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Randomized controlled trials include interim monitoring guidelines to stop early for safety, efficacy, or futility. Futility monitoring facilitates re-allocation of limited resources. However, conventional methods for interim futility monitoring require a trial to accrue nearly half of the outcome data to make a reliable early stopping decision, limiting its benefit. As early stopping for futility will not inflate type-I error, these analyses are an appealing venue for incorporating external data to improve efficiency. We propose a Bayesian approach to futility monitoring leveraging real world data using Semi-Supervised MIXture Multi-source Exchangeability Models, which accounts for both measured and unmeasured differences between data sources. We implement futility monitoring using predictive probabilities and investigate the optimal timing with respect to the expected sample size under the null hypothesis. Because we only incorporate external data during the interim futility analysis the proposed design is not limited by type-I error inflation. When the external and trial data are exchangeable, the proposed method provides a roughly 70 person reduction in expected sample size under the null. Under scenarios where exchangeability does not hold, our approach still provides a 10–20 person reduction in expected sample size under the null with about 80% power. External data borrowing in interim futility monitoring is a promising venue to improve trial efficiency without type-I error inflation. Approaches that are acceptable to regulatory authorities and leverage the complementary strengths of real world and trial data are vital to more efficiently allocate limited resources amongst clinical trials. [ABSTRACT FROM AUTHOR]

To improve symptoms and reduce poor outcomes related to heart failure (HF), international guidelines recommend cardiac rehabilitation (CR), particularly for those with a reduced ejection fraction. Unfortunately, patient adherence to rehabilitation programs remains suboptimal, with dropouts ranging from 15.4 to 63.3%. An innovative and promising intervention that could improve adherence to rehabilitation is virtual reality (VR). This study aims to evaluate the effects of VR in patients with HF who undergo CR using this technology in terms of adherence (primary outcome), functional capacity, perceived exertion, angina, quality of life, heart rate, oxygen saturation, blood pressure, maximum oxygen uptake, minute ventilation/carbon dioxide production slope, oxygen pulse, blood values of NT-proBNP and HF related rehospitalization rates (secondary outcomes). A randomized controlled trial will be conducted in a sample of 80 patients referred to CR. Participants will be enrolled in a cardiological rehabilitation unit of a large university hospital in Italy and randomized (1:1) to the experimental intervention consisting of CR performed with high-quality immersive VR with PICO 4® Head Mounted Display headset and TREADMILL XR® software (Arm 1) or standard CR (Arm 2). Patients, according to guidelines, will perform 30-min of CR sessions with moderate intensity, twice a week for one month. Significant improvements in primary and secondary outcomes are expected in patients in the intervention group. If proven to be effective, VR could be an innovative, safe, and easy digital health intervention to improve adherence to CR in patients with HF, as well as important clinical outcomes. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of DiabeText, a low-intensity, multifaceted, mobile health (mHealth) intervention to support medication taking and lifestyle change targeted to people with type 2 diabetes (T2D). Phase III, 12-months, two-arm (1:1 allocation ratio), randomized parallel-group trial. We will recruit 740 adults with glycated hemoglobin (A1c) >8% (>64 mmol/mol) and with at least one prescription of a non-insulin antidiabetic drug. They will be allocated to a control (usual care) group or an intervention (DiabeText messaging intervention) group. The primary outcome measure will be A1c at 12 months follow-up. Secondary outcomes will include medication possession ratio and behavioral and psychological outcomes. Recent trials suggest that digital health interventions can effectively support diabetes self-management improving T2D control and reducing important T2D complications. In Spain this type of interventions is understudied. This trial will strengthen the evidence base of the impact of mHealth interventions to support diabetes self-management. If effective, DiabeText may offer a low-cost and highly scalable strategy to improve health at the population level in a sustainable way. ClinicalTrials.gov identifier NCT05006872 ; Official Title: Supporting People with Type 2 Diabetes in Effective Use of their Medicine Through a System Comprising Mobile Health Technology Integrated with Clinical Care. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic condition affecting nearly 1.9 million people in the United States. Young adults (YAs) with T1D face unique challenges in managing their condition, experiencing poorer health and well-being than other age groups. The current study is evaluating the Resilient, Empowered, Active Living (REAL) intervention, previously shown to improve glucose levels and quality of life among YAs with diabetes, using telehealth delivery (REAL-T) to expand reach and accessibility. This paper reports on the methodology and baseline participant characteristics of the REAL-T study. REAL-T is a two-arm randomized controlled trial that recruited 18–30 year olds with T1D via clinics and social media advertising. Data collection, which was adapted to be fully remote due to COVID-19, occurs every three months for one year. Participants receive either usual care or a 6-month telehealth occupational therapy intervention. The primary outcome is glycated hemoglobin (A1c); secondary outcomes include diabetes distress, quality of life, and continuous glucose monitor-derived measures. The study enrolled a diverse sample of 209 YAs with T1D. Analysis of baseline data indicates equivalence between the intervention and control groups. Study participants have notably higher diabetes distress and poorer mental well-being than similar populations. The REAL-T study successfully adapted to remote implementation during the COVID-19 pandemic. By examining long-term outcomes, mediating pathways, and cost-effectiveness, the study will contribute knowledge of the impact of tailored interventions for YAs with T1D, designed to reduce disparities and improve health and well-being in this population. [ABSTRACT FROM AUTHOR]

Genetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention. Females (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6–12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling. If efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden. Trial Registration: ClinicalTrials.gov NCT05325151 [ABSTRACT FROM AUTHOR]

Social anxiety disorder (SAD) is characterized by a fear of scrutiny in social or performance situations. Due to a number of barriers, many individuals do not seek treatment for SAD, resulting in a chronic and debilitating course. Cognitive behaviour therapy (CBT), and more recently Imagery Rescripting (ImR), have been found to be efficacious in the treatment of SAD when delivered face-to-face. However, the efficacy of these treatment approaches when delivered remotely, have not yet been examined in controlled trials. The authors propose a two-group randomized controlled trial comparing the efficacy of videoconferencing delivered CBT (vCBT) for SAD against a waitlist control group. The study will recruit 78 adults in total with a primary diagnosis of SAD of at least moderate severity. The manualised high-intensity vCBT intervention will be delivered weekly over an 8-week period. After treatment completion, the waitlist participants will receive a high-intensity videoconferencing delivered ImR (vImR) intervention also delivered weekly over an 8-week period. Treatment for both groups will be delivered in real time via an online videoconferencing platform. Outcome measures will be administered at baseline, mid-treatment, post-treatment, and 3-month follow-up. This trial will report findings on the efficacy of a remote synchronous high-intensity vCBT and vImR intervention for SAD and benchmark the two different treatment methodologies against standard face-to-face CBT. The results have the potential to inform best-practice remote psychological treatment for SAD. The trial was registered on the Australian New Zealand Clinical Trials Registry; ACTRN12623000313639 (5 April 2023). • Future research investigating high intensity remote CBT for SAD is urgently needed. • A randomized controlled trial will be conducted for videoconferencing CBT (vCBT). • An uncontrolled trial will be conducted for videoconferencing Imagery Rescripting (vImR). • vCBT and vImR outcomes will be benchmarked against face-to-face CBT for SAD. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) sequelae often have ripple effects on victims' families and spouses. Yet there has been a lag in the development and study of couple therapy for PTSD. To fill this gap, we present here a protocol for a study examining the efficacy of Cognitive Behavioral Conjoint Therapy (CBCT), a 15- session couple therapy protocol meant to alleviate PTSD and improve relationship satisfaction, in the Israeli context. The study will be a randomized controlled trial examining outcomes and processes of change via self-report questionnaires, qualitative interviews, and physiological measures (e.g., both partners' heart rate variability and electrodermal activity). We will employ a modified remote treatment protocol via video conferencing. The study will examine whether there is a reduction in couples' levels of symptomatic, emotional, and behavioral difficulties following CBCT and whether relationship satisfaction and couples' physiological synchrony increases. The study will also examine physiological and psychological change mechanisms in CBCT. Sixty Israeli couples (n = 120) will be randomly assigned to either a CBCT group or a wait-list control group. Outcomes will be assessed at four timepoints: before treatment, during treatment, post-treatment, and four months after treatment. The proposed study has the potential to shed light on the unique psychological and physiological mechanisms underlying CBCT and will be the first RCT study to employ this unique methodology in CBCT research, particularly in a video conferencing setting. This study may increase our ability to offer effective, cost-efficient, and attainable treatments for patients with PTSD and their spouses. [ABSTRACT FROM AUTHOR]

Although unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the F inancial I ncentives, R andomization, with S tepped T reatment (FIRST) Trial, a multi-site randomized controlled efficacy trial. PWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1 : Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2 : Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described. The FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH. ClinicalTrials.gov identifier: NCT03089320. • People with HIV (PWH) often are ambivalent about engaging in treatment of unhealthy alcohol use. • Contingency management holds promise for reducing unhealthy alcohol use among PWH. • Stepped care strategies are important given lack of consistent response to alcohol treatments. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that there are numerous benefits to scheduling postpartum visits as early as 3 weeks post-delivery. However, findings are not conclusive due to methodological limitations. This report discusses the unique aspects of a randomized controlled trial's (RCT) design, intervention, and strategies to maintain participant retention. This study was a four-year, prospective, open-label RCT conducted at the Virginia Commonwealth University Medical Center. Women who recently delivered a healthy, full-term baby vaginally, were randomized to receive a 3–4 or 6–8 weeks postpartum appointment and were followed for 18 months. A total of 364 women participated in this study. A large proportion of women were retained in the study as demonstrated by the high completion rates at the 18-month follow-up interview (Total sample: 87.6%; 3–4 weeks group: 88.0%; 6–8 weeks group: 87.3%). Similarly, high adherence to the protocol-directed postpartum visit schedule was reported in the overall study sample (79.7%), as well as in the 3–4 (70.5%) and 6–8 (90.0%) week postpartum groups. The study design offered unique features which ensured excellent participant completion and adherence rates, despite the presence of hard-to-track women who typically do not return for their postpartum visits. [ABSTRACT FROM AUTHOR]

Abstract Background Postmenopausal Latinas are a growing population group in the US who are at high risk for cardiovascular disease. Epidemiological studies have shown that excessive sitting is related to cardiovascular disease risk. Older women sit for prolonged periods and most individuals do not meet physical activity guidelines. Reducing sitting through increased standing may improve cardiovascular risk. More research is needed on how to intervene to increase standing in older Latinas. Objective To describe the protocol for a randomized controlled trial to increase standing in postmenopausal Latinas: the Arriba por la Vida Estudio (AVE). Design/methods Postmenopausal Latinas will be randomized to one of two study arms: an increase standing intervention or a heart healthy attention-comparison condition. A total of 250 overweight postmenopausal Latinas will be recruited and followed for 12 weeks. AVE is based on various models of behavior change including strategies such as self-monitoring, goal setting, and habit formation. Participants will receive three in-personhealth-counseling sessions (including one in-home visit) and five follow-up telephone calls using motivational interviewing techniques. Those in the attention-comparison condition will receive an equal number of contacts as the standing intervention with topics focused on healthy aging. The primary outcome is objectively-measured sitting time over three months measured via thigh-worn inclinometers and secondary outcomes include blood pressure, physical functioning and glucoregulatory and lipid biomarkers. Conclusions The findings from this study will provide valuable information about effective approaches to increase standing time in postmenopausal Latinas and its impact on cardiovascular disease risk. Trial registration This study is registered at clincialtrials.gov Identifier: NCT02905929 [ABSTRACT FROM AUTHOR]

Abstract Background Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. Purpose Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. Methods SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. Results Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5–90.7%) and confidence (50.0–74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. Conclusion Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management. [ABSTRACT FROM AUTHOR]

Abstract Background/Aims Behavioral nudges in the food environment increase healthy choices, but it is unknown if they improve diet and health. The ChooseWell 365 study will determine if an automated, personalized worksite intervention to nudge healthier choices improves overall diet and cardiometabolic health. Design Randomized controlled trial of 602 hospital employees who regularly use on-site cafeterias and pay with an employee ID. Intervention The intervention combines an environmental strategy (traffic-light labeling) with objective feedback and personalized nudges (health/lifestyle tips, social norms, incentives) to promote healthy food choices. The ChooseWell 365 software platform automatically generates personalized emails and letters that integrate employees' weight goals with health, lifestyle, and cafeteria purchasing data. Over one year, the intervention group receives two weekly emails. One provides a log of daily purchases; the second provides personalized health/lifestyle tips. The intervention group receives monthly mailed letters with social norm comparisons and financial incentives for healthier purchases. The one-year intervention will be completed in February 2019; all follow-up will be completed March 2020. Outcomes Weight, cardiometabolic risk factors, and dietary intake at one and two-year follow-up. Other outcomes include worksite food purchases by study participants and other non-participant employees who are socially connected (inferred from purchasing data) to participants. Conclusions ChooseWell 365 tests a novel strategy to deliver a scalable worksite prevention program that is integrated into the workday. The intervention is personalized but automated and therefore does not require costlier individual counseling. In the future, this program could be applied broadly in other worksite settings. [ABSTRACT FROM AUTHOR]

Little is known about effective strategies to improve advance care planning (ACP) for persons with cognitive impairment in primary care, the most common setting of care. We describe a randomized controlled trial to test the efficacy of a multicomponent communication intervention, "Sharing Healthcare Wishes in Primary Care" (SHARE). Planned enrollment of 248 dyads of adults 80 years and older with possible cognitive impairment and their care partner, from primary care clinics at 2 Mid-Atlantic health systems. The treatment protocol encompasses an introductory letter from the clinic; access to a designated facilitator trained in ACP; person-family agenda-setting to align perspectives about the family's role; and print education. The control protocol encompasses minimally enhanced usual care, which includes print education and a blank advance directive. Randomization occurs at the individual dyad-level. Patient and care partner surveys are fielded at baseline, 6-, 12-, and 24- months. Fidelity of interventionist delivery of the protocol is measured through audio-recordings of ACP conversations and post-meeting reports, and by ongoing monitoring and support of interventionists. The primary outcome is quality of end-of-life care communication at 6 months; secondary outcomes include ACP process measures. An exploratory aim examines end-of-life care quality and bereaved care partner experiences for patients who die by 24 months. Caregiver burden, clinician barriers, and impaired decisional capacity amplify the difficulty and importance of ACP discussions in the context of cognitive impairment: this intervention will comprehensively examine communication processes for this special subpopulation in a key setting of primary care. Registration: ClinicalTrials.gov : NCT04593472. [ABSTRACT FROM AUTHOR]

Fetal Alcohol Spectrum Disorders (FASD) result in lifelong disability and are a leading cause of preventable birth defects in the US, including for American Indian and Alaska Natives (AIANs). Prevention of alcohol exposed pregnancies (AEPs), which can cause FASD, is typically aimed at adult women who are risky drinkers and have unprotected sex. Among AIANs, AEP prevention research has been primarily conducted in reservation communities, even though over 70% of AIANs live in urban areas. Culturally appropriate AEP prevention for urban AIAN young women, regardless of current drinking or sexual behaviors, may maximize the potential for primary prevention at the beginning of the reproductive years for this underserved population. We developed a virtual randomized controlled trial (RCT) – fully implemented through technology – to evaluate Native WYSE CHOICES, a culturally tailored mobile app, with urban AIAN young women ages 16–20 nationally. While virtual RCTs are not new, this is the first engaging a solely urban AIAN population, historically excluded from research. Participants are recruited on a rolling basis through the project social media community, organizational partnerships, and in-person events. Eligible participants complete a baseline survey and are randomized to either the app's intervention or comparison arm – each of which provide about 3 h of content. Follow-up data are collected at 1-, 6-, and 12-months post-baseline. Our study offers a template for building trust and extending reach to this underserved population while also providing important lessons and insights on advances in virtual or hybrid research approaches. [ABSTRACT FROM AUTHOR]

Background Mindfulness-based relapse prevention (MBRP) is a method that combines cognitive behavioral relapse prevention with mindfulness practice. Research suggests that MBRP can effectively reduce withdrawal/craving in people with substance use disorder (SUD). An important part of MBRP is to practice mindfulness meditation to cope with high-risk situations for relapse, such as stimuli and situations associated with drug taking. Virtual reality cue exposure (VRCE) may be a complementary approach to MBRP as it allows for controlled and graded presentations of various high-risk situations with distal and proximal drug cues. The aim of the study is to investigate the effects of MBRP combined with VRCE, in comparison to MBRP alone or treatment as usual, on craving and emotional responses in people with methamphetamine use disorders. Method/design The study is a parallel randomized controlled study including 180 participants with methamphetamine use disorder. Three parallel groups will receive 8 weeks of MBRP combined with VRCE, MBRP alone, or treatment as usual, respectively. Craving, virtual cue reactivity, anxiety, depression, emotion regulation, mindfulness and drug-related attention bias will be assessed at pre-treatment, post-treatment, and 3 and 6 months of follow-up. Discussion This innovative study aims at investigating the effects of MBRP combined with VRCE in people with SUD. The combined intervention may have important clinical implications for relapse prevention due to its ease of application and high cost-effectiveness. This study may also stimulate research on the neuronal and psychological mechanisms of MBRP in substance use disorder. Trial registration number ChiCTR-INR-17013041. [ABSTRACT FROM AUTHOR]

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Methods/Design Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. Discussion This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. [ABSTRACT FROM AUTHOR]

Background Reducing ultraviolet radiation (UV) exposure and improving early detection may reduce melanoma incidence, mortality and health system costs. This study aims to evaluate the efficacy and cost-effectiveness of providing information on personal genomic risk of melanoma in reducing UV exposure at 12 months, according to low and high traditional risk. Methods In this randomized controlled trial, participants (target sample = 892) will be recruited from the general population, and randomized (1:1 ratio, intervention versus control). Intervention arm participants provide a saliva sample, receive personalized melanoma genomic risk information, a genetic counselor phone call, and an educational booklet on melanoma prevention. Control arm participants receive only the educational booklet. Eligible participants are aged 18–69 years, have European ancestry and no personal history of melanoma. All participants will complete a questionnaire and wear a UV dosimeter to objectively measure their sun exposure at baseline, 1- and 12-month time-points, except 1-month UV dosimetry will be limited to ~250 participants. The primary outcome is total daily Standard Erythemal Doses at 12 months. Secondary outcomes include objectively measured UV exposure for specific time periods (e.g. midday hours), self-reported sun protection and skin-examination behaviors, psycho-social outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the intervention costs and outcomes. Discussion This trial will inform the clinical and personal utility of introducing genomic testing into the health system for melanoma prevention and early detection at a population-level. Trial registration. Australian New Zealand Clinical Trials Registry ACTRN12617000691347. [ABSTRACT FROM AUTHOR]

Background Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a “treat-to-target” strategy congruent with specialty guidelines. Methods We have planned and initiated the Veterans Affairs (VA) Cooperative Study Program (CSP) 594, Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study. This large double-blind, non-inferiority trial will enroll 950 gout patients randomized to receive allopurinol or febuxostat. Patients will be followed for a total of 72 weeks encompassing 3 distinct 24-week study phases. During Phase I (0–24 weeks), participants will undergo gradual dose titration of ULT until achievement of serum uric acid (sUA) <6.0 mg/dL or <5.0 mg/dL if tophi are present. Dose escalation will not be allowed during final three study visits of Phase 2 (24–48 weeks) and during Phase 3 (48–72 weeks). The primary study outcome is the proportion of participants experiencing at least one gout flare during Phase 3. Subsequent to the 72-week study, participants will be followed passively for up to 10 years after the study to assess long-term health outcomes. Conclusion With its completion, the VA Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study will demonstrate the central role of gradual ULT dose escalation and a treat-to-target strategy in gout management. [ABSTRACT FROM AUTHOR]

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. Trial registration: Clinicaltrials.gov NCT02793921 . Registered 20 May 2016. [ABSTRACT FROM AUTHOR]

Background Recent studies have demonstrated the effectiveness of family-centered, pediatric weight management programs in reducing childhood obesity. Yet, programs to optimize the care of low-income children with obesity are needed. We sought to examine the comparative effectiveness of two, potentially scalable pediatric weight management programs delivered to low-income children in a clinical or community setting. Materials and methods The Clinic and Community Approaches to Healthy Weight Trial is a randomized trial in two communities in Massachusetts that serve a large population of low-income children and families. The two-arm trial compares the effects of a pediatric weight management program delivered in the Healthy Weight Clinics of two federally qualified health centers (FQHC) to the Healthy Weight and Your Child programs delivered in two YMCAs. Eligible children are 6 to 12 years old with a body mass index (BMI) ≥ 85th percentile seen in primary care at the two FQHCs. Both programs are one-year in duration and have at least 30 contact hours throughout the year. Measures are collected at baseline, 6 months, and 1 year. The main outcome is 1-year change in BMI (kg/m 2 ) and percent change of the 95th percentile (%BMIp 95 ). Conclusion The Clinic and Community Approaches to Healthy Weight Trial seeks to 1) examine the comparative effects of a clinical and community based intervention in improving childhood obesity, and 2) inform the care of >7 million children with obesity covered by the Children's Health Insurance Program or Medicaid. [ABSTRACT FROM AUTHOR]

Background Behavioral interventions for weight loss have been less effective in lower income and black women. These poorer outcomes may in part be related to these women having more frequent exposures to social and physical situations that are obesogenic, i.e., eating and sedentary cues or situations. Objectives Working with obese, lower income Black and White Women, Addressing People and Place Microenvironments (APP-Me) was designed to create awareness of self-behavior at times and places of frequent eating and sedentary behavior. Design APP-Me is being evaluated in a randomized controlled trial with 240 participants recruited from federally qualified health centers located in a single Midwestern city. All participants complete four weeks of ecological momentary assessments (EMA) of situations and behavior. At the end of the four weeks, participants are randomized to enhanced usual care (UC) or UC plus APP-Me. Methods APP-Me is an automated short messaging system (SMS). Messages are text, image, audio, or a combination, and are delivered to participants' mobile devices with the intent of creating awareness at the times and places of frequent eating or sedentary behavior. The EMA data inform the timing of message deliveries. Summary This project aims to create and test timely awareness messages in a subpopulation that has not responded well to traditional behavioral interventions for weight loss. Novel aspects of the study include the involvement of a low income population, the use of data on time and place of obesogenic behavior, and message delivery time tailored to an individual's behavioral patterns. [ABSTRACT FROM AUTHOR]

The optimum dose of vitamin D and corresponding serum 25-hydroxyvitamin D (25OHD) concentration for bone health is still debated and some health practitioners are recommending doses well above the Canada/USA recommended Dietary Reference Intake (DRI). We designed a three-year randomized double-blind clinical trial investigating whether there are dose-dependent effects of vitamin D supplementation above the Dietary Reference Intake (DRI) on bone health. The primary aims of this study are to assess, whether supplementation of vitamin D 3 increases 1) volumetric bone mineral density measured by high-resolution peripheral quantitative computed tomography (HR-pQCT); 2) bone strength assessed by finite element analysis, and 3) areal bone mineral density by dual X-ray absorptiometry (DXA). Secondary aims are to understand whether vitamin D 3 supplementation improves parameters of bone microarchitecture, balance, physical function and quality of life. Participants are men and women aged 55–70 years, with women at least 5-years post-menopause. The intervention is daily vitamin D 3 supplementation doses of 400, 4000 or 10,000 IU. Participants not achieving adequate dietary calcium intake are provided with calcium supplementation, up to a maximum supplemental dose of 600 mg elemental calcium per day. Results from this three-year study will provide evidence whether daily vitamin D 3 supplementation with adequate calcium intake can affect bone density, bone microarchitecture and bone strength in men and women. Furthermore, the safety of high dose daily vitamin D 3 supplementation will be explored. [ABSTRACT FROM AUTHOR]

Objective To describe the methodology of a 2-arm randomized controlled trial that compared the effects of a narrative and didactic version of the Witness CARES (Community Awareness, Reach, & Empowerment for Screening) intervention on colorectal cancer screening behavior among African Americans, as well as the cognitive and affective determinants of screening. Methods Witness CARES targeted cognitive and affective predictors of screening using a culturally competent, community-based, narrative or didactic communication approach. New and existing community partners were recruited in two New York sites. Group randomization allocated programs to the narrative or didactic arm. Five phases of data collection were conducted: baseline, post-intervention, three-month, six-month, and qualitative interviews. The primary outcome was screening behavior; secondary outcomes included cognitive and affective determinants of screening. Results A total of 183 programs were conducted for 2655 attendees. Of these attendees, 19.4% ( N = 516) across 158 programs (50% narrative; 50% didactic) were study-eligible and consented to participate. Half (45.6%) of the programs were delivered to new community partners and 34.8% were delivered at faith-based organizations. Mean age of the total sample was 64.7 years and 75.4% were female. Conclusion The planned number of programs was delivered, but the proportion of study-eligible attendees was lower than predicted. This community-based participatory research approach was largely successful in involving the community served in the development and implementation of the intervention and study. [ABSTRACT FROM AUTHOR]

Background Several hemostatic treatments intended to reduce the bleeding associated to total knee arthroplasty have been investigated with varying degrees of success. TT-173 is a new topical agent based on recombinant tissue factor that activates the extrinsic pathway of coagulation. This trial aim is to evaluate the efficacy and safety of TT-173 in total knee arthroplasty. Methods/design This is a phase II/III, sequential, simple blind, randomized, multicenter, placebo controlled and parallel clinical trial that will recruit 189 evaluable patients. Those randomized to treatment group will receive 2 mg of TT-173 over the surgical surfaces of the knee. Control patients will receive physiologic saline. The follow up will consist in 6 visits during a period of 35 (± 7) days. Primary endpoints will be the total blood loss and the incidence and severity of adverse events. Secondary and exploratory endpoints will include drainage production, decrease in hemoglobin level, transfusion ratio, analytical alterations, pain intensity, motion range, immunogenicity of TT-173 and the occurrence of systemic absorption. At the end of phase II, results will be evaluated by an independent committee that will recommend the continuation or the discontinuation of the trial. Discussion The design proposed maximizes the safety of the participants, avoids the risk of bias derived from the limitations of masking and enable the eventual discontinuation of the trial if this is recommended by the Interim Analysis Committee. If TT-173 proves its efficacy and safety in this indication, it would become a useful tool to improve the bleeding control in total knee arthroplasty. Trial registration ClinicalTrials.gov identifier: NCT02687399 . Registered the 9th of February 2016. [ABSTRACT FROM AUTHOR]

Electronic Nicotine Delivery Systems, also called electronic cigarettes or e-cigarettes, have been available for over a decade and use has been increasing dramatically. The primary reported reasons for use are to aid smoking cessation or reduction, yet a significant proportion appear to be long-term users of both products (“dual users”). Dual users may be motivated to quit smoking and might benefit from a behavioral intervention for smoking cessation. This paper describes the intervention development, as well as the design, methods, and data analysis plans for an ongoing randomized controlled trial (RCT). Formative research and learner verification were conducted to create a usable, understandable, and acceptable self-help intervention targeting dual users. The efficacy is being tested in an RCT with current dual users ( N = 2900) recruited nationally and randomized to one of three conditions. The Assessment Only (ASSESS) group only completes assessments. The Generic Self-Help (GENERIC) group receives non-targeted smoking cessation booklets and supplemental materials sent monthly over 18 months. The e-cigarette Targeted Self-Help (eTARGET) group receives the newly developed intervention (targeted booklets and supplemental materials) sent over the same period. All participants complete self-report surveys every 3 months over 2 years. The primary study outcome is self-reported 7-day point prevalence abstinence. Cost-effectiveness metrics for the GENERIC and eTARGET interventions will also be calculated. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) are prevalent and compromise health and wellbeing. Scalable solutions, such as digital therapeutics, may offer a population-based strategy for addressing SUDs. Two formative studies supported the feasibility and acceptability of the relational agent Woebot, an animated screen-based social robot, for treating SUDs (W-SUDs) in adults. Participants randomized to W-SUDs reduced their substance use occasions from baseline to end-of-treatment (EOT) relative to a waitlist control. To further develop the evidence base, the current randomized trial extends follow-up to 1-month post-treatment and will test the efficacy of W-SUDs relative to a psychoeducational control. This study will recruit, screen, and consent 400 adults online reporting problematic substance use. Following baseline assessment, participants will be randomized to 8 weeks of W-SUDs or a psychoeducational control. Assessments will be conducted at weeks 4, 8 (EOT), and 12 (1-month post-treatment). Primary outcome is past-month number of substance use occasions, summed across all substances. Secondary outcomes are number of heavy drinking days, the percent of days abstinent from all substances, substance use problems, thoughts about abstinence, cravings, confidence to resist substance use, symptoms of depression and anxiety, and work productivity. If significant group differences are found, we will explore moderators and mediators of treatment effects. The current study builds upon emerging evidence of a digital therapeutic for reducing problematic substance use by examining sustained effects and testing against a psychoeducational control condition. If efficacious, the findings have implications for scalable mobile health interventions for reducing problematic substance use. Trial Registration: NCT04925570 [ABSTRACT FROM AUTHOR]

Patients presenting to emergency departments (EDs) after a nonfatal opioid-involved overdose are at high risk for future overdose and death. Responding to this risk, the New York City (NYC) Department of Health and Mental Hygiene operates the Relay initiative, which dispatches trained peer "Wellness Advocates" to meet patients in the ED after a suspected opioid-involved overdose and follow them for up to 90 days to provide support, education, referrals to treatment, and other resources using a harm reduction framework. In this article, we describe the protocol for a multisite randomized controlled trial of Relay. Study participants are recruited from four NYC EDs and are randomized to receive the Relay intervention or site-directed care (the control arm). Outcomes are assessed through survey questionnaires conducted at 1-, 3-, and 6-months after the baseline visit, as well as through administrative health data. The primary outcome is the number of opioid-related adverse events, including any opioid-involved overdose or any other substance use-related ED visit, in the 12 months post-baseline. Secondary and exploratory outcomes will also be analyzed, as well as hypothesized mediators and moderators of Relay program effectiveness. We present the protocol for a multisite randomized controlled trial of a peer-delivered OD prevention intervention in EDs. We describe how the study was designed to minimize disruption to routine ED operations, and how the study was implemented and adapted during the COVID-19 pandemic. This trial is registered with ClinicalTrials.gov [ NCT04317053 ]. [ABSTRACT FROM AUTHOR]

Upstream interventions – e.g. housing programs and community health worker interventions– address socioeconomic and behavioral factors that influence health outcomes across diseases. Studying these types of interventions in clinical trials raises a methodological challenge: how should researchers measure the effect of an upstream intervention in a sample of patients with different diseases? This paper addresses this question using an illustrative protocol of a randomized controlled trial of collaborative-goal setting versus goal-setting plus community health worker support among patients multiple chronic diseases: diabetes, obesity, hypertension and tobacco dependence. At study enrollment, patients met with their primary care providers to select one of their chronic diseases to focus on during the study, and to collaboratively set a goal for that disease. Patients randomly assigned to a community health worker also received six months of support to address socioeconomic and behavioral barriers to chronic disease control. The primary hypothesis was that there would be differences in patients' selected chronic disease control as measured by HbA1c, body mass index, systolic blood pressure and cigarettes per day, between the goal-setting alone and community health worker support arms. To test this hypothesis, we will conduct a stratum specific multivariate analysis of variance which allows all patients (regardless of their selected chronic disease) to be included in a single model for the primary outcome. Population health researchers can use this approach to measure clinical outcomes across diseases. Clinical trials registration: ClinicalTrials.gov Identifier: NCT01900470 . [ABSTRACT FROM AUTHOR]

Unhealthy alcohol use is common among HIV-positive patients, yet effective evidence-based treatments are rarely provided in clinical settings providing HIV care. Further, given patient variability in response to initial treatments, stepped care approaches may be beneficial. We describe the rationale, aims and study design for the current S tarting T reatment for E thanol in P rimary care Trials ( STEP Trials ); three parallel randomized controlled effectiveness trials being conducted in five Infectious Disease Clinics. Participants meeting criteria for: 1) at-risk drinking, 2) moderate alcohol use with liver disease (MALD), or 3) alcohol use disorder (AUD) are randomized to integrated stepped care versus treatment as usual. For those with at-risk drinking or MALD, integrated stepped care starts with a one session brief intervention and follow-up 2-week telephone booster. Based on pre-specified nonresponse criteria, participants may be “stepped up” at week 4 to receive four sessions of motivational enhancement therapy (MET) and “stepped up” again at week 12 for addiction physician management (APM) and consideration of alcohol pharmacotherapy. For those with AUD, integrated stepped care begins with APM. Non-responders may be “stepped up” at week 4 to receive MET and again at week 12 for a higher level of care (e.g. intensive outpatient program). The primary outcome is alcohol consumption assessed at 24 weeks, and secondary outcome is the VACS Index, a validated measure of HIV morbidity and mortality risk. Results from the STEP Trials should inform future research and the implementation of interventions to address unhealthy alcohol use among HIV-positive individuals. [ABSTRACT FROM AUTHOR]

Background Contact with nature improves human health; stress reduction is a mediating pathway. Stay Healthy in Nature Everyday (SHINE) is a stress reduction and health promotion intervention for low-income families at an urban Federally Qualified Health Center. We plan to evaluate two service-delivery models for SHINE and present here the intervention design and evaluation protocol. Methods Behavioral change theory and environmental education literature informed the intervention. Outcomes were selected after review of the literature and field tested procedures to determine what was feasible and ethical in a busy clinic serving vulnerable populations. Design We designed a randomized controlled trial to examine two levels of intensity in behavioral counseling about the health benefits of nature. Dyads consisting of a caregiver and a child aged 4 to 18 who access our pediatric primary care center are eligible. All dyads receive a pediatrician's recommendation to visit parks to experience nature and written resources (a “park prescription”). The intervention group receives added case management and an invitation to three group outings into nature with transportation, meals and activities provided. Primary outcomes measured at baseline, one month and three months post-enrollment are caregiver stress measured by PSS-10 score and salivary α-amylase; secondary outcomes are park prescriptions adherence, physical activity recorded by pedometer and journaling, loneliness, family cohesion and affinity to nature as measured by a validated scales. Both groups receive incentives to participation. Discussion Our intervention represents a feasible integration of recent research findings on the health benefits of nature and primary care practice. [ABSTRACT FROM AUTHOR]

Background Family caregivers (FCs) to cancer patients are at increased risk for physical and emotional health problems as a result of being in the caregiver role. Current research on interventions for FCs has focused on psychological support or educational interventions, with very little investigation of exercise in maintaining or improving health. Based on our preliminary survey, participation in regular exercise to improve health was noted as a priority for FCs. The purpose of the study described in this protocol is to examine the impact of a 12-week structured exercise program on physical functioning (primary outcome), physical activity levels and psychological well-being (secondary outcomes), in FCs caring for adult cancer patients. In addition, the trial described here will examine the outcomes from a 12-week maintenance program, immediately following the initial program. Methods/design A mixed methods design using a randomized control trial (RCT) with a 50/50 allocation ratio for the quantitative portion, followed by face to face interviews and qualitative data analysis. Approximately 86 participants will be enrolled over a 10 month period. The intervention will consist of a structured exercise program of aerobic and resistance training. An intention to treat principle using mixed effects modeling will guide data analysis. Discussion FCs will continue to play a pivotal role in the care of cancer patients as the incidence and chronicity of cancer increases. The research described in this protocol will provide information about the impact of an exercise program in supporting FC health. Trial registration ClinicalTrials.gov Identifier: NCT02580461 [ABSTRACT FROM AUTHOR]

In this manuscript, we present the protocol for a study that applies incentive sensitization theory to improve vegetable intake in overweight and obese adults. This 8-week, randomized, controlled, community-based feeding study with an 8-week follow-up seeks to use repeated exposure to amounts of vegetables recommended by federal guidance to increase the primary outcome of the relative reinforcing value of vegetables compared to a snack food. A community-based design is used to give participants autonomy in choosing their method of exposure. Secondary outcomes include: 1) Determine potential moderators of incentive sensitization of vegetables, including genetic polymorphisms associated with food reinforcement and obesity, 6-n-propylthiouracil tasting status, and delay discounting. 2) Determine whether adding vegetables to the diet results in participants substituting low-energy-dense vegetables for energy-dense foods or whether energy-dense food consumption is independent of vegetable consumption. 3) Determine whether reductions in adiposity are associated with substitution of vegetables in the diet. 4) Determine if markers of bone turnover change. 5) Assess changes in self-reported secondary outcomes measured by questionnaire such as self-efficacy to eat vegetables. The results of this study will provide information about the drivers of individual choice to consume recommended amounts of vegetables. The understanding gained will help increase the effectiveness and sustainability of behavior-based interventions focused on improving vegetable intake. This information may also be used to assist in setting dietary guidance targets for the amounts and types of vegetables Americans can, and should, consume. [ABSTRACT FROM AUTHOR]

Background Despite the well-established risks of persistent smoking, 10–30% of cancer patients continue to smoke after diagnosis. Evidence-based tobacco treatment has yet to be integrated into routine oncology care. This paper describes the protocol, manualized treatment, evaluation plan, and overall study design of comparing the effectiveness and cost of two treatments across two major cancer centers. Methods/design A two-arm, two-site randomized controlled comparative effectiveness trial is testing the hypothesis that an Intensive Treatment (IT) intervention is more effective than a Standard Treatment (ST) intervention in helping recently diagnosed cancer patients quit smoking. Both interventions include 4 weekly counseling sessions and FDA-approved smoking cessation medication advice. The IT includes an additional 4 biweekly and 3 monthly booster sessions as well as dispensal of the recommended FDA-approved smoking cessation medication at no cost. The trial is enrolling patients with suspected or newly diagnosed cancer who have smoked a cigarette in the past 30 days. Participants are randomly assigned to receive the ST or IT condition. Tobacco cessation outcomes are assessed at 3 and 6 months. The primary study outcome is 7-day point prevalence biochemically-validated tobacco abstinence. Secondary study outcomes include the incremental cost-effectiveness of the IT vs. ST. Discussion This trial will answer key questions about delivering tobacco treatment interventions to newly diagnosed cancer patients. If found to be efficacious and cost-effective, this treatment will serve as a model to be integrated into oncology care settings nation-wide, as we strive to improve treatment outcomes and quality of life for cancer patients. [ABSTRACT FROM AUTHOR]

Background Mindfulness Based Cognitive Therapy (MBCT) has been shown to reduce the risk of relapse in patients with recurrent depression, but relapse rates remain high. To further improve outcome for this group of patients, follow-up interventions may be needed. Compassion training focuses explicitly on developing self-compassion, one of the putative working mechanisms of MBCT. No previous research has been done on the effectiveness of compassion training following MBCT in patients with recurrent depression. Aims To investigate the effectiveness of Mindfulness-Based Compassionate Living (MBCL) in reducing (residual) depressive symptoms in patients with recurrent depression who previously participated in MBCT. Methods/design A randomized controlled trial comparing MBCL in addition to treatment as usual (TAU) with TAU only, in patients suffering from recurrent depressive episodes who completed an MBCT course in the past. Assessments will take place at baseline, post-treatment and at six months follow-up. After the control period, patients randomized to the TAU condition will be offered MBCL as well. Outcome measures Primary outcome measure is severity of depressive symptoms according to the Beck Depression Inventory-II (BDI-II) at post-treatment. Secondary outcome measures are presence or absence of DSM-IV depressive disorder, rumination, self-compassion, mindfulness skills, positive affect, quality of life, experiential avoidance and fear of self-compassion. Discussion Our study is the first randomized controlled trial to examine the effectiveness of compassion training following MBCT in a recurrently depressed population. Trial registration ClinicalTrials.gov: NCT02059200, registered 30 January 2014. [ABSTRACT FROM AUTHOR]

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥ 140 mm Hg for non-diabetic or ≥ 130 mm Hg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12 months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5 years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6 mm Hg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy. [ABSTRACT FROM AUTHOR]

Continued smoking after a cancer diagnosis contributes to several negative health outcomes. Although many cancer patients attempt to quit smoking, high smoking relapse rates have been observed. This highlights the need for a targeted, evidence-based smoking-relapse prevention intervention. The design, method, and baseline characteristics of a randomized controlled trial assessing the efficacy of a self-help smoking-relapse prevention intervention are presented. Cancer patients who had recently quit smoking were randomized to one of two conditions. The Usual Care (UC) group received the institution's standard of care. The smoking relapse-prevention intervention (SRP) group received standard of care, plus 8 relapse-prevention booklets mailed over a 3 month period, and a targeted educational DVD developed specifically for cancer patients. Four hundred and fourteen participants were enrolled and completed a baseline survey. Primary outcomes will be self-reported smoking status at 6 and 12-months after baseline. Biochemical verification of smoking status was completed for a subsample. If found to be efficacious, this low-cost intervention could be easily disseminated with significant potential for reducing the risk of negative cancer outcomes associated with continued smoking. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is common during pregnancy and associated with adverse maternal and neonatal outcomes. Treatment with iron supplementation is recommended during pregnancy, but the optimal delivery route is unclear. Oral iron risks has high risk of gastrointestinal side effects and low absorption. Intravenous iron is infused directly but is expensive. The American College of Obstetricians and Gynecologists currently recommends oral iron to treat IDA in pregnancy with intravenous iron reserved as second-line therapy, if needed. This approach is associated with persistent anemia, increasing the risk of peripartum blood transfusion. We aim to provide data on optimal route of iron repletion for IDA in pregnancy. In IVIDA2, a double-blind, placebo controlled, multicenter randomized trial in the United States, 746 pregnant people with moderate-to-severe IDA (hemoglobin <10 g/dL and ferritin <30 ng/mL) at 24–28 weeks' gestation will be randomized 1:1 to either a single 1000 mg dose of intravenous ferric derisomaltose and oral placebo (1–3 times daily) or a single placebo infusion with 1–3 times daily 325 mg ferrous sulfate (65 mg elemental iron) tablet. The primary outcome is peripartum blood transfusion (blood transfusion from delivery to 7 days postpartum). Secondary outcomes include adverse medication reactions, maternal and neonatal hematologic indices, and offspring neurodevelopment. A central ethical review board—Advarra—granted ethical approval (Pro00060930). Participating centers—Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of Ethics and dissemination: A central ethical review board—Advarra—granted ethical approval (Pro00060930). Participating centers—Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of. [ABSTRACT FROM AUTHOR]

To (i) compare the acceptance of a newly developed, novel biofeedback device (PelviSense) with that of conventional biofeedback (CB) using an intravaginal probe for the treatment of stress urinary incontinence (SUI) in women, (ii) examine the feasibility and safety of using the PelviSense device as a pelvic floor muscle (PFM) training (PFMT) adjunct, and (iii) compare the PFMT adherence and effectiveness of CB, the PelviSense device, with PFMT alone for women with SUI. An assessor-blinded, three-arm, randomized controlled pilot trial was conducted among 51 women with SUI. Women were randomly allocated to one of three study groups (PelviSense-assisted PFMT, CB-assisted PFMT, or PFMT alone [control]). Outcome measures included the International Consultation on Incontinence Questionnaire-Short Form, the 1-h pad test, and the Modified Oxford Scale. Participants in the PelviSense-assisted PFMT group expressed good device acceptance. PFMT adherence was greater in the PelviSense-assisted PFMT group than in the unassisted or CB-assisted PFMT groups. Between-groups analysis revealed significant effects on improved SUI symptoms, urine loss severity, and PFM strength for the PelviSense-assisted PFMT group compared with the CB-assisted and PFMT alone groups. The pilot trial results demonstrated moderate to high PFMT adherence in the PelviSense-assisted PFMT group and supported the safety of using the PelviSense device. The preliminary results of the pilot trial showed that PelviSense-assisted PFMT was more effective for reducing SUI symptoms among women than unassisted or CB-assisted PFMT. Trial registration: This trial was registered in http://ClinicalTrials.gov (reference number: NCT04638348) before the recruitment of the first participant. • The results from this pilot trial were encouraging regarding adherence, safety, and the acceptability of the PelviSense device. • This pilot study demonstrate that the methodology is feasible for a fully powered study in recruitment and retention. • The preliminary results show that the PelviSense device may be effective in reducing the symptoms of UI and the severity of urine loss in women with SUI. [ABSTRACT FROM AUTHOR]

Suicide is the second‑leading cause of death among adolescents and young adults in the United States, with rates rising over much of the last decade. The design, testing, and implementation of interventions to prevent suicide in this population is a public health priority. This manuscript outlines the design and methods for a research study that compares two interventions aimed at reducing suicide and suicide attempts in youth. We will enroll 300 youth aged 12–24 at high risk for suicide in this randomized controlled parallel group superiority trial. Participants will be randomly assigned to one of two study arms: (1) Zero Suicide Quality Improvement (ZSQI) implemented within the Kaiser Permanente Northwest (KPNW) health system, or (2) ZSQI plus a stepped care intervention for suicide prevention (SC-SP), where the services offered (including care management and dialectical behavior therapy [DBT]) increase based on risk level. Outcomes will be assessed at baseline, as well as 3-, 6-, and 12-months post randomization. The study was conceptualized and designed collaboratively by investigators at UCLA and KPNW. To be reported in future manuscripts. The main objective of the study is to determine whether the SC-SP intervention is superior to ZSQI with regard to lowering rates of fatal and nonfatal suicide attempts. Interventions that incorporate the latest research need to be designed and tested under controlled conditions to make progress toward the goal of achieving zero suicide. The results from this trial will directly inform those efforts. Trial Registration. clinicaltrials.gov , NCT03092271 , https://clinicaltrials.gov/ct2/show/NCT03092271https://clinicaltrials.gov/ct2/show/NCT01379027. [ABSTRACT FROM AUTHOR]

Post-COVID-19 condition is frequently comprised of persistent cognitive sequela, including deficits in attention and executive functions (EFs), which can act as a barrier for regaining pre-illness functional levels. Goal Management Training (GMT) is a cognitive rehabilitation (CR) intervention for improving attention and EFs that has received empirical support in studies of other patient groups. The present study aims to determine the efficacy of GMT for improving everyday attention and EFs in adults who experience persistent cognitive deficits after COVID-19. This study protocol describes an open-label randomized controlled trial comparing the efficacy of GMT to a wait list control condition (WL), for improving persistent (> 2 months) cognitive sequela in post-COVID-19 condition. The study aims to recruit 240 participants aged 18 to 65 years with a history of SARS-CoV-2 infection and perceived attentional and EF difficulties in daily life. Participants will be block randomized (computer-algorithm) to either group-based GMT (n = 120) or WL (n = 120). GMT will be internet-delivered to groups of six participants in six two-hour sessions delivered once a week. The primary outcome will be the Metacognition Index of the Behavior Rating Inventory of Executive Function – Adult Version, a self-report measure assessing everyday EF difficulties, specifically metacognition, at six months post-treatment. Secondary outcomes include performance-based neurocognitive measures, and tertiary outcomes include rating scales of cognition, emotional health, quality of life, and fatigue. Study findings could contribute to providing an evidence-based treatment option for symptoms that are frequent and debilitating following a prevalent condition. NCT05494424 [ABSTRACT FROM AUTHOR]

Being overweight or obese is a large public health problem, especially in the African American/Black and Hispanic communities. Having a body mass index (BMI) > 25 can lead to chronic health conditions, such as heart disease, stroke, and type 2 diabetes. The transition into adulthood may be an excellent time to intervene due to young adults gaining independence; however, little research has focused on community college students and weight change. The purpose of this randomized controlled trial is to test the efficacy of an intervention tool that is personalized for weight loss through healthy eating and increased physical activity in Black and Hispanic community college students. Community college students who identify as Black or Hispanic (N = 256) will be recruited and randomized 1:1 to a 12-month, health coach and smartphone application (app) driven intervention or an attention-control condition. The intervention is implemented by health coaches, trained in a health coach specialty program at a university. The intervention includes a Smartphone app for tracking dietary intake, a Fitbit Inspire 2 for tracking physical activity, and daily personalized text messages from a health coach. The main outcome is percent weight loss at 6- and 12-month follow-up assessments. Secondary outcomes include self-efficacy for eating and physical activity, adherence to self-monitoring, Healthy Eating Index scores, and physical activity levels. If the intervention is demonstrated to be efficacious, broader dissemination across college/university campuses to assist young adults to develop sustainable healthy habits may be possible. ClinicalTrials.gov Identifier: NCT04412954 R01 Trial Number: 1R01NR018699–02. [ABSTRACT FROM AUTHOR]

Unplanned rehospitalizations occur frequently in older patients. Drug-related problems constitute a major and largely preventable cause with inappropriate prescribing being a substantial culprit. Solutions are needed to reduce this risk by targeting pharmacotherapy both during and after hospital stay. Therefore, we aim to perform a randomized controlled trial in geriatric inpatients to investigate the impact of a multifaceted clinical pharmacy intervention on health-related outcomes. The study concerns a monocenter, non-blinded, randomized controlled trial that will take place at the acute geriatric wards of a large academic hospital. Patients being in a palliative stage with active therapy withdrawal or patients discharged to another ward within the same hospital or another hospital are excluded. In total, 828 patients will be randomized (1:1) to the usual care or intervention group. The multifaceted clinical pharmacy intervention comprises medication reconciliation at admission and discharge, medication review, patient/caregiver education, intensified communication with primary care providers and post-discharge follow-up, which also includes a telepharmacology service. The primary endpoint is defined as the time to an all-cause, unplanned hospital revisit within six months after discharge. Other health-related outcomes such as drug-related readmissions, quality of life and number of potentially inappropriate medications will be analyzed as secondary endpoints. Patient inclusion started in February 2021. This study will provide useful insights regarding the impact of clinical pharmacy interventions on geriatric wards with the goal to optimize health-related outcomes such as hospital revisits. Trial registration: ClinicalTrials.gov Identifier: NCT04617340 • We plan to investigate a multifaceted clinical pharmacy intervention in geriatric inpatients. • The study targets geriatric inpatients owing to their high risk of unplanned hospital revisits. • A transitional care step was included as medication review alone has not been shown to be effective. • Our randomized controlled trial is powered for the time to a first unplanned hospital revisit within six months. [ABSTRACT FROM AUTHOR]

Fatigue is a common and distressing symptom that can last for months or years in up to one-third of cancer survivors. Despite its prevalence, the nature and mechanisms of cancer-related fatigue are poorly understood and the available treatments may not provide sufficient relief. Fatigue has been identified as a significant contributor to decreased quality of life, making it an important target for intervention. One approach that may be a safe and inexpensive treatment is bright light therapy. Methods This study is a 4-week blinded randomized controlled trial. Subjects will be men and women who meet criteria for cancer-related fatigue and have completed cancer treatment. Subjects will be randomly assigned to receive a Litebook treatment device that produces either bright white light (treatment) or dim red light (active control). The devices will be used daily for 30 min upon waking for a period of four weeks. The primary outcome, fatigue, will be measured with the Multidimensional Fatigue Symptom Inventory-SF. Secondary outcomes include mood disturbance, sleep quality, quality of life, diurnal cortisol, and inflammatory biomarkers. Fatigue assessments will be completed weekly and secondary outcomes will be assessed at pre- and post-intervention. Conclusions The current research will examine the effect of light exposure on cancer-related fatigue and its potential psychological, behavioral, and biological mechanisms. If successful, this research would support the use of light therapy for the management of persistent fatigue in cancer survivors, expanding existing treatment options. It may also improve upon the current understanding of the mechanisms that underlie cancer-related fatigue. [ABSTRACT FROM AUTHOR]

Background Statins are a class of medications that are particularly effective for lowering cholesterol and reducing cardiovascular morbidity and mortality. Despite a range of benefits, non-adherence to statin medication is prevalent with 50% to 75% of patients failing to adhere to treatment within the first 2-years. A previous review on interventions to improve adherence to cholesterol lowering medication concluded that rigorous trials were needed with emphasis on the patient's perspective and shared decision making. Motivational interviewing (MInt) is a promising patient-centered approach for improving adherence in patients with chronic diseases. This manuscript describes the rational and design of a randomized controlled trial (RCT) testing the efficacy of MInt in improving adherence to statin medication. Methods Patients filling their first statin prescription will be recruited to complete a 6-month observation run-in period (phase-1) after which medication possession ratio (MPR) will be assessed. Patients meeting criteria for non-adherence (MPR ≤ 60%) will be invited to participate in the trial. 336 non-adherent new statin users will undergo a fasting lipid panel, complete baseline questionnaires, and be randomly allocated to receive four sessions of adherence education delivered using MInt (EdMInt) or to an education control (EC) delivered at 3-month intervals. Final assessments will occur 12-months after the first EdMInt or EC session. The primary outcome is change in MPR adherence to statin medication from baseline to 12-months. Secondary outcomes include within-patient change in self-reported medication adherence, stage of change and self-efficacy for medication adherence, motivation to adhere to statin medication, and lipid profile. [ABSTRACT FROM AUTHOR]

Background Dutch practice nurses sub-optimally adhere to evidence-based smoking cessation guidelines. Web-based computer-tailoring could be effective in improving their guideline adherence. Therefore, this paper aims to describe the development of a web-based computer-tailored program and the design of a randomized controlled trial testing its (cost-)effectiveness. Methods Theoretically grounded in the I-Change Model and Self-Determination Theory, and based on the results of a qualitative needs assessment among practice nurses, a web-based computer-tailored program was developed including three modules with tailored advice, an online forum, modules with up-to-date information about smoking cessation, Frequently Asked Questions (FAQs) and project information, and a counseling checklist. The program's effects are assessed by comparing an intervention group (access to all modules) with a control group (access to FAQs, project information and counseling checklist only). Smoking cessation guideline adherence and behavioral predictors (i.e. intention, knowledge, attitude, self-efficacy, social influence, action and coping planning) are measured at baseline and at 6- and 12-month follow-up. Additionally, the program's indirect effects on smokers' quit rates and the number of quit attempts are assessed after 6 and 12 months. Discussion This paper describes the development of a web-based computer-tailored adherence support program for practice nurses and the study design of a randomized controlled trial testing its (cost-)effectiveness. This program potentially contributes to improving the quality of smoking cessation care in Dutch general practices. If proven effective, the program could be adapted for use by other healthcare professionals, increasing the public health benefits of improved smoking cessation counseling for smokers. [ABSTRACT FROM AUTHOR]

Small employers, especially those in low-wage industries, frequently lack the capacity and resources to implement evidence-based health promotion interventions without support and assistance. The purpose of this paper is to (a) describe the intervention design and study protocol of the HealthLinks Trial and (b) report baseline findings. This study is a three-arm randomized controlled trial testing the impact of the HealthLinks intervention on worksites' adoption and implementation of evidence-based interventions. Group 1 will receive HealthLinks , Group 2 will receive HealthLinks plus wellness committees, and Group 3 will be a delayed control group. Seventy-eight employers are participating in the study; and 3302 employees across the worksites participated in the baseline data collection. Employers and employees will participate in follow-up surveys at one and two years after baseline to measure implementation (one year) and maintenance (two years) of HealthLinks interventions. Study outcomes will determine whether HealthLinks is an effective approach to increasing evidence-based health promotion in small, low-wage worksites and whether wellness committees are a capacity-building tool that increases HealthLinks ' effectiveness. [ABSTRACT FROM AUTHOR]

Background Patients who are better informed and more engaged in their health care have higher satisfaction with health care and better health outcomes. While patient engagement has been a focus in the outpatient setting, strategies to engage inpatients in their care have not been well studied. We are undertaking a study to assess how patients' information needs during hospitalization can be addressed with health information technologies. To achieve this aim, we developed a personalized inpatient portal that allows patients to see who is on their care team, monitor their vital signs, review medications being administered, review current and historical lab and test results, confirm allergies, document pain scores and send questions and comments to inpatient care providers. The purpose of this paper is to describe the protocol for the study. Methods/design This pragmatic randomized controlled trial will enroll 426 inpatient cardiology patients at an urban academic medical center into one of three arms receiving: 1) usual care, 2) iPad with general internet access, or 3) iPad with access to the personalized inpatient portal . The primary outcome of this trial is patient engagement, which is measured through the Patient Activation Measure. To assess scalability and potential reach of the intervention, we are partnering with a West Coast community hospital to deploy the patient engagement technology in their environment with an additional 160 participants. Conclusion This study employs a pragmatic randomized control trial design to test whether a personalized inpatient portal will improve patient engagement. If the study is successful, continuing advances in mobile computing technology should make these types of interventions available in a variety of clinical care delivery settings. [ABSTRACT FROM AUTHOR]

Introduction Although cognitive behavior therapy (CBT) is the best evidenced psychological treatment for medically unexplained symptoms (MUS), effect sizes are rather moderate. Empirically evidenced deficits in emotion processing in patients with MUS make a CBT enriched with an emotion regulation training (ENCERT) a promising approach to increase treatment effects. Methods and design This protocol describes the development and implementation of a multicenter, randomized, active-controlled study with blinded outcome assessors to compare the efficacy of ENCERT with a conventional CBT for MUS. Individuals presenting with ≥ 3 disabling, chronic MUS and fulfilling other predefined inclusion criteria are randomized to 20 sessions either of ENCERT or conventional CBT. Power calculations are based on the severity index of the Screening of Somatoform Disorders-7T and obtained an optimal sample size of N = 244. Questionnaires on symptom severity, symptom-related psychological features, and emotion regulation skills are administered at baseline, end of therapy, and 6-months follow-up. An every-session monitoring of therapy progress, and regular patients'/therapists' ratings of quality of therapy, working alliance, outcome expectations, and adverse events are conducted. Primary statistical analysis shall verify the hypothesis of ENCERT being more efficacious than conventional CBT regarding symptom severity. Discussion Enriching CBT with transdiagnostic therapeutic strategies addressing emotion regulation is a promising and new approach to target not only somatic symptom coping but also symptom-associated problems and comorbid mental disorders. The current trial will not only allow examining the efficacy of ENCERT but also important variables and mechanisms of the process of therapy. Trial registration: NCT01908855 [ABSTRACT FROM AUTHOR]

Background Depressive and anxiety disorders contribute to a high disease burden. This paper investigates whether concise formats of cognitive behavioral- and/or pharmacotherapy are equivalent with longer standard care in the treatment of depressive and/or anxiety disorders in secondary mental health care. Methods A pragmatic randomized controlled equivalence trial was conducted at five Dutch outpatient Mental Healthcare Centers (MHCs) of the Regional Mental Health Provider (RMHP) ‘Rivierduinen’. Patients (aged 18–65 years) with a mild to moderate anxiety and/or depressive disorder, were randomly allocated to concise or standard care. Data were collected at baseline, 3, 6 and 12 months by Routine Outcome Monitoring (ROM). Primary outcomes were the Brief Symptom Inventory (BSI) and the Web Screening Questionnaire (WSQ). We used Generalized Estimating Equations (GEE) to assess outcomes. Results Between March 2010 and December 2012, 182 patients, were enrolled ( n = 89 standard care; n = 93 concise care). Both intention-to-treat and per-protocol analyses demonstrated equivalence of concise care and standard care at all time points. Severity of illness reduced, and both treatments improved patient’s general health status and subdomains of quality of life. Moreover, in concise care, the beneficial effects started earlier. Discussion Concise care has the potential to be a feasible and promising alternative to longer standard secondary mental health care in the treatment of outpatients with a mild to moderate depressive and/or anxiety disorder. For future research, we recommend adhering more strictly to the concise treatment protocols to further explore the beneficial effects of the concise treatment. The study is registered in the Netherlands Trial Register, number NTR2590. Clinicaltrials.gov identifier: NCT01643642 . [ABSTRACT FROM AUTHOR]

Using the case of a large-scale, multi-site Canadian Housing First research demonstration project for homeless people with mental illness, At Home/Chez Soi, we illustrate the value of qualitative methods in a randomized controlled trial (RCT) of a complex community intervention. We argue that quantitative RCT research can neither capture the complexity nor tell the full story of a complex community intervention. We conceptualize complex community interventions as having multiple phases and dimensions that require both RCT and qualitative research components. Rather than assume that qualitative research and RCTs are incommensurate, a more pragmatic mixed methods approach was used, which included using both qualitative and quantitative methods to understand program implementation and outcomes. At the same time, qualitative research was used to examine aspects of the intervention that could not be understood through the RCT, such as its conception, planning, sustainability, and policy impacts. Through this example, we show how qualitative research can tell a more complete story about complex community interventions. [ABSTRACT FROM AUTHOR]