BACKGROUND: Burnout in primary care undermines worker well-being and patient care. Many factors contribute to burnout, including high workloads, emotional stress, and unsupportive supervisors. Formative evidence suggests that burnout might be reduced if clinic leaders hold quarterly and brief (∼30 min) one-on-one check-ins with team members to acknowledge and address work-life stressors (e.g., schedules, workflow breakdowns, time off requests). This paper describes the intervention protocol for a randomized controlled trial (RCT) designed to evaluate the effectiveness and process of the check-ins in reducing burnout among primary care professionals.
METHODS: Two-arm RCT conducted at 12 primary care clinics of a healthcare system in the Pacific Northwest. Six clinics received an adaptive design, semi-structured intervention, including predefined training modules with evidence-based tactics to reduce burnout through the check-ins, followed by clinic-specific feedback sessions prior to offering and conducting quarterly leader-employee check-ins. Six clinics were randomized as waitlist controls. Burnout was measured using the Maslach Burnout Inventory (MBI) at baseline and at the 12-month follow-up. Secondary outcomes include organizational constraints, psychological safety, and supervisor support. Multilevel modeling and qualitative methods were applied to evaluate the effects and process of the intervention.
CONCLUSIONS: By focusing on modifiable work-life factors such as stressors and supervisor support, the check-ins intervention aims to reduce burnout rates among primary care professionals. Findings from this trial will shed light on the conditions upon which check-ins might reduce burnout. Results will also inform policies and interventions aimed at improving mental health and well-being in primary care settings.
RESULTS: gov: ID NCT05436548.

BACKGROUND: Blinding is a methodologically important aspect in randomised controlled trials yet frequently overlooked in trials of spinal manual therapy interventions for back pain. To help inform the blinding methods of a future, double-placebo-controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain, we set four objectives: (1) to assess the feasibility of blinding participants, randomly allocated to an active or placebo-control spinal manual therapy intervention protocol, (2) to assess the feasibility of blinding outcome assessors within the trial, (3) to explore the influence of spinal manual therapy experience and low back pain on blinding, and (4) to explore factors contributing to perceptions about intervention assignment among participants and outcome assessors.
METHODS: Two-parallel-group, single-centre, placebo-controlled, methodological blinding feasibility randomised trial. We will recruit between 60 and 100 adults with or without back pain and with or without experience of spinal manual therapy from Zurich, Switzerland. Participants will be randomised to either an active spinal manual therapy or a placebo-control spinal manual therapy protocol-both interventions delivered over two study visits, up to two weeks apart. The primary outcome is participant blinding using the Bang blinding index within each intervention arm immediately after each of the two study visits. Secondary outcomes are participant blinding using the James blinding index, outcome assessor blinding (Bang and James blinding indices), self-reported factors influencing perceived intervention assignment among participants and outcome assessors, and participant-reported credibility and expectancy of study interventions. Other outcomes-included to blind the study objective from participants-are lumbar spine range of motion, self-rated general health, satisfaction with care, pain intensity, and function. Intervention provider outcomes include intervention component fidelity and quality of intervention delivery.
BACKGROUND: The independent ethics commission of Canton Zurich granted ethical approval for this study (KEK 2023-00381). Written informed consent will be obtained from all participants. Findings will be disseminated in scientific conferences and a peer-reviewed publication and inform the blinding methods of a future double-placebo controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain-the SALuBRITY trial.
BACKGROUND: NCT05778396.

BACKGROUND: Patients undergoing video-assisted thoracoscopic lobectomy (VATL) often experience chronic postsurgical pain (CPSP). Postoperative pain can affect the recovery of postoperative lung function, prolong postoperative recovery time, and increase patient hospitalization expenses. Transcutaneous electrical acupoint stimulation (TEAS) is an alternative therapy based on acupuncture that has shown promise in postoperative recovery and pain management across various medical fields. However, research specifically focused on the improvement of CPSP after VATL is currently lacking. The purpose of this study is to evaluate whether TEAS can effectively reduce the severity and occurrence of chronic postsurgical pain in patients undergoing VATL. By investigating the potential benefits of TEAS in mitigating CPSP after VATL, this study aims to provide valuable clinical evidence to support the integration of TEAS into postoperative care protocols for patients undergoing VATL.
METHODS: This study is a prospective, single-center, double-blinded, randomized controlled trial to be conducted at the 920th Hospital of Joint Logistics Support Force. Eighty patients undergoing VATL will be randomly divided into an experimental group (TEAS group) and a control group (sham group). The experimental group will receive TEAS at bilateral PC6, LI4, LR3, LU5, TE5, and LI11. The control group will not receive TEAS at the same acupoints. Both groups will receive TEAS or no TEAS before anesthesia induction and 1-7 days after surgery, with each session lasting 30 min.
UNASSIGNED: The primary outcome will be the incidence of CPSP at 3 months after surgery. Secondary outcomes will include the incidence of CPSP at 6 months after surgery, the numerical rating scale (NRS) scores at 3 and 6 months after surgery, as well as the NRS scores at 24, 48, and 72 h after surgery, remifentanil consumption during general anesthesia, demand for rescue analgesics, number and duration of indwelling chest tubes, incidence of postoperative nausea and vomiting, and changes of norepinephrine (NE), cortisol (Cor), tumor necrosis factor (TNF- α), and interleukin 6 (IL-6) in serum.
BACKGROUND: ChiCTR2300069458. Registered on March 16, 2023.

BACKGROUND: Despite the critical importance of clinical trials to provide evidence about the effects of intervention for children and youth, a paucity of published high-quality pediatric clinical trials persists. Sub-optimal reporting of key trial elements necessary to critically appraise and synthesize findings is prevalent. To harmonize and provide guidance for reporting in pediatric controlled clinical trial protocols and reports, reporting guideline extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines specific to pediatrics are being developed: SPIRIT-Children (SPIRIT-C) and CONSORT-Children (CONSORT-C).
METHODS: The development of SPIRIT-C/CONSORT-C will be informed by the Enhancing the Quality and Transparency of Health Research Quality (EQUATOR) method for reporting guideline development in the following stages: (1) generation of a preliminary list of candidate items, informed by (a) items developed during initial development efforts and child relevant items from recent published SPIRIT and CONSORT extensions; (b) two systematic reviews and environmental scan of the literature; (c) workshops with young people; (2) an international Delphi study, where a wide range of panelists will vote on the inclusion or exclusion of candidate items on a nine-point Likert scale; (3) a consensus meeting to discuss items that have not reached consensus in the Delphi study and to \"lock\" the checklist items; (4) pilot testing of items and definitions to ensure that they are understandable, useful, and applicable; and (5) a final project meeting to discuss each item in the context of pilot test results. Key partners, including young people (ages 12-24 years) and family caregivers (e.g., parents) with lived experiences with pediatric clinical trials, and individuals with expertise and involvement in pediatric trials will be involved throughout the project. SPIRIT-C/CONSORT-C will be disseminated through publications, academic conferences, and endorsement by pediatric journals and relevant research networks and organizations.
CONCLUSIONS: SPIRIT/CONSORT-C may serve as resources to facilitate comprehensive reporting needed to understand pediatric clinical trial protocols and reports, which may improve transparency within pediatric clinical trials and reduce research waste.
BACKGROUND: The development of these reporting guidelines is registered with the EQUATOR Network: SPIRIT-Children ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials-protocols/#35 ) and CONSORT-Children ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#CHILD ).

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental conditions diagnosed during childhood and adolescence. In addition to the commonly observed symptoms of inattention, hyperactivity, and impulsivity, individuals with ADHD often experience impairments in executive functions (EFs). Goal management training (GMT) is a cognitive remediation intervention targeting EFs, with empirical support from studies with adult populations, including ADHD. The objective of the upcoming trial is to assess the effectiveness of GMT for adolescents with ADHD.
This pre-registered protocol outlines a multi-centre randomised controlled trial (RCT) comparing GMT to treatment as usual (TAU) to improve EFs. We aim to recruit 120 participants, aged 12 to 18 years, recently diagnosed with ADHD. Participants will be randomly allocated to the group-based GMT intervention in addition to TAU, or the TAU condition, through block randomisation with site stratification. GMT will be delivered in groups of four to six participants, with weekly two-hour sessions for seven weeks, complemented by separate parent and teacher sessions. TAU is standard community mental health treatment. The primary outcome measure will be parent-reported EF assessed with the Behaviour Rating Inventory of Executive Function 2 (BRIEF-2). Secondary outcomes will include ADHD symptom measures, social functioning, quality of life, and neuropsychological tests (attention span, inhibition, working memory, and visuo-motor speed). The outcome assessments will be conducted at baseline, 12 weeks, 12 months, and 24 months post-treatment.
The study findings will contribute to determine the effectiveness of a non-pharmacological ADHD treatment, including outcome trajectories up to 24 months post-treatment.

UNASSIGNED: Many patients suffer from post-operative pain after neurosurgery despite using intra-operative opioids. Opioid side effects are problematic in neurosurgical patients. Hence, non-opioid alternatives for the management of nociception and pain are needed. Previous studies comparing opioids with non-opioids in the neurosurgical population were few, from single centres, of small sample sizes and were equivocal in findings, which prevented change in clinical practice. To overcome these limitations, we are conducting a multi-centre trial with objectives to compare intra-operative rescue opioid requirements and post-operative pain scores (primary objectives), adverse events, quality of recovery from anaesthesia, quality of sleep and patient satisfaction during hospital stay, and persistent post-surgical pain and quality of life at 3 and 6 months (secondary objectives) in patients receiving opioid and non-opioid analgesia for brain tumour surgeries.
UNASSIGNED: This study protocol describes the methodology of a multi-centre randomised controlled trial. Ethics committee approval has been obtained from all five centres, the trial has been registered with the Clinical Trial Registry- India, and insurance has been obtained for this investigator-initiated funded study. In patients undergoing supra-tentorial brain tumour surgery (population), we will compare fentanyl (intervention) 1 µg/kg/h with dexmedetomidine (comparator) 0.5 µg/kg/h administered during surgery with regards to intra-operative rescue opioid requirement and post-operative pain (primary outcomes).
UNASSIGNED: We describe the study protocol of the multi-centre trial (protocol version 2, dated 29/01/2022). The first patient was recruited on 19/10/2022, and we will complete recruitment before March 2024.
UNASSIGNED: We expect our study to establish dexmedetomidine as an effective non-opioid analgesic vis-à-vis opioids in the neurosurgical population.

UNASSIGNED: Early decline of episodic memory is detectable in subjective cognitive decline (SCD). The left dorsolateral prefrontal cortex (DLPFC) is associated with encoding episodic memories. Repetitive transcranial magnetic stimulation (rTMS) is a novel and viable tool to improve cognitive function in Alzheimer\'s disease (AD) and mild cognitive impairment, but the treatment effect in SCD has not been studied. We aim to investigate the efficacy of rTMS on episodic memory in individuals with SCD, and to explore the potential mechanisms of neural plasticity.
UNASSIGNED: In our randomized, sham-controlled trial, patients (n = 60) with SCD will receive 20 sessions (5 consecutive days per week for 4 weeks) of real rTMS (n = 30) or sham rTMS (n = 30) over the left DLPFC. The primary outcome is the Auditory Verbal Learning Test-Huashan version (AVLT-H). Other neuropsychological examinations and the long-term potentiation (LTP)-like cortical plasticity evaluation serve as the secondary outcomes. These outcomes will be assessed before and at the end of the intervention.
UNASSIGNED: If the episodic memory of SCD improve after the intervention, the study will confirm that rTMS is a promising intervention for cognitive function improvement on the early stage of dementia. This study will also provide important clinical evidence for early intervention in AD and emphasizes the significance that impaired LTP-like cortical plasticity may be a potential biomarker of AD prognosis by demonstrating the predictive role of LTP on cognitive improvement in SCD.
UNASSIGNED: The study was approved by the Human Research Ethics Committee of the hospital (No. 2023-002-01). The results will be published in peer-review publications.
UNASSIGNED: https://www.chictr.org.cn/, identifier ChiCTR2300075517.

A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects.
CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30-40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models.
This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action.
Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting.

It has been suggested that vitamin C is involved in suppressing stress oxidation signaling in vitiligo disease. However, the effect of vitamin C supplementation on stress oxidative factors has not been investigated in vitiligo subjects. This study was designed to examine the effects on vitamin C supplementation on serum levels of stress oxidative factors and regimentation in vitiligo patients. Forty-four vitiligo patients will be recruited in this study. After block matching for sex and number of phototherapy sessions, they will be randomly assigned to receive 1000 mg/d vitamin C or placebo for 8 weeks. The weight, height, and waist circumference of participants will be measured. Determination of serum stress oxidative indices (CAT, SOD, GPX, MDA, TOS, TAC) will be done at study baseline and at the end of the trial. Also, the regimentation will be determined using the VASI score. This is the first randomized controlled trial that will determine the effect of vitamin C supplementation on serum levels of stress oxidative indices and regimentation in vitiligo patients. The results of this trial will provide clinical evidence on the effectiveness of vitamin C supplementation in controlling oxidative stress in vitiligo patients. Trial registration number: This study is registered in the Iranian Registry of Clinical Trials website (available at http://www.irct.ir , identifier: IRCT20230123057193N1), Registration date: 2023/04/17.

BACKGROUND: The leukodystrophy \"Vanishing White Matter\" (VWM) is an orphan disease with neurological decline and high mortality. Currently, VWM has no approved treatments, but advances in understanding pathophysiology have led to identification of promising therapies. Several investigational medicinal products are either in or about to enter clinical trial phase. Clinical trials in VWM pose serious challenges, as VWM has an episodic disease course; disease phenotype is highly heterogeneous and predictable only for early onset; and study power is limited by the small patient numbers. To address these challenges and accelerate therapy delivery, the VWM Consortium, a group of academic clinicians with expertise in VWM, decided to develop a core protocol to function as a template for trials, to improve trial design and facilitate sharing of control data, while permitting flexibility regarding other trial details. Overall aims of the core protocol are to collect safety, tolerability, and efficacy data for treatment assessment and marketing authorization.
METHODS: To develop the core protocol, the VWM Consortium designated a committee, including clinician members of the VWM Consortium, family and patient group advocates, and experts in statistics, clinical trial design and alliancing with industries. We drafted three age-specific protocols, to stratify into more homogeneous patient groups, of ages ≥ 18 years, ≥ 6 to < 18 years and < 6 years. We chose double-blind, randomized, placebo-controlled design for patients aged ≥ 6 years; and open-label non-randomized natural-history-controlled design for patients < 6 years. The protocol describes study populations, age-specific endpoints, inclusion and exclusion criteria, study schedules, sample size determinations, and statistical considerations.
CONCLUSIONS: The core protocol provides a shared uniformity across trials, enables a pool of shared controls, and reduces the total number of patients necessary per trial, limiting the number of patients on placebo. All VWM clinical trials are suggested to adhere to the core protocol. Other trial components such as choice of primary outcome, pharmacokinetics, pharmacodynamics, and biomarkers are flexible and unconstrained by the core protocol. Each sponsor is responsible for their trial execution, while the control data are handled by a shared research organization. This core protocol benefits the efficiency of parallel and consecutive trials in VWM, and we hope accelerates time to availability of treatments for VWM.
BACKGROUND: NA. From a scientific and ethical perspective, it is strongly recommended that all interventional trials using this core protocol are registered in a clinical trial register.