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American Journal of Human Genetics Nov 2023Polygenic risk scores (PRSs) hold promise for disease risk assessment and prevention. The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main... (Randomized Controlled Trial)
Randomized Controlled Trial
Polygenic risk scores (PRSs) hold promise for disease risk assessment and prevention. The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main challenges to the clinical implementation of PRSs in preventive care: defining and determining their clinical utility, implementing them in time-constrained primary care settings, and countering their potential to exacerbate healthcare disparities. The study processes used to test patients, report their PRS results to them and their primary care providers (PCPs), and promote the use of those results in clinical decision-making are modeled on common practices in primary care. The following diseases were chosen for their prevalence and familiarity to PCPs: coronary artery disease; type 2 diabetes; atrial fibrillation; and breast, colorectal, and prostate cancers. A randomized clinical trial (RCT) design and primary outcome of time-to-new-diagnosis of a target disease bring methodological rigor to the question of the clinical utility of PRS implementation. The study's pragmatic RCT design enhances its relevance to how PRS might reasonably be implemented in primary care. Steps the study has taken to promote health equity include the thoughtful handling of genetic ancestry in PRS construction and reporting and enhanced recruitment strategies to address underrepresentation in research participation. To date, enhanced recruitment efforts have been both necessary and successful: participants of underrepresented race and ethnicity groups have been less likely to enroll in the study than expected but ultimately achieved proportional representation through targeted efforts. The GenoVA Study experience to date offers insights for evaluating the clinical utility of equitable PRS implementation in adult primary care.
Topics: Adult; Humans; Male; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Primary Health Care; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors
PubMed: 37922883
DOI: 10.1016/j.ajhg.2023.10.001 -
American Heart Journal Jan 2024Atrial fibrillation (AF) is associated with increased risks of stroke and dementia. Early diagnosis and treatment could reduce the disease burden, but AF is often...
Realtime Diagnosis from Electrocardiogram Artificial Intelligence-Guided Screening for Atrial Fibrillation with Long Follow-Up (REGAL): Rationale and design of a pragmatic, decentralized, randomized controlled trial.
BACKGROUND
Atrial fibrillation (AF) is associated with increased risks of stroke and dementia. Early diagnosis and treatment could reduce the disease burden, but AF is often undiagnosed. An artificial intelligence (AI) algorithm has been shown to identify patients with previously unrecognized AF; however, monitoring these high-risk patients has been challenging. Consumer wearable devices could be an alternative to enable long-term follow-up.
OBJECTIVES
To test whether Apple Watch, used as a long-term monitoring device, can enable early diagnosis of AF in patients who were identified as having high risk based on AI-ECG.
DESIGN
The Realtime diagnosis from Electrocardiogram (ECG) Artificial Intelligence (AI)-Guided Screening for Atrial Fibrillation (AF) with Long Follow-up (REGAL) study is a pragmatic trial that will accrue up to 2,000 older adults with a high likelihood of unrecognized AF determined by AI-ECG to reach our target of 1,420 completed participants. Participants will be 1:1 randomized to intervention or control and will be followed up for 2 years. Patients in the intervention arm will receive or use their existing Apple Watch and iPhone and record a 30-second ECG using the watch routinely or if an abnormal heart rate notification is prompted. The primary outcome is newly diagnosed AF. Secondary outcomes include changes in cognitive function, stroke, major bleeding, and all-cause mortality. The trial will utilize a pragmatic, digitally-enabled, decentralized design to allow patients to consent and receive follow-up remotely without traveling to the study sites.
SUMMARY
The REGAL trial will examine whether a consumer wearable device can serve as a long-term monitoring approach in older adults to detect AF and prevent cognitive function decline. If successful, the approach could have significant implications on how future clinical practice can leverage consumer devices for early diagnosis and disease prevention.
CLINICALTRIALS
GOV: : NCT05923359.
Topics: Aged; Humans; Artificial Intelligence; Atrial Fibrillation; Electrocardiography; Follow-Up Studies; Stroke; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic
PubMed: 37913853
DOI: 10.1016/j.ahj.2023.10.005 -
Journal of Acupuncture and Meridian... Dec 2023: Pharmacopuncture therapy and acupotomy are commonly used in combination for Conventional Korean Medicine Treatments (CKMT) for the treatment of patients with lumbar...
Effect and Safety of Combining Pharmacopuncture Therapy and Acupotomy in the Treatment of Patients with Degenerative Lumbar Spinal Stenosis: a Study Protocol for a Pragmatic, Assessor-Blinded, Randomized, Controlled Trial.
BACKGROUND
: Pharmacopuncture therapy and acupotomy are commonly used in combination for Conventional Korean Medicine Treatments (CKMT) for the treatment of patients with lumbar spinal stenosis (LSS). The aim of this study is to evaluate the effect and safety of combining pharmacopuncture therapy and acupotomy in the treatment of LSS.
METHODS
: This study is designed as a pragmatic, assessor-blinded, randomized controlled trial with two parallel arms in a 1:1 ratio. A total of 104 participants diagnosed with LSS will be randomly assigned to an experimental group (pharmacopuncture therapy and acupotomy in addition to CKMT) or a control group (only CKMT). Patients in both groups will receive treatment two times weekly for 6 weeks. The primary outcome will be the mean change on the 100-mm visual analog scale (VAS) from the baseline to the end of the treatment (week 6). The secondary outcomes will include the mean change in the 100-mm VAS from baseline to week 10 and week 14, respectively. Proportion of patients who achieve the clinically important difference, Zurich Claudication Questionnaire, Roland-Morris disability questionnaire, self-reported maxium walking distance, EuroQol 5-dimension 5-level, and Patients' Global Impression of Change will also be assessed. Adverse events will be assessed at each visit. The outcomes will be measured for a total of 14 weeks, including a treatment period of 6 weeks and follow-up of 4, 8 weeks.
DISCUSSION
: The results of this trial will confirm the effect and safety of combining pharmacopuncture therapy and acupotomy in the treatment of patients with LSS.
Topics: Humans; Acupuncture; Acupuncture Therapy; Lumbar Vertebrae; Randomized Controlled Trials as Topic; Spinal Stenosis; Treatment Outcome; Pragmatic Clinical Trials as Topic
PubMed: 38115593
DOI: 10.51507/j.jams.2023.16.6.268 -
Journal of Crohn's & Colitis Feb 2024Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical...
BACKGROUND AND AIMS
Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The European consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid comparative pragmatic studies in inflammatory bowel diseases (IBDs).
METHODS
Statements were issued by a panel of 11 European experts in IBD management and trial methodology on four main topics: (I) study design; (II) eligibility, recruitment and organization, flexibility; (III) outcomes; (IV) analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement (1 to 9; cut-off ≥7 for approval) with the statements by 18 additional European experts in IBD.
RESULTS
At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: 7 for study design, 6 for eligibility, recruitment and organization, flexibility, 8 for outcomes, and 4 for analysis.
CONCLUSIONS
Pragmatic randomized clinical trials can address important questions in IBD clinical practice, and may provide complementary high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality pragmatic clinical trials that can aid decision making in choosing a management strategy for IBDs.
PubMed: 38367197
DOI: 10.1093/ecco-jcc/jjae026 -
JMIR Research Protocols Oct 2023Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg,...
A Hospital-Wide Open-Label Cluster Crossover Pragmatic Comparative Effectiveness Randomized Trial Comparing Normal Saline to Ringer's Lactate: Protocol and Statistical Analysis Plan of The FLUID Trial.
BACKGROUND
Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function, and death), few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients.
OBJECTIVE
The FLUID trial is a pragmatic, multicenter, 2×2 cluster crossover comparative effectiveness randomized trial that aims to evaluate the effectiveness of a hospital-wide policy that stocks either NS or RL as the main crystalloid fluid in 16 hospitals across Ontario, Canada.
METHODS
All hospitalized adult and pediatric patients (anticipated sample size 144,000 patients) with an incident admission to the hospital over the course of each study period will be included. Either NS or RL will be preferentially stocked throughout the hospital for 12 weeks before crossing to the alternate fluid for the subsequent 12 weeks. The primary outcome is a composite of death and hospital readmission within 90 days of hospitalization. Secondary outcomes include death, hospital readmission, dialysis, reoperation, postoperative reintubation, length of hospital stay, emergency department visits, and discharge to a facility other than home. All outcomes will be obtained from health administrative data, eliminating the need for individual case reports. The primary analysis will use cluster-level summaries to estimate cluster-average treatment effects.
RESULTS
The statistical analysis plan has been prepared "a priori" in advance of receipt of the trial data set from ICES and any analyses.
CONCLUSIONS
We describe the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04512950; https://classic.clinicaltrials.gov/ct2/show/NCT04512950.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/51783.
PubMed: 37801356
DOI: 10.2196/51783 -
Childhood Obesity (Print) Dec 2023Rapid weight gain during infancy is associated with risk for later obesity, yet little research to date has examined the effect of a responsive parenting (RP)... (Randomized Controlled Trial)
Randomized Controlled Trial
Rapid weight gain during infancy is associated with risk for later obesity, yet little research to date has examined the effect of a responsive parenting (RP) intervention with care coordination between pediatric primary care providers and Women, Infants, and Children nutritionists on infant weight. The Women, Infants, and Children Enhancements to Early Healthy Lifestyles for Baby (WEE Baby) Care study is a pragmatic, randomized clinical trial for mothers and infants ( = 288) designed to examine the effect of a patient-centered RP intervention that used advanced health information technology strategies to coordinate care to reduce rapid infant weight gain compared with standard care. General linear models examined intervention effects on infant conditional weight gain scores, weight-for-age scores, BMI, and overweight status (BMI-for-age ≥85th percentile) from birth to age 6 months, and mothers' use of food to soothe from age 2 to 6 months. There were no intervention effects on infant conditional weight gain scores or overweight status at 6 months. Infants in the RP intervention had lower mean weight-for-age scores [ = -0.04, standard error (SE) = 0.04 vs. = 0.05, SE = 0.04; = 0.008] and lower mean BMI ( = 16.05, SE = 0.09 vs. = 16.24, SE = 0.09; = 0.03) compared with standard care. Mothers' use of emotion-based food to soothe was lower in the RP intervention compared with standard care from age 2 to 6 months [ difference = -0.32, standard deviation (SD) = 0.81 vs. 0.00, SD = 0.90; = 0.01]. This pragmatic, patient-centered RP intervention did not reduce rapid infant weight gain or overweight but was associated with modestly lower infant BMI and reduced mothers' use of emotion-based food to soothe. clinicaltrials.gov identifier: NCT03482908.
Topics: Child; Female; Humans; Infant; Mothers; Overweight; Pediatric Obesity; Primary Health Care; Weight Gain
PubMed: 36367983
DOI: 10.1089/chi.2022.0137 -
BMJ Open Aug 2023Improving access to effective contraception has the potential to reduce unintended pregnancy and abortion rates. Community pharmacists could play an expanded role in...
Expanding community pharmacists' scope of practice in relation to contraceptive counselling and referral: a protocol for a pragmatic, stepped-wedge, cluster randomised trial (ALLIANCE).
INTRODUCTION
Improving access to effective contraception has the potential to reduce unintended pregnancy and abortion rates. Community pharmacists could play an expanded role in contraceptive counselling and referral to contraceptive prescribers particularly when women are already attending community pharmacy to obtain emergency contraceptive pills (ECPs) or to have medical abortion (MA) medicines dispensed. The ALLIANCE trial aims to compare the subsequent uptake of effective contraception (hormonal or intrauterine) in women seeking ECP or MA medicines, who receive the ALLIANCE community pharmacy-based intervention with those who do not receive the intervention.
METHODS AND ANALYSIS
ALLIANCE is a stepped-wedge pragmatic cluster randomised trial in Australian community pharmacies. The ALLIANCE intervention involves community pharmacists delivering structured, patient-centred, effectiveness-based contraceptive counselling (and a referral to a contraceptive prescriber where appropriate) to women seeking either ECPs or to have MA medicines dispensed. Women participants will be recruited by participating pharmacists. A total of 37 pharmacies and 1554 participants will be recruited. Pharmacies commence in the control phase and are randomised to transition to the intervention phase at different time points (steps). The primary outcome is the self-reported use of effective contraception at 4 months; secondary outcomes include use of effective contraception and the rate of pregnancies or induced abortions at 12 months. A process and economic evaluation of the trial will also be undertaken.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Monash University Human Research Ethics Committee (#34563). An explanatory statement will be provided and written consent will be obtained from all participants (pharmacy owner, pharmacist and women) before their commencement in the trial. Dissemination will occur through a knowledge exchange workshop, peer-reviewed journal publications, presentations, social media and conferences.
TRIAL REGISTRATION NUMBER
ACTRN12622001024730.
Topics: Female; Humans; Pregnancy; Australia; Contraceptive Agents; Counseling; Pharmacists; Referral and Consultation; Scope of Practice; Pragmatic Clinical Trials as Topic
PubMed: 37652588
DOI: 10.1136/bmjopen-2023-073154 -
The International Journal of Eating... Jun 2024To discuss the utility of pragmatic clinical trials (PCTs) to help advance research in eating disorders (EDs). (Review)
Review
OBJECTIVE
To discuss the utility of pragmatic clinical trials (PCTs) to help advance research in eating disorders (EDs).
METHODS
We describe challenges associated with traditional explanatory research trials and examine PCTs as an alternative, including a review of the PRECIS-2 tool.
RESULTS
There are many challenges associated with the design and completion of traditional RCTs within the field of EDs. Pragmatic clinical trials are studies that closely align with conditions available in everyday practice and focus on outcomes that are relevant to patients and clinicians. Results of PCTS maximize applicability and generalizability to clinical settings.
DISCUSSION
Available therapies established for the treatment of EDs provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In addition to a general overview of PCTs, we draw upon published literature and our own experiences involving adjunctive olanzapine for the treatment of children and youth with anorexia nervosa to help highlight challenges associated with randomized controlled trial (RCT) design and implementation, and offer pragmatic suggestions that would allow patients greater choice in treatment trials, while at the same time capturing outcomes that are most likely to advance treatment efforts.
CONCLUSIONS
Pragmatic clinical trials provide alternatives to RCT design that can help bolster research in EDs that aims to explore real-world effects of interventions.
PUBLIC SIGNIFICANCE
Available therapies established for the treatment of eating disorders (EDs) in children and adolescents provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In this article, we discuss the utility of pragmatic trials to help promote research that can help advance knowledge that is relevant to clinical care settings.
Topics: Humans; Feeding and Eating Disorders; Adolescent; Child; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 38578194
DOI: 10.1002/eat.24209 -
Research Square Jul 2023Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged...
Primary care delivery of behavioral weight loss services for adults with cardiovascular risk factors: development of pragmatic practice components and results of a randomized feasibility trial.
BACKGROUND
Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged stakeholders to cocreate and evaluate feasibility of primary care implementation strategies and of a pragmatic randomization procedure to be used for a future effectiveness trial.
METHODS
The study setting was a single, urban primary care office. Patients with BMI ≥ 27 and ≥ 1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support an initial weight loss goal of about 10 pounds in 10 weeks. All patients who affirmed weight loss interest were pragmatically enrolled in the trial and offered "Basic Lifestyle Services" (BLS), including a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of these resources. About half (n = 42) of participants were randomized by an automated EHR algorithm to also receive "Customized Lifestyle Services" (CLS), including weekly email messages adapted to individual weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned January to July 2020, with interference by the coronavirus pandemic. Weight measures were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed acceptability, appropriateness, and sustainability of intervention components.
RESULTS
Over 6 weeks, 426 patients were sent the EHR invitation message and 80 (18.8%) affirmed interest in the weight loss goal and were included for analysis. EHR data were available to ascertain a 6-month weight value for 77 (96%) patients. Overall, 62% of participants lost weight; 15.0% exhibited weight loss ≥ 5%, with no statistically significant difference between CLS or BLS arms (p = 0.85). CLS assignment increased participation in daily self-weighing (43% versus 21% of patients through 12 weeks) and enrollment in referral-based lifestyle support resources (52% versus 37%).
CONCLUSIONS
This preliminary study demonstrates feasibility of implementation strategies for primary care offices to offer and coordinate ILI core components, as well as a pragmatic randomization procedure for use in a future randomized comparative trial.
PubMed: 37547026
DOI: 10.21203/rs.3.rs-3074046/v1 -
Journal of the International AIDS... Oct 2023Urban refugee youth remain underserved by current HIV prevention strategies, including HIV self-testing (HIVST). Examining HIVST feasibility with refugees can inform...
Findings from the Tushirikiane mobile health (mHealth) HIV self-testing pragmatic trial with refugee adolescents and youth living in informal settlements in Kampala, Uganda.
INTRODUCTION
Urban refugee youth remain underserved by current HIV prevention strategies, including HIV self-testing (HIVST). Examining HIVST feasibility with refugees can inform tailored HIV testing strategies. We examined if HIVST and mobile health (mHealth) delivery approaches could increase HIV testing uptake and HIV status knowledge among refugee youth in Kampala, Uganda.
METHODS
We conducted a three-arm pragmatic controlled trial across five informal settlements grouped into three sites in Kampala from 2020 to 2021 with peer-recruited refugee youth aged 16-24 years. The intervention was HIVST and HIVST + mHealth (HIVST with bidirectional SMS), compared with standard of care (SOC). Primary outcomes were self-reported HIV testing uptake and correct status knowledge verified by point-of-care testing. Some secondary outcomes included: depression, HIV-related stigma, and adolescent sexual and reproductive health (SRH) stigma at three time points (baseline [T0], 8 months [T1] and 12 months [T2]). We used generalized estimating equation regression models to estimate crude and adjusted odds ratios comparing arms over time, adjusting for age, gender and baseline imbalances. We assessed study pragmatism across PRECIS-2 dimensions.
RESULTS
We enrolled 450 participants (50.7% cisgender men, 48.7% cisgender women, 0.7% transgender women; mean age: 20.0, standard deviation: 2.4) across three sites. Self-reported HIV testing uptake increased significantly from T0 to T1 in intervention arms: HIVST arm: (27.6% [n = 43] at T0 vs. 91.2% [n = 135] at T1; HIVST + mHealth: 30.9% [n = 47] at T0 vs. 94.2% [n = 113] at T1]) compared with SOC (35.5% [n = 50] at T0 vs. 24.8% [ = 27] at T1) and remained significantly higher than SOC at T2 (p<0.001). HIV status knowledge in intervention arms (HIVST arm: 100% [n = 121], HIVST + mHealth arm: 97.9% [n = 95]) was significantly higher than SOC (61.5% [n = 59]) at T2. There were modest changes in secondary outcomes in intervention arms, including decreased depression alongside increased HIV-related stigma and adolescent SRH stigma. The trial employed both pragmatic (eligibility criteria, setting, organization, outcome, analysis) and explanatory approaches (recruitment path, flexibility of delivery flexibility, adherence flexibility, follow-up).
CONCLUSIONS
Offering HIVST is a promising approach to increase HIV testing uptake among urban refugee youth in Kampala. We share lessons learned to inform future youth-focused HIVST trials in urban humanitarian settings.
Topics: Adolescent; Female; Humans; Male; Young Adult; HIV; HIV Infections; HIV Testing; Refugees; Self-Testing; Uganda
PubMed: 37850816
DOI: 10.1002/jia2.26185