Search

Background Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD. Methods This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8–17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants’ treatment evaluation with a correlational analysis of adverse events and OCD severity. Discussion The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data., Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD. Methods: This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8–17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants’ treatment evaluation with a correlational analysis of adverse events and OCD severity. Discussion: The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data. Trial registration: ClinicalTrials.gov identifier: NCT03595098. Registered on July 23, 2018.

Background: Endoscopic retrograde cholangiography (ERC) with stone extraction and papillotomy with subsequent laparoscopic cholecystectomy—the two-step approach—is the standard treatment of common bile duct stones in many countries. However, ERC is associated with a high risk of complications and more than half of patients require multiple ERCs. Meta-analyses of randomised clinical trials find no major differences of the two-step approach in comparison with laparoscopic cholecystectomy with intraoperative laparoscopic stone clearance—the one-step approach. Currently, there are insufficient data to ascertain superiority. Methods: The preGallstep trial is an investigator-initiated, multicentre randomised feasibility and pilot clinical trial with blinded outcome assessment. Eligible patients are patients with common bile duct stones (identified by magnetic resonance cholagiopancreatography), age 18 years or above with the possibility to perform both interventions within a reasonable time. We intent to randomise 150 participants allocated 1:1. The experimental intervention is the one-step approach. This consists of laparoscopic common bile duct exploration plus laparoscopic cholecystectomy. The control intervention is the two-step approach which consists of ERC plus sphincterotomy (first step) and subsequent laparoscopic cholecystectomy (second step). Feasibility outcomes include the proportion of eligible patients not wanting to participate, reasons for rejection to participate, difficulties during the informed consent procedure, difficulties with randomisation, difficulties with data management, difficulties with blinding patient charts and forms and difficulties with maintaining blinding for the outcome assessors. The primary pilot outcome is the proportion of participants with at least one postoperative complication according to the Clavien-Dindo score grade II and above until 90 days after randomisation. This outcome will be used for a future sample size calcula

Background: Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks of random errors using trial sequential analysis methodology. This systematic review investigates the benefits and harms of self-determination theory-based interventions compared to usual care in people with diabetes. Methods: We used the Cochrane methodology. Randomized clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory in any setting were eligible. A comprehensive search (latest search April 2022) was undertaken in CENTRAL, MEDLINE, Embase, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S, and CPCI-SSH to identify relevant trials. Two authors independently screened, extracted data, and performed risk-of-bias assessment of included trials using the Cochrane risk-of-bias tool 1.0. Our primary outcomes were quality of life, all-cause mortality, and serious adverse events. Our secondary outcomes were diabetes distress, depressive symptoms, and nonserious adverse events not considered serious. Exploratory outcomes were glycated hemoglobin and motivation (autonomy, controlled, amotivation). Outcomes were assessed at the end of the intervention (primary time point) and at maximum follow-up. The analyses were conducted using Review Manager 5.4 and Trial Sequential Analysis 0.9.5.10. Certainty of the evidence was assessed by GRADE. Results: Our search identified 5578 potentially eligible studies of which 11 randomized trials (6059 participants) were included. All trials were assessed at overall high risk of bias. We found no effect of self-determination theory-based interventions compared with usual care on quality of life (mean difference 0.00 points, 95%

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. Methods: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded. Trial Registration: ClinicalTrials.gov identifier: NCT03948256.

Background Non-suicidal self-injury (NSSI) is common in adolescents receiving psychiatric treatment and is a significant risk factor for suicidal behavior. There are few randomised clinical trials assessing interventions for NSSI in youth, and knowledge about internet-delivered interventions is limited. Objective We assessed the feasibility of Internet based Emotion Regulation Individual Therapy for Adolescents (ERITA) in psychiatric outpatients aged 13–17 years who engaged in NSSI. Method A randomised clinical feasibility trial with a parallel group design. Non-suicidal self-injury engaging patients were recruited from Child and Adolescent Mental Health Outpatient Services in the Capital Region of Denmark from May to October 2020. ERITA was provided as add-on to treatment as usual (TAU). ERITA is a therapist-guided, internet-based program of emotion regulation and skills training involving a parent. The control intervention was TAU. Feasibility outcomes were the proportion who completed follow-up interviews at end of intervention; proportion of eligible patients who participated in the trial; proportion of participants completing ERITA. We further investigated relevant exploratory outcomes, including adverse risk-related events. Results We included 30 adolescent participants, 15 in each group (ERITA vs. Treatment as usual). 90% (95% CI, 72%–97%) of the participants completed post-treatment interviews; 54% (95% CI, 40%–67%) of the eligible participants were included and randomised; and 87% (95% CI, 58%–98%) of the participants completed at least six out of 11 ERITA modules. We identified no difference for the primary exploratory clinical outcome of NSSI between the two groups. Conclusion There are few randomised clinical trials assessing interventions for NSSI in youth, and knowledge about internet-delivered interventions is limited. Based on our results we conclude that a large-scale trial seems feasible and w

Background: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients. Methods: We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799). Results: We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49–1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15–3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66–0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55–1.20). Conclusions: The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.

Background: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder which affects up to 3% of children and adolescents. OCD in children and adolescents is generally treated with cognitive behavioural therapy (CBT), which, in more severely affected patients, can be combined with antidepressant medication. The TECTO trial aims to compare the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation/relaxation training (FPRT) in children and adolescents aged 8 to 17 years. This statistical analysis plan outlines the planned statistical analyses for the TECTO trial. Methods: The TECTO trial is an investigator-initiated, independently funded, single-centre, parallel-group, superiority randomised clinical trial. Both groups undergo 14 sessions of 75 min each during a period of 16 weeks with either FCBT or FPRT depending on the allocation. Participants are randomised stratified by age and baseline Children’s Yale–Brown Obsessive-Compulsive Scale (CY-BOCS) score. The primary outcome is the CY-BOCS score. Secondary outcomes are health-related quality of life assessed using KIDSCREEN-10 and adverse events assessed by the Negative Effects Questionnaire (NEQ). Primary and secondary outcomes are assessed at the end of the intervention. Continuous outcomes will be analysed using linear regression adjusted for the stratification variables and baseline value of the continuous outcome. Dichotomous outcomes will be analysed using logistic regression adjusted for the stratification variables. The statistical analyses will be carried out by two independent blinded statisticians. Discussion: This statistical analysis plan includes a detailed predefined description of how data will be analysed and presented in the main publication before unblinding of study data. Statistical analysis plans limit selective reporting bias. This statistical analysis plan will increase the validity of the final trial results. Trial registration: ClinicalTrials.go

Aims: Infective endocarditis is a complex and highly mortal disease requiring lengthy treatment. Physical and mental deconditioning is common. Nonetheless, rehabilitation is virtually unexplored in this population. The aim of this trial was therefore to investigate the effects of cardiac rehabilitation in patients following endocarditis. Methods and results: In a randomized trial, adults with left-sided or cardiac device endocarditis were randomized 1:1 to 12 weeks of physical exercise training and five psycho-educational consultations (cardiac rehabilitation) vs. usual care without rehabilitation (control). Primary outcome was mental health measured by SF-36 Mental Component Summary (MCS) at 6 months. Secondary outcome was physical capacity measured by peak oxygen uptake (VO2) at 4 months. Exploratory outcomes were investigated. Low inclusion rate resulted in trial termination before reaching the target sample size. A total of 117 participants (mean age: 60 years, 81% male) were randomized to cardiac rehabilitation (n = 58) or to control (n = 59). Mental health and physical capacity at baseline were generally poor (MCS: 38.9-42.2 points, VO2 peak: 16.1-16.6 mL/kg/min). Cardiac rehabilitation compared with control showed no effect on mental health (MCS: 44.6 points vs. 48.8 points, P = 0.41) or physical capacity (VO2 peak: 19.9 mL/kg/min vs. 18.0 mL/kg/min, P = 0.09). Effects favouring the intervention were identified in exploratory outcomes including general fatigue (P = 0.005), and physical capacity as maximal power (W) (P = 0.005). Adherence to the intervention was 28%. Conclusions: Results indicate no effect of cardiac rehabilitation in patients following endocarditis; however, lack of statistical power and poor adherence render findings inconclusive. Valuable insight into patients' capabilities and safety was gained, and further investigations into rehabilitation needs and modes of delivery in this high-need population should be a future priority. Registrati

BACKGROUND: Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions regarding the efficacy of CBT. We investigate the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in youth with OCD in a trial designed to reduce risk-of-bias.METHODS: This is an investigator-initiated, independently funded, single-centre, parallel group superiority randomised clinical trial (RCT). Outcome assessors, data managers, statisticians, and conclusion drawers are blinded. From child and adolescent mental health services we include patients aged 8-17 years with a primary OCD diagnosis and an entry score of ≥16 on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We exclude patients with comorbid illness contraindicating trial participation; intelligence quotient < 70; or treatment with CBT, PRT, antidepressant or antipsychotic medication within the last 6 months prior to trial entry. Participants are randomised 1:1 to the experimental intervention (FCBT) versus the control intervention (FPRT) each consisting of 14 75-min sessions. All therapists deliver both interventions. Follow-up assessments occur in week 4, 8 and 16 (end-of-treatment). The primary outcome is OCD symptom severity assessed with CY-BOCS at end-of-trial. Secondary outcomes are quality-of-life and adverse events. Based on sample size estimation, a minimum of 128 participants (64 in each intervention group) are included.DISCUSSION: In our trial design we aim to reduce risk-of-bias, enhance generalisability, and broaden the outcome measures by: 1) conducting an investigator-initiated, independently funded RCT; 2) blinding investigators; 3) investigating a represent