Parallel-group Randomized Controlled Trials Research Articles

Efficacy and Tolerance of the Tampsec Vaginal Tampon for Treating Stress Urinary Incontinence. A Randomized Controlled Trial.

Stress urinary incontinence (SUI) is a highly prevalent condition in women. We hypothesized that the Tampsec™ vaginal tampon will be efficacious and well tolerated in its treatment. This was a multicenter open-label parallel-group randomized control trial. All participants were recommended to make lifestyle modifications and perform pelvic floor muscle training for SUI treatment. Additionally, women in the tampon group were instructed to use a Tampsec™ throughout the day. The primary outcome measure was a ≥50% reduction in pad weight by the end of treatment. Secondary outcome measures were women's perception of improvement evaluated using the Patient Global Impression of Improvement (PGI-I) questionnaire, decrease in the mean number of SUI episodes/day, and improvement in the impact of urinary incontinence (UI) on everyday life. Tampon tolerance and usability were also evaluated. Forty-six women with a positive urinary stress test were randomized 1:1 to tampon or control treatments. Regarding the primary outcome, a ≥50% reduction was achieved in 69.9% of patients in the tampon group and 26.1% in controls (RR 2.7; 95%CI 1.3-5.4). On the basis of PGI-I responses, the treatment was successful in 60.9% of women in the tampon group and 17.4% of controls (p = 0.003). The tampon group also reported greater decreases in SUI episodes/day (mean 2.0±2.2 vs 0.5±1.1; p = 0.007) and more improvement in the impact of UI on everyday life. Tolerance and usability were good in most women. The Tampsec™ tampon is efficacious and well tolerated in women with SUI. This treatment decreases the number of SUI episodes/day and improves UI-related quality of life.

Assessment of improvement in functional outcomes between a novel knee replacement design and conventional designs in 240 patients: a randomized controlled trial.

The introduction and development of new total knee arthroplasty (TKA) implant designs are industry driven. To date, an adequately powered randomized controlled trial (RCT) to provide evidence of the superiority of novel implant designs over conventional ones is often lacking. The aim of our RCT was to investigate the functional outcomes of a novel TKA implant design compared with 2 conventional TKA designs. Primary outcome was difference in the change in Oxford Knee Score (OKS) at 2 years. Secondary outcomes were Forgotten Joint Score, 15D quality of life questionnaire, UCLA activity score, and complications. We compared functional outcomes between a novel TKA implant design (Persona CR) and 2 conventional designs (NexGen CR, PFC CR). 240 patients with severe knee osteoarthritis were recruited to a pragmatic, single-center, prospective, parallel-group RCT between September 2015 and August 2018. The duration of follow-up was 2 years. Of 240 randomized patients, 225 were included in the intention-to-treat analysis (mean age 61.8 years; 67.5% females). The OKS exceeded minimal clinical important difference (MCID) from baseline to 2 years in all 3 treatment groups (Persona CR: 18.9 points, PFC CR: 20.3 points, NexGen CR: 19.4 points). At 2 years the difference between Persona CR and PFC CR in the change score was -1.0 (95% confidence interval [CI] -3.6 to 1.7). Similarly, the difference between Persona CR and NexGen CR was -0.9 (CI -3.6 to 1.9). At the time of final follow-up evaluation, OKS was equivalent between groups, as CI excluded between-group differences larger than 4 points. We showed no clinically relevant differences in functional outcomes measured with OKS, 15D, or FJS between the 2 conventional implant designs and the novel implant design at 2-year follow-up.

The Eczema Bathing Study: Weekly versus daily bathing for people with eczema? Protocol of an online, randomised controlled trial

Background A priority setting partnership for eczema (syn atopic eczema, atopic dermatitis) has identified that bathing frequency is a key area of patient interest. However, there are nolarge, high-quality randomised controlled trials (RCTs) investigating this. The Rapid Eczema Trials project is a novel programme of research that aims to deliver multiple online RCTs, using a citizen science approach. This project involves working with members of the public to co-design and conduct studies that answer questions of importance to them. The first trial to be conducted through this project is assessing the impact of bathing frequency on eczema. Methods This is an online, two-arm, parallel-group superiority RCT with internal pilot phase. People aged ≥1 year with eczemaliving in the United Kingdom are eligible. Exclusion criteria are: people with other types of eczema such as venous eczema, hand eczema and contact eczema; recently started a new eczema treatment; taking part in another eczema trial; Patient Oriented Eczema Measure (POEM) ≤2; planning to swim more than twice a week; unable/unwilling to change bathing practices. Participants are allocated 1:1 to either the weekly bathing group (bathe 1 or 2 times a week) or the daily bathing group (bathe 6 or more times a week) for 4 weeks. The primary outcome is POEM, assessed weekly over 4 weeks. Secondary outcomes include skin specific quality of life, eczema control, itch severity, use of usual eczema treatments, proportion who achieve an improvement in POEM of ≥3 points, global change in eczema and safety outcomes. A sample of participants will also be invited to a semi-structured interview to discuss their experience. The primary comparative analysis will be according to randomised allocation regardless of actual frequency of bathing. The trial will be reported in accordance with CONSORT guidelines. The study has received ethical approval by the London - Surrey Research Ethics Committee (2 Redman Place, London, E20 1JQ, United Kingdom) on 11/10/2023 ( approval number: 23/PR/0899). Trial registration ISRCTN12016473, 22/11/2023, https://doi.org/10.1186/ISRCTN12016473

Study protocol for a hybrid implementation-effectiveness trial of Game Changers for Cervical Cancer Prevention in Uganda.

Cervical cancer (CC) is the leading cause of cancer-related deaths among Uganda women, yet rates of CC screening are very low. Training women who have recently screened to engage in advocacy for screening among women in their social network is a network-based strategy for promoting information dissemination and CC screening uptake. Drawing on the Exploration, Preparation, Implementation and Sustainment (EPIS) framework for implementation science, this hybrid type 1 randomized controlled trial (RCT) of a peer-led, group advocacy training intervention, Game Changers for Cervical Cancer Prevention (GC-CCP), will examine efficacy for increasing CC screening uptake as well as how it can be implemented and sustained in diverse clinic settings. In the Preparation phase we will prepare the four study clinics for implementation of GC-CCP and the expected increase in demand for CC screening, by using qualitative methods (stakeholder interviews and client focus groups) to identify and address structural barriers to easy access to CC screening. In the Implementation phase, GC-CCP will be implemented over 36 months at each clinic, with screened women (index participants) enrolled as research participants receiving the intervention in the first 6 months as part of a parallel group RCT overseen by the research study team to evaluate efficacy for CC screening uptake among their enrolled social network members. All research participants will be assessed at baseline and months 6 and 12. Intervention implementation and supervision will then be transitioned to clinic staff and offered as part of usual care in the subsequent 30 months as part of the Sustainability phase. Using the RE-AIM framework, we will evaluate engagement in GC-CCP and CC advocacy (reach), alter CC screening (effectiveness), adoption into clinic operations, implementation outcomes (acceptability, feasibility, fidelity, cost-effectiveness) and maintenance. This is one of the first studies to use a network-driven approach and empowerment of CC screened peers as change agents to increase CC screening. If shown to be an effective and sustainable implementation strategy for promoting CC screening, this peer advocacy model could be applied to other preventative health behaviors and disease contexts. NIH Clinical Trial Registry NCT06010160 (clinicaltrials.gov; date: 8/17/2023).

Perinatal emotional skills groups for women and birthing people with borderline personality disorder: outcomes from a feasibility randomised controlled trial.

There is no clear evidence about how to support people with borderline personality disorder (BPD) during the perinatal period. Perinatal emotional skills groups (ESGs) may be helpful, but their efficacy has not been tested. To test the feasibility of conducting a randomised controlled trial (RCT) of perinatal ESGs for women and birthing people with BPD. Two-arm parallel-group feasibility RCT. We recruited people from two centres, aged over 18 years, meeting DSM-5 diagnostic criteria for BPD, who were pregnant or within 12 months of a live birth. Eligible individuals were randomly allocated on a 1:1 ratio to ESGs + treatment as usual (TAU), or to TAU. Outcomes were assessed at 4 months post randomisation. A total of 100% of the pre-specified sample (n = 48) was recruited over 6 months, and we obtained 4-month outcome data on 92% of randomised participants. In all, 54% of participants allocated to perinatal ESGs attended 75% of the full group treatment (median number of sessions: 9 (interquartile range 6-11). At 4 months, levels of BPD symptoms (adjusted coefficient -2.0, 95% CI -6.2 to 2.1) and emotional distress (-2.4, 95% CI -6.2 to 1.5) were lower among those allocated to perinatal ESGs. The directionality of effect on well-being and social functioning also favoured the intervention. The cost of delivering perinatal ESGs was estimated to be £918 per person. Perinatal ESGs may represent an effective intervention for perinatal women and birthing people with BPD. Their efficacy should be tested in a fully powered RCT, and this is a feasible undertaking. ISRCTN80470632.

Randomized controlled trials - The what, when, how and why.

Randomized controlled trials (RCTs) are at the top of the pyramid of evidence as they offer the best answer on the efficacy of a new treatment. RCTs are true experiments in which participants are randomly allocated to receive a certain intervention (experimental group) or a different intervention (comparison group), or no treatment at all (control or placebo group). Randomization, along with other methodological features such as blinding and allocation concealment, safeguard against biases. This review will focus on parallel group RCT design as it is the most common design in the field of Pediatric Urology. RCTs can be designed using a superiority, equivalency, or non-inferiority hypothesis, and are usually preceded by a pilot, where the trial protocol is implemented in a small number of patients, mimicking the larger, definitive study. Even though regarded as the best available option to bring out scientific data, RCTs might be prone to mislead. If RCTs are small and underpowered, a difference of even one single event between groups, may completely change the trial results. To safeguard against RCTs weakness, a fragility concept of statistical significance was developed and called the Fragility Index (FI). RCTs may not be appropriate, ethical, or feasible for all surgical interventions. They may have limitations such as prohibitive cost and unrealistic large sample sizes. Nearly 60% of surgical research questions cannot be answered by RCTs. Therefore, clinical practice should be based on the best available evidence on a given topic, regardless of the study design. However, even in these situations, conclusions drawn from observational studies must be interpreted with caution.

Early In-Bed Cycle Ergometry With Critically Ill, Mechanically Ventilated Patients: Statistical Analysis Plan for CYCLE (Critical Care Cycling to Improve Lower Extremity Strength), an International, Multicenter, Randomized Clinical Trial.

Survivors of critical illness are at risk of developing physical dysfunction following intensive care unit (ICU) discharge. ICU-based rehabilitation interventions, such as early in-bed cycle ergometry, may improve patients' short-term physical function. Before unblinding and trial database lock, we describe a prespecified statistical analysis plan (SAP) for the CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) randomized controlled trial (RCT). CYCLE is a 360-patient, international, multicenter, open-label, parallel-group RCT (1:1 ratio) with blinded primary outcome assessment at 3 days post-ICU discharge. The principal investigator and statisticians of CYCLE prepared this SAP with approval from the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes (including adverse events) and describes the planned primary, secondary, and subgroup analyses. The primary outcome of the CYCLE trial is the Physical Function Intensive Care Unit Test-scored (PFIT-s) at 3 days post-ICU discharge. The PFIT-s is a reliable and valid performance-based measure. We plan to use a frequentist statistical framework for all analyses. We will conduct a linear regression to evaluate the primary outcome, incorporating randomization as an independent variable and adjusting for age (≥65 years versus <65 years) and center. The regression results will be reported as mean differences in PFIT-s scores with corresponding 95% CIs and P values. We consider a 1-point difference in PFIT-s score to be clinically important. Additionally, we plan to conduct 3 subgroup analyses: age (≥65 years versus <65 years), frailty (Baseline Clinical Frailty Scale ≥5 versus <5), and sex (male versus female). CYCLE was funded in 2017, and enrollment was completed in May 2023. Data analyses are complete, and the first results were submitted for publication in 2024. We developed and present an SAP for the CYCLE RCT and will adhere to it for all analyses. This study will add to the growing body of evidence evaluating the efficacy and safety of ICU-based rehabilitation interventions. ClinicalTrials.gov NCT03471247; https://clinicaltrials.gov/ct2/show/NCT03471247 and NCT02377830; https://clinicaltrials.gov/ct2/show/NCT02377830. RR1-10.2196/54451.

The Eczema Bathing Study: Weekly versus daily bathing for people with eczema? Protocol of an online, randomised controlled trial

Background A priority setting partnership for eczema (syn atopic eczema, atopic dermatitis) has identified that bathing frequency is a key area of patient interest. However, there are nolarge, high-quality randomised controlled trials (RCTs) investigating this. The Rapid Eczema Trials project is a novel programme of research that aims to deliver multiple online RCTs, using a citizen science approach. This project involves working with members of the public to co-design and conduct studies that answer questions of importance to them. The first trial to be conducted through this project is assessing the impact of bathing frequency on eczema. Methods This is an online, two-arm, parallel-group superiority RCT with internal pilot phase. People aged ≥1 year with eczemaliving in the United Kingdom are eligible. Exclusion criteria are: people with other types of eczema such as venous eczema, hand eczema and contact eczema; recently started a new eczema treatment; taking part in another eczema trial; Patient Oriented Eczema Measure (POEM) ≤2; planning to swim more than twice a week; unable/unwilling to change bathing practices. Participants are allocated 1:1 to either the weekly bathing group (bathe 1 or 2 times a week) or the daily bathing group (bathe 6 or more times a week) for 4 weeks. The primary outcome is POEM, assessed weekly over 4 weeks. Secondary outcomes include skin specific quality of life, eczema control, itch severity, use of usual eczema treatments, proportion who achieve an improvement in POEM of ≥3 points, global change in eczema and safety outcomes. A sample of participants will also be invited to a semi-structured interview to discuss their experience. The primary comparative analysis will be according to randomised allocation regardless of actual frequency of bathing. The trial will be reported in accordance with CONSORT guidelines. The study has received ethical approval by the London - Surrey Research Ethics Committee (2 Redman Place, London, E20 1JQ, United Kingdom) on 11/10/2023 ( approval number: 23/PR/0899). Trial registration ISRCTN12016473, 22/11/2023, https://doi.org/10.1186/ISRCTN12016473

Interventions for Adjunctive Care in Patients With Inflammatory Bowel Disease and Permanent Ileostomy: A Systematic Review.

The evidence for the management of patients with Crohn's disease (CD) and permanent ileostomy (PI) is limited. We aimed to summarize the interventional studies related to the provision of adjunctive ostomy care in this population. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 5, 2024. Eligible studies were non-randomized or randomized controlled trials (RCTs), or comparative cohort studies predominantly recruiting participants with CD and/or ulcerative colitis (UC) with PI assessing interventions for the management of high stoma output, disease recurrence, peristomal skin care, pouching systems, behavioral interventions, mental health support, and diet. Out of 3217 records, 6 were eligible and all were RCTs (n = 95). Out of these, 5 adopted a crossover design, and 1 study was a double-blind parallel-group RCT. All except 1 were published more than 20 years ago (1976-2003). Two studies exclusively included patients with UC, one included CD, and the remaining included both UC and CD. Four studies assessed pharmacological interventions (loperamide, 5-aminosalysilate [5-ASA], azodisal sodium, and budesonide), one assessed oral supplement with different osmolarities, and one assessed dietary intervention (unrefined vs refined carbohydrate). A decrease in ileostomy output was the primary outcome of interest in 4 studies. None of the studies assessed interventions for peristomal skin care, quality of life, stoma pouching systems, behavioral interventions, mental health, or CD recurrence. This study highlights that the evidence base to inform care for patients with IBD and PI is almost non-existent. There is an urgent need for focused research in this area to inform evidence-based treatment decisions.

123 Green/grey spaces - What is the best urban setting to enhance physical activity? Preliminary findings of the Health Benefits of Outdoor Physical Activity (HOPA) study

Abstract Purpose Strategies aimed at increasing physical activity (PA) must be feasible and easy for participants to adhere to. Outdoor public spaces emerge as relevant venues due to their easy accessibility and lack of cost. However, it is not clear what kind of urban spaces (“nature-based” or “road/sidewalk-based”) contribute the most to increasing PA. This study seeks to investigate the effect of an outdoor intervention on enhancing PA levels and reducing sedentary time (SED) among inactive adults. Methods HOPA was a multi-centre parallel-group randomised control trial (ISRCTN64480977), carried out in three European cities (Lahti, Limerick, Tallinn). The sample comprised 101 adults, self-reported as inactive at baseline (IPAQ), aged between 25-65 years. Participants were instructed to engage in outdoor PA (walking/running) at least three times/week, at least 30 minutes/session, over eight weeks. They were randomly allocated into two groups, based on the type of outdoor spaces where they would perform their activities: “nature-based” and “road/sidewalk-based” spaces. PA (light PA, LPA; moderate-to-vigorous PA, MVPA) and SED were measured at baseline and during week-8 of the intervention, over 9-consecutive days, using activPAL accelerometers. Between- and within-group differences were analysed using General Linear Model, adopting a significance level of 95%. Results There were no significant between-groups differences. A significant time-effect was observed for total weekly LPA (ρ = 0.014;η2=0.06) and MVPA (ρ &amp;lt; 0.001;η2=0.126), but not for weekly average SED (ρ = 0.117). Specifically, LPA decreased from 511.1min/week to 489.1min/week in “nature-based” group, and from 539.3min/week to 498.2min/week in “road/sidewalk-based” group. Conversely, MVPA increased from 219.5min/week to 262min/week in “nature-based” group, and from 227.6min/week to 269.6min/week in “road/sidewalk-based” group. No significant group-time effect was observed, indicating that both “nature-based” and “road/sidewalk-based” groups provide changes in PA. Conclusions Outdoor spaces can be relevant venues for promoting PA engagement and increasing MVPA. Further analysis can provide insights into the relationship between environmental quality and PA, but these preliminary findings suggest that both “nature-based” and road/sidewalk-based” spaces have shown to be relevant to getting people active. Urban cities must develop strategic plans aimed at designing urban spaces that are conducive to PA, promoting its practice, that would positively impact population health. Funding EU-2020 (DOI:10.3030/869764).

Endotracheal Intubation Performance in Novices: Comparing the Training Effect Resulting From Two Airway Management Training Simulators.

Between 2011 and 2014, the Combat Casualty Training Consortium research study sought to evaluate all aspects of combat casualty care, including mortality, with a special focus on the incidence and causes of potentially preventable deaths among American combat fatalities. This study identified a major training gap in critical airway management. Because of the high rate of morbidity and mortality associated with poor or incorrect airway management, an effort to address this training gap was necessary. This experiment compared the training using the Advanced Joint Airway Management System, a novel high-fidelity airway simulator, relative to one of the most utilized simulators for endotracheal intubation (ETI) via a parallel group randomized control trial design. Before training, participants (n = 19) attempted an ETI on a cadaver using direct laryngoscopy. Performance during the attempt was recorded and scored by trained blinded raters. Participants were then randomly allocated to either novel or conventional training. Post-training, participants completed a second ETI under the same parameters. Analysis was completed via 2 × 2 mixed analysis of variance for (1) ETI Score, (2) Errors, (3) Critical Failures, and (4) Duration, across both the pre- and post-training tests and between the two groups. A priori power analysis required a total sample size of 84 participants in this experimental design. Consequently, this study is under-powered to reach statistical significance. Scores for all trainees did improve with training, yet analyses did not reveal a difference in overall ETI score between the novel and conventional training group, at baseline or at the post-training test (P = .249). The Advanced Joint Airway Management System simulator presents a training effect that is comparable to the conventional training model. However, given this study's small sample size, these results must be considered preliminary and further research is merited to draw firm conclusions about its impact on trainee performance. Future studies engaging larger cohorts of trainees and exploring the other capabilities of the Advanced Joint Airway Management System (cricothyroidotomy, needle chess decompression) are needed to further examine the educational potential of this novel airway management training system.

Remotely-delivered exercise training program for improving physical and cognitive functions among older adults with multiple sclerosis: Protocol for an NIH stage-I randomized controlled trial

BackgroundOlder adults with multiple sclerosis (MS) present with low physical activity participation, cognitive and ambulatory dysfunctions, and compromised quality of life (QOL). ObjectiveWe propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment. MethodsThis Stage-I study utilizes a parallel-group RCT design. Participants (N = 50; age ≥ 50 years) will be randomly assigned into exercise training (combined aerobic and resistance exercise) or active control (flexibility and stretching) conditions. The conditions will be undertaken within a participant's home/community over a 16-week period, and monitored remotely and supported by Zoom-based chats guided by social cognitive theory (SCT) via a behavioral coach. Participants will receive training manuals and equipment, one-on-one behavioral coaching, action-planning calendars, self-monitoring logs, and SCT-based newsletters. The primary outcomes include feasibility (e.g., recruitment and retention rates), exercise behavior and physical activity; other outcomes include physical function (lower-extremity function, mobility, walking), cognition (processing speed, learning and memory, executive function), MS symptoms, QOL, and vascular function. We will collect outcome data at baseline (Week 0), post-intervention (Week 16), and follow-up (Week-32). Data analysis will follow intent-to-treat principles using linear mixed-effects models. DiscussionThis Stage-I trial adopts an innovative approach for exercise training via telerehabilitation and is convenient and accessible for older adults with MS. If successful, the study will provide foundations for future research using remotely-delivered exercise intervention for managing the consequences of aging with MS.Trial Registration Number:NCT05930821

Effects of Custom Molded Foot Orthoses on Balance, Gait Speed, and Pain in Postmenopausal Osteoporotic Women: A Prospective Experimental Study

ABSTRACT Introduction Osteoporotic changes displace the center of pressure (COP) closer to the limits of stability, causing balance impairment and alteration of gait characteristics. Bone architecture destruction hinders the weight-bearing capacity of lower extremities, causing foot pain, redness, and swelling. Foot orthoses increase somatosensory input and shock absorption, thus improving balance, gait speed, and pain. Objectives The aim of this study was to evaluate and quantify the effects of custom-molded insoles on the balance, gait speed, and foot pain of postmenopausal osteoporotic women. Study Design This study is a parallel group randomized control trial. Methods A total of 44 postmenopausal osteoporotic women were recruited and randomized into two groups: experimental (EG) (n = 22) and control (CG) (n = 22). EG completed a 2-week intervention period with custom-molded insoles, whereas CG did not receive any intervention. Balance, gait speed, and foot pain were measured at baseline and after 2 weeks for both groups. Results The comparison of preintervention and postintervention outcomes for both groups highlighted that they were similar at baseline; however, EG showed significant improvement in all outcome measures after 2 weeks. Conclusions This study provides preliminary evidence that custom-molded insoles had a positive effect on the proprioceptive feedback of the lower limb, thus enhancing balance. The inclusion of a heel cup in the orthoses minimized the abnormal movement of the ankle that affected the mechanical stability of the lower limbs. Additionally, they increased the surface of contact, thus reducing the load per unit of surface, minimizing foot pain and discomfort. Clinical Relevance Osteoporotic falls and fractures have severe consequences and are a major public health concern; therefore, developing effective fall prevention strategies is crucial. Custom-molded insoles could help improve balance, gait speed, and pain, potentially reducing falls while also improving the quality of life for postmenopausal osteoporotic women.

Planning for the forgotten fourth trimester of pregnancy: A parallel group randomized control trial to test a postpartum planning intervention vs. standard prenatal care

BackgroundBlack and brown birthing people experience persistent disparities in adverse maternal health outcomes, partially due to inadequate perinatal care. The goal of this study is to design and evaluate a patient-centered intervention for obstetric patients with one or more cardiometabolic risk factors for severe maternal morbidity [gestational diabetes, diabetes mellitus, hypertensive disorders of pregnancy (chronic hypertension, preeclampsia, eclampsia, or gestational hypertension), or preconception obesity (BMI > 30)] to promote postpartum visit attendance. MethodsTo address identified unmet needs for postpartum support and barriers to postpartum care, we developed 20 thematic postpartum planning modules, each with corresponding patient educational materials, community resources, care coordination protocols, and clinician support tools (decision aids, electronic medical record prompts and fields). During prenatal care encounters, a research coordinator delivers the educational content (in English or Spanish), facilitates the participant's planning and shared decision-making, provides the participant with resources, and documents decisions in the electronic medical record. We will randomize 320 eligible patients with a 1:1 ratio to the intervention or standard prenatal care and evaluate the impact on postpartum visit attendance at 4–12 weeks and secondary outcomes (postpartum mental health, perceived future maternal and cardiometabolic risk, contraceptive use, primary care use, readmission, and patient satisfaction with care). DiscussionThrough engagement with patients and community stakeholders, we developed a guideline-based, locally tailored intervention to address drivers of engagement with postpartum care for high-risk obstetric patients. If demonstrated to be effective, the educational materials and electronic medical record based-tool can be adapted to other settings. Trial registrationThis trial was registered on ClinicalTrials.gov (NCT05430815) on June 23, 2022.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial

BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.MethodsMIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.ResultsDuring September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.ConclusionsThe multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.Trial registrationClinicalTrials.gov NCT03249688.

Efficacy of endometrial receptivity testing for recurrent implantation failure in patients with euploid embryo transfers: study protocol for a randomized controlled trial

BackgroundEmbryo implantation remains a critical barrier in assisted reproductive technologies. One of the main causes of unsuccessful embryo implantation is window of implantation (WOI) displacement, particularly in patients with recurrent implantation failure (RIF). Therefore, a reliable diagnostic tool for identifying the optimal WOI is essential. Previous data has suggested that a novel RNA-Seq-based endometrial receptivity testing (ERT) can diagnose WOI, guide personalized embryo transfer (pET), and improve pregnancy outcomes in patients with RIF compared to standard embryo transfer (sET). However, there is still a lack of evidence from randomized controlled trials (RCT) with sufficient power to determine whether pET based on ERT can increase the rate of live births as the primary outcome.MethodsThis trial is a prospective, single-blind, parallel-group RCT (1:1 ratio of pET versus sET). Infertile women with RIF who intend to undergo frozen-thawed embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) with the availability of at least one euploid blastocyst for transfer will be enrolled and assigned into two parallel groups randomly. Participants in the intervention group will undergo ERT and then pET based on the results of ERT, while those in the control group will undergo sET. The primary outcome is live birth rate.DiscussionThe findings of this study will provide evidence for the effect of pET guided by ERT on pregnancy outcomes in patients with RIF.Trial registrationChinese Clinical Trial Registry ChiCTR2100049041. Registered on 20 July 2021.

Effectiveness and uptake of a transdiagnostic emotion regulation mobile intervention among university students: Protocol for a randomized controlled trial

BackgroundGoing to university is a major life event, which can be stressful and negatively affect mental health. However, it also presents an opportunity to establish a foundation for positive life trajectories. To support university students, a mobile transdiagnostic emotion regulation (ER) intervention has been developed, offering both broad-based (universal) and targeted (indicated) preventative support. ER, a transdiagnostic factor underlying various mental health problems, is a critical intervention target in students, a demographic particularly susceptible to mental health issues. Cultivating ER can help manage immediate stressors and foster long-term wellbeing. This paper describes the study protocol for a Randomized Controlled Trial (RCT) evaluating the effectiveness and uptake of such mobile transdiagnostic ER intervention. MethodThe superiority parallel-group RCT involves 250 participants randomized to either the intervention condition (i.e., full access to the mobile intervention, (n = 125) or to a waitlist control condition (n = 125). Primary outcomes include ER skills and stress symptoms. Secondary outcomes include mental health parameters (anxiety, depression, resilience) and intervention uptake (i.e., objective engagement, subjective engagement, ER skills application in real life). Outcomes are assessed at baseline, week 3, 8 and 12, with continuous log-data collection for user engagement. DiscussionThis study evaluates the effectiveness and uptake of a transdiagnostic ER mobile intervention for the student population addressing their ER developmental needs. If successful, the results will validate our approach to intervention development and whether focusing on learning transfer (i.e., application of the learnt skills in real-life) and personalization using a recommendation system, can boost the real-world application of skills and intervention impact.

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy

IntroductionSmoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used...

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. Eighteen PICUs across the United Kingdom. Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose–response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = −0.05, −0.10 to 0.003, P = 0.067; IL-9: −0.01, −0.02 to −0.003, P = 0.005; MIP-1b: −0.02, −0.04 to −0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed.Trial registration: UMIN000015264, NCT03466671/UMIN000031412.