Prospective Multi-Center Longitudinal Study to Validate Accuracy of the Global Anatomic Staging System (GLASS) Score in Predicting Major Acute Limb Events in Patients With Chronic Limb Threatening Ischemia Undergoing Endovascular Intervention: The PROMOTE-GLASS Study Protocol.

INTRODUCTION: Developed by the Global Vascular Guidelines committee, the Global Limb Anatomic Staging System (GLASS) is an angiographic scoring system used for quantifying infrainguinal disease extent and predicting treatment success with endovascular techniques (EVT). Currently, no other risk prediction model is available for patients with chronic limb threatening ischemia (CLTI) undergoing EVT. GLASS' validation and adoption outside academic institutions for research are limited. Thus, this longitudinal multicenter prospective study aims to examine GLASS' validity and reliability in predicting major acute limb events and overall survival (OS) in patients with CLTI undergoing EVT. METHODS AND ANALYSIS: This prospective, international, multicenter, observational study will include patients with CLTI undergoing EVT (PROMOTE-GLASS) (ClinicalTrials.gov; ID: NCT06186544) identified through routine clinical referrals and emergency visits to vascular units in participating centers. Only patients who are referred for EVT will be recruited. The primary outcomes are immediate technical success, immediate technical failure, and 1-year limb base patency. The secondary outcomes are major adverse limb events, major lower limb amputation, and OS in patients presenting with CLTI who undergo EVT up to 1 year after the procedure. Clinical and imaging data will be analyzed at the end of follow-up to validate risk prediction. This protocol outlines our approach for identifying cases, GLASS score calculation, outcome measures assessment, and a statistical analysis plan. ANTICIPATED IMPLICATIONS: PROMOTE-GLASS holds significant implications and can potentially revolutionize clinical decision-making by assisting clinicians in identifying patients who are likely to benefit from EVT. Ultimately, reduce the need for more invasive procedures and improve patient outcomes. Furthermore, PROMOTE-GLASS can provide useful information, including patient selection, for future randomized controlled trials (RCTs) investigating EVT for CLTI. PROMOTE-GLASS anticipated implications on the vascular community are rooted in its potential to improve patient care, inform future research, and address limitations in existing literature regarding CLTI treatment outcomes.

Comparing the effects of Swiss-ball training and virtual reality training on balance, mobility, and cortical activation in individuals with chronic stroke: study protocol for a multi-center randomized controlled trial.

BACKGROUND: Balance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke. METHODS: A prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30-80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up. DISCUSSION: This trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024.

Internet-based cognitive behavioral intervention for adolescents with anxiety disorders: a study protocol for a parallel three armed randomized controlled trial.

BACKGROUND: Anxiety disorders are among the most prevalent mental health concerns affecting children and adolescents. Despite their high prevalence, statistics indicate that fewer than 25% of individuals in this demographic seek professional assistance for their condition. Consequently, there is a pressing need to develop innovative interventions aimed at improving treatment accessibility. OBJECTIVES: This study aims to assess the effectiveness of Internet-delivered Cognitive Behavioral Therapy (iCBT) for adolescents with anxiety, with a specific emphasis on involving parents in the treatment process. METHODS: The study is structured as a parallel three-armed randomized controlled trial, comparing Internet-delivered Cognitive Behavioral Therapy (iCBT) with planned feedback, iCBT with on-demand feedback, and a waitlist control group, each group including 56 participants. Participants in the two iCBT conditions will undergo a 14-week treatment regimen, while those in the waitlist control group will wait for 14 weeks before starting iCBT with planned feedback. Additionally, participants in the iCBT groups will be randomly assigned to receive a booster session or not. The study design is factorial including two factors: type of therapist feedback (factor 1) and booster or no booster (factor 2). The study population comprises adolescents aged between 12 and 17 years, residing in Denmark, diagnosed with an anxiety disorder according to DSM-5 criteria. The primary outcome measures are the Youth Online Diagnostic Assessment and the Spence Children's Anxiety Scale. Assessments will occur at baseline, post-treatment, and at 3-, 6-, and 12-month follow-ups post-treatment. DISCUSSION: The findings of this study are anticipated to contribute to improving the accessibility of evidence-based treatments for adolescents with anxiety. TRIAL REGISTRATION: The study is registered at clinicalTrials.gov, under protocol ID 22/59602. The Initial release was the 16.10.2023, first posted due to technical problems 16.04.2024. https://clinicaltrials.gov/study/NCT06368557?locStr=Odense,%20Denmark&country=Denmark&city=Odense&page=2&rank=13 .

A practical assessment protocol for clinically relevant P-glycoprotein-mediated drug-drug interactions.

Background: Drug-drug interactions (DDIs) may influence the effectiveness and safety of medication treatment, which may require additional monitoring, dose adjustment or avoidance of certain drugs. DDIs involving P-glycoprotein (P-gp) affect many drugs, but current official product information is often insufficient to guide the management of these DDIs in clinical practice. The aim of this paper is to describe a protocol to assess DDIs involving P-gp and to develop and implement practice recommendations for clinically relevant P-gp-mediated DDIs that affect clinical outcomes through changes in systemic drug exposure. Methods: A combined literature review and expert opinion approach will be used according to the following seven steps: set up an expert panel (step 1), establish core concepts and definitions (step 2), select potential P-gp-modulators (i.e., P-gp-inducers and -inhibitors) and P-gp-substrates to be evaluated (step 3), select and extract evidence-based data, and present findings in standardized assessment reports (step 4), discuss and adopt classifications and practice recommendations with the expert panel (step 5), publish and integrate information and alerts in clinical decision support systems (CDSS) (step 6), (re)assessments of DDIs and potential new DDIs when new information is available or when initiated by healthcare providers (step 7). Anticipated results: The expert panel will classify potential P-gp-modulators and -substrates as clinically relevant P-gp-inducer, -inhibitor and/or -substrate and draw conclusions about which combinations of classified modulators and substrates will lead to clinically relevant DDIs. This may include the extrapolation of conclusions for DDIs where limited or no data are available, based on the pharmacological characteristics of these drugs. For (potential) DDIs that are considered to be clinically relevant, practice recommendations will be developed. Discussion: This protocol describes a standardized, evidence- and expert opinion-based assessment of P-gp-mediated DDIs that affect clinical outcomes. This approach will generate alerts with practice recommendations for clinically relevant DDIs and transparent rationales for DDIs that are considered to be irrelevant. These recommendations will improve individual patient care by supporting healthcare professionals to make consistent decisions on how to manage P-gp mediated DDIs.

Efficacy of a pharmacist care protocol to manage uncomplicated female cystitis in community pharmacies: an open-label, multicenter, randomized, controlled, cluster study: the PharmaCyst' protocol.

BACKGROUND: Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. METHODS: PharmaCyst' is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student's t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher's exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. DISCUSSION: PharmaCyst' is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. TRIAL REGISTRATION: The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

A protocol for identifying the needs related to drug use, health and social (re)integration of people living in prison within five European countries.

BACKGROUND: Compared to the general population, people living in prison are at an increased risk to experience negative (mental) health outcomes. Moreover, delinquency and drug use have many risk factors in common. A need exists for increasing the knowledge about health needs, drug use patterns and the coverage of drug-related interventions in prison within Europe. The current protocol describes the design of a study about wellbeing, drug use and related care in prison. METHODS/DESIGN: A multicentre mixed method design is implemented in five European countries (Belgium, Cyprus, Greece, Lithuania and Luxembourg). Qualitative and quantitative data collection tools are combined in order to generate complementary and comprehensive results. First, a cross-sectional survey among people living in prison is conducted. This survey is based on a model questionnaire, the European Questionnaire on Drug use among people living in Prison, developed by the European Monitoring Centre for Drug and Drugs Addiction. Second, people living in prison and people who have been recently released from prison are involved in qualitative semi-structured face-to-face interviews. The main topics of interest are the use of drugs and other health related topics such as loneliness, anxiety, depression, infectious diseases, suicide and treatment. Third, data regarding health and social reintegration measures in prison is collected through a quantitative survey addressed to the prison authorities. DISCUSSION: This study protocol presentes a European study which aims to assess drug use among people living in prison and recently released people who use drugs as well as the existing care services in prisons. Hereby, factors related to the prison environment and their needs, both inside and outside prison are taken into account. Importantly, this study protocol describes a methodology which is developed to be executed in different prison settings within different countries simultaneously. Accordingly, for each country the protocol is adjustable to specific national legal requirements, regional differences and distinct local regulations of prison administrations. However, extensive modularity inevitably comes with significant limitations of comparability and generalizability of the results.

Inclusion of phase III clinical trial costs in health economic evaluations.

INTRODUCTION: Protocol-driven trial activities contribute to the utility gain demonstrated in the phase III clinical trial of a new drug. If this utility gain cannot be distinguished from the effects of the new drug itself, protocol-driven trial costs cannot be easily dismissed for consistency reasons. This study aims to estimate the impact of including per-patient costs of phase III clinical trials on the incremental cost-effectiveness ratio (ICER). METHODS: The analysis utilized a modeling approach with secondary data from an ad-hoc literature review, considering both societal and payer perspectives. While the costs of phase III clinical trials may cancel out during the period of "normal" life-years due to the incremental cost calculation, they do not cancel out when differential early treatment termination occurs (e.g., due to differential mortality). Assuming the presence of differential mortality, per-patient phase III trial costs were calculated for the period of added life-years. These costs were then included in the ICER of a new drug, under the assumption that direct patient-related costs constitute 30-70% of the total trial costs. Capital costs were also incorporated from a societal perspective. RESULTS: Based on assumptions of $40,000 out-of-pocket expenses per patient enrolled in a phase III trial and a life expectancy gain of three months, incremental costs increased by $27,000 from a societal perspective. From a payer perspective, the estimate was $12,000. CONCLUSIONS: The costs of phase III trials are a relevant component of the ICER, and excluding it is generally not appropriate for consistency reasons. Properly considering these trial costs is essential for a comprehensive evaluation of a new drug's cost-effectiveness.

Early minimally invasive image-guided endoscopic evacuation of intracerebral hemorrhage (EMINENT-ICH): a randomized controlled trial.

BACKGROUND: Spontaneous supratentorial intracerebral hemorrhage is the deadliest form of stroke with mortality rates over 50%. Currently, no sufficiently effective treatment to improve both mortality and functional outcome rates exists. However, it seems that minimally invasive surgery, especially endoscopic surgery, might be beneficial in improving survival and functional outcome rates, yet large confirmatory studies thereof are lacking. The aim of this trial is to compare whether early minimally invasive endoscopic surgery leads to improved functional outcome rates compared to the best medical treatment. METHODS: This is a prospective, parallel-arm, outcome assessor blinded multicenter trial across Switzerland. Endoscopic surgery will be compared to the best medical treatment in a 1:1 randomization over a total time of 12 months. The primary outcome is defined as improved functional outcome (mRS < 3) after 6 months; secondary outcomes include mortality and morbidity rates as well as patient reported outcomes and the temporal evolution of serum biomarkers for brain damage. DISCUSSION: Currently, large, randomized trials assessing the role and potential effect of early endoscopic surgery in intracerebral hemorrhage are lacking. Potential practical and methodological issues faced in this trial are patient enrollment, adherence to the hematoma evacuation technique used, potential patient cross-over, and the adaptive Bayesian statistical design. Nonetheless, this trial would be among the first to research the effects of early minimally invasive endoscopic surgery for SSICH and can provide class I evidence for future treatment options in intracerebral hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05681988. Registered on January 3, 2023.

Effect of Telenursing on Supportive Care Needs in Patients with Melanoma and Lung Cancer on Targeted Therapies: A Randomised Controlled Trial Study Protocol.

Background: Telenursing comprises a set of tools and interventions enabling nurses to provide remote care. This study aims to assess the impact of telenursing interventions on the supportive care needs of patients with melanoma and lung cancer who are receiving targeted therapies. Methods: This six-month monocentric, double-arm, randomised, controlled trial study protocol will assess the effect of telenursing on the supportive care needs (primary outcome) in 40 patients (20 in each group) after one month. The secondary outcomes will be monitored at baseline, one, three and six months: supportive care needs (at three and six months), therapeutic adherence, quality of life, usability and satisfaction, performance status, patient-reported outcomes and main adverse events. The SPIRIT guidelines will be used for the reporting. Results: The results from this trial will assess the impact of a telenursing intervention on cancer care. Conclusions: This trial could be a starting point for more extensive studies on telenursing interventions to promote nurses' skills, as well as the quality and safety of care in patients with cancer, highlighting the impact of more outstanding nursing contributions on cancer care. Trial and Protocol Registration: The study protocol was approved by the relevant Italian Ethics Committee Lazio Area 5 (RS1851/23, 2773; 6 September 2023) and was registered on ClinicalTrials.gov (trial registry number NCT06254196).

Parent Education and Counseling (PairEd-C) Intervention to Improve Family-Centered Care: Protocol for a Prospective Acceptability Study Using the Theoretical Framework of Acceptability.

BACKGROUND: Family-centered care (FCC) is an intervention approach based on a respectful relationship between family and health care providers (HCPs) to ensure the health and well-being of children and their families. Although HCPs have a better perception of FCC, the level of its implementation is low. Reasons for low implementation include limited understanding, lack of training, and lack of implementation guidelines and tools to support implementation. Thus, we developed the Parent Education and Counseling (PairEd-C) intervention to improve FCC in pediatric oncology settings and assess its acceptability. OBJECTIVE: The objective of this study is to assess the prospective acceptability of the PairEd-C intervention using the theoretical framework of acceptability (TFA) in the pediatric oncology department in a tertiary hospital in Ethiopia. METHODS: The study was conducted using an exploratory qualitative study design. We aimed to recruit 10 to 15 participants for the in-depth interview. The study participants were health service leaders working in child cancer, HCPs, social workers, and parents of children with cancer. The intervention was developed using the integration of the first phase of the Medical Research Council (MRC) framework for developing and testing complex interventions and the behavior change wheel (BCW) framework. The main PairEd-C intervention components align with the intervention functions of education, persuasion, training, environmental restructuring, modeling, and enablement, which were intended to improve FCC in the pediatric oncology unit by providing structured and comprehensive education and counseling of parents of children with cancer. The intervention was implemented by providing training for the health care team, facilitating discussion among HCPs and setting a shared plan, improving the commitment of the health care team, providing education for parents, improving parents' capacity to attend the intervention sessions, arranging discussion among parents of children with cancer, and provision of education and counseling on distress. The HCPs working in the unit received training on the designed intervention. The trained educators and the health care provider delivered the intervention. Data will be analyzed using deductive thematic coding with a framework analysis technique based on the 7 TFA constructs. Atlas ti. version 9 will be used for data analysis. RESULTS: Funding was acquired in 2017, and ethical clearance for conducting the study was obtained. We conducted the interviews with the study participants from December 2023 to January 2024. As of the acceptance of this protocol (June 2024), 12 study participants were interviewed. The data analysis process was started subsequently, and the manuscript will be completed and submitted for publication in early 2025. CONCLUSIONS: This acceptability study is expected to show that the designed intervention is acceptable to study participants, and the findings will be used to improve the intervention before progressing to the next step of our project. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54914.

The TELEhealth Shared decision-making COaching and navigation in Primary carE (TELESCOPE) intervention: a study protocol for delivering shared decision-making for lung cancer screening by patient navigators.

BACKGROUND: Lung cancer screening (LCS) can reduce lung cancer mortality but has potential harms for patients. A shared decision-making (SDM) conversation about LCS is required by the Centers for Medicare & Medicaid Services (CMS) for LCS reimbursement. To overcome barriers to SDM in primary care, this protocol describes a telehealth decision coaching and navigation intervention for LCS in primary care clinics delivered by patient navigators. The objective of the study is to evaluate the effectiveness of the intervention and its implementation potential, compared with an enhanced usual care (EUC) arm. METHODS: Patients (n = 420) of primary care clinicians (n = 120) are being recruited to a cluster randomized controlled trial. Clinicians are randomly assigned to 1) TELESCOPE intervention: prior to an upcoming non-acute clinic visit, patients participate in a telehealth decision coaching and navigation session about LCS delivered by trained patient navigators and nurse navigators place a low-dose CT scan (LDCT) order for each TELESCOPE patient wanting LCS, or 2) EUC: patients receive enhanced usual care from a clinician. Usual care is enhanced by providing clinicians in both arms with access to a Continuing Medical Education (CME) webinar about LCS and an LCS discussion guide. Patients complete surveys at baseline and 1-week after the scheduled clinic visit to assess quality of the SDM process. Re-navigation is attempted with TELESCOPE patients who have not completed the LDCT within 3 months. One month before being due for an annual screening, TELESCOPE patients whose initial LCS showed low-risk findings are randomly assigned to receive a telehealth decision coaching booster session with a navigator or no booster. Electronic health records are abstracted at 6, 12 and 18 months after the initial decision coaching session (TELESCOPE) or clinic visit (EUC) to assess initial and annual LCS uptake, imaging results, follow-up testing for abnormal findings, cancer diagnoses, treatment, and tobacco treatment referrals. This study will evaluate factors that facilitate or interfere with program implementation using mixed methods. DISCUSSION: We will assess whether a decision coaching and patient navigation intervention can feasibly and effectively support high-quality SDM for LCS and guideline-concordant LCS uptake for patients in busy primary care practices serving diverse patient populations. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT05491213) on August 4, 2022. PROTOCOL VERSION: Version 1, April 10, 2024.

Acupuncture for Residual Dizziness After Successful Repositioning Maneuvers in Patients with Benign Paroxysmal Positional Vertigo: Study Protocol for a Randomized Noninferiority Trial.

Introduction: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo among adults. Successful treatment often requires an appropriate canalith repositioning procedure (CRP), which has proven effective in the treatment of BPPV. However, some patients experience residual dizziness (RD) after CRP, affecting their daily activities and quality of life. Although oral betahistine is a common clinical treatment for RD, some patients may discontinue this medication due to adverse effects. Conversely, acupuncture has demonstrated efficacy in treating dizziness with minimal adverse effects. However, to date, no trials have directly compared the efficacy of acupuncture and betahistine in treating RD. Our goal was to assess the noninferiority of acupuncture in treating RD compared with the commonly used oral betahistine treatment. Methods and Analysis: A randomized, controlled, non-inferiority trial was conducted to compare the effectiveness of acupuncture and betahistine in patients with BPPV who experience RD after a successful CRP. Eighty-four participants were randomly assigned to two treatment groups, each receiving either acupuncture or betahistine. The assessors and statisticians were blinded to treatment allocation. The primary outcomes were the response rate and change in vertigo level, and secondary outcomes included Visual Analog Scores and the presence and change in depressive symptoms among patients. Scale measures were recorded at baseline, 2, 4, and 12 weeks after randomization. This trial aims to provide causal evidence supporting the non-inferiority of acupuncture therapy relative to oral betahistine, offering an alternative treatment avenue for patients intolerant to betahistine. Ethics and Dissemination: Ethics approval was obtained from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, with permission number 2023-095-KY. Written informed consent was obtained from the enrolled patients.

Diet and the gut microbiota-immune axis in the context of perinatal mental health: Protocol for a prospective cohort study.

BACKGROUND: Physiological and psychosocial changes experienced by women during the perinatal period may put them at risk for postpartum mental health disturbances. Accumulating evidence suggests that dietary patterns may influence mental health through the modulation of the gut microbiota and its effects on host immune activity. Thus, targeting the gut microbiota via dietary intake could serve as both a preventative and therapeutic strategy in improving perinatal mental health. OBJECTIVES: Here, we present a protocol for a prospective cohort study that primarily aims to determine if diet quality during pregnancy is protective against postpartum depression severity. Secondary objectives will examine if microbiota- and blood-based inflammatory markers may be associated with the relationship between prenatal diet quality and postpartum depression severity, as well as with associations between additional dietary and mental health outcomes. METHODS AND ANALYSIS: Dietary patterns and mental health symptoms will be documented in 100 pregnant women at 4 time points during pregnancy and postpartum. Participants will also provide stool and blood samples at the same time points to determine microbiota composition and predicted function and inflammatory factors, respectively. Stool microbiota will be analyzed using 16S ribosomal RNA gene sequencing and bioinformatics tools (QIIME 2/PICRUSt2). Inflammatory factors will be determined using high-sensitivity antibody-based immunoassays. Statistical analyses will include linear mixed models and hierarchical linear mixed effect models. ETHICS: The study was approved by the Research Ethics Boards of the Royal Ottawa Health Care Group (#2022002) and of the University of Ottawa (#H-06-22-8013). Informed consent will be obtained from all participants before their enrollment. DISCUSSION: Findings from this study will help develop evidence-based dietary recommendations and potential interventions for women susceptible to or suffering from postpartum mental health issues that are accessible, noninvasive, and have potential to play a role in prevention and treatment.

Acupuncture-assisted therapy for prolonged disorders of consciousness: study protocol for a randomized, conventional-controlled, assessor-and-statistician-blinded trial.

Background: Acupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients. Methods: A single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day's rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively. Discussion: This trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300076180.

Supporting Carers: Study Protocol of a Meta-Review of Psychosocial Interventions for Carers of People With Cancer.

BACKGROUND: While there is a clear need for psychosocial interventions that promote the well-being of carers of patients with cancer, the corresponding evidence base is disparate, complex, and difficult for end users to navigate and interpret. Carers remain undersupported with a lack of dedicated, effective, evidence-based programs. We will conduct a meta-review to synthesize this evidence and determine the state of science in this field. OBJECTIVE: This study aims to address the question, "what psychosocial interventions are available to promote the well-being of carers for people with cancer?" METHODS: A meta-review will synthesize the relevant reviews of psychosocial interventions that have been developed and evaluated with carers for people with cancer. A total of 4 electronic databases (PsycInfo, MEDLINE, CINAHL, and Cochrane Database of Systematic Reviews) will be searched for reviews published between January 2013 and December 2023. A team-based approach will be taken for screening and assessment of the returned records against the eligibility criteria to determine inclusion. Included reviews will be critically appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Relevant data on study characteristics, carer and patient populations, intervention details, and psychosocial outcomes will be extracted, synthesized, and the findings will be presented in a narrative format. RESULTS: It is anticipated that the study will be completed by October 2024. CONCLUSIONS: Ensuring that carers have access to evidence-based programs that promote their well-being as they care for loved ones is critical. This meta-review will contribute to program development and translation efforts by providing a clear picture of the intervention evidence base of carers of patients with cancer and identifying notable strengths, weaknesses, and gaps across the literature. The findings are anticipated to offer future directions to advance research in the field. TRIAL REGISTRATION: PROSPERO (CRD42023403219); https://tinyurl.com/4tnzv49s. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56403.

Efficacy of methylene blue in refractory septic shock: study protocol for a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Septic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors. METHODS: This study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors. DISCUSSION: This protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making. TRIAL REGISTRATION: This clinical trial has been registered at ChiCTR ( https://www.chictr.org.cn/ ) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

A custom tailored, evidence-based, theory-informed intervention for healthcare professionals to prevent burnout (LAGOM): study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Healthcare professionals in hospitals are exposed to a high level of professional stress, time pressure, workload, and often times poor organizational support. This makes them especially susceptible to burnout. In this pragmatic randomized controlled trial, we test the hypothesis that participation in a 9-week program (LAGOM) that was designed in close collaboration with healthcare professionals, incorporating both individual and organizational aspects reduces emotional exhaustion in healthcare professionals (primary outcome). METHODS: Eighty four nurses and physicians working at the Charité - Universitätsmedizin Berlin and the Immanuel Hospital Berlin are automatically randomized to the LAGOM program (n = 42) or to usual care (n = 42) in a one-to-one allocation rate. The primary outcome emotional exhaustion is measured by the Maslach Burnout Inventory-Human Services Survey at baseline, post-intervention, and 1-month follow-up via an online survey. Secondary outcomes include depersonalization, personal accomplishment, subjective stress, mental well-being, self-care, self-efficacy, working conditions, mindfulness, and adverse events. Electrophysiological measures for heart rate variation analysis are captured. The PRECIS-2 tool is used to characterize the degree of pragmatism in our trial. Data analysis and primary intention-to-treat analysis using repeated measures analysis of variance are performed blind to intervention allocation. Per-protocol, subgroup, and secondary outcome analyses are conducted exploratively. An advisory board consisting of various stakeholders accompanies the study process. DISCUSSION: If LAGOM proves to be effective in reducing symptoms of burnout, the program could make an important contribution to tackling the problem of the very high burnout rates among healthcare professionals and become an integral part of preventive services offered by hospitals. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00034060. Registered 31 May 2024.

A mixed methods study examining the impact of primary health care financing transitions on facility functioning and service delivery in Kenya: a study protocol.

Background: Kenya has experienced several health financing changes that have implications for financing primary healthcare (PHC). These include transitions from funding by two key donors (the World Bank and the Danish International Development Agency (DANIDA)) and the abolishment of conditional grants that were earmarked for financing primary healthcare facilities. This protocol lays out study plans to evaluate the impact and implementation experience of these financing changes on PHC facility functioning and service delivery in Kenya. Methods/design: A sequential mixed methods design will be applied to address our research objectives. Firstly, we will perform a document review to understand the evolution of policy changes understudy. Second, we will conduct an interrupted time series analysis across all 47 counties in Kenya to assess these financing changes' impact on health service utilization in all public primary healthcare facilities (level 2 and 3 facilities). Data for this analysis will be obtained from the Kenya Health Information System (KHIS). Third, we will carry out in-depth interviews with health financing stakeholders at the national, county, and health facility levels to examine their perceptions of the experiences with these changes in health financing. Discussion: This mixed methods study will contribute to evidence on the sustainability of financing primary healthcare in low and middle-income countries facing financing changes and donor transitions.

Evaluating the Impact of Primary Healthcare Financing Transitions on PHC Facilities in Kenya. In 2020, funding allocated for public primary healthcare (PHC) facilities was eliminated as conditional grants in Kenya. Through the support of the PHC-specific conditional grants, public PHC facilities would provide free healthcare services to patients. Additionally, the World Bank and Danish International Development Agency (DANIDA) are transitioning from providing funding support to PHC facilities in Kenya. DANIDA's PHC support grant will be terminated at a 25% yearly rate over four years, coinciding with the end of the World Bank Transforming Health Systems programme for Universal Health Care. Before obtaining the financing, these grants had county-specific requirements known as service performance objectives. These financing changes will likely impact the level of financing that PHC health facilities will access. Hence, the proposed study examines the impact of these financing changes on PHC facilities functioning and service delivery in Kenya, as well as the implementation experience of stakeholders in the health sector.

Conception vessel acupuncture research regularity in the treatment of diminished ovarian reserve: a multi-center, large-sample prospective cohort study protocol.

Background: Diminished ovarian reserve (DOR) refers to a decrease in the number or quality of oocytes in the ovarian cortex, which is a degenerative disease of the reproductive system, and can further develop into premature ovarian failure. There are few studies on acupuncture and moxibustion for DOR, which are still in the exploratory stage. Methods/design: This study was a real-world case registry study. According to whether the subjects received conception vessel acupuncture or not, they were divided into the basic treatment combined with conception vessel acupuncture group and the basic treatment group. A total of 1221 patients with DOR were enrolled and treated for 12 weeks. The percentage of patients with ≥30% improvement in anti-Müllerian hormone (AMH) was evaluated at the end of week 12. Secondary outcomes included Antral follicle count (AFC), modified Kupperman scale, basal FSH level, LH level, FSH/LH ratio, positive pregnancy, clinical pregnancy, early spontaneous abortion, ongoing pregnancy, and ectopic pregnancy. Discussion: This study provides clinical evidence and theoretical support for the treatment of DOR with conception vessel acupuncture and moxibustion, so as to guide and improve the efficacy of acupuncture and moxibustion. Trial registration: Acupuncture-Moxibustion Clinical Trial Registry ChiCTR2400080471. Registered on 30 January 2024.

The anticoagulation one year after ablation of atrial fibrillation in patients with atrial fibrillation (ALONE-AF) trial: Study protocol.

Background: The ideal long-term antithrombotic strategy for patients after successful catheter-based atrial fibrillation (AF) ablation is still uncertain. Presently, practices vary, and the advantages of oral anticoagulation (OAC) for the post-ablation population are not clearly established. To date, no randomized trials have addressed this therapeutic question. This study aimed to evaluate whether no OAC therapy is superior to apixaban in reducing the risk of stroke, systemic embolism, or major bleeding among patients without apparent recurrent atrial arrhythmias for at least 1 year after their AF ablation procedure. Methods: The ALONE-AF trial is a prospective, multicenter, open-label, randomized study with blinded outcome assessment. Patients with AF who have at least one non-gender stroke risk factor (as determined by the CHA2DS2-VASc score) and no documented recurrences of atrial arrhythmia for at least 12 months post-ablation will be randomly assigned to apixaban 5 mg b.i.d. or no OAC therapy. The primary endpoint is a composite outcome of stroke, systemic embolism, and major bleeding. Key secondary outcomes include clinically relevant non-major bleeding, all-cause mortality, myocardial infarction, transient ischemic attack, quality of life, and frailty analysis. Participants will be followed for a period of 2 years. The estimated total sample size is 840 subjects, with 420 subjects in each arm. Conclusion: The ALONE-AF trial aims to provide robust evidence for the optimal anticoagulation strategy for patients with stroke risk factors following successful AF ablation.