to estimate the incremental cost-effectiveness between HFDI plus consultation and consultation alone. CONCLUSION: Findings from this study will provide evidence regarding the effectiveness of an intervention that promotes participant adherence and improves access to healthy food. CLINICAL TRIAL REGISTRATION: NCT04876053.

PRE1BRAZIL Protocol: A Randomized Controlled Trial to Evaluate the Effectiveness and Safety of the DPP-4 Inhibitor Alogliptin in Delaying the Progression of Stage 2 Type 1 Diabetes.

Background: The incidence of Type 1 Diabetes Mellitus (T1DM) is on the rise. Since there is no curative treatment, it is urgent to look for therapies that can delay disease progression and protect pancreatic ß-cells. Dipeptidyl peptidase-4 inhibitors (DPP-4i) have shown potential in modulating inflammation and preventing ß-cell destruction. This protocol describes an upcoming trial to evaluate the effectiveness of the DPP-4i alogliptin in delaying the progression of stage 2 (presymptomatic) to stage 3 (symptomatic) T1DM. Patients and Methods: We propose a two-year, two-arm, multicenter, randomized, open-label clinical trial targeting Brazilian patients aged 18 to 35 with stage 2 T1DM. The study, facilitated by the custom-developed "PRE1BRAZIL" web application, aims to enroll 130 participants. They will be randomly assigned in a 1:1 ratio to either a treatment group (alogliptin 25 mg daily plus regular clinical and laboratory assessments) or a control group (regular assessments only). The primary outcome is the rate of progression to stage 3 T1DM. Secondary outcomes include changes in A1c levels, glucose levels during a 2-hour oral glucose tolerance test (OGTT), C-peptide levels, exogenous insulin requirements, Insulin-Dose Adjusted A1c (IDAA1c), and the incidence of diabetic ketoacidosis (DKA) in those advancing to stage 3. Discussion: This protocol outlines the first randomized clinical trial (RCT) to investigate the impact of a DPP-4i in the presymptomatic stage of T1DM. The trial is designed to provide critical insights into the role of DPP-4i in the secondary prevention of T1DM. Utilizing the "PRE1BRAZIL" web application is expected to enhance participant enrollment and reduce operational costs. Registration: Brazilian Registry of Clinical Trials.

Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3).

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

Study Protocol for the Healing Opioid Misuse and Pain Through Engagement Trial: Integrated Treatment for Individuals With Co-occurring Chronic Pain and Opioid Use Disorder.

Chronic pain and opioid use disorder (OUD) are public health crises and their co-occurrence has led to further complications and public health impacts. Provision of treatments for comorbid chronic pain and OUD is paramount to address these public health crises. Medications for OUD (MOUD) are gold standard treatments for OUD that have also demonstrated benefit in pain management. However, clinics that provide MOUD for chronic pain or OUD often lack behavioral treatments to address the challenges experienced by individuals with both conditions. Developing and implementing a behavioral treatment that complements MOUD may better equip clinics to provide comprehensive care to the growing proportion of clients who present with comorbid chronic pain and OUD. In the Healing Opioid misuse and Pain through Engagement (HOPE) Trial, we are using an effectiveness-implementation hybrid design to examine the benefits of an integrated behavioral treatment and to determine the feasibility of implementing the integrated treatment into clinics that provide MOUD. The treatment integrated 2 evidence-based treatments-Acceptance and Commitment Therapy and Mindfulness-Based Relapse Prevention-to target the emotional, behavioral, and physiological sequelae of OUD and chronic pain. Implementation feasibility will include assessing changes in implementation readiness and identifying facilitators and barriers to implementing the integrated treatment among all personnel employed in clinics that provide MOUD. This commentary offers an overview of the study and design and details adaptations we made to our study protocol, based largely on clinic personnel time constraints and variable clinic procedures during the COVID-19 pandemic.

The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.

BACKGROUND: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown. STUDY DESIGN: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial. ENDPOINTS: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness. ELIGIBILITY CRITERIA: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT. PATIENTS AND METHODS: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707).

E = mc2 : Education (E), medication (m), and conditional cash (c2 ) to improve uptake of antiseizure medications in a low-resource population: Protocol for randomized trial.

OBJECTIVE: Most people with epilepsy (PWE) could live seizure-free if treated with one or more antiseizure medications (ASMs). The World Health Organization (WHO) estimates that 75% of PWE in low-resource settings lack adequate antiseizure treatment. Limited education surrounding epilepsy and the out-of-pocket costs of ASMs in particular pose barriers to managing epilepsy in resource-poor, low-income settings. The aim of this study is to implement and test a novel strategy to improve outcomes across the epilepsy care cascade marked by (1) retention in epilepsy care, (2) adherence to ASMs, and (3) seizure reduction, with the measured goal of seizure freedom. METHODS: A randomized, double-blinded clinical trial will be performed, centered at the Ignace Deen Hospital in Conakry, Republic of Guinea, in Western Sub-Saharan Africa. Two hundred people with clinically diagnosed epilepsy, ages 18 years and above, will receive education on epilepsy and then be randomized to (i) free ASMs versus (ii) conditional cash, conditioned upon return to the epilepsy clinic. Participants will be followed for 360 days with study visits every 90 days following enrollment. SIGNIFICANCE: We design a randomized trial for PWE in Guinea, a low-resource setting with a high proportion of untreated PWE and a nearly completely privatized healthcare system. The trial includes a conditional cash transfer intervention, which has yet to be tested as a targeted means to improve outcomes for people with a chronic neurological disorder. The trial aims to provide an evidence base for the treatment of epilepsy in such settings. PLAIN LANGUAGE SUMMARY: We present a clinical trial protocol for a randomized, blinded study of 200 people with epilepsy in the low-resource African Republic of Guinea, providing an educational intervention (E), and then randomizing in a 1:1 allocation to either free antiseizure medication (m) or conditional cash (c2 ) for 360 days. Measured outcomes include (1) returning to outpatient epilepsy care, (2) adherence to antiseizure medications (ASMs), and (3) reducing the number of seizures. This study is an initial look at giving small amounts of cash for desired results (or "nudges") for improving epilepsy outcomes in the sub-Saharan African and brain disorder contexts.

Engaging carers in neuropsychological rehabilitation for brain cancer survivors: The "I'm aware: Patients And Carers Together" (ImPACT) program.

BACKGROUND: Cognitive impairment is a common late effect in child and adult brain cancer survivors (BCS). Still, there is a dearth of research aimed at therapeutic interventions and no standard treatment options for most BCS. OBJECTIVE: To describe 1) a novel neuropsychological rehabilitation program for BCS - the "I'm aware: Patients And Carers Together" (ImPACT) program, and 2) two studies that aim to assess the feasibility of the ImPACT program in child and adult BCS, respectively. The program adapts the holistic neuropsychological approach pioneered by Leonard Diller and Yehuda Ben-Yishay to an outpatient setting. METHODS: Two feasibility studies are described: 1) A single-armed study with 15 child BCS (10-17 years) (ImPACT Child); and 2) a randomized waitlist-controlled trial with 26 adult BCS (>17 years) (ImPACT Adult). In both studies, patients will undergo an 8-week program together with a cohabiting carer. Primary outcomes (i.e., cognitive and neurobehavioral symptoms), and secondary outcomes (i.e., behavioral and psychological symptoms, e.g., quality of life, fatigue) will be assessed at four time points: pre-, mid-, and post intervention, and 8 weeks follow-up. Adult waitlist controls will be assessed at equivalent time points and will be included in the intervention group after all study assessments. Semi-structured interviews will be conducted at follow-up. EXPECTED OUTCOMES: Results will provide feasibility data in support of future larger scale trials. DISCUSSION: The findings could potentially improve the management of cognitive impairment in BCS and transform available services. The program can be delivered in-person or remotely and harnesses existing resources in patients' lives.

Medical Imaging Decision And Support (MIDAS): Study protocol for a multi-centre cluster randomized trial evaluating the ESR iGuide.

OBJECTIVES: Medical imaging plays an essential role in healthcare. As a diagnostic test, imaging is prone to substantial overuse and potential overdiagnosis, with dire consequences to patient outcomes and health care costs. Clinical decision support systems (CDSSs) were developed to guide referring physicians in making appropriate imaging decisions. This study will evaluate the effect of implementing a CDSS (ESR iGuide) with versus without active decision support in a physician order entry on the appropriate use of imaging tests and ordering behaviour. METHODS: A protocol for a multi-center cluster-randomized trial with departments acting as clusters, combined with a before-after-revert design. Four university hospitals with eight participating departments each for a total of thirty-two clusters will be included in the study. All departments start in control condition with structured data entry of the clinical indication and tracking of the imaging exams requested. Initially, the CDSS is implemented and all physicians remain blinded to appropriateness scores based on the ESR imaging referral guidelines. After randomization, half of the clusters switch to the active intervention of decision support. Physicians in the active condition are made aware of the categorization of their requests as appropriate, under certain conditions appropriate, or inappropriate, and appropriate exams are suggested. Physicians may change their requests in response to feedback. In the revert condition, active decision support is removed to study the educational effect. RESULTS/CONCLUSIONS: The main outcome is the proportion of inappropriate diagnostic imaging exams requested per cluster. Secondary outcomes are the absolute number of imaging exams, radiation from diagnostic imaging, and medical costs. TRIAL REGISTRATION NUMBER: Approval from the Medical Ethics Review Committee was obtained under protocol numbers 20-069 (Augsburg), B 238/21 (Kiel), 20-318 (Lübeck) and 2020-15,125 (Mainz). The trial is registered in the ClinicalTrials.gov register under registration number NCT05490290.