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AbstractAs the COVID-19 pandemic spread across the world, immunocompromised individuals such as people with HIV (PWH) may have faced a disproportionate impact on their health and HIV outcomes, both from COVID-19 and from the strategies enacted to contain it. Based on the SPIRIT guidelines, we describe the protocol for an international multisite observational study being conducted by The International Nursing Network for HIV Research, with the Coordinating Center based at the University of California, San Francisco (UCSF) School of Nursing. Site Principal Investigators implement a standardized protocol to recruit PWH to complete the study online or in-person. Questions address demographics; HIV continuum of care indicators; mental and social health; COVID-19 and vaccination knowledge, attitudes, behaviors, and fears; and overall outcomes. Results of this study will contribute to knowledge that can inform responses to future public health crises to minimize their impacts on vulnerable populations such as PWH.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 opinionbased 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Community Health Workers, promotores, and navigators (henceforth, CHWs) emerged as critical members of the public health workforce addressing social, economic, and health inequities worsened by the COVID-19 pandemic. While there is increased appreciation for and utilization of CHW models, and recognition of the importance of tailoring and innovating these models during the pandemic, few studies have examined the processes of change by which CHW models operated during the COVID-19 pandemic and factors that facilitated or constrained CHW health equity efforts. This protocol paper describes and reflects on the research methodology used in our qualitative study focused on CHWs. The CATALYST study aims to examine the roles that CHWs served during the COVID-19 pandemic and facilitators and barriers related to CHW health equity strategies. This qualitative study incorporates the lived experiences of CHWs, low-income communities of color whom CHWs engaged, and institutional representatives and policymakers familiar with locally implemented CHW models during the pandemic. Through a community-based participatory research process, this study involves an abductive qualitative approach to data collection and analysis. We integrate community member expertise alongside CHW and health equity frameworks in designing the research questions and data collection process. Additionally, we use an analytic approach that combines inductive (drawn from qualitative data) and deductive codes (drawn from theoretical frameworks and practice-based evidence integrated through a participatory research process) and nimbly leverages flexible coding to address inductive themes and practice-based questions. Our collaborative process offers concrete strategies to develop qualitative research protocols with community partners, with evidence used to inform policy, programmatic, and relational changes to support and amplify CHW models to promote community health and health equity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Discussion Trial Registration Scientific research has consistently emphasised the high levels of stress encountered by family caregivers of individuals living with dementia. However, conventional self‐help approaches remain underutilised. The ‘Diversity‐On’ study addresses this issue. The study employs a storytelling approach to develop and evaluate an online self‐help program that is participatory and diversity‐sensitive, thereby ensuring congruence with diverse identities and lifeworlds.The study uses a mixed‐methods design, comprising the allocation and implementation of the intervention, the development of stories, a process evaluation (N = 20) and an outcome evaluation (quantitative: N = 130, qualitative: N = 20). The study's primary focus is its comprehensive participatory approach, integrated throughout the research process. The study is dependent on the input of a number of stakeholders, all of whom are committed to advocating for the concerns of patients.Given its participatory methodology and intersectional perspective, the ‘Diversity‐On’ study is anticipated to yield a number of significant outcomes. The study has the potential to empower family caregivers of individuals living with dementia who are under high stress, empowering them to take part in self‐help groups despite multiple barriers, thus alleviating their burden. Additionally, it has the capacity to promote the well‐being of caregiving relatives who are providing care and are experiencing high levels of stress. The study's objective is to maintain home care arrangements for as long as possible, in accordance with the values and preferences of care recipients and their families. The study intends to develop and assess a customised online self‐help resource that is suitable for a diverse range of users and that remains accessible beyond the study period.The project is subsequently registered in ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. Methods: The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. Discussion: Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. Trial registration: ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341 [ABSTRACT FROM AUTHOR]

Introduction: A prosthetic limb technology has grown tremendously in the past few years, offering hope for increased functioning and better quality of life to people with upper limb amputation. However, the phenomenon of prosthetic rejection remains a challenge, particularly among paediatric users because of the prosthesis-related factors in functionality and appearance as well as the training and prosthetics services. Aim: One solution is to involve an Occupational therapist (OT), engineer (3D printed prosthesis expert), prosthesis user (experienced child), and their parent in designing the prosthesis. However, these collaborations have not been implemented as intended in the engineering field. Hence, this current study aimed to report on a comprehensive study protocol based on 3-corner collaborative design in order to develop and improve three-dimensional (3D) printed upper limb prosthesis design and a home-based self-care training module. Methods: The 3D upper limb prosthesis and training module was designed using a 3-corner collaborative design (participatory design approach). The participatory design process (involved experienced children with transradial deficiency; parent; OT and engineer) and data collection techniques included semi-structured interviews, participant observation, the Delphi technique, and face-to-face discussion. Discussion: The 3-corner collaborative design (participatory design approach) process helped us design an interactive platform to design a new 3D printed upper limb prosthesis features such as sizes, weight, control, and obtaining information on training that possible to manufacture tailor-made, customized, and personalized parts according to the users' deficiency; making them more suitable for the development of prostheses for each user, which must be customized. [ABSTRACT FROM AUTHOR]

This paper describes the research protocol for the Educational and Developmental Gains in Early Childhood (EDGE) Study, which will examine the implementation of two years of funded kindergarten prior to the first year of school in Victoria, Australia. EDGE will examine whether children's language, cognitive, social-emotional, and behavioural outcomes are improved after two years of kindergarten compared to one year. The experiences of (and impacts on) teachers, service leaders, and families will also be examined. The study includes a cross-sectional cohort of 95 early childhood education and care (ECEC) services, and an embedded longitudinal observational cohort of children attending these services. Case studies of 15–20 ECEC services will also be collected, in addition to interviews with policy stakeholders. [ABSTRACT FROM AUTHOR]

Aim: Young women with type 1 diabetes are a high‐risk population for eating disorders (ED). Prevention programs are lacking. In young women without diabetes, the Body Project has produced reductions in ED risk factors, ED symptoms and future ED onset. Therefore, the Body Project was adapted to type 1 diabetes, the Diabetes Body Project (DBP). In this protocol, we describe the multi‐site randomized controlled trial (RCT) to evaluate efficacy of the DBP. Methods: This is an ongoing RCT with four sites (Europe and US). In total 280, 14–35 year‐old, women with type 1 diabetes ≥1 year and some level of body image concerns will be recruited in 2023. Participants are randomized to either virtual DBP groups or an educational control. The study constitutes 5 measurement points distributed over 2 years. The primary aim is to test if DBP will produce significantly greater reductions in ED behaviours, ED symptoms and future ED onset. The secondary aim is to test if DBP has significantly greater improvements in diabetes distress, quality of life and glycaemic outcomes. Results: We expect that DBP will be more efficacious in reducing ED behaviours, ED symptoms and ED onset compared to the control condition. Additionally, we hope to gain new knowledge on how DBP may affect diabetes‐related outcomes. Conclusions: If DBP proves efficacious, it has potential for immediate, clinical implementation at low‐cost and may contribute to broad prevention of future ED onset among young women with type 1 diabetes. ClinicalTrials.gov Identifier: NCT05399446. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking has major detrimental effects on oral health. Tobacco interventions in dental settings are effective, but rarely delivered. The American Dental Hygienists Association recommends that oral health providers: Ask patients about tobacco use, Advise quitting tobacco use, and Refer to state quitlines (Ask-Advise-Refer; AAR). While AAR connects patients to counseling, it does not directly connect patients to medication. Nicotine replacement therapy sampling (NRTS) is an empirically supported intervention to provide starter packs of nicotine replacement therapy (NRT) to people who smoke. NRTS combined with AAR could be an effective tobacco treatment intervention for dental settings. Methods: This manuscript describes the study protocol for the Free Samples for Health (FreSH) study, a group randomized clinical trial testing the effectiveness of NRTS + AAR vs. AAR alone on long-term smoking abstinence. Fifty dental practices in the Midwest and Northeast nodes of the National Dental Practice-Based Research Network are randomly assigned to provide AAR and either a 2-week supply of 14-mg nicotine patches and 4-mg nicotine lozenges (NRTS condition) or an electric toothbrush (ET condition). Approximately 1,200 patients who currently smoke—regardless of interest in quitting— are recruited during dental visits. Participants complete a baseline survey in-person, then after visit, 1-, 3-, and 6-month follow-up surveys remotely. The primary outcome is carbon monoxide-confirmed 7-day point prevalence abstinence from combustible tobacco measured at 6 months post-enrollment. Secondary outcomes include: 24-h intentional quit attempts, change in cigarettes smoked per day, NRT utilization, attitudes toward NRT, intention to use NRT, and intention to quit smoking. A key informant process evaluation and cost effectiveness analysis will provide information for future implementation of NRTS. Discussion: This is the first clinical trial to assess the effectiveness of NRTS on promoting smoking cessation in dental settings. If effective, this treatment could be implemented to increase the provision of smoking cessation interventions in dental settings to provide an additional treatment access point for people who smoke. Trial Registration. Registered at ClincalTrials.gov (NCT05627596) on 11/25/2022. [ABSTRACT FROM AUTHOR]

Background: This randomized clinical trial protocol aimed to investigate the comparative efficacy of an enhanced recovery after surgery (ERAS) protocol versus traditional perioperative care programs in patients with intradural extramedullary spinal tumors. Methods: The study included 180 patients aged 18–80 years, who were randomly assigned to two groups: Group A receiving traditional perioperative care and Group B receiving accelerated rehabilitation perioperative care. The nurse responsible for patient care was informed of the group assignment, but the patients themselves remained blinded to the intervention. The primary outcome measure was the Karnofsky Performance Scale score, which assessed functional status. The secondary outcomes included the Japanese Orthopedic Association Scale, Numeric Pain Rating Scale, length of postoperative hospital stay, duration of urethral catheterization, patient satisfaction questionnaire, and complication rates. Follow-up assessments were conducted telephonically 1 month, 3 months, and 6 months after the surgery. Discussion: This study protocol provided a structured approach to assess the potential benefits of ERAS during the perioperative period for patients with intradural extramedullary tumors, aiming to improve patient outcomes and overall care efficiency. Trial registration: This study has been registered with the China Clinical Trials Registry (Project No: ChiCTR2200063347). Registered on September 5 2022. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) entails physical, psychological, and social burden and holds a significant impact on quality of life. Experiential avoidance, cognitive fusion, shame, and self-criticism have been identified as possible therapeutic targets for improving mental health in people with IBD. Traditional face-to-face psychological therapy continues to provide obstacles for patients seeking assistance. Online psychological therapies centered on acceptance, mindfulness, and compassion have been shown to improve psychological distress in other populations. Objective: This paper presents the study protocol of a two-arm Randomized Controlled Trial (RCT) of an ACT and compassion-based, online intervention -- eLIFEwithIBD - on the improvement of psychological distress, quality of life, work and social functioning, IBD symptom perception, illness-related shame, psychological flexibility, and self-compassion. Methods: The eLIFEwithIBD intervention is an adaptation of the LIFEwithIBD programme (delivered through an in-person group format) and entails an ACT, mindfulness, and compassion-based intervention designed to be delivered as an e-health tool for people with IBD. This protocol outlines the structure and contents of the eLIFEwithIBD intervention. Participants were recruited by an advertisement on the social media platforms of Portuguese Associations for IBD in January 2022. A psychologist conducted a brief interview with 80 patients who were interested in participating. Fifty-five participants were selected and randomly assigned to one of two conditions [experimental group (eLIFEwithIBD + medical TAU; n = 37) or control group (medical TAU; n = 18)]. Outcome measurement took place at baseline, post-intervention, and 4-month followup. All analyses are planned as intent-to-treat (ITT). Results: The eLIFEwithIBD intervention is expected to empower people with IBD by fostering psychological strategies that promote illness adjustment and well-being and prevent subsequent distress. The eLIFEwithIBD aims to gain a novel and better understanding of the role of online contextual behavioral interventions on improving the quality of life and mental health of people with IBD. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05405855, NCT05405855. [ABSTRACT FROM AUTHOR]

This editorial emphasizes the importance of high-quality study protocols in psycho-oncology research. Study protocols allow for the evaluation of research methods and can help reduce bias in empirical evidence. The editorial introduces a research topic that includes study protocols on interventions in psycho-oncology, the assessment of unique perspectives of cancer-affected individuals, and the precision assessment of cancer-related burdens. The aim of this research topic is to inform future directions in psycho-oncology care and research. The text also discusses the value of study protocols in assessing mental disorders, psychosocial distress, and the need for psychosocial support in cancer patients and their relatives. It mentions the development of a pediatric chronic graft-vs.-host disease symptom scale and a companion caregiver-proxy measure. The text concludes by providing resources for researchers interested in writing study protocols. [Extracted from the article]

Background: Rheumatoid arthritis (RA) is a chronic disease with a global prevalence rate of 1%. Patients with RA often associate specific foods like tomatoes and eggplants with adverse symptoms. These plants contain solanine, which could potentially contribute to bone and joint damage. Despite patient reports, there is a lack of randomized controlled trials (RCTs) investigating the effects of nightshades on patients with RA. This study aims to assess the effect of nightshade elimination diet (NED) on inflammatory and rheumatologic marker levels in rheumatoid arthritis patients for the first time. Methods: A single-blinded controlled trial will be conducted to evaluate the effect of an NED on 40 participants over 8 weeks (2 months). Participants will be equally divided into intervention and placebo groups. Both groups will receive general anti-inflammatory dietary recommendations, with the intervention group undergoing an NED during the study. Clinical symptoms will be assessed using questionnaires, and blood samples will be collected to measure relevant indicators. Discussion: This RCT signifies a groundbreaking exploration into NED effects on RA markers, potentially initiating crucial discussions in the field. Its outcomes could serve as a cornerstone for larger and more robust trials, offering pivotal insights to nutritionists and physicians for the nuanced management of patients with RA. Trial registration: Iranian Registry of Clinical Trials IRCT20230220057465N1 (https://irct.behdasht.gov.ir/trial/68959). Registered on 8 April 2023. [ABSTRACT FROM AUTHOR]

Background: Gaining insight into the obstacles holding women from engaging in physical activity during pregnancy is crucial for planning future interventions to enhance their physical activity during this period. This research aims to identify barriers to physical activity among pregnant women using an explanatory sequential mixed-methods approach. The study protocol... [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions. Methods: This multicenter, prospective, non-randomized, observational study will be conducted in real-world settings. A total of 204 eligible patients will be consecutively enrolled in the study. Patients in the combination treatment group will receive Yinmei Kuijie decoction in combination with 5-ASA, whereas those in the control group will be treated with 5-ASA alone. The primary endpoint will be a clinical response at week 12, defined as a ≥3 point and ≥30% reduction from baseline in the Mayo total score with ≥1 reduction in rectal bleeding or rectal bleeding score = 0 or 1. Secondary efficacy endpoints at week 12 will include health-related quality of life, mucosal healing, and inflammation indicators. Conclusion: The results of this study may provide evidence of the efficacy and safety of Yinmei Kuijie decoction combined with 5-ASA in treating patients with mildly to moderately active UC under real-world principles. The results will provide a basis for further confirmatory studies on the efficacy of Yinmei Kuijie decoction.

Abstract 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.

Abstract 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.

Abstract 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 .

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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.

Abstract Background Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. Methods The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. Discussion Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. Trial registration ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341

Background and Aims: Tenecteplase is used as the standard of care treatment for thrombolysis in acute ischemic stroke (AIS) patients within 4.5 h of symptom onset. Documented reports were less certain to claim the benefits of it in an extended window period. EAST-AIS (CTRI/2022/03/040718) trial is designed to determine the success rate of thrombolysis in an extended window period for good clinical outcomes. Study Design: It is a randomized, placebo-controlled trial of tenecteplase administered within 4.5–24 h of stroke onset (with or without large vessel occlusion) based on evidence of salvageable tissue through baseline computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) scan. Criteria of patient inclusion are as follows: patients of both genders (male and female), age >18 years, pre-stroke modified Ranking Scale (mRS) 5, CTP showing penumbra–ischemic core ratio >1.8, absolute difference in volume >10 ml, and ischemic core volume

Abstract Background Cigarette smoking has major detrimental effects on oral health. Tobacco interventions in dental settings are effective, but rarely delivered. The American Dental Hygienists Association recommends that oral health providers: Ask patients about tobacco use, Advise quitting tobacco use, and Refer to state quitlines (Ask-Advise-Refer; AAR). While AAR connects patients to counseling, it does not directly connect patients to medication. Nicotine replacement therapy sampling (NRTS) is an empirically supported intervention to provide starter packs of nicotine replacement therapy (NRT) to people who smoke. NRTS combined with AAR could be an effective tobacco treatment intervention for dental settings. Methods This manuscript describes the study protocol for the Free Samples for Health (FreSH) study, a group randomized clinical trial testing the effectiveness of NRTS + AAR vs. AAR alone on long-term smoking abstinence. Fifty dental practices in the Midwest and Northeast nodes of the National Dental Practice-Based Research Network are randomly assigned to provide AAR and either a 2-week supply of 14-mg nicotine patches and 4-mg nicotine lozenges (NRTS condition) or an electric toothbrush (ET condition). Approximately 1,200 patients who currently smoke—regardless of interest in quitting— are recruited during dental visits. Participants complete a baseline survey in-person, then after visit, 1-, 3-, and 6-month follow-up surveys remotely. The primary outcome is carbon monoxide-confirmed 7-day point prevalence abstinence from combustible tobacco measured at 6 months post-enrollment. Secondary outcomes include: 24-h intentional quit attempts, change in cigarettes smoked per day, NRT utilization, attitudes toward NRT, intention to use NRT, and intention to quit smoking. A key informant process evaluation and cost effectiveness analysis will provide information for future implementation of NRTS. Discussion This is the first clinical trial to assess the effectiveness of NRTS on promoting smoking cessation in dental settings. If effective, this treatment could be implemented to increase the provision of smoking cessation interventions in dental settings to provide an additional treatment access point for people who smoke. Trial Registration. Registered at ClincalTrials.gov (NCT05627596) on 11/25/2022.

Abstract Background This randomized clinical trial protocol aimed to investigate the comparative efficacy of an enhanced recovery after surgery (ERAS) protocol versus traditional perioperative care programs in patients with intradural extramedullary spinal tumors. Methods The study included 180 patients aged 18–80 years, who were randomly assigned to two groups: Group A receiving traditional perioperative care and Group B receiving accelerated rehabilitation perioperative care. The nurse responsible for patient care was informed of the group assignment, but the patients themselves remained blinded to the intervention. The primary outcome measure was the Karnofsky Performance Scale score, which assessed functional status. The secondary outcomes included the Japanese Orthopedic Association Scale, Numeric Pain Rating Scale, length of postoperative hospital stay, duration of urethral catheterization, patient satisfaction questionnaire, and complication rates. Follow-up assessments were conducted telephonically 1 month, 3 months, and 6 months after the surgery. Discussion This study protocol provided a structured approach to assess the potential benefits of ERAS during the perioperative period for patients with intradural extramedullary tumors, aiming to improve patient outcomes and overall care efficiency. Trial registration This study has been registered with the China Clinical Trials Registry (Project No: ChiCTR2200063347). Registered on September 5 2022.

Abstract Background Rheumatoid arthritis (RA) is a chronic disease with a global prevalence rate of 1%. Patients with RA often associate specific foods like tomatoes and eggplants with adverse symptoms. These plants contain solanine, which could potentially contribute to bone and joint damage. Despite patient reports, there is a lack of randomized controlled trials (RCTs) investigating the effects of nightshades on patients with RA. This study aims to assess the effect of nightshade elimination diet (NED) on inflammatory and rheumatologic marker levels in rheumatoid arthritis patients for the first time. Methods A single-blinded controlled trial will be conducted to evaluate the effect of an NED on 40 participants over 8 weeks (2 months). Participants will be equally divided into intervention and placebo groups. Both groups will receive general anti-inflammatory dietary recommendations, with the intervention group undergoing an NED during the study. Clinical symptoms will be assessed using questionnaires, and blood samples will be collected to measure relevant indicators. Discussion This RCT signifies a groundbreaking exploration into NED effects on RA markers, potentially initiating crucial discussions in the field. Its outcomes could serve as a cornerstone for larger and more robust trials, offering pivotal insights to nutritionists and physicians for the nuanced management of patients with RA. Trial registration Iranian Registry of Clinical Trials IRCT20230220057465N1 ( https://irct.behdasht.gov.ir/trial/68959 ). Registered on 8 April 2023.

Background: Gaining insight into the obstacles holding women from engaging in physical activity during pregnancy is crucial for planning future interventions to enhance their physical activity during this period. This research aims to identify barriers to physical activity among pregnant women using an explanatory sequential mixed-methods approach. The study protocol is explained in this article. Methods: This research employs an explanatory sequential mixed-methods design. The project will be implemented in two separate phases. In the first phase, a quantitative cross-sectional study will be conducted on 358 eligible pregnant women aged 18-45 years living in Babol City, Iran. Quantitative data collection will involve using the barriers to physical activity during pregnancy scale (BPAPS) and questionnaires gathering demographic and obstetric data. The qualitative investigation will employ individual semi-structured interviews utilizing a content analysis approach. Ultimately, incorporating qualitative data will inform the interpretation of quantitative findings. Results: The results will be presented in alignment with the study objectives. Initially, the mean score of BPAPS and its subscales, along with the correlation between demographic and obstetric variables, will be reported. Subsequently, the qualitative phase will encompass the reporting of categories and the main themes. Finally, the quantitative phase findings will be interpreted, incorporating insights gained from the qualitative phase. Conclusion: Since regular physical activity during pregnancy has many benefits for maternal and fetal health, the study’s findings after its implementation can play a vital role in strategic planning to address women’s false beliefs and misconceptions regarding physical activity during pregnancy. In addition, this study will contribute to designing interventions to remove barriers to physical activity and encourage it in pregnant women, hence improving their overall health and well-being during pregnancy.

Abstract Background Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects. Methods/design The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p

Abstract Background Significant concomitants of the sick role maladaptation in colorectal cancer (CRC) patients include inappropriate cognitions, emotional states, and overt conducts associated to disease. This protocol was developed to implement and evaluate the effects of a self-led, virtual reality-based cognitive behavioral therapy (VR-CBT) on the sick role adaptation among working-age CRC patients. Methods This is an assessor-blinded, randomized controlled trail that adheres to the SPIRIT 2013 Statement guidelines. A total of 60 working-age CRC patients will be recruited from the colorectal wards of a cancer center and randomly assigned to the VR-CBT group or attention control (AC) group. The VR-CBT group will receive a 7-sessions VR-CBT targeted to sick role adaptation, while the AC group will receive weekly attention at the same time the VR-CBT group receives the intervention. The sick role adaptation, anxiety and depression, illness perceptions, and quality of life will be measured at baseline, 1, 2 and 3-month after completion of the intervention. Side-effects related to VR in the VR-CBT group will be measured at the end of each session. The participants will receive invitations to participate in semi-structured interviews to explore their experiences with the intervention. Discussion The positive outcomes and user experience of VR-CBT will advance researches on the effectiveness of psychosocial interventions that aims to promote adaptation to the unexpected sick role on cancer populations. This protocol can be tested as an accessible and feasible alternative to traditional high-cost treatment in a randomized controlled study to improve the outcomes of younger cancer survivors. Trial registration. The protocol was registered on 21 June, 2023 in Chinese Clinical Trial Registry (No.: ChiCTR2300072699) at https://www.chictr.org.cn/ .

Abstract Background Infertility produces infertility-related stress in both members of infertile couples, especially for infertile women. Some studies verified the negative relationship between infertility-related stress and outcomes of infertility treatments. Effective mental health care during fertility treatment is urgently needed, but there has been a lack of efficient support services. To reduce the infertility-related stress of infertile women, expressive art therapeutic schemes will be organized and implemented by certified international expressive art therapists. Methods This study is a randomized controlled trial. Participants in the intervention group will receive expressive art therapies after the baseline investigation. Expressive art therapies will be led by the certified international expressive art therapist. The interventions include progressive muscle relaxation training, music meditation and drawing therapy. Participants in the control group will receive routine care. The Hospital Anxiety and Depression Scale (HADS) and Fertility Problem Inventory (FPI) will be used to investigate the anxiety, depression, and infertility-related stress of all participants at admission and at discharge. Discussion This study will verify the effectiveness and efficiency of expressive art therapies for infertile women. The results will provide new knowledge on mental health care strategies for infertile women. Trial registration ChiCTR, ChiCTR2300070618. Registered 14 April 2023.

Abstract Background The concept of sexual satisfaction in menopausal women is very different from that in premenopausal women, and this difference is due to aging and physical, hormonal, cultural, and psychological changes. Therefore, the first step in discovering methods for assessing sexual satisfaction in postmenopausal women is to develop a measurement instrument. This study was conducted to develop and evaluate the psychometric properties of a sexual satisfaction instrument for postmenopausal women. Methods The current study is an exploratory-sequential mixed-methods research project that will be divided into two parts: qualitative and quantitative. Aligned with the primary objective of the research, which is to elucidate the concept of sexual satisfaction in postmenopausal women, the hybrid concept analysis model developed by Schwartz and Kim will be employed. This model comprises three key phases: the theoretical phase, the fieldwork phase, and the final analytical phase. Those who met the inclusion criteria and exhibited maximum variance in terms of age, educational level, employment status, and menopausal duration were recruited. The conventional content analysis will be carried out following the steps proposed by Graneheim and Lundman. Second, in the quantitative phase, the psychometric properties of the instrument were evaluated, including the content, face and construct validity and reliability via internal consistency and stability. The psychometric properties described in the COSMIN checklist will be utilized for designing the instrument. Discussion A valid and reliable scale for evaluating the sexual satisfaction of postmenopausal women should be developed, and educational content should be designed to improve the sexual satisfaction of this group of women.

Abstract Background Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. Methods This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. Discussion The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients.Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients.Design: Clinical study protocol, SPIRIT compliant.Setting: Prospective, single-center, randomized, and sham-controlled trial.Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients.Exposures: Intraoral or sham acupuncture.Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the “Drooling Severity and Frequency Scale” and “Functional Oral Intake Scale.” Results : : The results from this study will be published in peer-reviewed journals.Conclusion : : Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.

Abstract Background Intensive care medicine continues to improve, with advances in technology and care provision leading to improved patient survival. However, this has not been matched by similar advances in ICU bedspace design. Environmental factors including excessive noise, suboptimal lighting, and lack of natural lights and views can adversely impact staff wellbeing and short- and long-term patient outcomes. The personal, social, and economic costs associated with this are potentially large. The ICU of the Future project was conceived to address these issues. This is a mixed-method project, aiming to improve the ICU bedspace environment and assess impact on patient outcomes. Two innovative and adaptive ICU bedspaces capable of being individualised to patients’ personal and changing needs were co-designed and implemented. The aim of this study is to evaluate the effect of an improved ICU bedspace environment on patient outcomes and operational impact. Methods This is a prospective multi-component, mixed methods study including a randomised controlled trial. Over a 2-year study period, the two upgraded bedspaces will serve as intervention beds, while the remaining 25 bedspaces in the study ICU function as control beds. Study components encompass (1) an objective environmental assessment; (2) a qualitative investigation of the ICU environment and its impact from the perspective of patients, families, and staff; (3) sleep investigations; (4) circadian rhythm investigations; (5) delirium measurements; (6) assessment of medium-term patient outcomes; and (7) a health economic evaluation. Discussion Despite growing evidence of the negative impact the ICU environment can have on patient recovery, this is an area of critical care medicine that is understudied and commonly not considered when ICUs are being designed. This study will provide new information on how an improved ICU environment impact holistic patient recovery and outcomes, potentially influencing ICU design worldwide. Trial registration ACTRN12623000541606. Registered on May 22, 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385845&isReview=true .

Abstract Background The interplay of ethical stress, heavy workloads, and job dissatisfaction poses challenges to both the recruitment and retention of health and social care professionals. Person-centred care, rooted in ethical principles, involves collaborative care, and is expected to improve care and job satisfaction. However, prior research on the impact of person-centred care practices on professionals’ work-related health and job satisfaction has yielded mixed results, and most studies emanate from residential care. Understanding how person-centred care practices influence health and social care professionals across different care settings thus requires further exploration through rigorous methodology. The overall aim of PCC@Work is to follow, describe, assess, and explore the impact of person-centred care practices in hospital wards, primary care centres and municipal care on health and social care professionals’ work-related health and job satisfaction. Methods PCC@Work is designed as a prospective, longitudinal cohort study combined with qualitative studies. A web-based questionnaire will be distributed on five occasions within two years to health and social care professionals in the three care settings. In addition, focus groups and interviews will be conducted with a selection of health and social care professionals to explore their experiences of work-related health and job satisfaction in relation to person-centred practices. Discussion PCC@Work will highlight some of the knowledge gaps on the impact of person-centred care practices regarding work-related health and job satisfaction of health and social care professionals. The uniqueness of the project lies in the multi-method design, combining a prospective longitudinal cohort study with qualitative studies, and the involvement of various professions and settings. This means we will be able to provide a comprehensive and representative understanding of person-centred care practices as a critical component for effective change in the working conditions of health and social care.

Background Carbapenem-resistant Enterobacterales (CRE) pose a significant global health threat, with increasing prevalence worldwide, including in Indonesia. Despite the public health impact, comprehensive data on the burden of CRE in Indonesia remains fragmented. This protocol outlines a systematic review and meta-analysis aiming to estimate the prevalence of CRE in Indonesia, summarize trends over time, and identify key resistance mechanisms. Methods We will conduct a systematic search across multiple electronic databases, including PubMed, Scopus, and local Indonesian databases, for studies reporting the prevalence of CRE in Indonesia from 2008 to 2024. Eligibility criteria include observational studies (cross-sectional, cohort, and case-control) and surveillance reports. Data extraction will focus on CRE prevalence, bacterial species, sample types, resistance mechanisms, and study settings (hospital vs. community). Quality assessment of studies will be performed using the Newcastle-Ottawa Scale (NOS). Meta-analysis will be conducted using a random-effects model to estimate pooled prevalence, and subgroup analysis will explore variations by geographical region, period, and healthcare setting. Discussion This systematic review and meta-analysis will provide the first comprehensive overview of CRE prevalence in Indonesia, contributing to an improved understanding of the national burden and resistance patterns. The findings will guide public health policies and inform antimicrobial stewardship efforts in Indonesia. Registration PROSPERO CRD42024580177