Search

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: Ventral hippocampus (vHipp) in schizophrenia is in a state of hyperactivity and hypermetabolism, where the glutamate/gamma-aminobutyric acid (GABA) imbalance leads to downstream dopamine hyperactivity in the midbrain-limbic system. High-frequency deep brain stimulation (DBS) can disrupt the abnormal synchronization of functional circuits and modulate local brain networks. Methods: The DBS-HITS study is a crossover randomized controlled trial. DBS will be applied to bilateral vHipp in six patients. They will be randomly assigned to receive 3-month high-frequency active stimulation and then 3-month sham stimulation, or vice versa. After 6-month crossover trial phase, all participants will undergo personalized active stimulation. Researchers will assess clinical symptoms and neurocognition, collect EEG and PET-CT data during planned follow-ups. Adverse event will be researcher-assessed or participant self-reported throughout the trial. Discussion: To our knowledge, the DBS-HITS study is the first hippocampal DBS randomized controlled trial for schizophrenia. The goal of the DBS-HITS study is to assess the efficacy and safety of hippocampal DBS in treatment-resistant schizophrenia (TRS) and to investigate its impact on hippocampal activity and glutamate/GABA metabolism. The study is expected to deepen our understanding of the effects and side-effects of neuromodulation in TRS to facilitate individualized DBS treatment. Trial registration: NCT05694000 in ClinicalTrial.gov, registered on January 23, 2023. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer. Methods: The RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac. The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI. Conclusion: The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes. Trial registration: This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808. [ABSTRACT FROM AUTHOR]

Background: Healthcare professionals face high levels of occupational stress, time pressure, workload, and poor organizational support. This makes them particularly vulnerable to burnout. The COVID-19 pandemic has further exacerbated this situation. This single-arm, multicenter, mixed-methods feasibility study pilots the LAGOM program: A tailored, evidence-based intervention to prevent burnout and reduce stress among healthcare professionals. Methods: Participants will include healthcare professionals (N = 30) working at Charité–Universitätsmedizin Berlin and Immanuel Hospital, Berlin. LAGOM focuses on support for individual behavior change and personal resources and also addresses the organizational level. The intervention´s feasibility will be evaluated through a non-randomized feasibility trial with a mixed methods process evaluation. The exploratory primary study aims are to assess the acceptability and feasibility of the (1) evaluation procedures and of the (2) intervention content and structure using study records, standardized questionnaires, protocol checklists, and diaries. Exploratory effectiveness analysis will take place as well. Further, semi-structured interviews (n = 3 to 6) and electrophysiological measurements (n = 20) will be conducted. Discussion: Custom-tailored, well-implemented multi-level interventions are needed to prevent burnout and reduce stress among healthcare professionals. Long-term strategies are warranted to sustainably implement effective programs. This feasibility study helps to refine trial procedures and content of the LAGOM program for a randomized controlled trial to evaluate the intervention's effectiveness. Trial registration: German Clinical Trials Register: DRKS00032014, registered 17th October 2023. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is a common mental disease that significantly impact the daily lives of those affected. Acupuncture has shown promising therapeutic effects in the treatment of MDD, but its underlying mechanisms remain unclear. This study aims to evaluate the influence of acupuncture on the brain function of patients with MDD and it's therapeutic effects on MDD. Methods: This study plans to recruit 112 participants, who will be randomly allocated to either the acupuncture group or the sham acupuncture group in a 1:1 ratio. Both groups will undergo 8 weeks of treatment, consisting of three sessions per week, with each session lasting for 30 min. A follow-up period of 3 months will be conducted after the treatment. Assessments will be conducted at weeks 0, 8, 12, 16, and 20 in this study. The primary outcome measure will be functional near-infrared spectroscopy (fNIRS) brain imaging, while secondary outcome measures will include Beck Depression Inventory II (BDI-II), Self-Rating Anxiety Scale (SAS), 36-Item Short Form Survey Instrument (SF-36), Traditional Chinese Medicine (TCM) syndrome score scale, and symptom elimination rate. Discussion: While acupuncture has been confirmed to have a certain degree of therapeutic efficacy in the treatment of MDD, research on the mechanisms underlying acupuncture's treatment of MDD remains limited, particularly with regards to its impact on the brain function of individuals with MDD. This study aims to explore both the clinical effectiveness and treatment mechanisms of acupuncture for MDD, with a specific focus on its influence on brain function. This research endeavors to provide new insights into the potential of acupuncture as a therapeutic approach for the treatment of MDD in the future. Trial Registration: www.chictr.org.cn, ID: ChiCTR2300076292. Registered on 28 September 2023. [ABSTRACT FROM AUTHOR]

Background: The abandonment of psychotherapeutic treatments is influenced by various factors, including patient characteristics, therapist traits, and the therapeutic relationship. Despite the well-documented importance of these factors, limited empirical research has focused on the role of the therapeutic relationship and the characteristics of therapist-patient dyads in predicting treatment dropout. This study protocol outlines a longitudinal research project aimed at predicting dropout and non-response in psychotherapy for individuals with personality disorders. The research seeks to identify predictive factors related to psychotherapy outcomes, focusing on patient, therapist, and dyadic elements. Specifically, the study will examine the influence of therapist characteristics (e.g., personality traits, countertransference, responsiveness) on treatment outcomes, explore the impact of relational factors (e.g., treatment expectations, epistemic trust, therapeutic alliance) on therapy effectiveness, and assess how the therapeutic alliance within therapist-patient dyads affects the likelihood of dropout and non-response. Methods: The longitudinal study will include 100 therapist-patient dyads (200 participants) recruited from various Mental Health Services in Milan, Italy. Validated instruments will be administered to both patients and therapists at four-time points: T0 (baseline), T1 (3 months), T2 (6 months), and T3 (1 year). Data will be collected at baseline and at the one-year mark to evaluate the relationships between therapist, patient, and dyadic factors and treatment outcomes. Discussion: Identifying predictive variables associated with high dropout rates can help preempt treatment discontinuation, reducing the financial and operational burdens on mental health services. Understanding these factors will enable the development of targeted interventions to improve treatment engagement and reduce attrition. This approach could enhance outcomes for individuals with personality disorders and lead to more efficient resource allocation and sustainable delivery of mental health care. [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 opinion-based assessment of P-gp-mediated DDIs that affect clinical outcomes. This approach will generate alerts with practice recommendations for clinically relevant DDIs and transparent rationales for DDIs that are considered to be irrelevant. These recommendations will improve individual patient care by supporting healthcare professionals to make consistent decisions on how to manage P-gp mediated DDIs. [ABSTRACT FROM AUTHOR]

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: 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]

Research has documented chronic non-specific low back pain (CNSLBP) as one of the primary causes of absenteeism at work, often accompanied by the use of health insurance and healthcare services. Considering little research on the consequences of open/closed kinetic chain (O/CKC) exercises in water on CNSLBP improvement, the present study is to investigate the effects of such interventions on the electrical activity of selected lumbar muscles, pain, lumbopelvic control (LPC), ground reaction force (GRF), and psychological factors in men with CNSLBP. This is a randomized controlled trial that involves individuals with CNSLBP between the ages of 40 and 60 years. Participants are randomly assigned, using block randomization, to one of the following groups: open kinetic chain (OKC) exercises, closed kinetic chain (CKC) exercises, or controls. The training groups engage in the exercises for eight weeks, with three sessions per week and 60 min each at the University of Bu-Ali Sina pool, following the prescribed workout routine. The primary outcomes of the electrical activity of the multifidus (MF), transversus abdominis (TrA), gluteus medius (GM), and quadratus lumborum (QL) muscles are measured by an electromyography (EMG) device. Additionally, the pressure biofeedback (BFB) device and the visual analog scale (VAS) are utilized to assess LPC and pain intensity, respectively. The secondary outcomes of the GRF, along with foot pressure and kinesiophobia, are subsequently measured by the Tampa Scale of Kinesiophobia (TSK). By comparing the outcomes between the OKC exercise group, CKC exercise group, and control group, this study aims to determine the differential effects of these two water-based exercise interventions on the various physical and psychological parameters in individuals with CNSLBP. The findings provide valuable insights into the most effective approach to water-based rehabilitation for individuals with CNSLBP. By comparing the outcomes of OKC and CKC exercises, healthcare professionals can make informed decisions when designing tailored rehabilitation programs for this patient population. The results also contribute to the development of evidence-based guidelines for the management of CNSLBP using water-based exercises. [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]

Tianyu Bai,&ast; E Zhou,&ast; Kai Wang, Weizheng Li, Jieyu Bi, Jiacheng Ju Department of Acupuncture and Moxibustion, Shandong Provincial Third Hospital Shandong University, Jinan, Shandong, 250031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianyu Bai, Email Baitianyu19820217@163.comBackground: Resting-state functional magnetic resonance imaging (rs-fMRI) is a noninvasive way to evaluate brain physiological activity by detecting blood oxygen level fluctuations. Diminished ovarian reserve (DOR) indicates ovarian aging. Before 40, patients may have menstrual abnormalities, poor reproduction, and poor assisted reproductive results. Without treatment, it can cause early ovarian failure. Studies have shown that acupuncture can ameliorate sex hormones and antral follicle count (AFC) in DOR patients.Objective: Despite limited studies on its mechanism, acupuncture have been shown to treat DOR. There is no relevant research on brain functional magnetic resonance and brain functional connectivity of acupuncture in treating DOR. We design this clinical trial to preliminarily elucidate the neuroimaging method of controlling the brain functional network and acupuncture impact in DOR patients using rs-fMRI.Methods: This study will involve 30 DOR patients and 30 healthy individuals. DOR patients will have rs-fMRI before and after 3 menstrual cycles of acupuncture, whereas healthy individuals will need one rs-fMRI scan. The primary end measures will be follicle-stimulating hormone (FSH) and AFC. In contrast, the secondary outcomes will be luteinizing hormone(LH), estradiol (E2), anti-Müllerian hormone (AMH), modified Kupperman scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS), and rs-fMRI alterations.Results: This study uses rs-fMRI technology to identify the brain regions that differ between DOR patients and healthy people before and after acupuncture treatment. This study will connect brain regions, examine the effects of acupuncture on menstruation and pregnancy on DOR patients’ brain function networks, and discuss neuroimaging methods.Conclusion: Acupuncture may have the potential to regulate menstruation and increase the chances of pregnancy promotion in patients with DOR.Keywords: clinical trials, study protocol, rs-fMRI, acupuncture, DOR, brain functional networks

Abstract Background The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany. Methods We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence. Results The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach. Discussion BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care. Trial registration German Clinical Trial Register DRKS00028840. Registered on April 2022.

Abstract Introduction Major depressive disorder (MDD) is a common mental disease that significantly impact the daily lives of those affected. Acupuncture has shown promising therapeutic effects in the treatment of MDD, but its underlying mechanisms remain unclear. This study aims to evaluate the influence of acupuncture on the brain function of patients with MDD and it’s therapeutic effects on MDD. Methods This study plans to recruit 112 participants, who will be randomly allocated to either the acupuncture group or the sham acupuncture group in a 1:1 ratio. Both groups will undergo 8 weeks of treatment, consisting of three sessions per week, with each session lasting for 30 min. A follow-up period of 3 months will be conducted after the treatment. Assessments will be conducted at weeks 0, 8, 12, 16, and 20 in this study. The primary outcome measure will be functional near-infrared spectroscopy (fNIRS) brain imaging, while secondary outcome measures will include Beck Depression Inventory II (BDI-II), Self-Rating Anxiety Scale (SAS), 36-Item Short Form Survey Instrument (SF-36), Traditional Chinese Medicine (TCM) syndrome score scale, and symptom elimination rate. Discussion While acupuncture has been confirmed to have a certain degree of therapeutic efficacy in the treatment of MDD, research on the mechanisms underlying acupuncture’s treatment of MDD remains limited, particularly with regards to its impact on the brain function of individuals with MDD. This study aims to explore both the clinical effectiveness and treatment mechanisms of acupuncture for MDD, with a specific focus on its influence on brain function. This research endeavors to provide new insights into the potential of acupuncture as a therapeutic approach for the treatment of MDD in the future. Trial Registration www.chictr.org.cn , ID: ChiCTR2300076292. Registered on 28 September 2023.

Abstract Background Healthcare professionals face high levels of occupational stress, time pressure, workload, and poor organizational support. This makes them particularly vulnerable to burnout. The COVID-19 pandemic has further exacerbated this situation. This single-arm, multicenter, mixed-methods feasibility study pilots the LAGOM program: A tailored, evidence-based intervention to prevent burnout and reduce stress among healthcare professionals. Methods Participants will include healthcare professionals (N = 30) working at Charité–Universitätsmedizin Berlin and Immanuel Hospital, Berlin. LAGOM focuses on support for individual behavior change and personal resources and also addresses the organizational level. The intervention´s feasibility will be evaluated through a non-randomized feasibility trial with a mixed methods process evaluation. The exploratory primary study aims are to assess the acceptability and feasibility of the (1) evaluation procedures and of the (2) intervention content and structure using study records, standardized questionnaires, protocol checklists, and diaries. Exploratory effectiveness analysis will take place as well. Further, semi-structured interviews (n = 3 to 6) and electrophysiological measurements (n = 20) will be conducted. Discussion Custom-tailored, well-implemented multi-level interventions are needed to prevent burnout and reduce stress among healthcare professionals. Long-term strategies are warranted to sustainably implement effective programs. This feasibility study helps to refine trial procedures and content of the LAGOM program for a randomized controlled trial to evaluate the intervention’s effectiveness. Trial registration German Clinical Trials Register: DRKS00032014 , registered 17th October 2023.

Abstract Background Over the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer. Methods The RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac. The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI. Conclusion The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808 .

Abstract Background The abandonment of psychotherapeutic treatments is influenced by various factors, including patient characteristics, therapist traits, and the therapeutic relationship. Despite the well-documented importance of these factors, limited empirical research has focused on the role of the therapeutic relationship and the characteristics of therapist-patient dyads in predicting treatment dropout. This study protocol outlines a longitudinal research project aimed at predicting dropout and non-response in psychotherapy for individuals with personality disorders. The research seeks to identify predictive factors related to psychotherapy outcomes, focusing on patient, therapist, and dyadic elements. Specifically, the study will examine the influence of therapist characteristics (e.g., personality traits, countertransference, responsiveness) on treatment outcomes, explore the impact of relational factors (e.g., treatment expectations, epistemic trust, therapeutic alliance) on therapy effectiveness, and assess how the therapeutic alliance within therapist-patient dyads affects the likelihood of dropout and non-response. Methods The longitudinal study will include 100 therapist-patient dyads (200 participants) recruited from various Mental Health Services in Milan, Italy. Validated instruments will be administered to both patients and therapists at four-time points: T0 (baseline), T1 (3 months), T2 (6 months), and T3 (1 year). Data will be collected at baseline and at the one-year mark to evaluate the relationships between therapist, patient, and dyadic factors and treatment outcomes. Discussion Identifying predictive variables associated with high dropout rates can help preempt treatment discontinuation, reducing the financial and operational burdens on mental health services. Understanding these factors will enable the development of targeted interventions to improve treatment engagement and reduce attrition. This approach could enhance outcomes for individuals with personality disorders and lead to more efficient resource allocation and sustainable delivery of mental health care.

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

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

Aim(s): The aim of this study is to understand factors that challenge retention and support nurses to stay in general practice. Background: One in four general practice nurse positions in England expected to be left unfilled within the next 10 years. Cultural and structural issues associated with working in general practice have been linked with nurses leaving general practice, re‐evaluating their professional futures, adjusting work‐life balance and bringing forward retirement. This has implications for the future of the general practice nursing workforce and patient care more broadly. Design: Exploratory qualitative interview study funded by the General Nursing Council Trust for England and Wales. University of York ethics approval (Ref: HSRGC/2023/586/A) was gained in September 2023. The study will be conducted between September 2023 and August 2024. Methods: Qualitative interviews will be conducted with a range of nurses working in, or who have worked in, general practice as well as nurse leaders associated with general practice across England and Wales. Recruitment will be via professional and social media networks and snowballing techniques. We aim to purposively recruit 30–40 participants for maximum variation. Cultural and structural influences which may contribute to retention decisions will be explored. Data will be analysed following framework analysis. Discussion/Conclusion: This study will explore how underpinning cultural and structural issues may impact on retention of this highly skilled professional group and identify factors to support retention. Implications for the Profession and/or Patient Care: By exploring factors that support or discourage nurses to remain in general practice, retention strategies can be better planned on order to address the general practice nursing workforce crisis. Impact: What problem did the study address? This study will address the retention crisis in nursing in general practice by exploring how cultural and structural issues may impact on retention of this highly skilled professional group and identify factors to support retention. Where and on whom will the research have an impact? From the study findings, recommendations will be developed to inform future policy and practice. Key factors to address attrition will be generated to support employers and policy makers in future primary care workforce planning, as well as supporting nurses, at an individual level, in negotiating their roles in practice. Reporting Method: Standards for Reporting Qualitative Research (O'Brien et al., 2014). Patient or Public Contribution: As this is a workforce study protocol, there is no patient or public contribution. [ABSTRACT FROM AUTHOR]

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