Sequential Assignment Research Articles

Solid-state NMR MAS CryoProbe enables structural studies of human blood protein vitronectin bound to hydroxyapatite

The low sensitivity of nuclear magnetic resonance (NMR) is a major bottleneck for studying biomolecular structures of complex biomolecular assemblies. Cryogenically cooled probe technology overcomes the sensitivity limitations enabling NMR applications to challenging biomolecular systems. Here we describe solid-state NMR studies of the human blood protein vitronectin (Vn) bound to hydroxyapatite (HAP), the mineralized form of calcium phosphate, using a CryoProbe designed for magic angle spinning (MAS) experiments. Vn is a major blood protein that regulates many different physiological and pathological processes. The high sensitivity of the CryoProbe enabled us to acquire three-dimensional solid-state NMR spectra for sequential assignment and characterization of site-specific water-protein interactions that provide initial insights into the organization of the Vn-HAP complex. Vn associates with HAP in various pathological settings, including macular degeneration eyes and Alzheimer's disease brains. The ability to probe these assemblies at atomic detail paves the way for understanding their formation.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART)

BackgroundThis study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. MethodFor Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. ResultsPhase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DiscussionAdding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

Sequential multiple assignment randomised trial to develop an adaptive mobile health intervention to increase physical activity in people poststroke in the community setting in Ireland: TAPAS trial protocol

IntroductionStroke is the second-leading cause of death and disability globally. Participation in physical activity (PA) is a cornerstone of secondary prevention in stroke care. Given the heterogeneous nature of stroke,...

Efficient UCB-Based Assignment Algorithm Under Unknown Utility with Application in Mentor-Mentee Matching

The assignment problem, crucial in various real-world applications, involves optimizing the allocation of agents to tasks for maximum utility. While it has been well-studied in the optimization literature when the underlying utilities between all agent-task pairs are known, research is sparse when the utilities are unknown and need to be learned from data on the fly. This paper addresses this gap, as motivated by mentor-mentee matching programs at many U.S. universities. We develop an efficient sequential assignment algorithm, with the aim of nearly maximizing the overall utility simultaneously over different time periods. Our proposed algorithm is to use stochastic bandit feedback to adaptively estimate the unknown utilities through linear regression models, integrating the Upper Confidence Bound (UCB) algorithm in the multi-armed bandit problem with the Hungarian algorithm in the assignment problem. We provide theoretical bounds of our algorithm for both the estimation error and the total regret. Additionally, numerical studies are also conducted to demonstrate the practical effectiveness of our algorithm.

A Bayesian Approach to Atmospheric Circulation Regime Assignment

Abstract The standard approach when studying atmospheric circulation regimes and their dynamics is to use a hard regime assignment, where each atmospheric state is assigned to the regime it is closest to in distance. However, this may not always be the most appropriate approach as the regime assignment may be affected by small deviations in the distance to the regimes due to noise. To mitigate this we develop a sequential probabilistic regime assignment using Bayes’s theorem, which can be applied to previously defined regimes and implemented in real time as new data become available. Bayes’s theorem tells us that the probability of being in a regime given the data can be determined by combining climatological likelihood with prior information. The regime probabilities at time t can be used to inform the prior probabilities at time t + 1, which are then used to sequentially update the regime probabilities. We apply this approach to both reanalysis data and a seasonal hindcast ensemble incorporating knowledge of the transition probabilities between regimes. Furthermore, making use of the signal present within the ensemble to better inform the prior probabilities allows for identifying more pronounced interannual variability. The signal within the interannual variability of wintertime North Atlantic circulation regimes is assessed using both a categorical and regression approach, with the strongest signals found during very strong El Niño years. Significance Statement Atmospheric circulation regimes are recurrent and persistent patterns that characterize the atmospheric circulation on time scales of 1–3 weeks. They are relevant for predictability on these time scales as mediators of weather. In this study we propose a novel approach to assigning atmospheric states to six predefined wintertime circulation regimes over the North Atlantic and Europe, which can be applied in real time. This approach introduces a probabilistic, instead of deterministic, regime assignment and uses prior knowledge on the regime dynamics. It allows us to better identify the regime persistence and indicates when a state does not clearly belong to one regime. Making use of an ensemble of model simulations, we can identify more pronounced interannual variability by using the full ensemble to inform prior knowledge on the regimes.

Comparison of pharmacokinetics and safety between CE-fosphenytoin sodium, fosphenytoin sodium, and phenytoin sodium after intravenous and intramuscular administration in healthy volunteers.

Background: Captisol®-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium. Objective: We aim to compare the intravenous and intramuscular bioavailability and safety between CE-fosphenytoin sodium, fosphenytoin sodium (Cerebyx®), and phenytoin sodium (intravenous injection only). Methods: In pivotal study 1, 54 subjects were divided into three sequence groups that receive intravenous injection of 250mg of phenytoin sodium equivalent (PE), CE-fosphenytoin sodium (T), or fosphenytoin sodium (R1) and 250mg of phenytoin sodium (R2) in period 1. After a 14-day washout period, 36 subjects were randomized to two treatment sequence groups (T-R1 or R1-T, n = 18 per group) in period 2, in which the subjects who received R2 in period 1 were removed, those who received T in period 1 used R1 (T-R1), while those who previously received R1 used T (R1-T). In pivotal study 2, a single intramuscular dose of T (400mg PE) or R1 (400mg PE) was administered according to the individual sequential treatment assignment in each period. There was a washout (14days) period before receiving the next period study drug. Results: T and R1 have similar pharmacokinetic characteristics regarding total and free phenytoin, showing bioequivalence of both drugs in the intravenous and intramuscular administration. The geometric mean ratio was close to 1 (0.98-1.06). The AUC of total and free phenytoin in subjects who intravenously received T and R1 was very similar to those who received R2, although their Cmax was lower than that of the subjects who received R2. Overall, treatment with T and R1 was safe and well-tolerated, without serious adverse events (SAEs) or grade III adverse events (AEs). With intravenous (i.v.) or intramuscular (i.m.) treatment, the incidence of drug-related AEs using T was similar to that using R1. Treatment with T and R1 had clearly superior tolerability than that with R2. Conclusion: CE-fosphenytoin sodium is a promising substitute for fosphenytoin sodium. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/, CTR20202154 (11 November 2020).

Optimal-Control-Based Cβ Chemical Shift Encoding for Efficient Signal Assignment of Solid Proteins.

Fast magic-angle spinning (MAS) solid-state NMR spectroscopy is a powerful tool for gaining structural and dynamic information on solid proteins. To access such information site-specifically, the signal assignment process is unavoidable. In the assignment process, Cα and Cβ chemical shifts are of paramount importance in identifying the type of amino acid residues. Conventionally, however, recording the Cβ chemical shift of solid proteins with relatively short transverse relaxation time is often limited by the long delay required for the magnetization transfer to Cβ spins and its evolution, that is, by the sensitivity drop. In this article, we propose a new method that encodes the Cβ chemical shifts onto the intensities of the scalar-coupled Cα signals by combining an optimal control-based spin manipulation pulse and a spin-state filter. This reduces the total required transverse evolution to less than half of that for the previously proposed method, opening up the concept of the Cβ-encoding nearest-neighbor NMR, for the first time, to solid proteins. Also, the total measurement time was shorter than that required for the explicit Cβ shift evolution. We demonstrate the sequential signal assignment for microcrystalline protein GB1, and then discuss the prospects for more challenging proteins.

Chatbot-interfaced and cognitive-affective barrier-driven messages to improve colposcopy adherence after abnormal Pap test results in underserved urban women: A feasibility pilot study.

Challenges in ensuring adherence to colposcopy and follow-up recommendations, particularly within underserved communities, hinder the delivery of appropriate care. Informed by our established evidence-based program, we sought to assess the feasibility and acceptability of a novel cognitive-affective intervention delivered through a Chatbot interface, aimed to enhance colposcopy adherence within an urban inner-city population. We developed the evidence-based intervention, CervixChat, to address comprehension of colposcopy's purpose, human papillomavirus (HPV) understanding, cancer-related fatalistic beliefs, procedural concerns, and disease progression, offered in both English and Spanish. Females aged 21-65, with colposcopy appointments at an urban OBGYN clinic, were invited to participate. Enrolled patients experienced real-time counseling messages tailored via a Chatbot-driven barriers assessment, dispatched via text one week before their scheduled colposcopy. Cognitive-affective measures were assessed at baseline and through a 1-month follow-up. Participants also engaged in a brief post-intervention satisfaction survey and interview to capture their acceptance and feedback on the intervention. The primary endpoints encompassed study adherence (CervixChat response rate and follow-up survey rate) and self-evaluated intervention acceptability, with predefined feasibility benchmarks of at least 70% adherence and 80% satisfaction. Among 48 eligible women scheduled for colposcopies, 27 (56.3%) agreed, consented, and completed baseline assessments. Participants had an average age of 34 years, with 14 (52%) identifying as non-Hispanic White. Of these, 21 (77.8%) engaged with the CervixChat intervention via mobile phones. Impressively, 26 participants (96.3%) attended their diagnostic colposcopy within the specified timeframe. Moreover, 22 (81.5%) completed the follow-up survey and a brief interview. Barriers assessment revealed notable encodings in the Affect and Values/Goals domains, highlighting concerns and understanding around HPV, as well as its impact on body image and sexual matters. Persistent and relatively high intrusive thoughts and lowered risk perceptions regarding cervical cancer were reported over time, unaffected by the intervention. Post-intervention evaluations documented high satisfaction and perceived usefulness, with recommendations for incorporating additional practical and educational content. Our findings underscore the robust satisfaction and practicality of the CervixChat intervention among a diverse underserved population. Moving forward, our next step involves evaluating the intervention's efficacy through a Sequential Multiple Assignment Randomized Trial (SMART) design. Enhanced by personalized health coaching, we aim to further bolster women's risk perception, address intrusive thoughts, and streamline resources to effectively improve colposcopy screening attendance.

Abstract 12491: Impact of Augmented Treatments on Physical Activity Outcomes in a Sequential Multiple Assignment Randomized Trial

Background: Nearly half of women do not meet aerobic physical activity (PA) guidelines. Despite proven efficacy of PA interventions, response varies. Little is known about when treatment should be augmented. The Working Women Walking Program is a Sequential Multiple Assignment Randomized Trial testing two initial treatments (Fitbit vs. Fitbit+text messages) for eight weeks and two augmented treatments (personal calls vs. group meetings) added at eight weeks for non-responders to the initial treatments. Aims: We aim to compare the two augmented treatments among non-responders to the initial treatments on PA after 34 weeks of the program. Methods: Participants ( N = 301; women ages 18-70) were randomly assigned to an initial treatment of either Fitbit ( n = 149) or Fitbit+text messages ( n = 152). Both groups received a Fitbit and PA prescription (increase daily steps by ≥600 above baseline). Response to treatment was defined as (a) wearing the Fitbit 10 hours per day 3 of 7 days weekly in weeks 6-8 and (b) reaching a step goal ≥600 steps above baseline for 2-3 weeks in weeks 6-8. Non-responders were randomly assigned to an augmented treatment with personal calls ( n = 72; 50.7%) or group meetings ( n = 70; 49.3%). Objective PA was assessed with the waist-worn ActiGraph accelerometer (≥4 days with one weekend day and ≥10 hours daily wear time) at baseline and 34 weeks to assess daily steps and minutes of light and moderate-vigorous intensity PA (MVPA). Self-report PA was measured with the International PA Questionnaire to assess daily MVPA and walking. Results: Across all PA measures, there were no significant differences between augmented treatments (personal calls vs. group meetings). Overall, both treatments showed non-significant increases in objective PA, including steps ( d = .15; p = .30), light PA ( d = .11; p = .39), and MVPA ( d = .22; p = .15), but showed significant increases in self-report PA, including ( d = 1.02; p < .001) and walking ( d = .73; p = .30). Conclusion: In this sample of working women who were non-responsive to an initial PA treatment (Fitbit or Fitbit+texts), augmenting with personal calls or group meetings did not yield a difference in PA outcomes. Next, we will explore participant characteristics that may differentiate response to augmented treatments.

Abstract 15365: The Effect of Mobile Phone Messaging in the Reduction of Ambulatory Blood Pressure in Adults: A Systematic Review

Introduction: Ample evidence supports a lower risk for cardiovascular disease (CVD) with controlled blood pressure (BP), yet hypertension (HTN) remains a leading cause of CVD. Mobile health such as text messaging is commonly included in BP management programs; however, the association of texting with BP interventions is less well known. We sought to examine the effectiveness of mobile messaging on BP in adults in the ambulatory setting. Methods: In this systematic review, we searched 4 databases from date of inception through February 2023 using search terms (texting, messaging, mobile phone, BP, HTN). After removing duplicate citations, two reviewers independently reviewed the references for eligibility (randomized control trial [RCT], participants > 18 years of age, participants either with elevated BP, and/or a diagnosis of HTN). Results: A total of 1,786 RCTs were identified of which 48 met eligibility criteria, for a combined total of 19,720 participants from 21 countries, including 13 US studies. Twenty-seven studies reported significant reductions in BP (systolic, diastolic or both). All three RCTs using texting and pharmacist counseling (n=3) demonstrated significant changes in BP, while 13 of 16 RCTs with texting and provider involvement observed significant improvement in BP. For the studies reporting between group changes in systolic BP from baseline, 7 studies noted significant improvements in BP (Figure 1). Conclusions: Despite heterogeneity in study components, we found text messaging when used with other intervention components was associated with BP reductions among adults with HTN. Larger studies using novel designs such as SMART (sequential multiple assignment randomized trials) are warranted to understand efficacy of texting with other intervention components.

Increasing the reach of evidence-based interventions for weight management and diabetes prevention among Medicaid patients: study protocol for a pilot Sequential Multiple Assignment Randomised Trial

IntroductionOver 40% of US adults meet criteria for obesity, a major risk factor for chronic disease. Obesity disproportionately impacts populations that have been historically marginalised (eg, low socioeconomic status, rural,...

Optimising stochastic task allocation and scheduling plans for mission workers subject to learning-forgetting, fatigue-recovery, and stress-recovery effects

This study addresses the stochastic bi-objective task allocation and scheduling problems for mission workers subject to the complex (and joint) effect of learning-forgetting, fatigue-recovery, and stress-recovery processes. The mission consists of work-rest cycles with different types of tasks. Some task types are repetitive, not necessarily back-to-back, with some predecessors for other task types. The workers are multi-skilled, whose experience, learning, fatigue, and stress levels are updated, affecting their performance dynamically. A Markov Decision Process (MDP) is applied to formulate this stochastic problem, considering speed and accuracy as two measures of workforce performance. A decision could be “to repeat a task of a certain type” or “take a rest break till another worker becomes available”. The developed MDP model finds the optimal task allocation and work-break schedule for workers by minimising the sum of the tasks’ completion times and maximising their quality. Completion time is a continuous variable, and the quality index is a binary random variable, i.e., high or moderate, having a continuous probability of occurrence. The model is of a general form with a potential application in similar settings. The paper used the Sequential Greedy Assignment (SGA) and the Monte-Carlo Tree Search (MCTS) to solve the problem with their results compared. Numerical results with those from a sensitivity analysis are discussed.

Examining engagement effects in an adaptive preventive intervention for college student drinking.

This study determined the characteristics of engagement and whether engagement in an adaptive preventive intervention (API) was associated with reduced binge drinking and alcohol-related consequences. Incoming students were recruited for a sequential multiple assignment randomized trial (SMART; N = 891, 62.4% female, 76.8% non-Hispanic White) with an assessment-only control group. The API occurred during the first semester of college, with outcomes assessed at the end of the semester. The API involved two stages. Stage 1 included universal intervention components (personalized normative feedback [PNF] and self-monitoring). Stage 2 bridged heavy drinkers to access additional resources. We estimated the effect of engagement in Stage 1 only and in the whole API (Stages 1 and 2) among the intervention group, and the effect of the API versus control had all students assigned an API engaged, on alcohol-related outcomes. Precollege binge drinking, intention to pledge a fraternity/sorority, and higher conformity motives were most associated with lower odds of Stage 1 engagement. Action (readiness to change) and PNF engagement were associated with Stage 2 engagement. API engagement was associated with significant reductions in alcohol-related consequences among heavy drinkers. Compared to the control, we estimated the API would reduce the relative increase in alcohol-related consequences from baseline to follow-up by 25%, had all API students engaged. Even partial engagement in each component of the "light-touch" API rendered benefits. Analyses suggested that had all students in the intervention group engaged, the API would significantly reduce the change in alcohol-related consequences over the first semester in college. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sequenced treatment alternatives to relieve adolescent depression (STAR-AD): a multicentre open-label randomized controlled trial protocol

BackgroundAdolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well.MethodsWe developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment.DiscussionThe results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD.Trial registrationThis protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Modified interactive Q-learning for attenuating the impact of model misspecification with treatment effect heterogeneity.

A sequential multiple assignment randomized trial, which incorporates multiple stages of randomization, is a popular approach for collecting data to inform personalized and adaptive treatments. There is an extensive literature on statistical methods to analyze data collected in sequential multiple assignment randomized trials and estimate the optimal dynamic treatment regime. Q-learning with linear regression is widely used for this purpose due to its ease of implementation. However, model misspecification is a common problem with this approach, and little attention has been given to the impact of model misspecification when treatment effects are heterogeneous across subjects. This article describes the integrative impact of two possible types of model misspecification related to treatment effect heterogeneity: omitted early-stage treatment effects in late-stage main effect model, and violated linearity assumption between pseudo-outcomes and predictors despite non-linearity arising from the optimization operation. The proposed method, aiming to deal with both types of misspecification concomitantly, builds interactive models into modified parametric Q-learning with Murphy's regret function. Simulations show that the proposed method is robust to both sources of model misspecification. The proposed method is applied to a two-stage sequential multiple assignment randomized trial with embedded tailoring aimed at reducing binge drinking in first-year college students.

Motivational Enhancement Interventions to Increase Pre-Exposure Prophylaxis Use in Sexual Minority Men Who Use Stimulants: Protocol for a Pilot Sequential Multiple Assignment Randomized Trial.

Although pre-exposure prophylaxis (PrEP) could substantially mitigate HIV risk, sexual minority men who use stimulants commonly experience difficulties with engaging in PrEP clinical services. Motivational interviewing (MI) and contingency management (CM) reduce substance use and condomless anal sex (CAS) in this population, but these motivational enhancement interventions require modifications to promote engagement along the PrEP care continuum. PrEP Readiness Interventions for Supporting Motivation (PRISM) is a pilot sequential multiple assignment randomized trial testing the feasibility, acceptability, and preliminary effectiveness of distinct combinations of telehealth MI and CM in 70 cisgender sexual minority men who use stimulants that are not currently taking PrEP. A national sample was recruited via social networking applications to complete a baseline assessment and mail-in HIV testing. Those with nonreactive HIV results were randomized to receive either (1) a 2-session MI intervention focusing on PrEP use (session 1) and concomitant stimulant use or CAS (session 2) or (2) a CM intervention with financial incentives for documented evidence of PrEP clinical evaluation by a medical provider (US $50) and filling a PrEP prescription (US $50). At the 3-month follow-up assessment, participants who reported they had not filled a prescription for PrEP were randomized a second time to either (1) switch to a second-stage intervention (ie, MI+CM or CM+MI) or (2) continue with assessments only. Outcomes for both responders and nonresponders were reassessed at a 6-month follow-up. The primary outcome is documented evidence of filling a PrEP prescription over 6 months. Self-reported secondary outcomes include PrEP clinical evaluation by a medical provider, stimulant use, and CAS. Qualitative exit interviews were conducted with a subgroup of responders and nonresponders to characterize their experiences with the MI and CM interventions. Implementation of PRISM underscores challenges in reaching sexual minority men who use stimulants to optimize HIV prevention efforts. Approximately 1 in 10 (104/1060) eligible participants have enrolled. Of the 104 who enrolled, 87 (84%) completed mail-in HIV testing. We delivered 5 preliminary HIV-positive results, including posttest counseling with referrals to confirmatory testing. Lessons learned from PRISM underscore the central importance of a flexible, participant-centered approach to support the engagement of sexual minority men who use stimulants. Leveraging telehealth platforms to deliver motivational enhancement interventions also expanded their reach and potential public health impact with this high-priority population. Further research is needed to determine the effectiveness of telehealth MI and CM for supporting PrEP use in sexual minority men who use stimulants. ClinicalTrials.gov NCT04205487; https://clinicaltrials.gov/study/NCT04205487. DERR1-10.2196/48459.

Solution-state NMR assignment and secondary structure analysis of the monomeric Pseudomonas biofilm-forming functional amyloid accessory protein FapA.

FapA is an accessory protein within the biofilm forming functional bacterial amyloid related fap-operon in Pseudomonas, and maybe a chaperone for FapC controlling its fibrillization. To allow further structural analysis, here we present a complete sequential assignment of 1Hamide, 13Cα, 13Cβ, and 15N NMR resonances for the functional form of the monomeric soluble FapA protein, comprising amino acids between 29 and 152. From these observed chemical shifts, the secondary structure propensities (SSPs) were determined. FapA predominantly adopts a random coil conformation, however, we also identified small propensities for α-helical and β-strand conformations. Notably, these observed SSPs are smaller compared to the ones we recently observed for the monomeric soluble FapC protein. These NMR results provide valuable insights into the activity of FapA in functional amyloid formation and regulation, that will also aid developing strategies targeting amyloid formation within biofilms and addressing chronic infections.

Sequential multiple assignment randomised controlled trial protocol for developing an adaptive intervention to improve depressive symptoms among family caregivers of people with dementia

ObjectivesFamily caregivers of people with dementia (FC-of-PWD) suffer from a high level of stress and depressive symptoms, which usually require different interventions at different stages. Although some standalone interventions such...

Study protocol for a sequential multiple assignment randomized trial to reduce risky drinking among service members and their partners

BackgroundMilitary spouses and partners in relationships with a heavy drinking service member report high levels of mental health concerns and consequences, which are compounded when both partners drink heavily. Military spouses and partners —termed “concerned partners” (CPs)—may be an important gateway for motivating service members (SMs) to seek care. However, CPs may first need to reduce their own drinking and improve their communication to effectively support and encourage changes for their service member partner. Partners Connect is a web-based intervention aimed at improving communication and relationship quality and increasing SM help-seeking. MethodsThe current study design is a two-stage Sequential Multiple Assignment Randomized Trial (SMART) to develop an adaptive CP intervention to decrease CP drinking and increase SM help-seeking. CPs aged 18 and older (n = 408) will be recruited via social media and followed for six months. In stage one, we will randomize CPs to either a 4-session web-based intervention (Partners Connect) or to receive communication resources from the Gottman Institute website. The goal is to have CPs invite their SM to complete an online personalized normative feedback (PNF) session. If their SM completes the PNF at stage one, CPs will be considered “responders,” if the SM does not complete, CPs who are “non-responders” will be re-randomized during stage two to receive either (1) a CRAFT workbook or (2) phone-based CRAFT if in Partners Connect; or (1) Partners Connect or (2) a CRAFT workbook if in Gottman. DiscussionBy first intervening with the service member's CP, we aim to better equip them to engage their service member partner in treatment services. In doing so, we develop a model that increases treatment accessibility and appeal among a group that may not otherwise seek care.ClinicalTrials.gov Identifier: NCT05619185

Which trial do we need? A sequential multiple assignment randomized trial to determine the optimal Clostridioides difficile treatment sequence

Which trial do we need? A sequential multiple assignment randomized trial to determine the optimal Clostridioides difficile treatment sequence