Two-arm Randomized Clinical Trial Research Articles

A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy treatment (ACT).

TPS12151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapy among people who experience cancer, presenting pain, numbness, tingling, and motor weakness. CIPN worsens quality of life and disrupts active treatment regimens. Currently, duloxetine is the only ASCO-recommended painful CIPN treatment after chemotherapy completion. Still, it has undesirable side effects, i.e., fatigue, sleep disturbance, and digestive symptoms, posing a pressing need for well-tolerated, evidence-based interventions. Our pilot study demonstrated the feasibility and preliminary efficacy of acupuncture in relieving CIPN pain. Based on that, we developed the ACT trial to evaluate the effect of acupuncture on improving pain and other related symptoms among cancer survivors with CIPN pain. Methods: ACT is a prospective phase III multicenter, parallel two-arm randomized clinical trial at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSK) (ClinicalTrials.gov Identifier: NCT04917796). ACT aims to determine the efficacy of an eight-week electroacupuncture (EA) treatment vs. sham acupuncture (SA) on improving CIPN symptoms severity in cancer survivors. We plan to enroll 250 participants to detect an effect size of at least 0.45 for the primary pain outcome at 12 weeks post-randomization between EA vs. SA, with 80% power and a 1% Type I error rate, assuming a 10% loss to follow-up. Major eligibility criteria include 1) adults who have no evidence of disease or stable diseases, 2) who have completed neurotoxic chemotherapy such as platinum agents, taxanes, vinca alkaloids, and bortezomib at least three months before enrollment, and 3) who have a clinical diagnosis of CIPN with moderate to severe pain, defined as a score of at least four on the Brief Pain Inventory (BPI) average pain item. We randomly allocate participants to receive ten real or sham acupuncture treatments over eight weeks at two centers and their regional clinics. Aside from patient-reported outcome measures (i.e., BPI, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, EORTC Quality of Life Questionnaire-CIPN 20), we conduct quantitative sensory testing to assess changes in sensory function. The primary study endpoint is week 12, and the secondary study endpoint is week 24. Progress: 1) We are currently transitioning this trial to a multicenter trial, with DFCI being the coordinating center and MSK a subsite; 2) As of January 18, 2024, a total of 133 of the planned 250 participants have been enrolled; 3) The DSMB last reviewed the trial in December 2023, and suggested that the trial continue as planned at MSK. We anticipate initiating participant enrollment at DFCI in February 2024. Accrual completion is expected by December 2024. Clinical trial information: NCT04917796 .

A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy treatment (ACT).

TPS12151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapy among people who experience cancer, presenting pain, numbness, tingling, and motor weakness. CIPN worsens quality of life and disrupts active treatment regimens. Currently, duloxetine is the only ASCO-recommended painful CIPN treatment after chemotherapy completion. Still, it has undesirable side effects, i.e., fatigue, sleep disturbance, and digestive symptoms, posing a pressing need for well-tolerated, evidence-based interventions. Our pilot study demonstrated the feasibility and preliminary efficacy of acupuncture in relieving CIPN pain. Based on that, we developed the ACT trial to evaluate the effect of acupuncture on improving pain and other related symptoms among cancer survivors with CIPN pain. Methods: ACT is a prospective phase III multicenter, parallel two-arm randomized clinical trial at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSK) (ClinicalTrials.gov Identifier: NCT04917796). ACT aims to determine the efficacy of an eight-week electroacupuncture (EA) treatment vs. sham acupuncture (SA) on improving CIPN symptoms severity in cancer survivors. We plan to enroll 250 participants to detect an effect size of at least 0.45 for the primary pain outcome at 12 weeks post-randomization between EA vs. SA, with 80% power and a 1% Type I error rate, assuming a 10% loss to follow-up. Major eligibility criteria include 1) adults who have no evidence of disease or stable diseases, 2) who have completed neurotoxic chemotherapy such as platinum agents, taxanes, vinca alkaloids, and bortezomib at least three months before enrollment, and 3) who have a clinical diagnosis of CIPN with moderate to severe pain, defined as a score of at least four on the Brief Pain Inventory (BPI) average pain item. We randomly allocate participants to receive ten real or sham acupuncture treatments over eight weeks at two centers and their regional clinics. Aside from patient-reported outcome measures (i.e., BPI, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, EORTC Quality of Life Questionnaire-CIPN 20), we conduct quantitative sensory testing to assess changes in sensory function. The primary study endpoint is week 12, and the secondary study endpoint is week 24. Progress: 1) We are currently transitioning this trial to a multicenter trial, with DFCI being the coordinating center and MSK a subsite; 2) As of January 18, 2024, a total of 133 of the planned 250 participants have been enrolled; 3) The DSMB last reviewed the trial in December 2023, and suggested that the trial continue as planned at MSK. We anticipate initiating participant enrollment at DFCI in February 2024. Accrual completion is expected by December 2024. Clinical trial information: NCT04917796 .

Causal interpretation of the hazard ratio in randomized clinical trials.

Although the hazard ratio has no straightforward causal interpretation, clinical trialists commonly use it as a measure of treatment effect. We review the definition and examples of causal estimands. We discuss the causal interpretation of the hazard ratio from a two-arm randomized clinical trial, and the implications of proportional hazards assumptions in the context of potential outcomes. We illustrate the application of these concepts in a synthetic model and in a model of the time-varying effects of COVID-19 vaccination. We define causal estimands as having either an individual-level or population-level interpretation. Difference-in-expectation estimands are both individual-level and population-level estimands, whereas without strong untestable assumptions the causal rate ratio and hazard ratio have only population-level interpretations. We caution users against making an incorrect individual-level interpretation, emphasizing that in general a hazard ratio does not on average change each individual's hazard by a factor. We discuss a potentially valid interpretation of the constant hazard ratio as a population-level causal effect under the proportional hazards assumption. We conclude that the population-level hazard ratio remains a useful estimand, but one must interpret it with appropriate attention to the underlying causal model. This is especially important for interpreting hazard ratios over time.

Co-action and changes in alcohol use during a smoking cessation attempt.

Three smoking cessation studies (CARE, Break Free, Por Nuestra Salud [PNS]) were used to measure changes in average alcohol consumption, binge drinking and alcohol-related problems during a smoking cessation attempt and to explore co-action with smoking abstinence. CARE and PNS were longitudinal cohort cessation studies; Break Free was a two-arm randomized clinical trial. Texas, USA. Participants were current smokers who were recruited from the community and received smoking cessation interventions. All participants received nicotine replacement therapy and smoking cessation counseling. CARE included 424 smokers (1/3 White, 1/3 African American and 1/3 Latino); Break Free included 399 African American smokers; PNS included 199 Spanish-speaking Mexican-American smokers. Weekly alcohol consumption was collected multiple times pre and post-quit, and binge drinking and alcohol-related problems were collected at baseline and 26 weeks post-quit. Analyses included only those who indicated current alcohol use. Average alcohol consumption decreased from baseline to 26 weeks post-quit in CARE (F = 17.09, P < 0.001), Break Free (F = 12.08, P<0.001) and PNS (F = 10.21, P < 0.001). Binge drinking decreased from baseline to 26 weeks post-quit in CARE (F = 3.94, P = 0.04) and Break Free (F = 10.41, P < 0.001) but not PNS. Alcohol-related problems decreased from baseline to 26 weeks post-quit in CARE (Chi-sq = 6.41, P = 0.010) and Break Free (Chi sq = 14.44, P = 0.001), but not PNS. Among current drinkers, alcohol use/problems appear to decrease during a smoking cessation attempt and remain low through 26 weeks after the quit attempt. Little evidence was found for co-action, with smoking abstainers and relapsers showing similar change in alcohol use/problems.

Efficacy of neck muscle activation versus strengthening for adults with chronic cervical radiculopathy: a study protocol for a randomised clinical trial

IntroductionChronic cervical radiculopathy is a common condition characterised by neck and arm pain, numbness and weakness. Both neck muscle activation and strengthening exercises are widely recognised treatments for cervical radiculopathy,...

BEhavioral Health Stratified Treatment (B.E.S.T.) to optimize transition to adulthood for youth with intellectual and/or developmental disabilities

Youth with intellectual and/or developmental disabilities (IDD) often struggle with depression and anxiety, which adversely impacts transition to adulthood. Integrated behavioral health care coordination, wherein care coordinators and behavioral health specialists collaborate to provide systematic, cost-effective, patient-centered care, is a promising strategy to improve access to behavioral health services and address factors that impact transition to adulthood, including depression/anxiety symptoms. Current care coordination models (e.g., Title V Maternal and Child Health Bureau [MCHB]) do not include behavioral health services. The CHECK (Coordinated HealthCarE for Complex Kids) mental health model, hereby refined and renamed BEhavioral Health Stratified Treatment (B.E.S.T.), is a behavioral health intervention delivery program designed for integration into care coordination programs. This study aims to determine whether an integrated behavioral health care coordination strategy (i.e., MCHB care coordination plus B.E.S.T.) would be more acceptable and lead to better youth health and transition outcomes, relative to standard care coordination (i.e., MCHB care coordination alone). Results would guide future investment in improving outcomes for youth with IDD.This study is a two-arm randomized clinical trial of 780 transition-aged youth with IDD (13–20 years) to evaluate the comparable efficacy of MCHB Care Coordination alone vs. MCHB Care Coordination plus B.E.S.T. on the following outcomes: 1) decreased symptoms and episodes of depression and anxiety over time; 2) improved health behaviors, adaptive functioning and health related quality of life; 3) increased health care transition (HCT) readiness; and 4) improved engagement and satisfaction with care coordination among stakeholders.

Efficacy of an environmental enrichment intervention for endometriosis: a pilot study.

We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of EE interventions in patients with this painful, inflammatory chronic disease. To adapt and test the efficacy of an EE intervention on pelvic pain, mental health, perceived stress, quality of life, and systemic inflammation in endometriosis patients through a randomized clinical trial (RCT). A multidisciplinary team with expertise in physiology, neuroscience, psychology, and women's health adapted and implemented a two-arm RCT comparing an EE intervention with a wait-list control group. Six EE modules administered on alternate weeks were provided to patients in the intervention (N = 29); controls received education only. Survey data and biospecimens were collected at baseline, end-of-study, and 3-months post-intervention to assess pain (Brief Pain Inventory, BPI), endometriosis-related quality of life-QoL (Endometriosis Health Profile-30, EHP30), anxiety (Generalized Anxiety Disorder 7, GAD7), depression (Patient Health Questionnaire for Depression 8, PHQ8), pain catastrophizing (Pain Catastrophizing Score, PCS), stress (Perceived Stress Scale-14, PSS14), and saliva cortisol levels (AM, PM). Compared to the wait-list controls, participants in the EE intervention showed significantly decreased GAD-7 scores at the end of the intervention and 3-month follow-up. Depression, perceived stress, and QoL improved at the 3-month follow-up compared to baseline. While pain levels did not improve, they significantly correlated with anxiety, depression, QoL and pain catastrophizing scores. This pilot RCT demonstrated significant improvements in anxiety and depressive symptoms, QoL, and perceived stress, supporting enriched environments as an integrative psychosocial intervention to be used as adjuvant to the standard of care for endometriosis pain.

Effects of an online program including mindfulness, exercise therapy and patient education compared to online exercise therapy and patient education for people with Patellofemoral Pain: protocol for a randomized clinical trial

BackgroundPatellofemoral pain (PFP) is a common knee disorder that causes persistent pain, lower self-reported function and quality of life. People with PFP also present with altered psychological factors, which are associated with higher levels of pain and dysfunction. Mindfulness-based interventions (MBI) generally consist of meditative practices developed to provide a holistic approach to chronic conditions. However, the effects of MBI on clinical and psychological outcomes for people with PFP remains understudied.MethodsThis assessor-blinded, parallel, two-arm randomized clinical trial aims to investigate the effects of adding an 8-week online MBI program to exercise therapy and patient education on clinical and psychological factors for people with PFP. We also aim to investigate whether psychological factors mediate changes in pain and function. Sixty-two participants with PFP will be recruited and randomized into one of two treatment groups (Mindfulness or Control group). Both groups will receive an 8-week intervention involving exercise therapy and education delivered through an online platform. The Mindfulness group will additionally receive a MBI component including formal and informal practices. Outcomes will be assessed online at baseline, intervention endpoint (follow-up 1) and 12 months after intervention completion (follow-up 2). Comparisons between groups will be performed at all time points with linear mixed models. A mediation analysis will be performed using a 3-variable framework.DiscussionExercise therapy and patient education are considered the “best management” options for PFP. However, unsatisfactory long-term prognosis remains an issue. It is known that people with PFP present with altered psychological factors, which should be considered during the evaluation and treatment of people with PFP. Adding a MBI to the current best treatment for PFP may improve short and long-term effects by addressing the underlying psychological factors.Trial registrationRegistro Brasileiro de Ensaios Clínicos (ReBEC) RBR-4yhbqwk, registered in April 6, 2021.

The Fragility Index in randomised clinical trials supporting clinical practice guidelines for acute coronary syndrome: measuring robustness from a different perspective.

In randomised clinical trials (RCTs) rejecting the null hypothesis, the fragility index (FI) yields the minimum number of participants who would need to have had a different outcome for the results of the trial to become non-significant. We evaluated the robustness of RCTs supporting ACC/AHA and ESC clinical practice guidelines (CPGs) for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) using the FI. There were 407 RCTs among the 2128 studies cited in the 2013 and 2014 ACC/AHA and 2017 and 2020 ESC CPGs for STEMI and NSTE-ACS, respectively. The FI could be calculated in 132 RCTs (32.4%) meeting the needed criteria for its estimation (2-arm RCT, 1:1 allocation, binary outcome, p < 0.05). The median FI was 12 (interquartile range: 4-29). Hence, a change in the outcome status of 12 patients would be needed to reverse the statistical significance of the primary endpoint in 50% of the RCTs. The FI was ≤1% than their sample size in 55.7% RCTs, whereas in 47% of RCTs, the FI was lower than the number of patients lost to follow-up. Some study design features were associated with higher FI (international, multicentre, private funding; all p < 0.05), whilst baseline patient characteristics were not substantially different by FI (e.g., age, female sex, white study participants; all p > 0.05), except for geographic enrolment (p = 0.042). FI might be useful to evaluate the robustness of those RCTs with statistically significant findings for the primary endpoint that have an impact on key guideline recommendations.

Use of Bayesian decision analysis to maximize value in patient-centered randomized clinical trials in Parkinson’s disease

ABSTRACT A fixed one-sided significance level of 5% is commonly used to interpret the statistical significance of randomized clinical trial (RCT) outcomes. While it is necessary to reduce the false positive rate, the threshold used could be chosen quantitatively and transparently to specifically reflect patient preferences regarding benefit–risk tradeoffs as well as other considerations. How can patient preferences be explicitly incorporated into RCTs in Parkinson’s disease (PD), and what is the impact on statistical thresholds for device approval? In this analysis, we apply Bayesian decision analysis (BDA) to PD patient preference scores elicited from survey data. BDA allows us to choose a sample size () and significance level () that maximizes the overall expected value to patients of a balanced two-arm fixed-sample RCT, where the expected value is computed under both null and alternative hypotheses. For PD patients who had previously received deep brain stimulation (DBS) treatment, the BDA-optimal significance levels fell between 4.0% and 10.0%, similar to or greater than the traditional value of 5%. Conversely, for patients who had never received DBS, the optimal significance level ranged from 0.2% to 4.4%. In both of these populations, the optimal significance level increased with the severity of the patients’ cognitive and motor function symptoms. By explicitly incorporating patient preferences into clinical trial designs and the regulatory decision-making process, BDA provides a quantitative and transparent approach to combine clinical and statistical significance. For PD patients who have never received DBS treatment, a 5% significance threshold may not be conservative enough to reflect their risk-aversion level. However, this study shows that patients who previously received DBS treatment present a higher tolerance to accept therapeutic risks in exchange for improved efficacy which is reflected in a higher statistical threshold.

Survival rate of the Hall technique compared with resin composite restoration in multi-surface cavities in primary teeth: a 1-year randomized clinical trial.

Hall technique (HT) has been indicated for teeth with dentinal caries lesion; however, extensive cavities, with more than two surfaces still seem challenging for restorative treatment in pediatric dentistry, resulting in a higher failure rate and an increased need for retreatment. To compare the survival rate of the Hall technique preformed metal crown (HT) with resin composite restoration (RC) for multi-surface cavitated caries lesions in primary molars. In this multicenter two-arm randomized clinical trial, children between 4 and 9 years of age with at least one primary molar with cavitated caries lesion involving more than two surfaces, including one buccal or palatal/lingual surface, were selected from 17 Brazilian cities. A total of 364 teeth were allocated into two groups: (1) teeth treated with selective caries removal and RC and (2) treated with the HT. The survival rate was assessed at 6 and 12 months after the interventions. Survival analysis was performed with the Kaplan‒Meier method. Cox regression was used to determine the influence of explanatory variables on the survival rate (α=5%). After 12 months, 292 teeth were re-evaluated. A total of 358 teeth were re-evaluated at least once during the study and included in the survival analysis. The HT (87.8%) resulted in a higher survival rate than RC restoration (75.7%) (p=0.004). HT has a higher survival rate than RC as a treatment for multi-surface cavitated caries lesions in primary teeth. ClinicalTrials.gov: NCT02782390.

Visual Error Augmentation During Bimanual Therapy in Individuals Post Stroke

<h3>Research Objectives</h3> To investigate the influence of visual error augmentation during bimanual upper extremity therapy in individuals' post-stroke. <h3>Design</h3> Two-arm randomized clinical trial with blinded rater. Individuals were randomized into the treatment or control group. Individuals received 9 treatments across 3 weeks, and completed upper extremity evaluations before treatment, 1 week after treatment, and 8 weeks after treatment. <h3>Setting</h3> Translational research hospital in which clinicians and researchers are integrated in the same space. <h3>Participants</h3> The target population for the study was chronic stroke participants (at least 8 months post-injury), 18 years or older, with a history of a single stroke event, with mild-moderate upper extremity impairment (Fugl-Meyer Score 15-50) and residual active elbow flexion/extension when supported against gravity. 69 participants were assessed for eligibility, 38 participants met inclusion criteria and were randomized into the study. 19 subjects were allocated in each group, but 3 in each group were lost due to participant withdrawal. One participant in the control group was lost to follow-up. 16 participants in the treatment group, and 15 participants in the control group were analyzed in the results. <h3>Interventions</h3> Both groups completed a bimanual reaching and balancing exercise in a virtual reality environment. The treatment group received visual error augmentation, which visually shifted the cursor in the direction of error to enhance neuroplasticity associated with motor recovery. <h3>Main Outcome Measures</h3> Upper Extremity Fugl-Meyer, and bimanual asymmetry. <h3>Results</h3> No clinically significant difference between treatment and control group for functional motor recovery (p=0.665) and no significant difference in the interaction between time and groups (p=0.069); however, both groups did improve over time (p=0.005). For asymmetry of trajectory between paretic and non-paretic hand in the superior-inferior direction there is a significant difference between time instants (p< 0.001), while no significant difference was found in groups (p=0.266) or in the interaction between time and groups (p=0.066). <h3>Conclusions</h3> This is an example of supplemental treatment using interactive visual feedback for post-stroke upper extremity rehabilitation. <h3>Author(s) Disclosures</h3> N/A.

Impact of COVID-19 Pandemic on Physical Activity, Pain, Mood, and Sleep in Adults with Knee Osteoarthritis.

To examine changes in physical activity, sleep, pain and mood in people with knee osteoarthritis (OA) during the ongoing COVID-19 pandemic by leveraging an ongoing randomized clinical trial (RCT). Participants enrolled in a 12-month parallel two-arm RCT (NCT03064139) interrupted by the COVID-19 pandemic wore an activity monitor (Fitbit Charge 3) and filled out custom weekly surveys rating knee pain, mood, and sleep as part of the study. Data from 30 weeks of the parent study were used for this analysis. Daily step count and sleep duration were extracted from activity monitor data, and participants self-reported knee pain, positive mood, and negative mood via surveys. Metrics were averaged within each participant and then across all participants for pre-pandemic, stay-at-home, and reopening periods, reflecting the phased re-opening in the state of Massachusetts. Data from 28 participants showed small changes with inconclusive clinical significance during the stay-at-home and reopening periods compared to pre-pandemic for all outcomes. Summary statistics suggested substantial variability across participants with some participants showing persistent declines in physical activity during the observation period. Effects of the COVID-19 pandemic on physical activity, sleep, pain, and mood were variable across individuals with OA. Specific reasons for this variability could not be determined. Identifying factors that could affect individuals with knee OA who may exhibit reduced physical activity and/or worse symptoms during major lifestyle changes (such as the ongoing pandemic) is important for providing targeted healthcare services and management advice towards those that could benefit from it the most.

Study protocol for the management of impacted maxillary central incisors: a multicentre randomised clinical trial: the iMAC Trial

BackgroundFailure of eruption of the maxillary permanent incisor teeth usually presents in the mixed dentition between the ages of 7 and 9 years. Missing and unerupted maxillary incisors can be regarded as unattractive and have a potentially negative impact on facial and dental aesthetics. The presence of a supernumerary tooth (or odontoma) is commonly responsible for failed eruption or impaction of the permanent maxillary incisors. The primary objective of this trial is to investigate the success of eruption associated with maxillary incisor teeth that have failed to erupt because of a supernumerary tooth in the anterior maxilla.MethodsThis protocol describes an interventional multicentre two-arm randomised clinical trial. Participants meeting the eligibility criteria will be randomised (unrestricted equal participant allocation [1:1]) to either space creation with an orthodontic appliance, removal of the supernumerary tooth and application of direct orthodontic traction or space creation with an orthodontic appliance, removal of the supernumerary tooth and monitoring. The primary outcome of this trial is to determine the prevalence of successfully erupted maxillary central permanent incisors at 6 months following removal of the supernumerary tooth. Secondary outcome measures include (1) the effect of initial tooth position (assessed radiographically) on time taken for the tooth to erupt, (2) time taken to align the unerupted tooth to the correct occlusal position, (3) gingival aesthetics and (4) changes in the self-reported Oral Health Related-Quality of Life (OHRQoL) (pre-and post-treatment).DiscussionThere is a lack of high-quality robust prospective studies comparing the effectiveness of interventions to manage this condition. Furthermore, the UK national clinical guidelines have highlighted a lack of definitive treatment protocols for the management of children who present with an unerupted maxillary incisor due to the presence of a supernumerary tooth. The results of this trial will inform future treatment guidelines for the management of this condition in young children.Trial registrationISRCTN Registry ISRCTN12709966. Registered on 16 June 2022.

South Asians Active Together (SAATH): Protocol for a multilevel physical activity intervention trial for South Asian American mother and daughter dyads

South Asian (SA), including Asian Indian and Pakistani Americans, have a high burden of cardiometabolic risk factors and low levels of physical activity (PA). Increasing PA in the U.S. population is a national priority; however, SA American women and girls experience unique barriers to PA that are not addressed by current promotion efforts. To address this gap, our community-based participatory research partnership developed the South Asians Active Together (SAATH) intervention. This study is a two-arm randomized clinical trial to evaluate the effects, mediators, and implementation of the 18-week SAATH intervention. A total of 160 mother-daughter dyads will be randomized in a 1:1 ratio to the SAATH intervention and control groups. The intervention was designed for mother-daughter dyads and targets individual, interpersonal, and family levels through (1) group exercise classes, (2) mother-daughter discussions, and (3) peer group discussions. The intervention targets the environment level through community partner meetings aimed at creating environment changes to enhance PA opportunities for SA women and girls. The control group will receive PA education materials. We hypothesize that dyads who receive the intervention will have significantly greater increases in moderate- and vigorous-intensity PA (MVPA) from baseline to 4 months, compared to the control group. MVPA will be measured at 12 months in intervention participants to examine if changes are sustained. A process evaluation will use the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. This study will fill knowledge gaps about the effectiveness and implementation of culturally adapted, community-based PA interventions for SA women and girls.

Effect of Telenursing on Caregiver Burden of Care and Incidence of some Complications in Patients with Acute Stroke Discharged from Neurological Wards: A Randomized Control Trial

Background: Brain stroke is the main cause of death and disability worldwide. This disease can cause major complications in patients and place a great burden of care on caregivers. Therefore, this study was conducted to determine the effect of telenursing on the burden of care in caregivers and the rate of complications in patients with acute brain stroke discharged from neurological wards. Methods: This two-arm parallel-group single-blind randomized clinical trial study was carried out on 72 patients with acute brain stroke discharged from neurological wards in Qom, Iran, in 2019. The patients and their caregivers were divided to control and intervention groups using random block allocation. In addition to the usual training of the ward, the intervention group received training and counseling based on their needs through phone calls for 4 weeks. However, the control group received only the usual ward training. Immediately after discharge from the hospital and 1 month later, the average care load in caregivers and urinary problems, bedsores, and the number of falls in patients were measured. A demographic questionnaire, Caregiver Burden Inventory, Braden Scale, Morse Scale, and a urinary problem checklist were used for data collection. The data were analyzed using the chi-square test, Mann-Whitney U test, independent t-test, and paired t-test by SPSS software (version 24). Results: After the intervention, the mean scores of the caregiver’s burden of care in the control and counseling groups were 35.22 ± 17.215 and 8.00 ± 7.556, respectively (P &lt; 0.001). In addition, the counseling group experienced remarkably fewer urinary problems (P &lt; 0.001) and falling (P = 0.011). Conclusions: This study showed that telenursing reduced the burden of care in caregivers and decreased urinary tract infections and the number of falls in patients with acute stroke. Therefore, nurses and healthcare providers can use this program to improve the lifestyle of patients with acute brain stroke and their caregivers.

Effects of the Sleep SAAF responsive parenting intervention on rapid infant weight gain: A randomized clinical trial of African American families

Responsive parenting (RP) interventions reduce rapid infant weight gain but their effect for underserved populations is largely unknown. The Sleep SAAF (Strong African American Families) study is a two-arm randomized clinical trial for primiparous African American mother-infant dyads that compares an RP intervention to a child safety control over the first 16 weeks postpartum. Here we report on intervention effects on rapid infant weight gain and study implementation. Families were recruited from a mother/baby nursery shortly after delivery. Community Research Associates (CRAs) conducted intervention home visits at 3 and 8 weeks postpartum, and data collection home visits at 1, 8, and 16 weeks postpartum. To examine rapid infant weight gain, conditional weight gain (CWG) from 3 to 16 weeks, the primary outcome, and upward crossing of 2 major weight-for-age percentile lines were calculated. Among the 212 mother-infant dyads randomized, 194 completed the trial (92% retention). Randomized mothers averaged 22.7 years, 10% were married, and 49% participated in the Supplemental Nutrition Assistance Program (SNAP). Adjusting for covariates, mean CWG was lower among RP infants (0.04, 95% CI [-0.33, 0.40]) than among control infants (0.28, 95% CI [-0.08, 0.64]), reflecting non-significantly slower weight gain (p = 0.15, effect size d = 0.24). RP infants were nearly half as likely to experience upward crossing of 2 major weight-for-age percentile lines (14.1%) compared to control infants (24.2%), p = 0.09, odds ratio = 0.52 (95% CI [0.24, 1.12]). Implementation data revealed that participating families were engaged in the intervention visits and intervention facilitators demonstrated high fidelity to intervention materials. Findings show that RP interventions can be successfully implemented among African American families while suggesting the need for modifications to yield stronger effects on infant weight outcomes.

Advances in clinical trials methodology: Intervention optimization approaches in emergency medicine.

The classical two-arm randomized clinical trial (RCT) is designed to test the efficacy or effectiveness of an intervention, which may consist of one or more components. However, this approach does not enable the investigator to obtain information that is important in intervention development, such as which individual components of the intervention are efficacious, which are not and possibly should be removed, and whether any components interact. The Multiphase Optimization Strategy (MOST) is a new framework for development, optimization, and evaluation of interventions. MOST includes the RCT for purposes of evaluation, but inserts a phase of research before the RCT aimed at intervention optimization. The optimization phase requires one or more separate trials similar in scope to an RCT, but employing a different experimental design. The design of the optimization trial is selected strategically so as to maximize the amount of scientific information gained using the available resources. One consideration in selecting this experimental design is the type of intervention to be optimized. If a fixed intervention, i.e. one in which the same intervention content and intensity is provided to all participants, is to be optimized, a factorial experiment is often appropriate. If an adaptive intervention, i.e. one in which intervention content or intensity is varied in a principled manner, is to be optimized, a sequential multiple-assignment randomized trial (SMART) is often a good choice. The objective of this article is to describe MOST and the scientific rationale for its use; describe two current applications of MOST in emergency medicine research, one using a factorial experiment and the other using a SMART; and discuss funding strategies and potential future applications in studying the care of individuals with acute illness, injury, or behavioral disorders.

The effect of low-molecular-weight heparin on live birth rate of patients with unexplained early recurrent pregnancy loss: A two-arm randomized clinical trial.

The effect of anticoagulant medication in unexplained early recurrent pregnancy loss (RPL) patients is controversial. This clinical trial evaluated the effect of low-molecular-weight heparin (LMWH) on pregnancy outcomes in these patients. The study was performed as a single-blind randomized clinical trial between 2016 and 2018. Samples were selected from patients who were referred to Avicenna RPL clinic with a history of at least two previously happened early unexplained miscarriages. The eligibility was defined strictly to select unexplained RPL patients homogenously. One hundred and seventy-three patients who got pregnant recently were allocated randomly into two groups LMWH plus low-dose aspirin treatment (Group A = 85) and low-dose aspirin treatment only (Group B = 88)) and were followed up till their pregnancy termination (delivery/abortion). A per-protocol analysis was carried out and all statistical tests were two-sided with a P < 0.05 significance level. The live birth rates (LBRs) in Groups A and B were 78% and 77.1%, respectively, which did not show any statistically significant difference between the two groups, neither in rates nor in time of abortion. In subgroup analysis for polycystic ovary syndrome (PCOS) patients, the odds ratio for study outcome (intervention/control) was 2.25 (95% confidence interval: 0.65-7.73). There was no major adverse event whereas minor bleeding was observed in 18% of patients in Group A. LMWH does not improve the LBR in unexplained RPL patients, however, it is recommended to evaluate its effect separately in PCOS patients.

Elastic meta-analytic-predictive prior for dynamically borrowing information from historical data with application to biosimilar clinical trials

A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an approved reference product. Focusing on two-arm randomized clinical trials that aim to establish the equivalence between a test biosimilar product and the reference product, we propose the elastic meta-analytic-predictive (EMAP) prior method to leverage rich historical data available on the reference product to improve the power of the biosimilar trials. We first extract the prior information from multiple historical studies through meta-analysis, and then we discount the resulting meta-analytic-predictive (MAP) prior adaptively according to the congruence between the historical reference data and the trial reference arm data via an elastic function. The EMAP prior method is information-borrowing consistent in that asymptotically it achieves full information borrowing when trial reference arm data are congruent to historical reference data, and no information borrowing when trial reference arm data are not congruent to historical reference data. As a result, the method asymptotically controls the type I error rate at the nominal value. Extensive simulation studies show that the EMAP prior outperforms the robust MAP prior. The EMAP prior generates comparable or higher power and provides better-controlled type I errors. We illustrate the proposed methodology using two trial examples.