Cluster-randomized Clinical Trial Research Articles

A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care

SummaryBackgroundPatients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina.MethodsRegional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient–provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350.FindingsParticipants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = −0·095, P = 0·027), and self-efficacy (B = 0·063, P = 0·001), suggesting the intervention was associated with improved patient–provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy.InterpretationThese findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted.FundingNational Institutes of Health.

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru

Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Effectiveness of the MULTIPAP Plus intervention in youngest-old patients with multimorbidity and polypharmacy aimed at improving prescribing practices in primary care: study protocol of a cluster randomized trial

BackgroundThe progressive ageing of the population is leading to an increase in multimorbidity and polypharmacy, which in turn may increase the risk of hospitalization and mortality. The enhancement of care with information and communications technology (ICT) can facilitate the use of prescription evaluation tools and support system for decision-making (DSS) with the potential of optimizing the healthcare delivery process.ObjectiveTo assess the effectiveness and cost-effectiveness of the complex intervention MULTIPAP Plus, compared to usual care, in improving prescriptions for young-old patients (65-74 years old) with multimorbidity and polypharmacy in primary care.Methods/designThis is a pragmatic cluster-randomized clinical trial with a follow-up of 18 months in health centres of the Spanish National Health System. Unit of randomization: family physician. Unit of analysis: patient.PopulationPatients aged 65–74 years with multimorbidity (≥ 3 chronic diseases) and polypharmacy (≥ 5 drugs) during the previous 3 months were included.Sample sizen = 1148 patients (574 per study arm).InterventionComplex intervention based on the ARIADNE principles with three components: (1) family physician (FP) training, (2) FP-patient interview, and (3) decision-making support system.OutcomesThe primary outcome is a composite endpoint of hospital admission or death during the observation period measured as a binary outcome, and the secondary outcomes are number of hospital admission, all-cause mortality, use of health services, quality of life (EQ-5D-5L), functionality (WHODAS), falls, hip fractures, prescriptions and adherence to treatment. Clinical and sociodemographic factors will be explanatory variables.Statistical analysisThe main result is the difference in percentages in the final composite endpoint variable at 18 months, with its corresponding 95% CI. Adjustments by the main confounding and prognostic factors will be performed through a multilevel analysis. All analyses will be carried out in accordance to the intention-to-treat principle.DiscussionIt is important to prevent the cascade of negative health and health care impacts attributable to the multimorbidity-polypharmacy binomial. ICT-enhanced routine clinical practice could improve the prescription process in patient care.Trial registrationClinicalTrials.gov NCT04147130. Registered on 22 October 2019

Non-pharmacological Options in Postoperative Hospital-Based and Rehabilitation Pain Management (NOHARM): Protocol for a Stepped-Wedge Cluster-Randomized Pragmatic Clinical Trial.

IntroductionOpioids may be necessary for guideline-concordant acute perioperative pain management, but their use carries risks for unintended prolonged use and addiction. Guidelines recommend use of validated non-pharmacological pain care (NPPC) approaches in conjunction with prescribed opioids and other analgesics. Our protocol outlines a population-level, pragmatic trial that will test a bundled intervention comprised of an electronic health record (EHR) portal-based conversation guide, EHR clinical decision support (CDS), and a suite of self-management educational and support materials to encourage and advance NPPC use.MethodsWe are conducting a stepped-wedge, cluster-randomized pragmatic trial spanning seven surgical specialties across six geographically diverse locations within the Mayo Clinic Enterprise. Thirty two surgical practices across six locations (Rochester, Minnesota; Mankato, Minnesota; La Crosse, Wisconsin; Eau Claire, Wisconsin; Phoenix, Arizona; Jacksonville, Florida) comprise 22 distinct practice clusters that are randomly assigned to one of five steps using constrained randomization. Steps “go live” by initiating the intervention at 7-month intervals between March 2021 and July 2023. Patients over 18 years of age who are scheduled for qualifying procedures within “live” consenting practices are sent a Healing After Surgery guide via their patient portals pre-operatively, directing them to identify their preferred NPPC modalities among 13 approaches. These selections create CDS options for care teams to support patients with self-management materials that reinforce safe NPPC use.Planned OutcomesPatients’ clinical, demographic, and outcome data will be abstracted from the Epic EHR. Primary outcomes will be the Patient Reported Outcomes Measurement Information System (PROMIS) pain interference and physical functioning computer adaptive tests (CAT) collected at 1, 2, and 3 months postoperatively via the patient portal. We will mail printed versions of the 6-item PROMIS short forms to portal non-responders to minimize bias. Secondary outcomes will include the PROMIS anxiety CAT, opioid consumption, and self-reported NPPC use.Trial RegistrationClinicalTrials.gov identifier, NCT04570371.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-022-00393-x.

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Rationale and design of switch Swedeheart: A registry-based, stepped-wedge, cluster-randomized, open-label multicenter trial to compare prasugrel and ticagrelor for treatment of patients with acute coronary syndrome

European treatment guidelines recommend prasugrel over ticagrelor for treating patients with non-ST-elevation acute coronary syndrome (ACS), prompting several Swedish administrative regions to transition from ticagrelor to prasugrel as the preferred treatment for patients with ACS. We aim to systematically evaluate this transition to determine the relative efficacy of prasugrel versus ticagrelor in a real-world cohort of patients with ACS. The SWITCH SWEDEHEART trial is a prospective, multicenter, open-label, cross-sectional, stepped-wedge cluster-randomized clinical trial, in which administrative regions in Sweden will constitute the clusters. At the start of the study, all clusters will use ticagrelor as the P2Y12 inhibitor drug of choice for ACS. The order in which the clusters will implement the transition from ticagrelor to prasugrel will be randomly assigned. Every 9 months, 1 cluster will switch from ticagrelor to prasugrel as the P2Y12 inhibitor of choice for patients with ACS. The primary endpoint is the composite 1-year rate of the death, stroke, or myocardial infarction. The SWITCH SWEDEHEART study will provide an extensive randomized comparison between ticagrelor and prasugrel. Novel therapies are frequently costly and supported by evidence from few or small studies, and systematic evaluation after the introduction is rare. This study will establish an important standard for introducing and evaluating the effects of health care changes within our societies.

How to Improve Healthcare for Patients with Multimorbidity and Polypharmacy in Primary Care: A Pragmatic Cluster-Randomized Clinical Trial of the MULTIPAP Intervention.

(1) Purpose: To investigate a complex MULTIPAP intervention that implements the Ariadne principles in a primary care population of young-elderly patients with multimorbidity and polypharmacy and to evaluate its effectiveness for improving the appropriateness of prescriptions. (2) Methods: A pragmatic cluster-randomized clinical trial was conducted involving 38 family practices in Spain. Patients aged 65–74 years with multimorbidity and polypharmacy were recruited. Family physicians (FPs) were randomly allocated to continue usual care or to provide the MULTIPAP intervention based on the Ariadne principles with two components: FP training (eMULTIPAP) and FP patient interviews. The primary outcome was the appropriateness of prescribing, measured as the between-group difference in the mean Medication Appropriateness Index (MAI) score change from the baseline to the 6-month follow-up. The secondary outcomes were quality of life (EQ-5D-5 L), patient perceptions of shared decision making (collaboRATE), use of health services, treatment adherence, and incidence of drug adverse events (all at 1 year), using multi-level regression models, with FP as a random effect. (3) Results: We recruited 117 FPs and 593 of their patients. In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was −2.42 (95% CI from −4.27 to −0.59) and, between baseline and a 12-month follow-up was −3.40 (95% CI from −5.45 to −1.34). There were no significant differences in any other secondary outcomes. (4) Conclusions: The MULTIPAP intervention improved medication appropriateness sustainably over the follow-up time. The small magnitude of the effect, however, advises caution in the interpretation of the results given the paucity of evidence for the clinical benefit of the observed change in the MAI. Trial registration: Clinicaltrials.gov NCT02866799.

Impact of COVID-19 on the Patient Enrollment for a Pragmatic, Cluster Randomized Clinical Trial for Fibromyalgia

The goal was to present our experience on adapting to the challenges of the COVID-19 pandemic during enrollment to a pragmatic clinical trial. Transcutaneous Electrical Nerve Stimulation (TENS) in Physical Therapy (PT) Study (FM-TIPS) is a pragmatic, cluster-randomized clinical trial examining if the addition of TENS to routine PT improves movement-evoked pain in patients with fibromyalgia(FM). FM patients (n=600) will be enrolled from 33 PT clinics (17 PT only, 16 PT with TENS) across six healthcare systems. During the planning year, COVID-19 impacted PT practice and in-person interactions requiring the study team to adapt clinician training and data capture procedures. We will discuss the pandemic's impact during the patient enrollment. We developed alternative strategies to protect study integrity and minimize missing data due to potential restrictions of in-person visits including procedures for electronic consent and training participants in TENS use virtually and/or in-person using personal protective equipment and social distancing. Assessment of the primary outcome variable and questionnaires were transitioned for the patient to perform at home virtually with embedded patient-specific instructional videos. To enhance clinic engagement, weekly enrollment updates, monthly meetings, newsletters, and action plans for underperforming clinics were developed. To increase patient communication, a “welcome” touchpoint by phone, reminder emails, and touchpoints ahead of primary and secondary data collection points were added. Several clinics were added to increase the heterogeneity of the sample, to replace clinics that are unable to participate due to site closures or understaffing, and to decrease the enrollment burden on participating sites. COVID-19 posed considerable challenges to the statistical design and analysis of this pragmatic trial. We developed a plan for uneven enrollment across clinics and a sub-analysis of data for patients enrolled during or after the pandemic. Conducting this trial during COVID-19 required greater flexibility for providers and patients to facilitate continued enrollment. FM-TIPS work is supported by the National Institutes of Health (NIH) through the NIH HEAL Initiative under award number UG3AR076387 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. This work also received logistical and technical support from the PRISM Resource Coordinating Center under award number U24AT010961 from the NIH through the NIH HEAL Initiative. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or its HEAL Initiative.

Facilitators and Barriers to Implementation of a Transcutaneous Electrical Nerve Stimulation Intervention in a Pragmatic Clinical Trial

Fibromyalgia TENS in Physical Therapy (PT) Study (FM-TIPS) is testing feasibility and efficacy of Transcutaneous Electrical Nerve Stimulation (TENS). We present our experience for implementing TENS into PT clinics and virtual training to participants on TENS in a pragmatic clinical. FM-TIPS is a pragmatic, cluster-randomized clinical trial examining if the addition of TENS to routine PT improves movement-evoked pain in fibromyalgia (FM). FM patients (n=600) will be enrolled from 35 PT clinics across six Midwest healthcare systems into either a TENS or no-TENS group. All subjects randomized by TENS clinics receive TENS starting on Day 1. The no-TENS clinics start after completion of the primary outcome on Day 60. In the TENS group, Physical therapists (PTs) provide TENS education in person, while in the no-TENS group, study staff provide TENS education virtually. To facilitate implementation, we selected a study-specific TENS unit that provides mixed frequency TENS with intensity as the only adjustable parameter. All PTs were trained in proper use of the TENS unit in-person. While most PTs embraced the addition of TENS, some had not used TENS and had difficulty adapting practice to include TENS. For virtual visits in the no-TENS group, a standardized procedure was developed and completed by study staff PTs. TENS units were shipped to subject's and zoom visits were scheduled at the subject's convenience within a 10-day window. Most subjects completed virtual TENS training and implementation without difficulties. Technology limitations provided a significant barrier for some subjects. Most clinics have adopted and incorporated TENS intervention. Implementing virtual TENS training in a pragmatic trial can be successful for participant intervention. Due to the current COVID-19 pandemic, participants are more aware of the need to complete interventions via virtual mechanisms. Barriers to virtual TENS instruction are often due to internet and device limitations. FM-TIPS work is supported by the National Institutes of Health (NIH) through the NIH HEAL Initiative under award number UG3AR076387 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. This work also received logistical and technical support from the PRISM Resource Coordinating Center under award number U24AT010961 from the NIH through the NIH HEAL Initiative. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or its HEAL Initiative.

The effect of three-part breathing exercise on smoking cessation: A 6-month cluster-randomized clinical trial

IntroductionNegative affect was identified as an important barrier to smoking cessation. Three-part breathing exercise showed a significant effect on decreasing negative affect immediately after being practiced. Thus, this study evaluated the effect of three-part breathing exercise on smoking cessation. MethodsA 6-month cluster-randomized clinical trial was conducted. Forty-three participants recruited from 8 companies in Bangkok Metropolitan areas were randomly assigned at the cluster level into either the intervention or control groups. Control group (n = 23) received counseling for smoking cessation once a week for 12 weeks. Intervention group (n = 20) received counseling for smoking cessation plus a three-part breathing exercise program once a week for 12 weeks. The primary outcomes were 7-day point prevalence and continuous abstinence rate as validated by saliva cotinine. The secondary outcomes were cigarette cravings, nicotine withdrawal symptoms, affect and quality of life. ResultsThe results revealed no significant difference in smoking abstinence rate between the three-part breathing exercise and control group. Participants demonstrated significant pre-post improvement in cigarette cravings, nicotine withdrawal symptoms, affect, and quality of life within each group. ConclusionThere were no statistically significant differences between the two groups. However, the improvement in abstinence rate from the three-part breathing exercise was deemed clinically relevant. Thus, it may be recommended to smokers interested in smoking cessation and more research is needed on this topic.

Effectiveness of a Suicide Prevention Module for Adults in Substance Use Disorder Treatment

Individuals with substance use disorders (SUDs) are at high risk for suicide. The Preventing Addiction Related Suicide (PARS) module is the first suicide prevention module developed in and for community substance use intensive outpatient programs (IOPs). To evaluate the effectiveness of PARS on suicide-related outcomes (ie, knowledge, attitudes, and help-seeking behavior) compared with usual care. This stepped-wedge cluster-randomized clinical trial was conducted from 2017 to 2020, with follow-up assessments conducted after treatment and at 1, 3, and 6 months. Participants included adult outpatients in SUD treatment at community IOPs across western Washington state. Data were analyzed from July 1, 2020, to January 20, 2022. The intervention, PARS, was a 1-session secondary prevention module administered by trained SUD counselors consisting of didactic presentations and group discussions about suicide risk factors, warning signs, and actions to take if suicide risk is observed in self or others. The control group received usual care. Primary outcomes were suicide knowledge, attitudes about suicide, and help-seeking behavior among patients enrolled in an IOP. A total of 906 participants (mean [SD] age, 37.5 [12.0] years; 540 [59.6%] men) were included, with 478 participants receiving usual care and 428 participants receiving PARS. In intent-to-treat analysis from baseline to after treatment, there was a greater improvement in suicide knowledge (d = 0.15; 95% CI, 0.08 to 0.23; P < .001) and a greater reduction in maladaptive attitudes (d = 0.18; 95% CI, 0.14 to 0.25; P < .001) for PARS participants compared with those receiving usual care. Improvements were maintained at follow-up for suicide knowledge (1 month: d = 0.16; 95% CI, 0.07 to 0.22; P < .001; 3 months: d = 0.12; 95% CI, 0.05 to 0.19; P = .001; 6 months: d = 0.13; 95% CI, 0.06 to 0.20; P < .001) and reductions in maladaptive attitudes (1 month: d = 0.20; 95% CI, 0.12 to 0.23; P < .001; 3 months: d = 0.10; 95% CI, 0.05 to 0.16; P < .001; 6 months: d = 0.14; 95% CI, 0.09 to 0.19; P < .001), with 788 participants (87.0%) of the sample responding across time points. From baseline to 6 months, there was a greater improvement in help-seeking in the PARS group vs usual care (d = 0.16; 95% CI, 0.01 to 0.32; P = .04). This stepped-wedge cluster-randomized clinical trial found that PARS was superior to usual care in improving suicide knowledge, maladaptive attitudes, and help-seeking in adults undergoing community addiction treatment. As a 1-session IOP module developed in partnership with community addiction agencies, PARS has the potential for wide impact in the national suicide prevention strategy. ClinicalTrials.gov Identifier: NCT03166709.

A Geriatric Assessment Intervention to Reduce Treatment Toxicity Among Older Adults With Advanced Lung Cancer: A Subgroup Analysis From a Cluster Randomized Controlled Trial.

IntroductionMore older adults die from lung cancer worldwide than breast, prostate, and colorectal cancers combined. Current lung cancer treatments may prolong life, but can also cause considerable treatment-related toxicity.ObjectiveThis study is a secondary analysis of a cluster-randomized clinical trial which evaluated whether providing a geriatric assessment (GA) summary and GA-guided management recommendations can improve grade 3-5 toxicity among older adults with advanced lung cancer.MethodsWe analyzed participants aged ≥70 years(y) with stage III & IV (advanced) lung cancer and ≥1 GA domain impairment starting a new cancer treatment with high-risk of toxicity within the National Cancer Institute’s Community Oncology Research Program. Community practices were randomized to the intervention arm (oncologists received GA summary & recommendations) versus usual care (UC: no summary or recommendations given). The primary outcome was grade 3-5 toxicity through 3 months post-treatment initiation. Secondary outcomes included 6-month (mo) and 1-year overall survival (OS), treatment modifications, and unplanned hospitalizations. Outcomes were analyzed using generalized linear mixed and Cox proportional hazards models with practice site as a random effect. Trial Registration: NCT02054741.Results & ConclusionAmong 180 participants with advanced lung cancer, the mean age was 76.3y (SD 5.1), 39.4% were female and 82.2% had stage IV disease. The proportion of patients who experienced grade 3-5 toxicity was significantly lower in the intervention arm vs UC (53.1% vs 71.6%, P=0.01). More participants in the intervention arm received lower intensity treatment at cycle 1 (56.3% vs 35.3%; P<0.01). Even with a cycle 1 dose reduction, OS at 6mo and 1 year was not significantly different (adjusted hazard ratio [HR] intervention vs. UC: 6mo HR=0.90, 95% CI: 0.52-1.57, P=0.72; 1 year HR=0.89, 95% CI: 0.58-1.36, P=0.57). Frequent toxicity checks, providing education and counseling materials, and initiating direct communication with the patient’s primary care physician were among the most common GA-guided management recommendations. Providing a GA summary and management recommendations can significantly improve tolerability of cancer treatment among older adults with advanced lung cancer.

Long term outcome of prevention of liver cancer by hepatitis B vaccine: Results from an RCT with 37 years

We aimed to evaluate the long-term efficacy of the hepatitis B vaccine in China. In an initial efficacy study, participants were collected from a cluster-randomized clinical trial conducted in 1983-90 in Qidong. All the participants in the vaccination group were vaccinated at birth, 1 and 6 months of age, and no intervention was implemented to the control group. In this 37-year extended follow-up study, the Poisson regression method was employed to derive rates per 105 person-years. The frailty Cox proportional hazard regression models obtained the hazard ratio (HR). Cumulative incidence/mortality rates were calculated and compared with log-rank tests. 41,136 in the vaccination and 41,730 in the control group were recorded. The incidence rate of liver cancer was significantly lower in the vaccinated group than in the control group [HR, 0.28; 95% confidence interval (CI) 0.11–0.70, P = 0.007]. The vaccine offers 72% (95% CI, 30–89) protection to prevent the occurrence of liver cancer. There is 70% (95% CI, 23–88) protective efficacy against liver cancer deaths and 64% (95% CI, 27–82) benefits in the prevention of deaths associated with liver diseases. Hepatitis B vaccine given at birth shows excellent protective effects in preventing the development of liver cancer and reducing mortality from liver cancer and liver diseases.

Protocol paper: Multi-site, cluster-randomized clinical trial for optimizing functional outcomes of older cancer survivors after chemotherapy

BackgroundCancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy. MethodsA cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months. DiscussionIf successful, GEMS would be an option for a standardized APP-led survivorship care intervention. Trial RegistrationClinicalTrials.govNCT05006482, registered on August 9, 2021.

Baseline Physical Activity Behaviors and Relationships with Fitness in the Army Training at High Intensity Study.

United States Army soldiers must meet physical fitness test standards. Criticisms of the Army Physical Fitness Test (APFT) include limited testing of only aerobic and muscular endurance activity domains; yet, it is unclear what levels of aerobic and muscle strengthening activity may help predict performance in aspects of the new Army Combat Fitness Test (ACFT). This study explored relationships between baseline self-reported aerobic and muscle strengthening activities and APFT- and ACFT-related performance. Baseline participant data (N = 123) were from a cluster-randomized clinical trial that recruited active-duty military personnel (mean age 33.7 ± 5.7 years, 72.4% White, 87.0% college-educated, 81.5% Officers). An online survey was used for self-report of socio-demographic characteristics and weekly aerobic and muscle-strengthening physical activity behaviors. Participants also completed the APFT (2 min push-ups, 2 min sit-ups, 2-mile run) and ACFT-related measures (1-repetition maximum deadlift, pull-up repetitions or timed flexed arm hang, horizontal jump, and dummy drag). Bivariate logistic regression found greater aerobic and muscle-strengthening activity predicted better APFT performance, while better ACFT-related performance was predicted by greater muscle-strengthening activity. Although our data are mostly from mid-career officers, command policies should emphasize the new Holistic Health and Fitness initiative that encourages regular aerobic and muscle-strengthening physical activity for soldiers.

Ficus septica exudate, a traditional medicine used in Papua New Guinea for treating infected cutaneous ulcers: in vitro evaluation and clinical efficacy assessment by cluster randomised trial

Infected cutaneous ulcers are major health problems for children living in rural areas of Papua New Guinea. The inaccessibility of affected populations and lack of access to basic healthcare, make a local plant-based therapy an attractive treatment option. We assessed Ficus septica exudate in biological assays relevant to wound healing. We then carried out a clinical trial to determine the exudate's efficacy in healing small cutaneous ulcers compared with Savlon antiseptic cream, and soap and water washing. Pre-clinical in vitro assessment of the exudate was carried out using assays to monitor the pro-inflammatory responses of M1 macrophages and neutrophils, antibacterial assays using known ulcer pathogens, an Ames test for mutagenicity and LC-MS chemical analysis of the exudate. An open label cluster-randomised clinical trial was performed, enrolling participants from three different clusters with skin lesions less than 1 cm in diameter. Each cluster comprising 50 participants was randomly assigned to one of three treatment arms namely topical exudate, topical Savlon antiseptic cream, and standard care (soap and water treatment), all administered daily for 2 days. The primary outcome was clinical healing/improvement measured at days 7 and 14, assessed by three dermatologists using blinded photographs. The primary analysis was assessed as non-inferiority of F. septica treatment based on the risk difference for healing/improvement. In vitro, the exudate which is rich in the alkaloid ficuseptine, was found to be non-mutagenic whilst also inhibiting pro-inflammatory responses and exhibiting antibacterial activity. When administered to participants enrolled in the clinical trial, no significant differences were observed between the healing efficacy of F. septica exudate and the two comparator treatments (Savlon antiseptic cream and soap/water treatment). At day 14, but not at day 7, the efficacy of F. septica exudate for healing/improving the ulcers was non-inferior to Savlon antiseptic cream or water/soap treatment. F. septica exudate is non-mutagenic and has both bactericidal and anti-inflammatory properties. When applied topically to small cutaneous ulcers, the exudate has a healing effect that is non-inferior to Savlon antiseptic cream and standard treatment with soap and water at day 14. Our findings, which should be confirmed in larger clinical trials, have important public health implications.

Impact of a procalcitonin-based algorithm on the quality of management of patients with uncomplicated adhesion-related small bowel obstruction assessed by a textbook outcome: a multicenter cluster-randomized open-label controlled trial

BackgroundAcute adhesion-related small bowel obstruction (ASBO) is a common digestive emergency, accounting for 1 to 3% of all digestive emergencies. The efficacy of conservative management in this setting is a subject of debate, as it may delay the decision to perform surgery and increase the frequency of bowel resection (e.g., in the presence of bowel necrosis) or, in contrast, prompt an excessive number of unnecessary laparotomies. Thus, the decision to perform surgery is difficult. We propose that the introduction of the procalcitonin (PCT)-based algorithm improves the quality of the management of patients with ASBO by aiding the decision of whether or not to perform surgery.MethodsThis is a 1:1 cluster-randomized clinical trial (use of algorithm: no algorithm) using an independent computer to ensure that investigators cannot interfere with the randomization. Each cluster will correspond to one investigating center. All patients in a center will be managed in the same way. Before randomization, each principal investigator will provide a commitment to participate in the study to avoid the risk of “empty clusters”. The patients included will constitute two parallel arms (use of algorithm versus no algorithm), with no expected crossover between arms. The inclusion criteria are being an adult with uncomplicated acute ASBO (i.e., absence of fever, abdominal pain and distension, nausea and/or vomiting, and the absence of gas and/or stool, in conjunction with a contrast-enhanced CT scan, for patients with previous abdominal surgery) who is able to express consent with a signed written informed consent form. Patients with complicated acute ASBO (strangulation or peritonitis) will be excluded.DiscussionThere is an ongoing debate on the management of uncomplicated ASBO. The main points are to avoid a surgery if it is unnecessary and to avoid delayed surgery if it is necessary. Currently, there are no robust criteria to objectively determine the failure of non-surgical treatment or to establish the indications for surgery in acute ASBO. Our team proposes the use of procalcitonin (PCT) to help distinguish patients for whom conservative management is likely to be successful from those for whom surgical management is required. The results from a randomized control trial could help in the selection of patients through clear inclusion and exclusion criteria and simplify or clarify the management algorithm. In conclusion, PCT may be useful in evaluating the proper strategy for ASBO.Trial registration The trial is registered at clinical trials under the reference: NCT03905239

The COVID-19 pandemic has highlighted the need to invest in care home research infrastructure

The COVID-19 pandemic resulted in catastrophic levels of morbidity and mortality for care home residents. Despite this, research platforms for COVID-19 in care homes arrived late in the pandemic compared with other care settings. The Prophylactic Therapy in Care Homes Trial (PROTECT-CH) was established to provide a platform to deliver multi-centre cluster-randomized clinical trials of investigational medicinal products for COVID-19 prophylaxis in UK care homes. Commencing set-up in January 2021, this involved the design and development of novel infrastructure for contracting and recruitment, remote consent, staff training, research insurance, eligibility screening, prescribing, dispensing, and adverse event reporting; such infrastructure being previously absent. By the time this infrastructure was in place, the widespread uptake of vaccination in care homes had changed the epidemiology of COVID-19 rendering the trial unfeasible. Whilst some of the resources developed through PROTECT-CH will enable the future establishment of care home platform research, the near absence of care home trial infrastructure and nationally-linked databases involving the care home sector will continue to significantly hamper progress. These issues are replicated in most other countries. Beyond COVID-19, there are many other research questions that require addressing to provide better care to people living in care homes. PROTECT-CH has exposed a clear need for research funders to invest in, and legislate for, an effective care home research infrastructure as part of national pandemic preparedness planning. Doing so would also invigorate care home research in the interim, leading to improved healthcare delivery specific to those living in this sector.

Association of fasting blood glucose to high-density lipoprotein cholesterol ratio with short-term outcomes in patients with acute coronary syndrome

BackgroundBiochemical markers are crucial for determining risk in coronary artery disease (CAD) patients; however, the relationship between fasting blood glucose to high-density lipoprotein cholesterol (FG/HDL-C) ratio and short-term outcomes in acute coronary syndrome (ACS) patients remains unknown. Therefore, we have investigated the relationship between the FG/HDL-C ratio and short-term outcomes in ACS patients.MethodsWe used data from a pragmatic, stepped-wedge, cluster-randomized clinical trial to perform a post hoc analysis. A total of 11,284 individuals with ACS were subdivided into quartiles according to their FG/HDL-C ratios. We used a multivariate logistic regression model, two-piecewise linear regression model, and generalized additive model (GAM) to evaluate the relationship between the FG/HDL-C ratio and short-term outcomes (major adverse cardiovascular events [MACEs] and cardiovascular [CV] death within 30 days).ResultsThe FG/HDL-C ratio was remarkably linked to an enhanced risk of MACEs and CV death in individuals with ACS in the highest quartile (MACEs, odds ratio [OR]: 1.49; 95% confidence interval [CI], [1.11, 1.99]; P < 0.01; CV death, OR: 1.69; 95% CI, [1.01, 1.41]; P = 0.04). The GAM suggested that the relationship between the FG/HDL-C ratio and MACEs and CV death was non-linear. The two-piecewise linear regression model demonstrated that the threshold values were 3.02 and 3.00 for MACEs and CV death, respectively.ConclusionsA higher FG/HDL-C ratio is associated with a higher risk of MACEs and CV death in patients with ACS.

Support Models for Addiction Related Treatment (SMART) for pregnant women: Study protocol of a cluster randomized trial of two treatment models for opioid use disorder in prenatal clinics.

The prevalence of opioid use disorder (OUD) in pregnancy increased nearly five-fold over the past decade. Despite this, obstetric providers are less likely to treat pregnant women with medication for OUD than non-obstetric providers (75% vs 91%). A major reason is many obstetricians feel unprepared to prescribe medication for opioid use disorder (MOUD). Education and support may increase prescribing and overall comfort in delivering care for pregnant women with OUD, but optimal models of education and support are yet to be determined. We describe the rationale and conduct of a matched-pair cluster randomized clinical trial to compare the effectiveness of two models of support for reproductive health clinicians to provide care for pregnant and postpartum women with OUD. The primary outcomes of this trial are patient treatment engagement and retention in OUD treatment. This study compares two support models: 1) a collaborative care approach, based upon the Massachusetts Office-Based-Opioid Treatment Model, that provides practice-level training and support to providers and patients through the use of care managers, versus 2) a telesupport approach based on the Project Extension for Community Healthcare Outcomes, a remote education model that provides mentorship, guided practice, and participation in a learning community, via video conferencing. This clustered randomized clinical trial aims to test the effectiveness of two approaches to support practitioners who care for pregnant women with an OUD. The results of this trial will help determine the best model to improve the capacity of obstetrical providers to deliver treatment for OUD in prenatal clinics. Clinicaltrials.gov trial registration number: NCT0424039.