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Abstract Introduction 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 and analysis 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. Ethics and dissemination 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. Trial registration NCT05778396.

Introduction: 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 and analysis: 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. Ethics and dissemination: 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. Trial registration: NCT05778396. [ABSTRACT FROM AUTHOR]

Introduction: 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. Planned Outcomes: 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. Trial Registration: ChiCTR2300069458. Registered on March 16, 2023. [ABSTRACT FROM AUTHOR]

Abstract Introduction 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. Planned Outcomes 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. Trial Registration ChiCTR2300069458. Registered on March 16, 2023.

Abstract 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. Discussion 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. Trial Registration 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 ).

Abstract Background 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. Methods 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. Discussion 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. Trial registration Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting.

Abstract 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

Background Steroids have pleiotropic neuroprotective actions including the regulation of inflammation and apoptosis which may influence the effects of ischemia on neurons, glial cells, and blood vessels. The effect of low‐dose methylprednisolone in patients with acute ischemic stroke in the endovascular therapy era remains unknown. This trial investigates the efficacy and safety of low‐dose methylprednisolone (2 mg/kg IV for 3 days) as adjunctive therapy for patients with acute ischemic stroke undergoing endovascular therapy within 24 hours from symptom onset. Methods The MARVEL (Methylprednisolone as Adjunctive Therapy for Acute Large Vessel Occlusion: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy) trial is an investigator‐initiated, prospective, randomized, double‐blind, placebo‐controlled multicenter clinical trial. Up to 1672 eligible patients with anterior circulation large‐vessel occlusion stroke presenting within 24 hours from symptom onset are planned to be consecutively randomized to receive methylprednisolone or placebo in a 1:1 ratio across 82 stroke centers in China. Results The primary outcome is the ordinal shift in the modified Rankin scale score at 90 days. Secondary outcomes include 90‐day functional independence (modified Rankin scale score, 0–2). The primary safety end points include mortality rate at 90 days and symptomatic intracerebral hemorrhage within 48 hours of endovascular therapy. Conclusion The MARVEL trial will provide evidence of the efficacy and safety of low‐dose methylprednisolone as adjunctive therapy for patients with anterior circulation large‐vessel occlusion stroke undergoing endovascular therapy.

Background: 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. Methods: 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. Discussion: 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. Trial registration: Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331. Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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. Discussion: 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. Ethics and dissemination: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Clinical trials transparency requires trial registration and the posting of results on a public register. US regulations also require the posting of protocols and statistical analysis plans (SAPs). For US Federal agency funded trials to be started on or after 21 January 2019, informed consent forms (ICFs) must also be posted. Posting these documents is not mandatory in other countries. We aimed to assess compliance with US regulations of trials conducted in the US or in other countries with respect to ICFs, protocols, SAPs, and results. Methods: This cross-sectional analysis (27 April 2023) comprised completed medicines trials to be started on or after 21 January 2019 registered on ClinicalTrials.gov. Trial data were registered by funder type (i.e., 'US federal agencies', industry, and 'all others') and development phase. Results: Of 5,584 trials, 40% were conducted solely in the US. 47% and 12% of US and non-US trials had posted results. Some 40% of US trials had posted protocols and SAPs as did 9% of trials conducted in other countries. Only 10% (US) and 2% (other countries) of trials had posted ICFs. When the margin of the last 2 and 12 months after primary completion date were considered in the analysis, ICF posting rate did not change, but posting results increased to 64% for US trials. 'US Federal agencies' funded trials were significantly more likely to post ICFs than industry [OR 23.9 (12.5-45.7; <.001)] or 'all others' [OR 3.16 (1.79-5.56; <.001)]. Conclusion: Future interventions should be considered to encourage timely posting of trial results and information. [ABSTRACT FROM AUTHOR]

Background and Aims: 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. Methods: 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). Results: 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. Conclusion: We expect our study to establish dexmedetomidine as an effective non-opioid analgesic vis-à-vis opioids in the neurosurgical population. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to assess the efficacy of a technology-based parent school program designed for parents of children aged 1-3 to improve their parenting abilities. Method: The research is a parallel-group, single-blind (participant) randomized controlled trial. The research will be conducted with parents with children aged 18 and 24 months in a hospital's well-child outpatient clinic in Turkey. The data of the research will be collected with Parent and Child Descriptive Data Form, Parenting Skill Assessment Form, Skill Assessment Form the Toddler Development, Development of the Psychosocial Status Assessment Form for Parents (1-3 aged), and The Self-Efficacy for Parenting Tasks Index-Toddler Scale (SEPTI-TS) (1-3 years). The minimum sample size of the research is planned to be a total of 68 participants (intervention group=34, control group=34). The program will last 10 weeks. Parents in the intervention group will read the modules on the website and then participate in the online group interaction. Parents will receive counseling throughout the program. In addition, motivational messages will be sent to parents during the follow-up phase. The modules will deal with the child's physical growth, cognitive and language development, and social-emotional development. The modules will be aided by videos and messages. This study was planned based on Meleis' Transition Theory. Results: Following the Technology-Based Parent School Program, parents are expected to have child-rearing skills and self-efficacy in terms of the development of their children. Usage in practice: The parent school will be a guide to support parents in physical, cognitive, social-emotional, and language development of the 1-3-year-old child.

Background: Conflict in the Democratic Republic of Congo has led to large numbers of refugees fleeing to Uganda and Rwanda. Refugees experience elevated levels of adverse events and daily stressors, which are associated with common mental health difficulties such as depression. The current cluster randomised controlled trial aims to investigate whether an adapted form of Community-based Sociotherapy (aCBS) is effective and cost-effective in reducing depressive symptomatology experienced by Congolese refugees in Uganda and Rwanda. Methods: A two-arm, single-blind cluster randomised controlled trial (cRCT) will be conducted in Kyangwali settlement, Uganda and Gihembe camp, Rwanda. Sixty-four clusters will be recruited and randomly assigned to either aCBS or Enhanced Care As Usual (ECAU). aCBS, a 15-session group-based intervention, will be facilitated by two people drawn from the refugee communities. The primary outcome measure will be self-reported levels of depressive symptomatology (PHQ-9) at 18-weeks post-randomisation. Secondary outcomes will include levels of mental health difficulties, subjective wellbeing, post-displacement stress, perceived social support, social capital, quality of life, and PTSD symptoms at 18-week and 32-week post-randomisation. Cost effectiveness of aCBS will be measured in terms of health care costs (cost per Disability Adjusted Life Year, DALY) compared to ECAU. A process evaluation will be undertaken to investigate the implementation of aCBS. Conclusion: This cRCT will be the first investigating aCBS for mental health difficulties experienced by refugees and will contribute to knowledge about the use of psychosocial interventions for refugees at a time when levels of forced migration are at a record high. Trial registration: ISRCTN.org identifier: ISRCTN20474555.

To assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. The BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy – Colorectal questionnaire is recorded pre-treatment and at follow-up. The primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life. The BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC. • Locoregional relapses post-cystectomy cause considerable mortality and morbidity. • The BART randomised trial compares adjuvant radiotherapy versus observation in high-risk MIBC. • Radiotherapy using modern techniques enables a contemporary analysis of efficacy and safety. • Primary endpoint is 2-year LRFS with 15% benefit hypothesised. [ABSTRACT FROM AUTHOR]

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. Discussion: 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. Trial registration: 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. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of 177Lu‐PNT2002, a novel radiolabelled small molecule that binds with high affinity to prostate‐specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) to all sites of metastasis, vs SBRT alone, in men with oligorecurrent metastatic hormone‐sensitive prostate cancer (mHSPC). Patients and Methods: The 177Lutetium‐PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR) trial is an open‐label, randomized, stratified, two‐arm, single‐centre, Phase 2 trial to compare the efficacy and safety of neoadjuvant 177Lu‐PNT2002 plus SBRT vs SBRT alone in men with oligorecurrent mHSPC. Key eligibility criteria include one to five lesions identified on a PSMA positron emission tomography (PET)/computed tomography (CT) scan centrally reviewed by a board‐certified nuclear medicine physician. Key exclusion criteria include castrate‐resistant disease, de novo oligometastatic disease and receipt of androgen deprivation therapy (ADT) within 6 months of trial enrolment. The trial aims to enrol 100 patients who will be centrally randomized to one of the two treatment arms, in a 1:1 ratio. Patients in the control arm receive SBRT to all sites of disease. Patients in the experimental arm receive two cycles of neoadjuvant 177Lu‐PNT2002 (6.8 GBq) 6–8 weeks apart, followed by an interval PSMA PET/CT in 4–6 weeks and dose‐adapted SBRT to all sites of disease 1–2 weeks later. The primary endpoint is progression‐free survival. Secondary endpoints are radiographic and prostate‐specific antigen‐based progression, acute and late physician‐scored toxicity, patient‐reported quality of life, ADT‐free survival, time to progression, overall survival, locoregional control, and duration of response. Enrolment in the study commenced in September 2022. Results and Conclusions: The addition of 177Lu‐PNT2002 to metastasis‐directed therapy alone may potentially further forestall disease progression. The results of this Phase 2 trial will determine, for the first time in a randomized fashion, the added benefit of 177Lu‐PNT2002 to SBRT in patients with oligorecurrent mHSPC. [ABSTRACT FROM AUTHOR]

Background and Aims: 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. Methods: 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). Results: 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. Conclusion: We expect our study to establish dexmedetomidine as an effective non-opioid analgesic vis-à-vis opioids in the neurosurgical population.

Background: The reduction of goal-directed behavior is the main characteristic in motivational negative symptoms of psychosis as it accounts for the long-term decline in psychological well-being and psychosocial functioning. However, the available treatment options are largely unspecific and show only small effects on motivational negative symptoms. Interventions that directly target the relevant psychological mechanisms are likely to be more effective. For "Goals in Focus", we translated findings from basic clinical research on mechanisms underlying motivational negative symptoms into a tailored and comprehensive novel psychological outpatient treatment program. With this study, we will test the feasibility of the therapy manual and the trial procedures. We also aim to examine first estimates of the effect size that can be expected from "Goals in Focus" to inform the sample size calculation of a subsequent fully powered trial. Methods: Thirty participants diagnosed with a schizophrenia spectrum disorder and at least moderate motivational negative symptoms will be randomly assigned to either 24 sessions of "Goals in Focus" over the course of 6 months (n = 15) or to a 6-month wait-list control group (n = 15). Single-blind assessments will be conducted at baseline (t0) and 6 months after baseline completion (t1). Feasibility outcomes include patient recruitment, retention, and attendance rates. Acceptability will be rated by trial therapists and by participants at end of treatment. Primary outcome for effect size estimation is the motivational negative symptom subscale sum score of the Brief Negative Symptom Scale at t1 corrected for baseline values. Secondary outcomes include psychosocial functioning, psychological well-being, depressive symptoms, expressive negative symptoms, negative symptom factor scores, and goal pursuit in everyday life. Discussion: The feasibility and acceptability data will be used to improve trial procedures and the "Goals in Focus" intervention where necessary. The treatment effect on the primary outcome will provide the basis for the sample size calculation for a fully powered RCT. Trial registration: 1) ClinicalTrials.gov, NCT05252039. Registered on 23 February 2022. 2) Deutsches Register Klinischer Studien, DRKS00018083. Registered on 28 August 2019. [ABSTRACT FROM AUTHOR]

A number of principal investigators may have limited access to biostatisticians, a lack of biostatistical training, or no requirement to complete a timely statistical analysis plan (SAP). SAPs completed early will identify design or implementation weak points, improve protocols, remove the temptation for p-hacking, and enable proper peer review by stakeholders considering funding the trial. An SAP completed at the same time as the study protocol might be the only comprehensive method for at once optimizing sample size, identifying bias, and applying rigor to study design. This ordered corpus of SAP sections with detailed definitions and a variety of examples represents an omnibus of best practice methods offered by biostatistical practitioners inside and outside of industry. The article presents a protocol template for clinical research design, enabling statisticians, from beginners to advanced.

Background: Prehabilitation is gaining increasing interest and shows promising effects on short- and long-term outcomes among patients undergoing major surgery. The effect of multimodal, interdisciplinary prehabilitation has not yet been studied in patients with severe heart failure scheduled for the implantation of a left-ventricular assist device (LVAD). Methods: This randomized controlled multi-center study evaluates the effect of preoperative combined optimization of nutritional and functional status. Patients in the intervention group are prescribed daily in-bed cycling and oral nutrition supplements (ONS) from study inclusion until the day before LVAD-implantation. Patients in the control group receive standard of care treatment. The primary outcomes for the pilot study that involves 48 patients are safety (occurrence of adverse events), efficacy (group separation regarding the intake of macronutrients), feasibility of the trial protocol (compliance (percentage of received interventions) and confirmation of recruitment rates. Secondary outcomes include longitudinal measurements of muscle mass, muscle strength, physical function and quality of life, next to traditional clinical outcomes (30-day mortality, hospital and ICU length of stay, duration of mechanical ventilation and number of complications and infections). If the pilot study is successful, a larger confirmatory, international multicenter study is warranted.

Abstract Background To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline. Methods We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.e. a total of 64 components of the 33 SPIRIT items). We descriptively analysed the adherence to SPIRIT guidelines as proportion of adequately reported items (median and interquartile range [IQR]) and stratified the results by year of approval and sponsor. Results The proportion of reported SPIRIT items increased from a median of 64.9% (IQR, 57.6–69.2%) in 2012 to a median of 72.5% (IQR, 65.3–78.3%) in 2016. Industry-sponsored RCTs reported more SPIRIT items in 2012 (median 67.4%; IQR, 64.1–69.4%) compared to non-industry-sponsored trials (median 59.8%; IQR, 46.5–67.7%). This gap between industry- and non-industry-sponsored trials increased in 2016 (industry-sponsored: median 75.6%; IQR, 71.2–79.0% vs non-industry-sponsored: median 65.3%; IQR, 51.6–76.3%). Conclusions The adherence to SPIRIT guidelines has improved in the UK from 2012 to 2016 but remains on a modest level, especially for non-industry-sponsored RCTs.

BackgroundGestational diabetes mellitus (GDM) is a common complication of pregnancy associated with serious adverse outcomes for mothers and their offspring. Achieving glycaemic targets is the mainstream in the treatment of GDM in order to improve pregnancy outcomes. As GDM is usually diagnosed in the third trimester of pregnancy, the time frame for the intervention is very narrow. Women need to get new knowledge and change their diet very quickly. Usually, these patients require additional frequent visits to healthcare professionals. Recommender systems based on artificial intelligence could partially substitute healthcare professionals in the process of educating and controlling women with GDM, thus reducing the burden on the women and healthcare systems. We have developed a mobile-based personalized recommendation system DiaCompanion I with data-driven real time personal recommendations focused primarily on postprandial glycaemic response prediction. The study aims to clarify the effect of using DiaCompanion I on glycaemic levels and pregnancy outcomes in women with GDM.MethodsWomen with GDM are randomized to 2 treatment groups: utilizing and not utilizing DiaCompanion I. The app provides women in the intervention group the resulting data-driven prognosis of 1-hour postprandial glucose level every time they input their meal data. Based on the predicted glucose level, they can adjust their current meal so that the predicted glucose level falls within the recommended range below 7 mmol/L. The app also provides reminders and recommendations on diet and lifestyle to the participants of the intervention group. All the participants are required to perform 6 blood glucose measurements a day. Capillary glucose values are retrieved from the glucose meter and if not available, from the woman’s diary. Additionally, data on glycaemic levels during the study and consumption of major macro- and micronutrients will be collected using the mobile app with electronic report forms in the intervention group. Women from the control group receive standard care without the mobile app. All participants are prescribed with insulin therapy if needed and modifications in their lifestyle. A total of 216 women will be recruited. The primary outcome is the percentage of postprandial capillary glucose values above target (>7.0 mmol/L). Secondary outcomes include the percentage of patients requiring insulin therapy during pregnancy, maternal and neonatal outcomes, glycaemic control using glycated hemoglobin (HbA1c), continuous glucose monitoring data and other blood glucose metrics, the number of patient visits to endocrinologists and acceptance/satisfaction of the two strategies assessed using a questionnaire.DiscussionWe believe that the approach including DiaCompanion I will be more effective in patients with GDM for improving glycaemic levels and pregnancy outcomes. We also expect that the use of the app will help reduce the number of clinic visits.Trial registration numberClinicalTrials.gov, Identifier NCT05179798.

Background: Conflict in the Democratic Republic of Congo has led to large numbers of refugees fleeing to Uganda and Rwanda. Refugees experience elevated levels of adverse events and daily stressors, which are associated with common mental health difficulties such as depression. The current cluster randomised controlled trial aims to investigate whether an adapted form of Community-based Sociotherapy (aCBS) is effective and cost-effective in reducing depressive symptomatology experienced by Congolese refugees in Uganda and Rwanda. Methods: A two-arm, single-blind cluster randomised controlled trial (cRCT) will be conducted in Kyangwali settlement, Uganda and Gihembe camp, Rwanda. Sixty-four clusters will be recruited and randomly assigned to either aCBS or Enhanced Care As Usual (ECAU). aCBS, a 15-session group-based intervention, will be facilitated by two people drawn from the refugee communities. The primary outcome measure will be self-reported levels of depressive symptomatology (PHQ-9) at 18-weeks post-randomisation. Secondary outcomes will include levels of mental health difficulties, subjective wellbeing, post-displacement stress, perceived social support, social capital, quality of life, and PTSD symptoms at 18-week and 32-week post-randomisation. Cost effectiveness of aCBS will be measured in terms of health care costs (cost per Disability Adjusted Life Year, DALY) compared to ECAU. A process evaluation will be undertaken to investigate the implementation of aCBS. Conclusion: This cRCT will be the first investigating aCBS for mental health difficulties experienced by refugees and will contribute to knowledge about the use of psychosocial interventions for refugees at a time when levels of forced migration are at a record high. Trial registration: ISRCTN.org identifier: ISRCTN20474555. There is a need to evaluate community-based psychosocial interventions for refugees. Community-based sociotherapy has been used to support communities in post-conflict situations but has not been evaluated in a randomised controlled trial. This protocol outlines a proposed randomised controlled trial of community-based sociotherapy adapted for Congolese refugees in Uganda and Rwanda. [ABSTRACT FROM AUTHOR]

Abstract Background Lumbrokinase has been widely used for patients with acute ischemic stroke (AIS) in China; however, because rigorously designed studies are lacking, safety and efficacy of lumbrokinase in the treatment of acute ischemic stroke remains largely unknown. In this multicenter, randomized, and controlled trial, we aim to compare lumbrokinase plus aspirin versus aspirin alone in patients with acute ischemic stroke. Methods A total of 220 eligible participants will be randomized to either the intervention or control group with a 1:1 ratio. These participants must be diagnosed with acute ischemic stroke for the first time, whose symptoms appear within 72 h. Their NIHSS score must be greater than 5 and less than 15, and their age must be between 35 and 85 years old. They must have not received intravenous thrombolysis, arterial thrombolysis, or intravascular intervention. Participants in the intervention group will be treated with lumbrokinase plus aspirin for the first 90 days. Participants in the control group will use placebo plus aspirin for the first 90 days. Then, all participants will be treated with aspirin only and followed up for another 90 days (180-day follow-up). The primary outcome is the modified Rankin Scale (mRS) score. The secondary outcomes are National Institutes of Health Stroke Scale (NIHSS) score, Activity of Daily Living (ADL) Scale score, coagulation function, and serum hypersensitive C-reactive protein. The exploratory outcomes are fasting lipid panel, recurrence rate, the occurrence of cardiovascular and cerebrovascular events, and the mortality rate. Safety evaluations include liver function and kidney function, serum fibrinogen, adverse events, serious adverse events, and bleeding events. Adherence of participants will also be assessed. Discussion This trial will investigate the efficacy and safety of lumbrokinase plus aspirin as compared to aspirin alone in the treatment of acute ischemic stroke. Trial registration Chinese Clinical Trial Registry, ChiCTR2000032952 . Registered on May 16, 2020.

Abstract Background Despite the success of gold standard cognitive-behavioral therapy for problem and disordered gambling, the majority of individuals with gambling problems do not seek or receive professional treatment. Thus, the development of less intrusive self-directed interventions has been encouraged. Bibliotherapy for problem gambling has shown promise, both alone and in combination with motivational interviews, but there is still a lack of online self-directed intervention research. The current randomized controlled trial proposes to assess the additive benefit of a single digital motivational interview delivered in conjunction with an online self-directed treatment program for problem gambling and gambling disorder. Methods A two-arm randomized controlled trial will be conducted, wherein eligible participants (N=270) will be recruited across Canada via internet advertisements posted to several platforms. All participants will receive access to an online self-directed gambling intervention program. Participants will be randomly assigned to either complete the online program alone or receive a digital motivational interview, conducted through an online audioconferencing platform (i.e., Microsoft Teams) to supplement the online program. The primary outcomes of gambling severity, frequency, and expenditures will be tracked along with secondary outcomes (i.e., depression, anxiety, general distress, alcohol use, and online program user data) over a 24-month period. It is expected that participants in both groups will experience a reduction in symptoms across the board, but more substantial improvements will be observed in the group that receives a supplemental motivational interview. Discussion The results of this trial will expand upon prior gambling intervention research by informing best practices for the provision of online self-help for problem gambling. Trial registration ISRCTN ISRCTN13009468 . Registered on 7 July 2020.

Background: To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline.Methods: We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.e. a total of 64 components of the 33 SPIRIT items). We descriptively analysed the adherence to SPIRIT guidelines as proportion of adequately reported items (median and interquartile range [IQR]) and stratified the results by year of approval and sponsor.Results: The proportion of reported SPIRIT items increased from a median of 64.9% (IQR, 57.6-69.2%) in 2012 to a median of 72.5% (IQR, 65.3-78.3%) in 2016. Industry-sponsored RCTs reported more SPIRIT items in 2012 (median 67.4%; IQR, 64.1-69.4%) compared to non-industry-sponsored trials (median 59.8%; IQR, 46.5-67.7%). This gap between industry- and non-industry-sponsored trials increased in 2016 (industry-sponsored: median 75.6%; IQR, 71.2-79.0% vs non-industry-sponsored: median 65.3%; IQR, 51.6-76.3%).Conclusions: The adherence to SPIRIT guidelines has improved in the UK from 2012 to 2016 but remains on a modest level, especially for non-industry-sponsored RCTs. [ABSTRACT FROM AUTHOR]

Treatment of large vessel occlusion (LVO) using mechanical thrombectomy with or without intravenous thrombolysis has demonstrated better outcomes compared to medical treatment alone. Large-bore aspiration catheters have been recently introduced. Their effectiveness and safety have not been demonstrated in a randomized trial. The SUMMIT MAX study is designed to address this question.SUMMIT MAX is a randomized controlled trial where the effectiveness and safety of the large-bore Monopoint Reperfusion system (Route 92 Medical, San Mateo, CA), will be compared to the currently largest available FDA-cleared aspiration thrombectomy device the AXS Vecta Aspiration system (Stryker Neurovascular, Fremont, CA). The study is a multi-center, prospective, randomized, controlled, interventional, open label clinical trial. The hypothesis is that the effectiveness measured by the recanalization rate (modified thrombolysis in cerebrovascular infarction - mTICI) and safety measured by symptomatic intracranial hemorrhage rate (sICH) of the medical monopoint reperfusion system is non-inferior to the AXS Vecta Aspiration system.Up to 250 subjects are enrolled with at least 50% of subjects enrolled by US sites. The primary effectiveness endpoint is successful arterial revascularization defined as an mTICI score ≥ 2b after use of the assigned device adjudicated by an independent core lab. The primary safety endpoint is defined as sICH within 24 h (−8/+24) post-procedure. Secondary endpoints include successful arterial revascularization defined as a mTICI score ≥ 2b after use of the assigned device with or without adjunctive therapy; device-related serious adverse events; all asymptomatic hemorrhages; time from groin puncture to final angiogram; and rate of first pass effect defined as mTICI 2b after first pass with the assigned device stratified by age (≤85, ≥ 86).SUMMIT MAX is a randomized controlled trial comparing the effectiveness and safety of a new large bore class of aspiration devices to the currently largest FDA-cleared aspiration device available. [ABSTRACT FROM AUTHOR]

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. 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. 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. ClinicalTrials.gov : ID NCT05436548 [ABSTRACT FROM AUTHOR]

The hydroponic production of microgreens has potential to develop, at both an industrial, and a family level, due to the improved production platforms. The literature review found numerous studies which recommend procedures, parameters and best intervals for the development of microgreens. This paper aims to develop, based on the review of the literature, a set of procedures and parameters, included in a test protocol, for hydroponically cultivated microgreens. Procedures and parameters proposed to be included in the trial protocol for evaluating platforms for growing microgreens in hydroponic conditions are: (1) different determinations: in controlled settings (setting the optimal ranges) and in operational environments settings (weather conditions in the area/testing period); (2) procedures and parameters related to microgreen growth (obtaining the microgreens seedling, determining microgreen germination, measurements on the morphology of plants, microgreens harvesting); (3) microgreens production and quality (fresh biomass yield, dry matter content, water use efficiency, bioactive compound analysis, statistical analysis). Procedures and parameters proposed in the protocol will provide us with the evaluation information of the hydroponic platforms to ensure: number of growing days to reach desired size; yield per area, crop health, and secondary metabolite accumulation. [ABSTRACT FROM AUTHOR]

Background: Lumbrokinase has been widely used for patients with acute ischemic stroke (AIS) in China; however, because rigorously designed studies are lacking, safety and efficacy of lumbrokinase in the treatment of acute ischemic stroke remains largely unknown. In this multicenter, randomized, and controlled trial, we aim to compare lumbrokinase plus aspirin versus aspirin alone in patients with acute ischemic stroke.Methods: A total of 220 eligible participants will be randomized to either the intervention or control group with a 1:1 ratio. These participants must be diagnosed with acute ischemic stroke for the first time, whose symptoms appear within 72 h. Their NIHSS score must be greater than 5 and less than 15, and their age must be between 35 and 85 years old. They must have not received intravenous thrombolysis, arterial thrombolysis, or intravascular intervention. Participants in the intervention group will be treated with lumbrokinase plus aspirin for the first 90 days. Participants in the control group will use placebo plus aspirin for the first 90 days. Then, all participants will be treated with aspirin only and followed up for another 90 days (180-day follow-up). The primary outcome is the modified Rankin Scale (mRS) score. The secondary outcomes are National Institutes of Health Stroke Scale (NIHSS) score, Activity of Daily Living (ADL) Scale score, coagulation function, and serum hypersensitive C-reactive protein. The exploratory outcomes are fasting lipid panel, recurrence rate, the occurrence of cardiovascular and cerebrovascular events, and the mortality rate. Safety evaluations include liver function and kidney function, serum fibrinogen, adverse events, serious adverse events, and bleeding events. Adherence of participants will also be assessed.Discussion: This trial will investigate the efficacy and safety of lumbrokinase plus aspirin as compared to aspirin alone in the treatment of acute ischemic stroke.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000032952 . Registered on May 16, 2020. [ABSTRACT FROM AUTHOR]

Background: Individuals with mood disorders frequently experience cognitive impairment, which impacts on the long-term trajectory of the disorders, including being associated with persisting difficulties in occupational and psychosocial functioning, residual mood symptoms, and relapse. Current first-line treatments for mood disorders do little to improve cognitive function. Targeting cognition in clinical research is thus considered a priority. This protocol outlines a prospectively-registered randomised controlled trial (RCT) which examines the impact of adding group-based Cognitive Remediation (CR) to Interpersonal and Social Rhythm Therapy (IPSRT-CR) for individuals with mood disorders. Methods: This is a pragmatic, two-arm, single-blinded RCT comparing IPSRT-CR with IPSRT alone for adults (n = 100) with mood disorders (Major Depressive Disorder or Bipolar Disorder) with subjective cognitive difficulties, on discharge from Specialist Mental Health Services in Christchurch, New Zealand. Both treatment arms will receive a 12-month course of individual IPSRT (full dose = 24 sessions). At 6 months, randomisation to receive, or not, an 8-week group-based CR programme (Action-based Cognitive Remediation – New Zealand) will occur. The primary outcome will be change in Global Cognition between 6 and 12 months (treatment-end) in IPSRT-CR versus IPSRT alone. Secondary outcomes will be change in cognitive, functional, and mood outcomes at 6, 12, 18, and 24 months from baseline and exploratory outcomes include change in quality of life, medication adherence, rumination, and inflammatory markers between treatment arms. Outcome analyses will use an intention-to-treat approach. Sub-group analyses will assess the impact of baseline features on CR treatment response. Participants' experiences of their mood disorder, including treatment, will be examined using qualitative analysis. Discussion: This will be the first RCT to combine group-based CR with an evidence-based psychotherapy for adults with mood disorders. The trial may provide valuable information regarding how we can help promote long-term recovery from mood disorders. Many issues have been considered in developing this protocol, including: recruitment of the spectrum of mood disorders, screening for cognitive impairment, dose and timing of the CR intervention, choice of comparator treatment, and choice of outcome measures. Trial registration: Australian and New Zealand Clinical Trials Registry, ACTRN12619001080112. Registered on 6 August 2019. [ABSTRACT FROM AUTHOR]

Abstract Background Clearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain. Objectives and methods Aims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries. We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results. We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; and the use of routinely collected data for RCTs. Discussion The ASPIRE study and associated substudies will provide important information on the impact of measures to improve the reporting of RCT protocols and on multiple aspects of RCT design, trial registration, premature discontinuation, and non-publication of RCTs observing potential changes over time.

Abstract Background No treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain. Methods The DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators. Discussion This trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI. Trial registration Chinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019.

Background: Despite the success of gold standard cognitive-behavioral therapy for problem and disordered gambling, the majority of individuals with gambling problems do not seek or receive professional treatment. Thus, the development of less intrusive self-directed interventions has been encouraged. Bibliotherapy for problem gambling has shown promise, both alone and in combination with motivational interviews, but there is still a lack of online self-directed intervention research. The current randomized controlled trial proposes to assess the additive benefit of a single digital motivational interview delivered in conjunction with an online self-directed treatment program for problem gambling and gambling disorder.Methods: A two-arm randomized controlled trial will be conducted, wherein eligible participants (N=270) will be recruited across Canada via internet advertisements posted to several platforms. All participants will receive access to an online self-directed gambling intervention program. Participants will be randomly assigned to either complete the online program alone or receive a digital motivational interview, conducted through an online audioconferencing platform (i.e., Microsoft Teams) to supplement the online program. The primary outcomes of gambling severity, frequency, and expenditures will be tracked along with secondary outcomes (i.e., depression, anxiety, general distress, alcohol use, and online program user data) over a 24-month period. It is expected that participants in both groups will experience a reduction in symptoms across the board, but more substantial improvements will be observed in the group that receives a supplemental motivational interview.Discussion: The results of this trial will expand upon prior gambling intervention research by informing best practices for the provision of online self-help for problem gambling.Trial Registration: ISRCTN ISRCTN13009468 . Registered on 7 July 2020. [ABSTRACT FROM AUTHOR]

Introduction: The chronic neuropathic pain associated with postherpetic neuralgia (PHN) can last for several months or even many years, seriously affecting the affected person's work, sleep, mood, and daily life activities. In generaly, current treatments for PHN are at best limited and unsatisfactory, and adverse reactions are common, especially in elderly patients. Electroacupuncture (EA) is widely used clinically to manage painful diseases, but there remains a lack of evidence to support the effectiveness of EA on PHN. This study is designed to assess the efficacy and safety of EA on PHN, and to provide evidence-based medical evidence for EA treatment of PHN. Methods: This multicenter, prospective, randomized controlled trial will recruit 448 patients with PHN at seven clinical centers. Multicenter stratified variable block randomization will be used, and the eligible patients will be randomly allocated in a ratio of 1:1 to the EA group or sham EA group. The EA group will receive 4 weeks of EA treatment, given as 30-min treatment sessions, once daily, 5 times per week, for a total of 20 treatments; the sham EA group will receive sham EA treatment under the same conditions. Planned Outcomes: The primary outcome measure is the 11-point Numeric Rating Scale pain score at week 4. The secondary outcome measures, including mechanical pain threshold, pain area of PHN, average number of pain episodes, the short-form McGill Pain Questionnaire 2, Zoster Brief Pain Inventory, the Depression, Anxiety, and Positive Outlook Scale, Patient Global Impression of Change, safety of EA, and use of concomitant medications, among others. The primary analysis of the outcomes will be the mixed-effect model with repeated measurement between groups on an intent-to-treat population. Trial Registration: Clinicaltrials.gov identifier: NCT04560361. Registered 23 September 2020 (https://clinicaltrials.gov/ct2/show/NCT04560361?term=NCT04560361&draw=2&rank=1). [ABSTRACT FROM AUTHOR]

Background: Increasing social interactions through communication technologies could offer a cost-effective prevention approach that slows cognitive decline and delays the onset of Alzheimer's disease. This paper describes the protocol of an active project named “Internet-based conversational engagement clinical trial (I-CONECT)” (ClinicalTrials.gov: NCT02871921). The COVID-19 pandemic related protocol modifications are also addressed in the current paper.Methods: I-CONECT is a multi-site, assessor-blind, randomized controlled behavioral intervention trial (RCT). We aim to randomize 320 socially isolated adults 75+ years old [160 Caucasian and 160 African American participants, 50:50 split between those with normal cognition and mild cognitive impairment (MCI)] recruited from the community to either the video chat intervention group or the control group (1:1 allocation). Those in the video chat group receive a computer and Internet service for the duration of the study, which they use to video chat with study staff for 30 min/day 4×/week for 6 months (high dose), and then 2×/week for an additional 6 months (maintenance dose). Both video chat and control groups have a brief (about 10 min) telephone check-in with study staff once per week. The primary outcome is the change in global cognitive function measured by Montreal Cognitive Assessment (MoCA) from baseline to 6 months. Secondary outcomes include changes in cognition in memory and executive function domains, emotional well-being measured by NIH Toolbox emotional battery, and daily functional abilities assessed with the Revised Observed Tasks of Daily Living (OTDL-R). Eligible participants have MRIs at baseline and 6 months. Participants contribute saliva for genetic testing (optional consent), and all video chats, weekly check-in calls and neuropsychological assessment sessions are recorded for speech and language analysis. The pandemic halted research activities and resulted in protocol modifications, including replacing in-person assessment with remote assessment, remote deployment of study equipment, and revised targeted sample size.Discussion: This trial provides user-friendly hardware for the conversational-based intervention that can be easily provided at participants' homes. The trial aspires to use age and culture-specific conversational materials and a related platform developed in this trial for enhancing cognitive reserve and improving cognitive function.

Background: Antiviral therapy can lead to regression of fibrosis in chronic hepatitis B (CHB), but it has a limited effect on cirrhosis. Chinese medicines (CMs), particularly Fuzheng Huayu Tablet (扶正化瘀片, FZHY), have an antifibrotic effect in patients with CHB. Objective: To observe the safety and efficacy of adjunctive FZHY in patients with hepatitis B virus (HBV) cirrhosis, this study was designed as a randomized, placebo-controlled, double-blind, parallel assignment, multicenter trial at 20 centers in China. The total 700 naive patients will be enrolled with compensate cirrhosis due to HBV, and randomly assigned into 2 groups, receiving entecavir (0.5 mg, daily) and FZHY placebo (1.6 g, 3 times a day), or entecavir (0.5 mg, daily) and FZHY (1.6 g, 3 times a day), respectively. The primary endpoint was histological improvement at week 48. The secondary outcome is the decline values of liver fibrosis using the noninvasive methods from baseline to week 48 in each arm of the study. Adverse events such as stomach upset, headache, fatigue, dizziness, nausea will be strictly recorded. Discussion: Through this study, we hope to generate a solid evidence for the therapeutic strategy of HBV cirrhosis with a combination of anti-viral such as ETV and anti-fibrotic herbal product such as FZHY. Protocol version: Version 1.3, Date: 2014.12.4. Trial registration number: NCT02241590. [ABSTRACT FROM AUTHOR]

Abstract Background In medical oncology settings, early specialist palliative care interventions have demonstrated improvements in patient quality of life and survival compared with usual oncologic care. However, the effect of early specialist palliative care interventions in surgical oncology settings is not well studied. Methods The Surgery for Cancer with Option for Palliative Care Expert (SCOPE) Trial is a single-center, prospective, single-blind, randomized controlled trial of a specialist palliative care intervention for cancer patients undergoing non-palliative surgery. It will enroll 236 patients scheduled for major abdominal operations for malignancy, who will be randomized 1:1 at enrollment to receive usual care (control arm) or specialist palliative care consultation (intervention arm). Intervention arm patients will receive consultations from a palliative care specialist (physician or nurse practitioner) preoperatively and postoperatively. The primary outcome is physical and functional wellbeing at 90 days postoperatively. Secondary outcomes are quality of life at 90 days postoperatively, posttraumatic stress disorder symptoms at 180 days postoperatively, days alive at home without an emergency room visit in the first 90 postoperative days, and overall survival at 1 year postoperatively. Participants will be followed for 3 years after surgery for exploratory analyses of their ongoing quality of life, healthcare utilization, and mortality. Discussion SCOPE is an ongoing randomized controlled trial evaluating specialist palliative care interventions for cancer patients undergoing non-palliative oncologic surgery. Findings from the study will inform ways to identify and improve care of surgical patients who will likely benefit from specialist palliative care services. Trial registration ClinicalTrials.gov Identifier: NCT03436290 First Registered: 16 February 2018 Enrollment Began: 1 March 2018 Last Update: 20 December 2018

Abstract Background Inadequate and poor quality outcome reporting in clinical trials is a well-documented problem that impedes the ability of researchers to evaluate, replicate, synthesize, and build upon study findings and impacts evidence-based decision-making by patients, clinicians, and policy-makers. To facilitate harmonized and transparent reporting of outcomes in trial protocols and published reports, the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT) is being developed. The final product will provide unique InsPECT extensions to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) reporting guidelines. Methods The InsPECT SPIRIT and CONSORT extensions will be developed in accordance with the methodological framework created by the EQUATOR (Enhancing the Quality and Transparency of Health Research Quality) Network for reporting guideline development. Development will consist of (1) the creation of an initial list of candidate outcome reporting items synthesized from expert consultations and a scoping review of existing guidance for reporting outcomes in trial protocols and reports; (2) a three-round international Delphi study to identify additional candidate items and assess candidate item importance on a 9-point Likert scale, completed by stakeholders such as trial report and protocol authors, systematic review authors, biostatisticians and epidemiologists, reporting guideline developers, clinicians, journal editors, and research ethics board representatives; and (3) an in-person expert consensus meeting to finalize the set of essential outcome reporting items for trial protocols and reports, respectively. The consensus meeting discussions will be independently facilitated and informed by the empirical evidence identified in the primary literature and through the opinions (aggregate rankings and comments) collected via the Delphi study. An integrated knowledge translation approach will be used throughout InsPECT development to facilitate implementation and dissemination, in addition to standard post-development activities. Discussion InsPECT will provide evidence-informed and consensus-based standards focused on outcome reporting in clinical trials that can be applied across diverse disease areas, study populations, and outcomes. InsPECT will support the standardization of trial outcome reporting, which will maximize trial usability, reduce bias, foster trial replication, improve trial design and execution, and ultimately reduce research waste and help improve patient outcomes.

Abstract Background It has been suggested that vitamin D and its receptors involve in suppressing fibrogenic signaling in non-alcoholic fatty liver disease (NAFLD). However, the effect of vitamin D supplementation on fibrogenic factors has not been investigated in NAFLD individuals with steatohepatitis. This study was designed to examine the effects on vitamin D supplementation on serum levels of vitamin D receptor (VDR), fibrogenic factors, and fibrogenic microRNAs (MiR) in NAFLD patients. Methods Forty-six NAFLD patients will be recruited in this study. After block matching for sex and BMI, they will be randomly assigned to receive 4000 IU/day vitamin D or placebo for 12 weeks. Weight, height, and waist circumference will be measured. Determination of serum fibrogenic MiRs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, calcium, blood glucose, serum insulin, lipid profile, liver markers (ALT, AST, total, direct, and indirect bilirubin) will be done at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. Discussion This is the first randomized controlled trial that will determine the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors, and fibrogenic MiRs in NAFLD patients. The results of this trial will provide clinical evidence on the effectiveness of vitamin D supplementation in controlling liver fibrosis in NAFLD patients. Trial registration Iranian Registry of Clinical Trials, IRCT201405251485N13. Registered on 14 March 2017.

BackgroundSepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis.MethodsThe DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU.Participants and interventionsDIRECT will collect microbiological and pharmacokinetic samples from approximately 200 children and adults with sepsis admitted to one of four ICUs in Brisbane. In Phase 1, we will evaluate Oxford Nanopore Technologies MinION sequencing direct from blood in 50 blood culture-proven sepsis patients recruited from consecutive patients with suspected sepsis. In Phase 2, a further 50 consecutive patients with suspected sepsis will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing.Outcome measuresThe primary outcome is time to effective antimicrobial therapy, defined as trough drug concentrations above the MIC of the pathogen. Secondary outcomes are diagnostic accuracy of MinION sequencing from whole blood, time to pathogen identification and susceptibility testing using sequencing direct from whole blood and from positive blood culture broth.DiscussionRapid pathogen sequencing coupled with antimicrobial dosing software has great potential to overcome the limitations of conventional diagnostics which often result in prolonged inappropriate antimicrobial therapy. Reduced time to optimal antimicrobial therapy may reduce sepsis mortality and ICU length of stay. This pilot study will yield key feasibility data to inform further, urgently needed sepsis studies. Phase 2 of the trial protocol is registered with the ANZCTR (ACTRN12620001122943).Trial registrationRegistered with the Australia New Zealand Clinical Trials Registry Number ACTRN12620001122943

Background: Sepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis. Methods: The DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU. Participants and interventions: DIRECT will collect microbiological and pharmacokinetic samples from approximately 200 children and adults with sepsis admitted to one of four ICUs in Brisbane. In Phase 1, we will evaluate Oxford Nanopore Technologies MinION sequencing direct from blood in 50 blood culture-proven sepsis patients recruited from consecutive patients with suspected sepsis. In Phase 2, a further 50 consecutive patients with suspected sepsis will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing. Outcome measures: The primary outcome is time to effective antimicrobial therapy, defined as trough drug concentrations above the MIC of the pathogen. Secondary outcomes are diagnostic accuracy of MinION sequencing from whole blood, time to pathogen identification and susceptibility testing using sequencing direct from whole blood and from positive blood culture broth. Discussion: Rapid pathogen sequencing coupled with antimicrobial dosing software has great potential to overcome the limitations of conventional diagnostics which often result in prolonged inappropriate antimicrobial therapy. Reduced time to optimal antimicrobial therapy may reduce sepsis mortality and ICU length of stay. This pilot study will yield key feasibility data to inform further, urgently needed sepsis studies. Phase 2 of the trial protocol is registered with the ANZCTR (ACTRN12620001122943). Trial registration: Registered with the Australia New Zealand Clinical Trials Registry Number ACTRN12620001122943 [ABSTRACT FROM AUTHOR]

Zinc inhibits replication of the SARS‐CoV virus. We aimed to evaluate the safety, feasibility, and biological effect of administering high‐dose intravenous zinc (HDIVZn) to patients with COVID‐19. We performed a Phase IIa double‐blind, randomized controlled trial to compare HDIVZn to placebo in hospitalized patients with COVID‐19. We administered trial treatment per day for a maximum of 7 days until either death or hospital discharge. We measured zinc concentration at baseline and during treatment and observed patients for any significant side effects. For eligible patients, we randomized and administered treatment to 33 adult participants to either HDIVZn (n = 15) or placebo (n = 18). We observed no serious adverse events throughout the study for a total of 94 HDIVZn administrations. However, three participants in the HDIVZn group reported infusion site irritation. Mean serum zinc on Day 1 in the placebo, and the HDIVZn group was 6.9 ± 1.1 and 7.7 ± 1.6 µmol/l, respectively, consistent with zinc deficiency. HDIVZn, but not placebo, increased serum zinc levels above the deficiency cutoff of 10.7 µmol/l (p <.001) on Day 6. Our study did not reach its target enrollment because stringent public health measures markedly reduced patient hospitalizations. Hospitalized COVID‐19 patients demonstrated zinc deficiency. This can be corrected with HDIVZn. Such treatment appears safe, feasible, and only associated with minimal peripheral infusion site irritation. This pilot study justifies further investigation of this treatment in COVID‐19 patients. [ABSTRACT FROM AUTHOR]

The hydroponic production of microgreens has potential to develop, at both an industrial, and a family level, due to the improved production platforms. The literature review found numerous studies which recommend procedures, parameters and best intervals for the development of microgreens. This paper aims to develop, based on the review of the literature, a set of procedures and parameters, included in a test protocol, for hydroponically cultivated microgreens. Procedures and parameters proposed to be included in the trial protocol for evaluating platforms for growing microgreens in hydroponic conditions are: (1) different determinations: in controlled settings (setting the optimal ranges) and in operational environments settings (weather conditions in the area/testing period); (2) procedures and parameters related to microgreen growth (obtaining the microgreens seedling, determining microgreen germination, measurements on the morphology of plants, microgreens harvesting); (3) microgreens production and quality (fresh biomass yield, dry matter content, water use efficiency, bioactive compound analysis, statistical analysis). Procedures and parameters proposed in the protocol will provide us with the evaluation information of the hydroponic platforms to ensure: number of growing days to reach desired size; yield per area, crop health, and secondary metabolite accumulation.

Abstract Background It has been suggested that the antioxidant, anti-inflammatory and hypolipidemic activities of cardamom may improve diabetes. However, the effect of this spice has not been investigated in diabetic subjects. This study was planned to determine the effects of green cardamom on blood glucose, lipids and oxidative stress status in type 2 diabetic patients. Methods/design Eighty overweight or obese patients with type 2 diabetes will be selected. They will be randomly assigned to receive 3 g/d green cardamom or placebo for 10 weeks. The socio demographic, physical activity and 24-h food recall questionnaires will be collected for each subject. Weight, height and waist circumference will be measured. Determination of blood glucose, lipid profile, and oxidative stress biomarkers including serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and glutathione peroxidase (GPx) and superoxide dismutase (SOD) in red blood cells will be performed. The homeostasis model assessment-estimated insulin resistance (HOMA-IR) index and the quantitative insulin-sensitivity check index (QUICKI) will be calculated. Also, serum levels of irisin, and Sirtuin1 (SIRT1) will be measured. Discussion This trial will be the first study to explore the effects of green cardamom supplementation on glycemic control, lipid profile and oxidative stress in patients with type 2 diabetes mellitus. The results from this trial will provide evidence on the efficacy of green cardamom in type 2 diabetes mellitus. Trial registration number ( http://www.irct.ir , identifier: IRCT2016042717254N5), Registration date: 23.11.2016.

Background: No treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain.Methods: The DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators.Discussion: This trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]