Active Comparator Group Research Articles

Effects of prebiotics on microbial diversity and abundance in young children with acute malnutrition: study protocol for a multi-centered, double-blinded randomized controlled trial.

The anti-inflammatory and antimicrobial benefits of prebiotics may present an affordable and cost-effective strategy for not only the prevention but also treatment of malnutrition. Therefore, the present trial has been designed with the aim to evaluate the role of prebiotics on the gut microbiome of severe acute malnourished (SAM) children. The study is designed as a prospective, double-blinded, triple-armed, multi-centered randomized controlled trial, with 6-59months old uncomplicated SAM children recruited to the experimental group receiving ready-to-use therapeutic food (RUTF) plus prebiotics and the active comparator group receiving RUTF plus starch for 2months duration (8weeks). Healthy children with matching age and gender will be recruited to placebo comparator group and will receive starch as a placebo during the study period. A total of 58 participants will be recruited to each arm with 1:1:1 allocation ratio following a pre-defined inclusion and exclusion criteria. The results of the gut microbiome diversity will serve as the primary outcome, while weight-for-height/length z-score, mid-upper-arm circumference, neurodevelopment assessment, and body mass accumulation will serve as the secondary outcome. Data collection and evaluations will be conducted at baseline and at the end of the trial (week 8), while the safety monitoring will be conducted at every second week. For analysis, the principles of intention-to-treat will be followed. Conclusively, the results of the present trial would provide useful insights and high-quality data for the treatment and management of SAM children by evaluating the effect of RUTF plus prebiotic on the gut microbiome diversity of children, leading to medical evidence for designing the large-scale studies. The present trial is registered at ClinicalTrials.gov with identifier No: NCT06155474 and registration date 4 December 2023.

Long COVID Brain Fog Treatment: Findings from a Pilot Randomized Controlled Trial of Constraint-Induced Cognitive Therapy.

Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study's objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae. Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed. Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M (SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001, d=2.6) and brain fog (M=-4 points, p<.001, d=-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p=.048. CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

Assessment of endocrine therapy adherence in a nurse-led cancer survivorship clinic: Results from the Linking You to Support and Advice (LYSA) trial.

1627 Background: The care of those living with and beyond a cancer diagnosis requires dedicated cancer survivorship services to ensure optimal symptom control and quality of life. Supporting adherence to adjuvant endocrine therapy is also an essential component of care. We examined endocrine therapy adherence rates, and factors associated with non-adherence, in patients with early-stage breast cancer enrolling in a survivorship trial (LYSA). Methods: Women with early-stage hormone positive breast (n=168) cancers within 12 months of completing primary therapy, were enrolled in a randomized control trial with parallel arms (PMID 36357934). Experimental arm had access to nurse-led symptom management, dietetic consultation, and undertook bimonthly electronic patient reported outcome (ePRO). Active comparator group had access to conventional care and ePRO was completed at beginning and end of study. Endocrine therapy adherence was reported as the ability to take medication as prescribed over prior 4 weeks (Michigan Oncology Quality Consortium Adherence Tool), with response quantified as Excellent (adherence close to 100%), Very Good (80%), Good (60%), Fair (40%) and Poor (20%). Adherence Objective (Secondary) was adherence rate at 12 months after study entry in both arms, and factors associated with non-adherence. Results: A total of 148/168 women with breast cancer who completed the LYSA study reported adjuvant endocrine therapy use (74 experimental arm, 74 active comparator) during study conduct. Therapies included aromatase inhibitors (53%), tamoxifen (39%) and ovarian suppression combinations (8%). At study entry ≥ 80% adherence was reported in 74% of overall cohort (75% experimental, 72% comparator, p=0.7), with 1.6% reporting not taking any medication. By end of study (12 months), ≥ 80% adherence was reported in 74% overall (77% experimental, 71% comparator, p=0.4), while non-adherence rates were 2.9%. Among the pre-specified reasons for non-adherence at study end, “simply missing it” ranked highest (10%), and 5% “experienced side effects”. Post-menopausal patients were more likely than pre-menopausal to report excellent (versus sub-excellent) adherence at study end (OR 4.60, 95%CI 1.45 – 16.13, p = 0.012, adjusted for arm, age, and ECOG). Additional exploration of reasons for non-adherence will be presented. Conclusions: Adjuvant endocrine therapy adherence rates in both arms at 12 months after study entry collected via ePRO were good (≥ 90% reporting excellent or very good adherence). Additional factors potentially associated with non-adherence are being analyzed including self-care agency, symptom burden and quality of life. Clinical trial information: NCT05035173 .

Study protocol for a randomized controlled trial of supportive parents – coping kids (SPARCK)—a transdiagnostic and personalized parent training intervention to prevent childhood mental health problems

BackgroundTo meet the scientific and political call for effective prevention of child and youth mental health problems and associated long-term consequences, we have co-created, tested, and optimized a transdiagnostic preventive parent-training intervention, Supportive parents – coping kids (SPARCK), together with and for the municipal preventive frontline services. The target group of SPARCK is parents of children between 4 and 12 years who display symptoms of anxiety, depression, and/or behavioral problems, that is, indicated prevention. The intervention consists of components from various empirically supported interventions representing different theorical models on parent–child interactions and child behavior and psychopathology (i.e., behavioral management interventions, attachment theory, emotion socialization theory, cognitive-behavioral therapy, and family accommodation intervention). The content and target strategies of SPARCK are tailored to the needs of the families and children, and the manual suggests how the target strategies may be personalized and combined throughout the maximum 12 sessions of the intervention. The aim of this project is to investigate the effectiveness of SPARCK on child symptoms, parenting practices, and parent and child stress hormone levels, in addition to later use of specialized services compared with usual care (UC; eg. active comparison group).MethodsWe describe a randomized controlled effectiveness trial in the frontline services of child welfare, health, school health and school psychological counselling services in 24 Norwegian municipalities. It is a two-armed parallel group randomized controlled effectiveness and superiority trial with 252 families randomly allocated to SPARCK or UC. Assessment of key variables will be conducted at pre-, post-, and six-month follow-up.DiscussionThe current study will contribute with knowledge on potential effects of a preventive transdiagnostic parent-training intervention when compared with UC. Our primary objective is to innovate frontline services with a usable, flexible, and effective intervention for prevention of childhood mental health problems to promote equity in access to care for families and children across a heterogeneous service landscape characterized by variations in available resources, personnel, and end user symptomatology.Trial registrationClinicalTrials.gov ID: NTCT05800522

Healthy Outcomes through Peer Educators: Feasibility of a peer support diabetes prevention programme for African-American grandmother caregivers.

To assess the protocol feasibility and intervention acceptability of a community-based, peer support diabetes prevention programme (DPP) for African-American (AA) grandmother caregivers at risk for diabetes. Grandmother caregivers were randomized in a 2:1 ratio to DPP (active comparator) or DPP plus HOPE (Healthy Outcomes through Peer Educators; intervention). DPP + HOPE incorporated support from a peer educator who met with participants in person or by telephone every week during the 1-year intervention. Outcomes included: (1) recruitment rates, outcome assessment, and participation adherence rates assessed quantitatively; and (2) acceptability of the programme assessed through end-of-programme focus groups. We successfully consented and enrolled 78% (n = 35) of the 45 AA grandmothers screened for eligibility. Eighty percent of participants (aged 64.4 ± 5.7 years) were retained up to Week 48 (74% for DPP [n = 17] and 92% for DPP + HOPE [n = 11]). All grandmothers identified social support, neighbourhood safety, and access to grocery stores as influences on their health behaviours. At Month 12, the active comparator (DPP) group and the intervention group (DPP + HOPE) had a mean change in body weight from baseline of -3.5 ± 5.5 (-0.68, -6.29) kg and - 4.4 ± 5.7 (-0.59, -8.2) kg, respectively. This viable study met the aim of educating and equipping AA grandmothers with the practical and sustained support needed to work toward better health for themselves and their grandchildren, who may be at risk for diabetes. The intervention was both feasible and acceptable to participating grandmothers and their organizations.

Telehealth acceptance and commitment therapy for adolescents with transdiagnostic health-related anxiety: A pilot randomized controlled trial

Health-related anxiety is an under-researched and pressing issue to understand in adolescents, particularly given the COVID-19 pandemic. The present study is a randomized, waitlist-controlled trial of 10 weekly, 50-min sessions of telehealth ACT targeting health-related anxiety in adolescents as compared to a waitlist. A sample of 30 adolescents (ages 12–17), plus one caretaker each (N = 60), currently struggling with clinical levels of health-related anxiety were enrolled. The majority of caretakers and adolescents were White, non-Hispanic/Latine, and female. Data were analyzed using multilevel modeling across pre-, mid-, post-treatment, and one-month follow-up. Adolescents reported small, significant decreases in health-related anxiety as compared to the waitlist. Caretakers reported small to medium significant decreases in child general anxiety and small to medium improvements in parental psychological inflexibility. No additional significant differences were found between groups for caretaker- or adolescent-rated variables. Both adolescents and caretakers reported positive acceptability of the treatment. Limitations of this study include a small, homogenous sample, a lack of an active comparison group, and a short period of intervention and measurement. However, this study is the first randomized controlled trial examining ACT as a potential treatment for health-related anxiety in adolescents, and thereby adds to the growing literature supporting the use of ACT as a potential treatment option for youth with anxiety and related problems.

A collaborative network trial to evaluate the effectiveness of implementation strategies to maximize adoption of a school-based healthy lunchbox program: a study protocol.

An important impediment to the large-scale adoption of evidence-based school nutrition interventions is the lack of evidence on effective strategies to implement them. This paper describes the protocol for a "Collaborative Network Trial" to support the simultaneous testing of different strategies undertaken by New South Wales Local Health Districts to facilitate the adoption of an effective school-based healthy lunchbox program ('SWAP IT'). The primary objective of this study is to assess the effectiveness of different implementation strategies to increase school adoption of the SWAP across New South Wales Local Health Districts. Within a Master Protocol framework, a collaborative network trial will be undertaken. Independent randomized controlled trials to test implementation strategies to increase school adoption of SWAP IT within primary schools in 10 different New South Wales Local Health Districts will occur. Schools will be randomly allocated to either the intervention or control condition. Schools allocated to the intervention group will receive a combination of implementation strategies. Across the 10 participating Local Health Districts, six broad strategies were developed and combinations of these strategies will be executed over a 6 month period. In six districts an active comparison group (containing one or more implementation strategies) was selected. The primary outcome of the trial will be adoption of SWAP IT, assessed via electronic registration records captured automatically following online school registration to the program. The primary outcome will be assessed using logistic regression analyses for each trial. Individual participant data component network meta-analysis, under a Bayesian framework, will be used to explore strategy-covariate interactions; to model additive main effects (separate effects for each component of an implementation strategy); two way interactions (synergistic/antagonistic effects of components), and full interactions. The study will provide rigorous evidence of the effects of a variety of implementation strategies, employed in different contexts, on the adoption of a school-based healthy lunchbox program at scale. Importantly, it will also provide evidence as to whether health service-centered, collaborative research models can rapidly generate new knowledge and yield health service improvements. This trial is registered prospectively with the Australian New Zealand Clinical Trials Registry (ACTRN12623000558628).

Providing Lesbian, Gay, Bisexual, Transgender, Nonbinary, and Queer Adolescents With Nurturance, Trustworthiness, and Safety: Protocol for Pilot Cluster Randomized Controlled Trial Design.

Sexual and gender minority youths (lesbian, gay, bisexual, transgender, nonbinary, and queer individuals) face elevated risks of substance use (eg, alcohol and tobacco) and mental health issues (eg, depressive symptoms and suicidality) compared to their cisgender heterosexual peers. These inequities are hypothesized to be reduced by building supportive high school environments via the training of school staff. An intervention that trains school staff to better understand and support sexual and gender minority youths and engage in positive bystander behaviors that protect them from bullying exposure may reduce disparities in drug and alcohol use among them. Experts, school staff, and sexual and gender minority youths developed Providing LGBTQ+ Adolescents with Nurturance, Trustworthiness, and Safety (PLANTS), a web-based intervention to train school staff on how to support, affirm, and protect sexual and gender minority youths. This paper describes the design of the PLANTS pilot trial primarily aimed at assessing its acceptability, usability, appropriateness, and feasibility. We hypothesize PLANTS will have high acceptability, usability, appropriateness, and feasibility as rated by the school staff. Secondary objectives focus on implementation, safety, and pre-post changes in high school staff outcomes, including self-efficacy and skills (eg, active-empathic listening and bullying intervention). Exploratory objectives focus on the impact of PLANTS on student health outcomes. In a 2-arm cluster randomized controlled trial, high schools in Massachusetts are allocated to PLANTS or an active comparator group (publicly available sexual and gender minority youths resources or training). High school staff complete pretest and posttest surveys containing validated scales. Primary outcomes are validated measures of acceptability, usability, appropriateness, and feasibility of the intervention completed by staff during posttest surveys. To test our primary hypotheses for each outcome, we will calculate means and 95% CIs and P values using 1-sample 2-sided t tests against a priori thresholds or benchmarks of success. Secondary outcomes include staff's active-empathetic listening skills, self-efficacy for working with sexual and gender minority youths, bystander intervention behaviors for bullying and cyberbullying, and self-efficacy for PLANTS' change objectives completed during pretest and posttest staff surveys. Staff can also complete a posttest interview guided by the Information-Motivation-Behavior model and Consolidated Framework for Implementation Research. Exploratory outcomes include student-level data collected via the 2021 and 2023 MetroWest Adolescent Health Surveys, a health behavior surveillance system in 30 Massachusetts schools. School enrollment began in May 2023 and participant enrollment began in June 2023. Data collection is expected to be completed by February 2024. This pilot trial will yield important information about the PLANTS intervention and provide necessary information to conduct a fully powered trial of the efficacy of PLANTS for reducing the deleterious health inequities experienced by sexual and gender minority youths. ClinicalTrials.gov NCT05897827; https://clinicaltrials.gov/study/NCT05897827. DERR1-10.2196/55210.

Mind over memory: reducing fear and avoidance of memory loss (REFRAME) study in older adults

AbstractBackgroundFear of Alzheimer’s disease and related dementias (ADRD) is a growing concern among older adults. High levels of fear are associated with poorer health outcomes, lower levels of psychological well‐being, and the perpetuation of harmful cognitive‐behavioral cycles that can potentially hasten cognitive decline. Interventions that disrupt these cycles could bring both immediate and long‐term benefits for reducing ADRD‐related fears. Given the projected increase in the number of people living with ADRD and accompanying fears, effective interventions are needed to address the emotional needs of older adults. We evaluated a brief psychological intervention aimed at promoting adaptive coping in older adults with heightened ADRD‐related fear and examined its effects on broader health outcomes.MethodEighty‐one older adults experiencing heightened ADRD‐related fear were recruited to participate in a 3‐week online intervention aimed at reducing fear (primary outcome) and improving secondary health‐related outcomes (i.e., anxiety, depression, social function). Participants were randomly assigned to REFRAME or active comparison group. Both groups completed psychoeducation and mindfulness activities designed to reduce fear. The REFRAME group completed an additional behavioral activation module designed to disrupt patterns of avoidant behavioral coping. Participants completed measures at baseline, weeks 1‐3 of the intervention, post‐intervention, and 4‐week follow‐up. Outcomes were analyzed using linear mixed effects models.ResultParticipants ranged from 55 to 90 years, (M = 65.4, SD = 7.1). Intervention adherence was high (&gt;75%) across both groups. ADRD‐related fear decreased significantly over time in both groups. Anxiety, depression, and self‐reported memory failures also decreased significantly in both groups, while social function and well‐being improved. The REFRAME group exhibited a greater reduction in depression compared to the control group.ConclusionOur brief psychological intervention had positive effects on ADRD‐related fear among older adults. However, further research is needed to determine the long‐term benefits and their effectiveness in at‐risk populations (e.g., people with a family history of dementia), as well as the acceptability of this intervention in clinical settings. These findings highlight the potential benefits of disrupting harmful cognitive‐behavioral cycles, as this may encourage older adults to stay engaged in healthy behaviors for longer, ultimately improving their quality of life.

Cumulative Review of Hypertension in Patients with Chronic Lymphocytic Leukemia (CLL) and Other Hematologic Malignancies Treated with Acalabrutinib

Background: Patients (pts) with CLL have a high rate of comorbidities, including cardiovascular disease (CVD). Comorbid CVD is correlated with higher mortality in this pt population. Hypertension (HTN) is the most common concurrent CVD in pts with CLL and is associated with development of complications such as stroke and heart failure. The incidence of new or worsening HTN in treatment-naive CLL pts receiving placebo within the CLL12 trial was 8.3% over a 69.3-month observation period (Langerbeins et al. Hematol Oncol. 2023). New and/or worsening HTN has been observed in pts with CLL treated with Bruton tyrosine kinase inhibitor (BTKi) therapy. Studies have shown new or worsening HTN with ibrutinib (7−30%) and zanubrutinib (11−20%) (Christensen et al. Expert Rev Hematol. 2022). Acalabrutinib (acala), a selective, second-generation BTKi, demonstrated a lower rate of HTN (8.6%) vs ibrutinib (22.8%) in the head-to-head ELEVATE-RR study at a median follow-up of 40.9 months (Byrd et al. J Clin Oncol. 2021). Here, we performed a cumulative analysis of new or worsening HTN from the acala global development program and compared these data against real-world prevalence and incidence of HTN for pts with CLL prior to treatment initiation using claims data. Methods: Safety reports of new or worsening HTN were obtained from 11 clinical trials with acala (the safety database analysis comprised 2034 pts from studies in CLL [86.3%] and mantle cell lymphoma [6.1%], with the remainder from other B-cell malignancies). The clinical trials analyzed included therapy with acala (monotherapy or in combination with obinutuzumab) and active comparator groups (described in Table 1). Using the narrow Standardized MedDRA Query and the related MedDRA preferred terms for “HTN,” exposure-adjusted incidence rates in events/100 person-years were determined, and as a comparison, HTN prevalence was assessed at median treatment exposure for acala monotherapy. HTN prevalence (proportion of pts with HTN 6 months before treatment initiation) and incidence rates (number of new cases of HTN per 100 person-years during the 5 years before any treatment initiation) were also assessed based on ICD-10 codes from 3 adjudicated closed claims databases (Optum, MarketScan, and IQVIA). Results: In the claims database analysis, prevalence of HTN ranged from 47.3% to 66.1% in pts with TN CLL prior to treatment initiation. HTN prevalence with acala monotherapy at median treatment exposure (45.5 months) was 55.7%. Exposure-adjusted incidence rates of HTN were analyzed from 11 clinical trials; 1225 pts received acala monotherapy (947 pts with CLL), 223 pts received acala + obinutuzumab (all pts with CLL), 264 pts received ibrutinib as a comparator (all pts with CLL), and 322 pts received other comparators (all pts with CLL). Among the 1225 pts treated with acala monotherapy, 165 pts (147 with CLL) experienced a treatment-emergent adverse event of HTN (median age 66 years; 66.1% [n=109] male; 59.4% [n=98] with history of HTN at baseline). The exposure-adjusted incidence rates of HTN with acala monotherapy (3.844) and acala + obinutuzumab (3.926) were similar to that of other comparators (4.788 [excluding ibrutinib]) ( Table 1). In the ELEVATE-RR study specifically (subgroup of the current analysis), the exposure-adjusted incidence rate of HTN with acala (3.053) was approximately one-third that of ibrutinib (8.590). The exposure-adjusted incidence rate of HTN in pts treated with acala monotherapy without history of HTN was 3.239. Conclusions: Our data showed that HTN is a common comorbidity in pts with CLL as demonstrated in the claims database and clinical trial database analyses where 59.4% of pts who experienced HTN with acala monotherapy had history of HTN at baseline. The incidence rates of new or worsening HTN with acala monotherapy and acala + obinutuzumab were low (3.844 and 3.926, respectively). This is supported by similar incidence proportion of new or worsening HTN in pts receiving placebo (8.3%) from CLL12 (median follow-up 69.3 months) and acala monotherapy (8.9%) from ELEVATE-TN (median follow-up 58.2 months; Sharman et al. EHA. 2022), and similar HTN prevalence at median treatment exposure vs before treatment initiation in claims databases. Our analysis, conducted predominantly in patients with CLL, suggests that acala monotherapy did not worsen pre-existing HTN or increase the risk of new-onset HTN.

PASI Improvement in the First 12 weeks from the Phase 3 VOYAGE 1, VOYAGE 2, ORION and ECLIPSE Guselkumab Clinical Trials

Background VOYAGE 1, VOYAGE 2, ORION, and ECLIPSE are Phase 3, double-blind trials of guselkumab 100 mg s/c at Weeks 0, 4, 12, then Q8W in moderate to severe plaque psoriasis. VOYAGE 1 and VOYAGE 2 included placebo and active comparator groups, ORION was placebo controlled, and ECLIPSE included an active comparator control group. The objective of this analysis was to evaluate PASI improvement among subjects treated with guselkumab over the induction phase of treatment. &#x0D; Methods Medan (interquartile) PASI improvements were evaluated at W4, W8, and W12. Analyses were performed using treatment failure rules, which considered non-responders as those who discontinued due to lack of efficacy or worsening of PsO, or use of a protocol prohibited PsO treatment. Mean PASI improvement responses were also assessed. &#x0D; Results VOYAGE 1 included 329 subjects randomized to receive guselkumab, while VOYAGE 2, ORION and ECLIPSE trials included 496, 62, and 534 subjects randomized to guselkumab, respectively. At W4, median PASI improvements were 56.70%, 56.85%, 37.15% and 67.50% for VOYAGE 1, VOYAGE 2, ORION and ECLIPSE, respectively. At W8, median PASI improvements were 82.60%, 85.00%, 78.55% and 89.70% for the studies, respectively. Similarly, at W12, median PASI improvements were 92.50%, 91.95%, 93.20% and 95.70%, respectively. &#x0D; Conclusions Median PASI improvements of approximately 60% were observed following 1st dose of guselkumab at W4, except ORION, and increased to greater than 90% after the 2nd dose of guselkumab at W12. This analysis provides information on the onset of action of guselkumab during the first few months of treatment.

Botulinum Toxin for the Management of Pelvic Floor Tension Myalgia and Persistent Pelvic Pain: A Systematic Review and Meta-analysis.

To systematically review the literature on use of botulinum toxin to treat pelvic floor tension myalgia and persistent pelvic pain. The ClinicalTrials.gov, PubMed, EMBASE, and Scopus databases were searched from inception to November 2022 by two independent assessors (B.L.K. and F.G.L.). Identified studies were screened by title and abstract and included after full-text review. Data extraction was subsequently performed and recorded in Microsoft Excel. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines after registration in PROSPERO (CRD42022289132). All randomized studies, prospective studies with more than five participants, and retrospective studies with more than 10 participants published in English or French and assessing the use of botulinum toxin for the treatment of pelvic floor tension myalgia and persistent pelvic pain in women were included. Meta-analyses were performed on randomized data. Of 4,722 articles identified, 24 satisfied inclusion criteria. A meta-analysis of five randomized controlled trials totaling 329 participants demonstrated no differences in patient- and clinician-reported outcome measures, including pain, dyspareunia, sexual function, and vaginal manometry. Mean duration of follow-up was 6 months. A qualitative analysis of 14 prospective and four retrospective studies including 804 participants is supportive of botulinum toxin; however, the quality of data is low, and there is marked heterogeneity between studies. Meta-analyses of randomized data do not support the use of botulinum toxin to treat pelvic floor tension myalgia and persistent pelvic pain. Failure of these data to confirm the findings of nonrandomized prospective studies that suggest a treatment benefit may be attributable to the absence of placebo control and confounding outcomes obtained from an active comparator group. Further randomized controlled trials with true placebo are strongly recommended. PROSPERO, CRD42022289132.

Effectiveness of the Triple P Program on Parental Stress and Self-efficacy in the Context of a Community Roll-out

This study evaluated the effectiveness of the Triple P (Primary Care and/or Group) parenting support program on various aspects of the parenting experience through a quasi-experimental pretest – post-test protocol with an active comparison group (Care as usual). A sample of 384 parents assigned to two groups (n Triple P = 291; n Care as usual = 93) completed three subscales of the Parenting Stress Index – 4 – Short Form (Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child) and the Parental Self-Agency Measure. The amount of intervention received by each parent was considered in the analyses. Path analysis showed that the type (Triple P vs Care as usual) and the amount of intervention (number of sessions attended) contributed independently to predicting changes in parenting experience between pretest and post-test. Receiving Triple P was systematically associated with more positive outcomes than receiving care as usual, whereas more intervention was positively associated with improved self-efficacy and parent-child relationship quality. Overall, the model explained between 4.0% and 12.6% of the variance in individual change, depending on the outcome, suggesting that unmeasured drivers of change came into play. A follow-up of parents in the Triple P group two to four years after the end of the program (n follow-up = 164) showed that the observed changes were maintained over time, with moderate to large effect sizes. These results help to broaden the evidence base on the effectiveness of this program in a sociocultural and linguistic context different from that in which it was developed.

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study.

Prolonged intermittent theta-burst stimulation (iTBS) is effective for major depressive disorder (MDD). However, whether longer piTBS treatment in a single session could have antidepressant efficacy remains elusive. Therefore, this double-blind, randomized, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily piTBS sessions for treating MDD patients with a history of poor responses to at least 1 adequate antidepressant trial in the current episode. All patients received 2 uninterrupted sessions per day for 10 weekdays (i.e., 2 weeks; a total of 20 sessions). Seventy-two patients were recruited and 1:1:1 randomly assigned to one of three groups: piTBS (piTBSx2), 10-Hz rTMS (rTMSx2), or sham treatment (shamx2, randomly assigned to piTBS or rTMS). 10-Hz rTMS group was included as an active comparison group to enhance assay sensitivity. piTBSx2 group had significantly more responders at week 2 than shamx2 group, but it did not yield better antidepressant effects regarding the %depression changes. The changes of antidepressant scores were not different among the three groups at week 1 (-26.2% vs. -23.3% vs. -22.%) or at week 2 (-34.1% vs. -37.1% vs. -30.1%). Longer treatment duration did not result in stronger placebo effects [sham(piTBS)x2: -31.7% vs. sham(rTMS)x2: -26.7%]. The present sham-controlled study confirmed that piTBS is an effective antidepressant option, but found no evidence to support that longer piTBS treatment duration resulted in more rapid or better antidepressant effects. A high placebo effect was observed, but longer treatment duration of brain stimulation was not linearly associated with stronger placebo effects.

Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial

BackgroundMajor depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. MethodsA total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). DiscussionThe clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.

Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up

Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150mg every 12weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256weeks. Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. Open-label study with no placebo or active-comparator group. Long-term continuous risankizumab treatment for up to 5years was well tolerated and demonstrated high and durable efficacy.

Additive extensive reading and syntactic development in second language writing: Analyses of syntactic complexity and sophistication in young EFL learners’ book reports

This study explores how input-driven activity through extensive reading leads to syntactic growth in young students’ written production. Twenty-six young students learning English as a foreign language participated in extensive reading as an additional activity after school for a month (ER group), and their syntactic development was inspected by analyzing 14 syntactic complexity and six syntactic sophistication indices in the students’ book reports written preceding and following the reading activity. This group’s performance in writing was compared with that of another group of students who did not participate in the reading activity (Comparison group). Results of analyses for syntactic complexity showed that the ER group significantly improved in the length of sentence, the number of clauses, the number of coordination, and the number of verb phrases. This group also improved in syntactic sophistication by using less frequent verbs and less frequent verb-construction combinations in writing after the reading activity. In contrast, the comparison group showed improvements only in the length of sentence. We discuss these findings and pedagogical implications in light of usage-based approaches to language learning.

Assessing the Feasibility and Acceptability of a Primary Care Socio-Ecological Approach to Improve Physical Activity Adherence among People with Type 2 Diabetes: The SENWI Project.

Maintaining an active lifestyle is a key health behavior in people with type 2 diabetes (T2D). This study assessed the feasibility and acceptability of a socio-ecological Nordic walking intervention (SENWI) to enhance healthy behaviors in primary healthcare settings. Participants included individuals with T2D (n = 33; age 70 (95% CI 69-74)) and healthcare professionals (HCPs, n = 3). T2D participants were randomly assigned to a SENWI, active comparator, or control group for twelve weeks. Feasibility and acceptability were evaluated based on a mixed methodology. Quantitative data reported adherence information, differences between follow-up and dropout participants and pre- and post-intervention on physical activity, sedentary behavior, and health outcomes. Qualitative data acquisition was performed using focus groups and semi-structured interviews and analyzed using thematic analysis. Thirty-three T2D invited participants were recruited, and twenty-two (66.7%) provided post-intervention data. The SENWI was deemed acceptable and feasible, but participants highlighted the need to improve options, group schedules, gender inequities, and the intervention's expiration date. Healthcare professionals expressed a lack of institutional support and resources. Nevertheless, no significant difference between the SENWI follow-up and dropout participants or pre- and post- intervention was found (only between the active comparator and control group in the physical quality of life domain). Implementing the SENWI in primary healthcare settings is feasible and acceptable in real-world conditions. However, a larger sample is needed to assess the program's effectiveness in improving healthy behaviors and its impact on health-related outcomes in the long term.

Biologic targets of prescription medications and risk of neurodegenerative disease in United States Medicare beneficiaries.

To identify prescription medications associated with a lower risk of three neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. We conducted a population-based, case-control study of U.S. Medicare beneficiaries in 2009 (42,885 incident neurodegenerative disease cases, 334,387 randomly selected controls). Using medication data from 2006-2007, we categorized all filled medications according to their biological targets and mechanisms of action on those targets. We used multinomial logistic regression models, while accounting for demographics, indicators of smoking, and health care utilization, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 141 target-action pairs and each neurodegenerative disease. For target-action pairs inversely associated with all three diseases, we attempted replication in a cohort study that included an active comparator group. We constructed the cohort by following controls forward for incident neurodegenerative disease from the beginning of 2010 until death or end of 2014, i.e., up to five years after the two-year exposure lag. We used Cox proportional hazards regression while accounting for the same covariates. The most consistent inverse association across both studies and all three neurodegenerative diseases was for xanthine dehydrogenase/oxidase blockers, represented by the gout medication, allopurinol. Allopurinol was associated with a 13-34% lower risk for each neurodegenerative disease group in multinomial regression, and a mean reduction of 23% overall, as compared to individuals who did not use allopurinol. In the replication cohort we observed a significant 23% reduction for neurodegenerative disease in the fifth year of follow-up, when comparing allopurinol users to non-users, and more marked associations with an active comparator group. We observed parallel associations for a related target-action pair unique to carvedilol. Xanthine dehydrogenase/oxidase blockade might reduce risk of neurodegenerative disease. However, further research will be necessary to confirm that the associations related to this pathway are causal or to examine whether this mechanism slows progression.

Assessment of Disruptive Life Events for Individuals Diagnosed With Schizophrenia or Bipolar I Disorder Using Data From a Consumer Credit Reporting Agency

There is a dearth of population-level data on major disruptive life events (defined here as arrests by a legal authority, address changes, bankruptcy, lien, and judgment filings) for patients with bipolar I disorder (BPI) or schizophrenia, which has limited studies on mental health and treatment outcomes. To conduct a population-level study on disruptive life events by using publicly available data on disruptive life events, aggregated by a consumer credit reporting agency in conjunction with electronic health record (EHR) data. This study used EHR data from 2 large, integrated health care systems, Kaiser Permanente Southern California and Henry Ford Health. Cohorts of patients diagnosed from 2007 to 2019 with BPI or schizophrenia were matched 1:1 by age at analysis, age at diagnosis (if applicable), sex, race and ethnicity, and Medicaid status to (1) an active comparison group with diagnoses of major depressive disorder (MDD) and (2) a general health (GH) cohort without diagnoses of BPI, schizophrenia, or MDD. Patients with diagnoses of BPI or schizophrenia and their respective comparison cohorts were matched to public records data aggregated by a consumer credit reporting agency (98% match rate). Analysis took place between November 2020 and December 2022. The differences in the occurrence of disruptive life events among patients with BPI or schizophrenia and their comparison groups. Of 46 167 patients, 30 008 (65%) had BPI (mean [SD] age, 42.6 [14.2] years) and 16 159 (35%) had schizophrenia (mean [SD], 41.4 [15.1] years). The majoriy of patients were White (30 167 [65%]). In addition, 18 500 patients with BPI (62%) and 6552 patients with schizophrenia (41%) were female. Patients with BPI were more likely to change addresses than patients in either comparison cohort (with the incidence ratio being as high as 1.25 [95% CI, 1.23-1.28]) when compared with GH cohort. Patients with BPI were also more likely to experience any of the financial disruptive life events with odds ratio ranging from 1.15 [95% CI, 1.07-1.24] to 1.50 [95% CI, 1.42-1.58]). The largest differences in disruptive life events were seen in arrests of patients with either BPI or schizophrenia compared with GH peers (3.27 [95% CI, 2.84-3.78] and 3.04 [95% CI, 2.57-3.59], respectively). Patients with schizophrenia had fewer address changes and were less likely to experience a financial event than their matched comparison cohorts. This study demonstrated that data aggregated by a consumer credit reporting agency can support population-level studies on disruptive life events among patients with BPI or schizophrenia.