It remains unclear whether the US clinical trial ecosystem is optimized to evaluate medical interventions efficiently. This study characterizes interventional clinical trials in the USA and examines trial progress over five years.

Using the Aggregate Analysis of ClinicalTrials.gov (AACT) database, we conducted a cross-sectional study of interventional trials initiated in 2023 and a follow-up cohort tracking five-year completion for trials started in 2018 and registered in ClinicalTrials.gov as of 05/01/2024 by sponsor and therapeutic area. Trials with at least one US site were included. Primary outcomes were enrollment, completion status, intervention type, study arm design, and plan to share individual participant data.

Over 7,500 trials met inclusion criteria for each cohort. Most trials started in 2018 (68.4%) and 2023 (62.5%) enrolled fewer than 100 participants. Median enrollment in 2023 was higher for NIH (90) than industry-sponsored (76) trials. Within five years, 60.5% of the 2018 trials were completed, with higher completion among industry (60.9%) than NIH-sponsored (54.3%) trials. In 2023, industry predominantly funded cancer studies and trials testing drug interventions, whereas the NIH prioritized mental health studies and behavioral interventions. More than one-quarter of trials used a single-group design, 72.0% did not plan to share participant-level data, and 72.6% of drug trials were early phase.

Many clinical trials are small, lack a control group, and are incomplete within five years, with differences by sponsor. Given the urgent need to improve health through rigorous evidence generation, there are likely opportunities to improve the US clinical trial ecosystem.

Climbing therapy offers a promising therapeutic strategy for Major Depressive Disorder (MDD).

A single-arm feasibility study of a 10-week manualised climbing therapy group programme for people diagnosed with DSM-5 MDD of at least moderate severity was conducted. Feasibility (measured by retention, adherence, acceptability, and tolerability) was the primary outcome. The Montgomery–Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire-9 (PHQ-9), the Positive and Negative Affect Schedule (PANAS), the Generalised Anxiety Disorder-7 (GAD-7), the General Self-Efficacy Scale (NGSE), and the Perceived Stress Scale (PSS) were completed one week before the intervention began (baseline/week 0) and post-intervention (week 11). Semi-structured interviews with participants and facilitators and were conducted and analysed using Thematic Analysis.

Out of a total of 12 participants, 9 completed the intervention. The mean age (SD) was 37.56 (7.86) years. The overall attendance rate was 88%, and there were no serious adverse events. The mean (SD) MADRS scores at baseline and week 11 were 25.67 (5.26) and 17.11 (8.25), p = 0.01; PHQ-9, 17.56 (3.87) and 13.78 (5.91), p = 0.07; PANAS-Positive, 18.78 (5.35) and 24.33 (8.50), p = 0.04; PANAS-Negative, 28.22 (10.26) and 27.33 (10.96), p = 0.76; GAD-7, 12.00 (4.09) and 10.11 (6.60), p = 0.22; NGSE, 21.78 (5.86) and 25.44 (6.22), p = 0.02; PSS, 25.78 (5.06) and 25.44 (7.00), p = 0.81. Achievement, confidence, and social connectedness were identified as key themes from the semi-structured interviews.

A climbing therapy programme for adults with MDD was feasible, acceptable and well-tolerated. Preliminary clinical findings encourage further investigation in a larger trial.

The optimal time between the cessation of one disease-modifying therapy (DMT) and initiation of another in relapsing-remitting multiple sclerosis (RRMS) is incompletely understood. Lymphopenia, an adverse effect of dimethyl fumarate (DMF), may prompt a washout period prior to initiating an alternate DMT to allow absolute lymphocyte count (ALC) recovery. We hypothesized that during the DMF-DMT treatment interval, there would be disease activity, either by MRI or clinical relapses, and that lymphopenia might be a risk factor.

A retrospective chart review was conducted, collecting data on demographics and disease activity (clinical relapse or MRI with new/enlarged T2/FLAIR or gadolinium-enhancing lesions in the brain or spinal cord). The DMF-DMT interval was defined as the time in years between stopping DMF and beginning a new DMT.

Of 109 patients, 32.1% experienced disease activity during the DMF-DMT interval. ALC decreased significantly during DMF therapy but was not associated with subsequent disease activity in the DMF-DMT interval (HR 1.09 [0.62, 1.91], p = 0.77). A Kaplan–Meier curve shows that the probability of experiencing disease activity was highest within the first year of DMF discontinuation, with the median time to first relapse after stopping DMF being 0.5 years.

Disease activity was most likely to occur early after DMF cessation but was not significantly related to ALC. Our data suggest that initiating a new DMT within 6 months of DMF cessation may reduce relapse risk and lesion accumulation in RRMS patients.

Asthma is a prevalent chronic pediatric condition associated with significant health disparities. The Better Asthma Control for Kids (BACK) program aims to reduce asthma disparities and improve asthma control for children in high-need schools in four regions of Colorado.

We conducted in-depth, semi-structured interviews (Dec 2023–June 2024) with key roles involved in BACK including school nurses, asthma navigators, and caregivers of participating students with asthma. Interviews and rapid qualitative analysis were informed by the Practical Robust, Implementation, and Sustainability Model (PRISM). We gathered perspectives, feedback, and recommendations about BACK to inform adaptation of the intervention and implementation strategy packages.

Participants (n = 39) included 6 asthma navigators, 17 school nurses, and 16 caregivers. Four overarching themes emerged: 1) perceived benefits of the BACK program, 2) challenges with school nurse engagement, communication, and perceptions of BACK, 3) difficulty with identification, documentation, and enrollment of students with asthma at the beginning of the school year, and 4) mismatches in program scope and alignment with school and family contexts.

Identifying key challenges and participant recommendations supported the research team’s “adapt and tailor to context” strategy in annual rapid evaluation and planning cycles. Obtaining feedback from program adopters, implementers, and recipients led to complementary recommendations to improve program delivery and user experiences. This approach may be transferable to other implementation-effectiveness trials, particularly those in schools or with other natural pauses that facilitate annual iterations in program delivery.

Clinicaltrials.gov identifier NCT06003569, registered on August 22, 2023, https://clinicaltrials.gov/study/NCT06003569

Non-code dose boluses of epinephrine are utilised in critically ill paediatric patients during periods of hemodynamic deterioration, often with the hopes of preventing a cardiac arrest. Data regarding the physiologic effects of these administrations are limited. The primary aim of this study was to use high-fidelity physiologic data to characterise the effects of intravenous non-code dose bolus epinephrine.

Paediatric patients in the cardiac ICU who received non-code dose bolus epinephrine were identified. Those who received fluid boluses or chest compressions within 2 minutes of bolus epinephrine were excluded. Autoregressive integrated moving average analyses with exogenous variables were conducted to characterise the time-dependent changes in hemodynamic indices. Cluster analyses were then conducted to determine patterns in hemodynamic changes associated with bolus epinephrine.

A total of 71 non-code dose bolus epinephrine administrations were included in the final analyses. Heart rate, blood pressure, and renal near infrared spectroscopy all demonstrated statistically significant changes after bolus epinephrine administration. Peak change in each was 40%, 52%, and 9%, respectively, with peaks occurring between 60 seconds and 120 seconds after administration. Three response-based clusters were identified.

Non-code dose bolus epinephrine is associated with a significant increase in heart rate, blood pressure, and systemic oxygen delivery. Cluster analysis using the peak change identified distinct clinical clusters.

To examine the impact the COVID-19 pandemic in Ireland on symptoms and functioning in individuals across a range of mental health disorders.

A systematic bibliographic search of case reports, cross-sectional and longitudinal studies was conducted between March 12th, 2020, and December 20th, 2024, among studies evaluating the impact of the COVID-19 pandemic on symptoms and functioning for individuals with pre-existing mental health disorders and for those who presented with self-harm or died by probable suicide in the Republic of Ireland. Studies were independently screened by two reviewers according to inclusion and exclusion criteria, with selected variables extracted and summarised. Risk of bias assessments and narrative synthesis of included studies were conducted.

Twenty-eight studies met inclusion criteria. Findings were heterogeneous and disorder specific. An increase in presentations of self-harm, anxiety disorders, and eating disorders to child and adolescent mental health services and emergency departments was noted, with relative stability of symptoms in other cohorts including bipolar disorder and treatment-resistant schizophrenia. Significant symptom deterioration, with poor quality of life and functioning was demonstrated in individuals with emotionally unstable personality disorder both cross-sectionally and longitudinally.

Most people with pre-existing mental disorders did not experience significant exacerbation associated with the pandemic, with exception of those with eating disorders and EUPD.

The National Dental PBRN Central Institutional Review Board (CIRB) at the University of Alabama-Birmingham (UAB) was established in 2014 to reduce administrative burden while allowing Local Context Review (LCR) by local institutions (LIs). The National Institutes of Health implemented a single IRB policy in 2018; CIRB meets its requirements.

The CIRB reviews study protocols, documents, consent forms, and HIPAA forms. Once CIRB approval is obtained, the study packet is sent to LIs for LCR. LIs may revise specific sections agreed on in reliance agreements but must make determinations regarding the HIPAA Privacy Rule. Once a LI completes a reliance agreement and the LCR, the CIRB becomes responsible for subsequent reviews.

The CIRB has reviewed 27 studies, 8 of which were declared exempt; LIs are responsible for exempt studies. Nineteen studies were declared expedited or full review. For all expedited/full review studies combined, the mean (SD) calendar days from initial submission to approval was 55.2 (35.2) days; for studies with available tracking, 35% of this time was due to waiting on study investigator responses. Post-approval submissions for 19 studies, such as revision amendments, continuing reviews, site amendments, prompt reports, and personnel amendments, totaled to 374.

The CIRB did not ensure a shorter approval time because LCR approvals must wait for initial CIRB approval, but LIs did benefit by starting with an already-approved packet. However, substantial benefits were realized later because subsequent amendments and annual reviews only required CIRB review, saving LIs from involvement in these reviews.