Risultati per: Position paper della French Headache Society sul trattamento dell'emicrania

New England Journal of Medicine, Volume 391, Issue 22, Page 2148-2157, December 5, 2024.

Introduction
Recent decades have seen a growth in multisectoral and transdisciplinary approaches to improving global health, particularly across human, animal and environmental health-related sciences that advocate for participatory, systems-based perspectives to understanding and promoting health and well-being in the context of social and ecological interactions. For several issues, including human health, animal health and food security, researchers have highlighted the need for transdisciplinary One Health approaches to assess the sustainability of interventions. To understand the current thinking and conceptualisation of sustainability across One Health disciplines, we present a protocol paper for an umbrella systematic review study planned in 2024.

Methods and analysis
A search strategy based on Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines was developed. The Medline, Embase, Global Health and Web of Science Core Collection were the four databases interrogated through the search strategy and included all articles found in the English language up to 14 April 2024. Meta-analyses, systematic, structured literature reviews and narrative reviews on sustainability will be included and a full-text review of all articles will be undertaken. The articles will be quality appraised using the AMSTAR 2 tool. Data that cover proposed factors influencing and characterising sustainability will be extracted across One Health disciplines including similarities and differences, and a summative content analysis will be completed to identify any emerging themes and develop an analytical framework. The conceptualisation of sustainability in the context of One Health multisectoral approaches will be summarised, a definition of sustainability proposed and include an identification of tools for measuring and assessing sustainability.

Ethics and dissemination
No primary data will be collected; therefore, ethical approval will not be required. The results will be disseminated in peer-reviewed literature and conference presentations. The findings will also be directly disseminated to the Quadripartite agencies.

Prospero registration number
CRD42018094031

Objectives
This study investigates the relationship between flat rate pricing for unlimited alcohol consumption in restaurants and bar and problematic alcohol consumption patterns identified by the Alcohol Use Disorders Identification Test (AUDIT) during the COVID-19 pandemic.

Methods
A cross-sectional study was conducted using data from the Japan Society and New Tobacco Internet Survey in February 2022. A total of 19 585 current drinkers (55% of drinkers were men, and the mean age was 48.3 years) were categorised based on AUDIT scores; non-problem drinking (an AUDIT Score of 0–7), problem drinking (an AUDIT Score of 8 or over), hazardous alcohol use (an AUDIT Score of 8–14) and probable alcohol use disorders (an AUDIT Score of 15 or over). A score of 2 or higher in the third question of the AUDIT is identified as binge drinking. The explanatory variable was the presence of using flat rate pricing for unlimited alcohol consumption in the previous 12 months during the COVID-19 pandemic (February 2021 to February 2022). The associations of using the flat rate pricing with the problem or binge drinking, and with hazardous alcohol use or probable alcohol use disorders were analysed.

Results
People who used flat rate pricing during the COVID-19 pandemic were likely to be problem drinking and binge drinking compared with non-users of flat rate pricing; the respective adjusted ORs were 4.64 (95% CI: 4.24 to 5.07) and 3.65 (95% CI: 3.33 to 4.00) through multivariable binary logistic regression. The users of the flat rate pricing were associated with hazardous alcohol use and probable alcohol use disorder; the adjusted relative risk ratios were 3.40 (95% CI: 3.06 to 3.77) and 8.58 (95% CI: 7.51 to 9.80) through multinomial logistic regression.

Conclusions
Overall, using flat rate pricing for unlimited alcohol consumption was associated with both binge drinking and problem drinking, including hazardous alcohol use and probable alcohol use disorders.

This crossover randomized clinical trial aims to determine the effect of different arm positions on blood pressure readings.

Introduction
Cerebral palsy (CP) presents a complex neurodevelopmental disorder with a spectrum of motor impairments stemming from early brain injury. Whereas CP is traditionally viewed as a non-progressive condition, emerging evidence suggests a progressive decline in mobility and function, particularly in adulthood. Despite the prevalence of self-reported age-related gait decline in adults with CP, objective evidence supporting this phenomenon remains limited. Moreover, mechanistic insights into these functional alterations and their comparison with typically developing (TD) peers are lacking. To address this gap, our study aims to objectively assess age-related changes in gait performance among individuals with CP while examining physiological differences compared with TD peers.

Methods and analysis
This protocol will compare the mobility of individuals with and without CP within two age groups (18–25 and 35–50 years old). Participants at Gross Motor Function Classification System levels I–II at age 18 will be invited to partake in the study. Every participant will be invited to complete four visits investigating a wide range of mobility related measures: walking performance, muscle strength, cardiopulmonary performance, fatigability, cost of walking and quantitative gait analysis. Through this comprehensive analysis encompassing gait performance metrics, self-reported outcomes, muscle strength, biomechanics and metabolical cost of walking, and fatigability, we seek to elucidate the underlying mechanisms driving age-related gait decline in adults with CP and inform targeted interventions to maintain function and quality of life.

Ethics and dissemination
The study has been approved by the French ethics board (#2022-A02510-43) and will be communicated through conferences, articles and to participants through layman terms.

Trial registration number
NCT06163950.

Objectives
The first COVID-19 lockdown raised concerns about reduced access to primary care, especially for people with chronic diseases particularly at risk in the absence of follow-up. However, the COVIQuest trial, evaluating the impact of a general practitioner (GP) phone call (intervention) to chronic patients with cardiovascular disease (CVD) or mental health disorder (MHD) concluded that the intervention had no effect at 1 month on the rate of self-reported hospitalisations in the CVD subtrial, whereas the intervention group in MHD subtrial might have a higher rate. This second part of the study aimed to describe the 6 month hospitalisation and specialised consultation rates, using the French health data system (Système National des Données de Santé). The secondary objective was to describe these rates during the same period in 2019.

Design
A cluster randomised controlled trial, with clusters being GPs.

Setting
Primary care, 149 GPs from eight French regions.

Participants
Patients ≥70 years old with chronic CVD or ≥18 years old with MHD.

Interventions
A standardised GP-initiated phone call aiming to evaluate patient’s need for urgent care (vs usual care for control groups).

Primary and secondary outcome measures
The occurrence of at least one hospitalisation at end point 31 October 2020 (randomisation 30 April 2020), excluding those starting on 30 April 2020, was measured as planned. Another main outcome was the occurrence of at least one specialised consultation during the same period. These 6 month effects were studied, using a logistic regression model within a generalised estimating equation framework, for each subtrial.

Results
4640 patients were included: 3274 cardiovascular (mean age 79.9±7.0 years; 57.8% male) and 1366 psychiatric (53.2±7.0; 36.5%). For both subtrials, the intervention patients were significantly more hospitalised than the control patients, respectively, 17.3% versus 14.9% of CVD patients (OR=1.26 (1.05 to 1.52)); 14.4% versus 10.7% of MHD patients (OR=1.40 (1.00 to 1.96)). During the same period in 2019, the hospitalisation rates were, respectively, 16.3%, 18.2%, 15.8% and 14.8%. The proportions of patients with at least one specialised consultation were not different between the intervention and control groups, respectively, 24.6% versus 24.3% for CVD patients (OR=1.06 (0.85 to 1.32)); 26.5% versus 24.4% for MHD patients (OR=1.15 (0.84 to 1.57)). During the same period in 2019, these rates were, respectively, 22.7%, 24.6%, 28.0% and 25.5%.

Conclusions
The intervention was associated with higher rates of hospitalisation at 6 months in patients with MHD or CVD. No intervention impact was found in outpatient care. These results are difficult to interpret because of a potential artefact induced by national campaigns promoting medical use during lockdown, overlapping the study inclusion period. This study showed that medico-administrative databases could represent a complementary cost-effective tool to clinical research for long-term and healthcare consumption outcomes.

Trial registration number
NCT04359875.

Background and objectives
Violence against women (VAW) is widespread and can have serious physical and mental health consequences, including post-traumatic stress disorder (PTSD) and sleep disorders. Victim-survivors often face barriers in accessing specialised care, highlighting the need for a multidisciplinary response, especially in healthcare settings. The Maison des Femmes (MdF) model provides holistic support to women experiencing VAW, including medical, psychological, social and legal support. The aim of this study is to examine whether the MdF’s comprehensive intervention programme offers advantages over standard care in improving mental health indicators, such as PTSD.

Method and analysis
Our pragmatic quasi-experimental study uses a non-randomised controlled cluster design. The intervention group comprises women enrolled in MdFs in five French cities, while the comparison group includes women receiving usual care in sociomedical structures located geographically close to MdF centres. Our study aims to recruit 360 women (180 per group), aged 18 years or older, who have experienced intimate partner violence or sexual violence and who seek care at the study centres. The primary analysis will compare the change in PTSD Checklist for DSM-5 (PCL-5) scores over 6 months in the two groups using multivariable linear regression with propensity score adjustment. Secondary outcomes include sleep disorders, quality of life, symptoms of anxiety and depression, self-esteem, sense of safety and well-being, initiation of legal and socioprofessional proceedings, and healthcare utilisation.

Ethics and dissemination
The study was approved by the ‘Comité de protection des personnes Ile de France III’ (CPP Committee for the Protection of Persons Ile de France III; institutional review board on 20 December 2023; Ref no. (Numéro SI): 23.04197.000491).
The results of the study will be communicated via academic publications; easily understandable briefs for a broader public; and proactive involvement with medical institutions, journalists and advocacy groups.

Trial registration number
NCT06226818. Version Number 1- february2024.

Circulation, Volume 150, Issue Suppl_1, Page A4134309-A4134309, November 12, 2024. Introduction:We report the case of a heart transplant patient on chronic immunosuppression diagnosed with cryptococcal meningitis. Up to 5% of solid organ transplant patients develop cryptococcosis, carrying a 50% mortality rate in central nervous system involvement.Case Presentation:This is a 57-year-old male with a past medical history of heart failure with reduced ejection fraction (HFrEF) status post orthotopic heart transplantation (on prednisone 7.5 mg daily, mycophenolate, tacrolimus and sirolimus), pulmonary sarcoid, and chronic hepatitis B (on tenofovir and entecavir) who presented with headache, nausea, vomiting and seizure-like activity. The patient’s heart rate was 129 beats per minute, blood pressure 188/92 mmHg, but was afebrile. He eventually underwent a lumbar puncture with the cerebrospinal fluid (CSF) positive for cryptococcal antigen (1:2560). The patient was started on liposomal amphotericin B and flucytosine. Mycophenolate and sirolimus were held in the setting of his infection. The patient’s hospital course was complicated by acute kidney injury likely secondary to elevated tacrolimus levels while on fluconazole. He was ultimately discharged with plans to repeat CSF studies as an outpatient.Discussion:Here we report a case of cryptococcal meningitis in a heart transplant patient in the context of pulmonary sarcoidosis, chronic hepatitis B and quadruple immunosuppression. Of note, as part of rejection surveillance, the patient undertook serial AlloSure and AlloMap testing. Sirolimus was added to his regimen due to persistently elevated AlloSure scores. Indeed, immunosuppressive agents are the leading risk factor for cryptococcosis in organ transplant patients. Our patient also has two important risk factors for cryptococcal infection. Firstly, sarcoidosis is associated with T-cell dysregulation, compromising cell-mediated immunity. Additionally, hepatitis B carriers have an increased predisposition for cryptococcal infections, notwithstanding that our patient had been on dual antiviral therapy.Conclusion:Quadruple immunosuppression in heart transplant patients, especially in the context of risk factors such as sarcoidosis and hepatitis B infection, can result in cryptococcal meningitis and should be considered in patients with suggestive symptoms. Effective prophylactic regimens for such higher risk patients may be a potential area for further investigation.

Circulation, Volume 150, Issue Suppl_1, Page ASa308-ASa308, November 12, 2024. Background:Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR), an impedance threshold device (ITD) and controlled, gradual, automated head and thorax elevation, collectively termed automated Head Up Position (AHUP) CPR, increases cerebral perfusion pressure (CerPP), brain blood flow, coronary perfusion pressure (CorPP), end tidal CO2 (ETCO2) and cerebral oximetry (rSO2) in animal models when compared with conventional (C) CPR. AHUP-CPR in patients is associated with increased neurologically favorable survival versus C-CPR. This study tested the hypothesis that AHUP CPR will increase cardiac stroke volume (SV) and other hemodynamics compared with C-CPR in a porcine model of cardiac arrest.Methods:Farm pigs (n=15) were sedated, anesthetized, and ventilated. Hemodynamics, including intracardiac conductance catheter based biventricular (BiV) pressure-volume (PV) loops, were continuously measured and recorded. After 10 minutes of untreated ventricular fibrillation, C-CPR was performed for 2 minutes in the supine position using an automated CPR device designed for pigs at a rate of 100 compressions/minute, depth of 21% of the chest antero-postero diameter, a 50% duty cycle, and no active decompression. ACD+ITD was then performed with 3 cm of active decompression for 2 minutes, followed by AHUP-CPR, where the head and thorax were initially raised to 10 cm and 8 cm for a 2-minute priming phase, followed by elevation over the next 2 minutes to 24 cm and 9 cm. A linear mixed-effects model with a random intercept for individual pigs was used for statistical analysis.Results:CerPP, CorPP, ETCO2, and rSO2, as well as BiV SV and cardiac output, increased progressively and significantly with implementation of AHUP-CPR (p

Circulation, Volume 150, Issue Suppl_1, Page A4142044-A4142044, November 12, 2024. Background:Myocarditis is a dreaded complication of immune-checkpoint inhibitor (ICI) therapy but challenging to diagnose. There are no published data comparing the two leading diagnostic criteria for ICI myocarditis and their association with cardiovascular events.Methods:Patients treated with ICI and cardiac Troponin (cTnT) measurements thereafter at a tertiary institution from 2011 to 2022 were identified. Charts were reviewed for ICI-related myocarditis according to the Bonaca et. al criteria and the ESC-ICOS guideline criteria. A propensity matched control group was identified of patients treated with ICI but without developing myocarditis. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, MACE (myocardial infarction, TIA/stroke, new heart failure diagnosis), and arrhythmias (V-tach, A-fib, complete heart block).Results:A total of 59 patients were identified as having a diagnosis of ICI-related myocarditis per Bonaca criteria (16 having definite, 13 probable and 30 possible myocarditis), and 47 met the ESC-ICOS guideline criteria. Mean age was 73.1±10.2 years, 60.1% were male, median follow-up was 2.5 years. ICI-related myocarditis as diagnosed by both diagnostic criteria had prognostic value for cardiac death (HR 13.94, 95%CI 1.84-105.64, p=0.011 per Bonaca, HR 6.22, 95%CI 1.77-21.88, p=0.004 per ESC-ICOS), MACE, (HR 3.17, 95%CI 1.34-7.47, p=0.008 per Bonaca, HR 2.97, 95%CI 1.37-6.45, p=0.006 per ESC-ICOS), and arrhythmias (HR 1.93, 95%CI 1.10-3.38, p=0.022 per Bonaca, HR 2.09, 95%CI 1.21-3.60, p

Circulation, Volume 150, Issue Suppl_1, Page A4141628-A4141628, November 12, 2024. Introduction:Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide. Lipid-lowering therapies (LLTs) are a key element to reduce the risk of recurrence of ASCVD events. However, despite concordant guidelines, LLTs are often underused in real-life setting.Research questions:The aim of this study is to describe the use of LLTs and its impact on morbi-mortality in the year following a first ASCVD event.Methods:This retrospective study used the national health data system (SNDS), collecting health insurance claims and hospital discharge data from 99% of the French population. Incident cases in 2021 were identified, corresponding to all adults with a first ASCVD event, based on ICD-10 hospital coding. ASCVD includes coronary artery disease [myocardial infarction, unstable angina or coronary revascularization], cerebrovascular events [ischemic stroke, carotid revascularization] and peripheral artery disease (PAD) requiring artery revascularization. In patients discharged alive from the index event, longitudinal analyses were performed at 1-year from discharge to describe LLT use, occurrence of major ASCVD events and all-cause mortality.Results:In 2021, 195,211 newly diagnosed ASCVD cases were identified among 43,1M adults (mean age: 70.3 (±13.7) yo; 62% of male). The first ASCVD event was myocardial infarction (N=51,614) or ischemic stroke (N=52,865) in 53.5% of incident cases. The remaining 46.5% corresponded mostly to coronary revascularization procedures (N=83,910), followed by PAD (N=26,925). In-hospital mortality was 5.5% (N=10,673). In patients analyzed at 1 year (N=180,875), 16.9% did not receive any LLT. This value rose to 26.7% among patients who had no received LLT prior to the ASCVD event. After a myocardial infarction, patients were more likely to receive LLT (91.9%) compared to after an ischemic stroke (72.9%) or revascularization for PAD (68.0%). Finally, 1-year all-cause mortality was higher in non-LLT compared to LLT patients (20.9% vs 4.0%). Additional data on the recurrence of ASCVD events as a function of LLT use are currently being analyzed and will be presented at the congress.Conclusion:Contrary to recommendations, the underuse of LLTs after a first ASCVD event remains very high, particularly after a stroke. This is associated with a significantly higher mortality at 1 year, justifying the need to reinforce implementation of the guidelines in real life for a better management of residual lipid risk.

Circulation, Volume 150, Issue Suppl_1, Page A4122486-A4122486, November 12, 2024. Background:Fetal cardiomyopathy (FCM) affects 8 per 100,000 live births, often with unknown etiology. Progress in fetal cardiac screening, genetic testing and management may have impacted historically poor outcomes.Aims:We sought to investigate genetic associations and clinical outcomes of FCM in the current era.Methods:This was a retrospective Fetal Heart Society Research Collaborative cohort study of FCM cases diagnosed from January 2017-December 2021 in 39 centers. Cases of fetal myocardial disease attributable to maternal diabetes, structural heart disease, arrhythmia or extra-cardiac conditions were excluded. Data including outcomes to 1 year after birth were collected. Significance of genetic testing results and FCM subtype were classified by each center.Results:There were 138 FCM cases diagnosed at a median gestational age of 27+4weeks (range 13-39 weeks). Suspected fetal heart disease (41%, 56/138) was the most common referral indication. There was a known family history of CM in 19% (26/138). FCM phenotypes included 38% (52/138) dilated, 24% (33/138) hypertrophic, 17% (24/138) non-compacted, 10% (14/138) mixed, 5% (7/138) restrictive, 3% (4/138) ventricular aneurysm, 3% (4/138) unspecified. Hydrops was present at diagnosis in 15% (20/138) and by delivery or at fetal demise in 26% (36/138). Of 128 continued pregnancies, 7% (9/128) had a fetal demise, 92% (118/128) a live birth and one was lost to follow-up. Among live births, 10% (12/118) received only palliative care. Of 106 actively treated, 75% (80/106) survived to 1 year; 7% (7/106) required ECMO, and 22% (23/106) were listed for transplant with 18 of these successfully transplanted. Of the cohort, a total of 80% (110/138) had genetic testing (including 30 with invasive prenatal testing), with 38% (52/138) having a confirmed genetic etiology and 28% (38/138) with a variant of uncertain significance (VUS) (Figure 1). Transplant-free survival to 1 year was similar for those with and without a genetic diagnosis (40%,21/52 vs 47%,40/86, p=0.48).Conclusion:Outcomes remain poor in FCM, with

Circulation, Volume 150, Issue Suppl_1, Page AOr108-AOr108, November 12, 2024. Background:Addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to automated head-up position (AHUP) cardiopulmonary resuscitation (CPR), the combination of active compression decompression CPR, an impedance threshold device, and controlled gradual elevation of the head and thorax, increases cerebral perfusion pressure. Optimal management of REBOA deflation after prolonged AHUP-CPR and ROSC is unknown.Hypothesis:We hypothesized that partial deflation of REBOA, rather than full deflation after ROSC, would result in better hemodynamic parameters.Aims:To compare hemodynamic parameters 1 minute before and 1 minute after complete (100%) versus partial (50%) REBOA deflation after prolonged AHUP-CPR and ROSC.Methods:Yorkshire pigs weighing ∼40 kg were anesthetized and ventilated. After 10 minutes of untreated ventricular fibrillation, AHUP-CPR was started and continued for a median time of 44 minutes. After ROSC, REBOA deflation was initiated in two ways: complete (100%) or partial (50%) deflation over 5 seconds. The following hemodynamic parameters were measured 1 minute before and 1 minute after deflation: mean aortic pressure (MAP), cerebral perfusion pressure (CerPP), and coronary perfusion pressure (CorPP). Data, in mmHg, are presented as mean ± SD, and compared using a paired t-test.Results:13 pigs were included, with 8 pigs in the 100% deflation group and 5 in the 50% deflation group. After ROSC in the 100% deflation group, MAP was 81.5±36.0 before deflation vs. 43.0±14.4 after (p=0.01), whereas in the 50% deflation group, MAP was 90.5±33.0 vs. 83.4±33.3 (p=0.02). CerPP was 72.3±34.4 before deflation vs. 35.9±14.6 (p=0.01) in the 100% deflation group, and 84.6±31.2 vs. 77.6±31.8 (p=0.02) with 50% deflation. Similarly, CorPP was 74.1±37.3 before deflation vs. 36.1±15.8 (p=0.01) after in the 100% deflation group, and 83.0±32.7 vs. 76.1±33.0 (p=0.02) in the 50% deflation group. The differences from before to after deflation were markedly less in the 50% deflation group versus the 100% deflation group: MAP (7.0±4.3 vs. 38.5±25.7, p=0.02), CerPP (7.1±4.4 vs. 36.3±24.4, p=0.02), and CorPP (6.0±4.2 vs. 39.8±25.2, p=0.02), respectively.Conclusion:In this porcine model of prolonged cardiac arrest, partial deflation of the REBOA balloon post ROSC resulted in strikingly higher hemodynamics compared with complete deflation. These findings highlight the need to develop a post-ROSC REBOA deflation strategy when used during AHUP-CPR.

Circulation, Volume 150, Issue Suppl_1, Page A4138483-A4138483, November 12, 2024. Background:Hypoplastic left heart syndrome (HLHS) is classified by subtype: mitral atresia and aortic atresia (MA-AA), mitral stenosis and aortic atresia (MS-AA), and mitral stenosis and aortic stenosis (MS-AS). It is controversial whether specific HLHS subtypes and presence of ventriculocoronary connections (VCC) are associated with transplant-free survival. We aimed to determine whether there is an increased risk of mortality associated with specific HLHS subtypes, whether this risk is stratified by the presence of VCC, and if a specific type of stage I palliation in patients with VCC improves survival. We also aimed to determine practice variation in the evaluation of HLHS patients with VCC.Methods:We performed a multicenter retrospective cohort study of fetuses and infants < 2 months of age with HLHS admitted between 1/2012-12/2016 to participating Fetal Heart Society institutions. Patients with HLHS variants were excluded. We collected patient specific data and surveyed participating centers for practice variation. Kaplan-Meier curves with log-rank test were used to assess transplant-free survival and cox proportional hazard analysis was performed with adjustment for center as a random intercept.Results:341 patients from nine centers were included. MA-AA was the most common subtype (177, 52%), followed by MS-AA (102, 30%), and MS-AS (62, 18%). VCC were diagnosed or suspected in 65 patients (19%). A total of 287 patients were live born with intention to treat. HLHS subtype was not associated with transplant-free survival (Figure 1A). Presence of VCC was associated with a lower transplant-free survival (p=0.026, Figure 1B). In the subset of patients diagnosed with VCC, there was not a significant difference in survival based on type of stage I palliation (Figure 1C). Cox proportional hazard modeling adjusted for center demonstrates that presence of VCC has a hazard ratio of 1.74 (CI 1.02-2.98), p =0.04. Survey data regarding practice variation for patients with VCC (Figure 2) demonstrates 33% of centers modify the type of stage I palliation based on presence of VCC.Conclusions:In a multicenter cohort of HLHS patients, patients with VCC had lower transplant-free survival compared to those without VCC, while subtype and type of stage I palliation did not have a statistical difference. There is considerable practice variation in the management of HLHS patients with VCC that may warrant further investigation.

Introduction
Buprenorphine is a highly effective treatment for opioid use disorder (OUD). However, provider observations and preliminary research suggest that the current standard maintenance dose may be insufficient for suppressing withdrawal and preventing cravings among people who use or have used fentanyl. Buprenorphine dosing guidelines were based on studies among people who use heroin and have not been formally re-evaluated since fentanyl became predominant in the unregulated drug supply. We aim to compare the effectiveness of a high (24 mg) vs standard (16 mg) maintenance daily dose of buprenorphine for improving retention in treatment, decreasing the use of non-prescribed opioids, preventing cravings and reducing opioid overdose risk in patients.

Methods and analysis
Adults who are initiating or continuing buprenorphine for moderate to severe OUD and have a recent history of fentanyl use (n=250) will be recruited at four outpatient substance use treatment clinics in Rhode Island. Patients continuing buprenorphine must be on doses of 16 mg or less and have ongoing fentanyl use to be eligible. Participants will be randomly assigned 1:1 to receive either a high (24 mg) or standard (16 mg) maintenance daily dose, each with usual care, and followed for 12 months to evaluate outcomes. Providers will determine the buprenorphine initiation strategy, with the requirement that participants reach the study maintenance dose within 7 days of randomisation. Providers may adjust the maintenance dose, if clinically needed, for participant safety. The primary study outcome is retention in buprenorphine treatment at 6 months postrandomisation, measured using clinical and statewide administrative data. Other outcomes include non-prescribed opioid use and opioid cravings (secondary), as well as non-fatal or fatal opioid overdose (exploratory).

Ethics and dissemination
This protocol was approved by the Brown Institutional Review Board (STUDY00000075). Results will be presented at conferences and published in peer-reviewed journals.

Trial registration number
NCT06316830.