Bouldering psychotherapy reduces depressive symptoms even when general physical activity is controlled for: A randomized controlled trial

Background Bouldering psychotherapy (BPT) combines psychotherapeutic elements with physical activity (PA). It might be effective for reducing symptoms of depression, but so far, no study has assessed individuals' levels of PA to control for whether positive effects on depression can also be found when adjusting for participants' levels of PA. This is important because PA itself has been proven effective in reducing depression and therefore might be an important variable to account for – especially in therapies using sport as one therapeutic mechanism. Methods Using a waitlist control group design, outpatients with depression were assessed at baseline and after eight, 16, and 24 weeks. The intervention group took part in an eight-week bouldering psychotherapy which met once a week for three hours. Self-report measures before and after the intervention included the Symptom Checklist-90-R (SCL-90-R), the Beck Depression Inventory (BDI-II), and the questionnaire on resources and self-management skills (FERUS). PA was assessed during the first 16-week period via FitBit Zip accelerometers. Results Altogether, 47 complete cases (20 men and 27 women) were included in the final analyses. Depression scores dropped by up to 6.74 (CI 2.80–10.67) points on the SCL-90-R depression scale and by up to 8.26 (CI 4.21–12.31) points on the BDI-II during the BPT intervention, the control group remained stable (SCL-90-R Cohen's d = 0.60; BDI-II: Cohen's d = .50). All Participants accrued an average of 6,515 steps per day, which is considered “low-active.” Participants of the BPT intervention were significantly more likely to reduce their depressive symptoms (p = .025) than participants of the control group, even when PA was controlled for in a regression analysis. Limitations Limitations of the study are the relatively small number of patients and the assessment of outcome scores via self-report. Conclusions This study provides evidence that short-term BPT can be effective for reducing symptoms of depression even if controlled for other therapeutically active confounders including antidepressant medication, psychotherapy and general level of PA

Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA

Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial

Importance: The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective: To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants: This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures: The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance: While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.status: publishe