Robot-assisted versus video-assisted thoracoscopic thymectomy for stage I-II thymic epithelial tumour: a protocol for the first multicentre, randomised controlled clinical trial

Background
Minimally invasive approaches, including video-assisted thoracoscopic thymectomy (VATT) and robot-assisted thoracoscopic thymectomy (RATT), have emerged as alternatives to median sternotomy for resectable thymic epithelial tumours (TETs). However, their comparative clinical efficacy remains inconclusive due to limited prospective evidence. This phase II randomised controlled trial aims to provide the first direct comparative analysis of perioperative outcomes between RATT and VATT in stage I–II TETs.

Methods and analysis
This phase II clinical trial is a prospective, multicentre, randomised controlled study. A total of 100 patients with stage I–II TETs will be recruited and randomly allocated into two groups: RATT and VATT groups, with a 1:1 ratio. Follow-up visits will be scheduled at 1 month, 3 months and 6 months postsurgery, and semiannual visits will continue until November 2027, including the record of tumour recurrence, metastasis, survival outcomes and overall long-term effects. The primary endpoint is total postoperative thoracic drainage. Secondary outcomes encompass intraoperative factors like R0 resection rate, operative time, postoperative drainage duration, hospital stay length, conversion rates, levels of stress markers, pain scores, quality of life assessments, perioperative complication rates, mortality rates and 3-year disease-free and overall survival rates.

Ethics and dissemination
The study protocol is approved by the ethics committees of Zhongshan Hospital, Fudan University (No. B2024-365), and will be conducted under the guidance of the Helsinki Declaration. All data and findings will be disseminated and published through peer review.

Trial registration number
NCT06654830.

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Effects of cupping therapy on chronic musculoskeletal pain and collateral problems: a systematic review and meta-analysis

Objectives
Chronic musculoskeletal pain (CMP) is a prevalent and distressing condition. Cupping therapy, one of the most popular complementary and alternative medicines, has been widely used to reduce CMP. But the evidence remains controversial on the effect of cupping therapy on CMP. The objective of this review and meta-analysis is to assess the effectiveness of cupping therapy in patients with CMP.

Design
Systematic review and meta-analysis.

Data sources
PubMed, Web of Science, EBSCO, Cochrane Library and CNKI (China National Knowledge Infrastructure) were searched through 20 December 2024.

Eligibility criteria for selecting studies
We included randomised control trials that compared cupping therapy for patients with CMP on outcomes (ie, pain intensity, functional disability and mental health).

Data extraction and synthesis
Two independent reviewers used standardised methods to search, screen and code included studies. Risk of bias was assessed using the Cochrane Collaboration and Evidence Project tools. Meta-analysis was conducted using random and fixed effects models. Findings were summarised in GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence profiles.

Results
The results showed that cupping therapy (standardised mean difference (SMD)=–1.17; 95% CI=–1.93 to –0.42; p=0.002; I2=94%) had a significant reduction effect on patients with CMP’s pain intensity with moderate quality based on a random-effect model. But cupping therapy had no improvement effects on functional disability (SMD=–0.24; 95% CI=–0.93 to 0.46; p=0.51; I²=93%) and mental health (SMD=0.08; 95% CI=–0.12 to 0.27; p=0.46; I²=0%).

Conclusions
This study indicates that cupping therapy may be efficient in alleviating pain intensity in patients with CMP with immediate effects. But it cannot improve functional disability and mental health significantly.

PROSPERO registration number
CRD42023406219.

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Functional vision tests as clinical trial outcome measures in ophthalmology: a scoping review

Objectives
To identify currently available functional vision tests and evaluate their use as clinical trial outcome measures in ophthalmology.

Design
Scoping review using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews) guidelines.

Methods
A literature search was conducted in MEDLINE and Embase (via Ovid) for articles published between 1 January 2003 and 1 August 2024. Additional grey literature was sourced from institutional repositories, conference proceedings and a manual citation search. Article screening was conducted against a predefined inclusion criteria by two independent, masked reviewers, with a third reviewer acting as arbiter. The inclusion criteria were English language articles which feature a test assessing functional vision in patients with an ophthalmological disease. Details of source characteristics, test methodology and accessibility and evidence of test validation were collected.

Results
Of 2665 articles returned by the search, 73 were included and 45 unique tests of functional vision were identified. Diseases affecting the peripheral retina were mainly affected, accounting for 77% (56 out of 73) of the diseases featured in all included studies. Overall, 82% (37 out of 45) functional vision tests reported evidence of statistical validation with varying robustness. Functional vision tests were mapped to domains of orientation and mobility, facial recognition, observer-rated task performance, visual search and driving. Obstacle courses assess vision-guided orientation and mobility, correlate highly with clinical measures of visual function in severe peripheral retinal disease and have been validated for use in clinical trials. Their requirement of physical space and time limits utility in multicentre trials; equivalent tests leveraging virtual reality and eye tracking technologies are in development. Early iterations of visual search tests to simulated realistic scenes have demonstrated discriminative ability, even in paediatric patients.

Conclusions
Functional vision tests can facilitate research into future novel ophthalmological treatments that prioritise patients in terms of how clinical benefit is defined. The principal barriers to the uptake of these tests are lack of accessibility, low quality validation and that many tests remain early in their development stage. This review captures the current landscape of functional vision tests and serves as a reference for investigators and regulatory bodies to evaluate the suitability of these tests for ophthalmic clinical trials.

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Effect of low-molecular-weight heparin on pregnancy outcomes in Chinese women with recurrent implantation failure undergoing frozen embryo transfer: a double-blind, randomised, placebo-controlled trial

Introduction
The incidence of recurrent implantation failure (RIF) can reach up to 10% among patients undergoing in vitro fertilisation and embryo transfer worldwide. However, the clinical efficacy of low-molecular-weight heparin (LMWH) in RIF remains a subject of controversy. Currently, there is a lack of high-quality clinical research validating the effectiveness of LMWH in treating patients with RIF, particularly during frozen embryo transfer (FET) cycles. Therefore, this randomised controlled trial aimed to investigate the impact of LMWH on pregnancy outcomes in women with RIF undergoing FET.

Methods and analysis
This prospective, single-centre, double-blind randomised, placebo-controlled clinical trial will be conducted in the Second Hospital of Shandong University, China. A total of 414 women with RIF, aged ≤40 years, who are undergoing FET cycles will be recruited and randomly assigned to the study group (LMWH) or the control group (placebo). Only one blastocyst which is from day 5 or day 6 and has a Gardner morphology score ≥4 BC will be transferred. LMWH 4000–6000 IU per day or placebo will be administered by subcutaneous injection from the day of transplantation. The primary outcome is the live birth rate. The secondary outcomes include the clinical pregnancy rate, biochemical pregnancy rate, embryo implantation rate, early miscarriage rate, ongoing pregnancy rate, ectopic pregnancy rate, pregnancy-related complications, perinatal complications, fetal birth weight, congenital malformations and other adverse reactions.

Ethics and dissemination
The protocol received approval from the Ethics Committee of the Second Hospital, Cheeloo College of Medicine, Shandong University (KYLL-2023-442). The findings will be disseminated in peer-reviewed publications.

Trial registration number
Chinese Clinical Trial Registry, ChiCTR2400083577.

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Analgesic effects of intrathecal bupivacaine with neostigmine or morphine among elective surgical patients in selected comprehensive specialised hospitals, Southern Ethiopia: a prospective cohort study

Objectives
To compare the analgesic effects of intrathecal neostigmine with bupivacaine, morphine with bupivacaine and bupivacaine alone among patients undergoing surgical procedures below the umbilicus.

Design and setting
A multicentre prospective cohort study was conducted from 29 May to 29 August 2023 at Wolaita Sodo University Comprehensive Specialized Hospital, Nigest Mohammed Eleni Memorial Comprehensive Specialized Hospital and Werabe Comprehensive Specialized Hospital. A systematic random sampling technique was used to select the participants from the sample of 180.

Participants
The study included American Society of Anesthesiologists classes I and II patients aged 18–85 years scheduled for elective surgeries under spinal anaesthesia with bupivacaine with neostigmine (50 µg), bupivacaine with morphine (100 µg) and bupivacaine alone at a dose of 17.5 mg.

The primary outcome measures
The duration of pain relief, the severity of pain and the time of first analgesic requirement.

The secondary outcome measures
Postoperative complications such as respiratory depression, pruritus, nausea and vomiting

Results
Administration of intrathecal bupivacaine with neostigmine group (NG) and morphine group (MG), respectively, produces a long duration of postoperative analgesia with a first analgesia request mean time of 9.4±3.18 and 9.65±4.9, while using bupivacaine group (BG) alone produces a shorter duration of postoperative analgesia with a mean first analgesia request time of 3.58±0.98 hours. The mean visual analog scale scores in 28 hours were 0.99, 0.79 and 2.05 for the NG, MG and BG, respectively. The overall postoperative pain severity was highest in the BG. The mean total analgesic consumption was 77.5, 73.8 and 189.2 mg for diclofenac, whereas 54.2, 63.9 and 151.7 mg for tramadol in the NG, MG and BG, respectively. Incidence of nausea (31.3%) and vomiting (30%) was highest in the NG, while pruritus (15%) and respiratory depression (15%) were more in the MG.

Conclusion
Compared with BG, MG and NG had longer-lasting postoperative analgesic effects, less severe pain and required fewer analgesics overall. Patients in the NG had more incidences of nausea and vomiting. The incidences of pruritus and respiratory depression were highest in the MG. Effective analgesia appeared to work better in the MG and NG. We recommend morphine and neostigmine as adjuvants to local anaesthetics for effective postoperative analgesia. We also recommend researchers compare different doses of neostigmine and morphine as adjuvants to bupivacaine in further studies.

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Taking action, return-to-work strategies used by Iranian cancer survivors: a qualitative study

Objectives
The transition back to work after cancer is a significant milestone for many survivors, affecting their financial stability, psychological well-being and overall quality of life. Return-to-work (RTW) process is often complicated by lingering physical and cognitive impairments, changes in self-identity and workplace dynamics. Understanding how cancer survivors navigate this process is crucial for the development of effective support systems. This study aimed to explore strategies employed by cancer survivors in managing the RTW process.

Design
This study employed a qualitative content analysis approach to explore RTW strategies used by cancer survivors.

Setting
The study was conducted at a referral cancer centre and the workplaces of cancer survivors located in East Azerbaijan, Iran.

Participants
A total of 22 cancer survivors were selected using purposive sampling. These participants had completed primary cancer treatment and had rich and diverse RTW-related experiences. Data were collected through semi-structured, face-to-face interviews and then analysed using the inductive content analysis approach described by Graneheim and Lundman (2004).

Results
‘Active Strategies for Returning to Work’ constituted the main theme and consisted of three categories, including assessing the situation, self-accommodation and impressing the workplace.

Conclusions
Cancer survivors actively engaged in RTW. They evaluate their situations before returning to work, seek to accommodate themselves to their circumstances and impress their workplaces to gain the necessary support. Healthcare providers, employers and families, as the most influential parties in the RTW process of cancer survivors, should recognise survivors’ positive strategies and provide informational, financial, emotional and occupational support.

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Efficacy and acceptability of different blood flow restriction training interventions during the rehabilitation of military personnel with lower limb musculoskeletal injuries: protocol for a two-phase randomised controlled trial

Background
Musculoskeletal injury (MSKI) is the leading cause of medical downgrading and discharge within the UK military, with lower limb MSKI having the greatest incidence, negatively impacting operational readiness. Pain is a primary limiting factor to rehabilitation progress following MSKI. Heavy-load resistance training (RT; ie, loads >70% 1-repetition maximum) is traditionally used but may be contraindicated due to pain, potentially prolonging recovery and leading to failure of essential physical employment standards for UK military personnel. Low-load RT with blood flow restriction (BFR) can promote favourable morphological and physiological adaption, as well as elicit hypoalgesia in healthy and clinical populations (eg, post-operative), and has proven a viable option in military rehabilitation settings. The acceptability and tolerance of higher relative BFR pressures in persistent pain populations are unknown due to the complexity of presentation and the perception of discomfort experienced during BFR exercise. Greater relative pressures (ie, 80% limb occlusion pressure (LOP)) elicit a greater hypoalgesic response in pain-free individuals, but greater perceived discomfort which may not be tolerated in persistent pain populations. However, lower relative pressure (ie, 40% LOP) has elicited hypoalgesia in pain-free individuals, which therefore may be more clinically acceptable and tolerated in persistent pain populations. The primary aim of both randomised controlled trials (RCT) is to investigate the efficacy and acceptability of using high-frequency, low-load BFR-RT in UK military personnel with lower limb MSKI where persistent pain is the primary limiting factor for progression.

Methodology
The presented protocol is a two-phase RCT based within a military rehabilitation setting. Phase One is a 1-week RCT to determine the most efficacious and acceptable BFR-RT protocol (7x BFR-RT sessions over 5 days at 40% or 80% LOP; n=28). Phase Two is a 3-week RCT comparing the most clinically acceptable BFR pressure, determined by Phase One (21x BFR-RT sessions over 15 days; n=26) to usual care within UK Defence Rehabilitation residential rehabilitation practices. Outcomes will be recorded at baseline, daily and following completion of the intervention. The primary outcome will be the brief pain inventory. Secondary outcomes include blood biomarkers for inflammation and pain (Phase Two only), injury-specific outcome measures, lower extremity function scale, objective measures of muscle strength and neuromuscular performance, and pressure pain threshold testing.

Ethics and dissemination
The study is approved by the Ministry of Defence Research Ethics Committee (2318/MODREC/24) and Northumbria University. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.

Trial registration number
Registered with Clinical Trials. The registration numbers are as follows: NCT06621914 (Phase One) and NCT06621953 (Phase Two).

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Is It Time to Replace Plasma With Prothrombin Complex Concentrate in Cardiac Surgery?

Bleeding after cardiac surgery with cardiopulmonary bypass is associated with adverse clinical outcomes and increased resource utilization. Broadly speaking, this bleeding can be due to inadequate surgical hemostasis or microvascular bleeding caused by bypass-induced platelet dysfunction and/or depletion of coagulation factors. The most common method of restoring coagulation factors in this setting is through the transfusion of thawed frozen plasma, which occurs in approximately 25% of cardiac surgeries. Plasma is generally regarded as a safe treatment, with very low rates of transfusion-related acute lung injury (

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Cuts to HIV Assistance Could Undo Years of Progress

Since 2015, global foreign aid has provided nearly 40% of HIV-related funding in low- and middle-income countries. With an anticipated 24% reduction in international aid—in addition to the potential discontinuation of the US President’s Emergency Plan for AIDS Relief (PEPFAR)—a modeling study estimates that 4.4 million to 10.8 million additional HIV infections will occur by 2030.

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[Viewpoint] The importance of long-term studies in children following viral infection of the central nervous system

Viruses are a major cause of central nervous system (CNS) infections in pediatric patients, often resulting in significant rates of morbidity and mortality. Many viruses have been implicated in neurodevelopmental disorders with long-term consequences that significantly impact families, healthcare systems, economies, and society. Unfortunately, however, long-term follow-up studies evaluating neurodevelopmental outcomes in pediatric survivors of viruses affecting the nervous system are limited. The disease burden of CNS infection is often highest in regions where resources are lowest, such as in low- and middle-income countries (LMICs).

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Temporal trends and patient determinants of geographical variation in oral anticoagulant treatment of atrial fibrillation: a Danish nationwide cohort study in 2013-2022

Objectives
To investigate temporal trends in the geographical variation in oral anticoagulant (OAC) treatment of patients with atrial fibrillation, to evaluate the extent to which regional differences in patient populations may explain this difference and to explore whether patient predictors of adherence may have a different impact across regions.

Design
Register-based cohort study from 1 January 2013 to 31 December 2022.

Setting
The study used data from nationwide health registers to explore differences in OAC adherence across the five administrative regions in Denmark.

Participants
Patients with atrial fibrillation and a CHA2DS2-VASc score ≥2 (n=291 666).

Outcome
Population adherence to OAC treatment operationalised as the proportion of days covered (PDC).

Results
A continuous rise in overall adherence (PDC) from 53% to 78% was observed during the study period. Concurrently, the predominant treatment shifted from vitamin K antagonists to direct OACs with a preference for rivaroxaban and apixaban. The adherence variation between the highest-performing and lowest-performing regions decreased from 18% in 2013 to 9% in 2022, whereas the relative between-regions rankings remained unchanged. Applying multivariate Poisson models adjusting for patient demographics, health status and socioeconomic factors did not substantially change the inter-regional variations; this suggests that different compositions of patient populations cannot explain these variations. However, the impact of socioeconomic factors and comorbidities among patients was unequal across regions. In regions with the lowest overall adherence, a higher risk of non-adherence was seen among patients having mental health disorders, low income and living alone.

Conclusions
The geographical variation in OAC adherence decreased over time as the overall adherence improved. However, substantial variation remained.

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Conditioned open-label placebos to facilitate opioid reduction in patients with chronic non-cancer pain: study protocol of a randomised controlled trial

Introduction
Chronic non-cancer pain presents a global health problem, with a significant increase in opioid prescriptions over recent decades. However, opioid therapy poses risks of adverse events, overdose and non-medical use. As a result, many patients seek to discontinue or reduce their opioid intake. Strategies for opioid tapering often lack efficacy, prompting the investigation of novel approaches like open-label placebo (OLP), that is, the administration of a placebo with full disclosure that it is a placebo. OLP has shown efficacy in chronic non-cancer pain syndromes and has been suggested as a promising candidate for medication tapering. This study aims to assess whether OLPs can enhance the reduction of daily morphine equivalent dose (MED) in chronic non-cancer pain patients and examines its potential in mitigating opioid withdrawal symptoms.

Methods and analysis
This study is designed as a randomised, controlled, single-centre trial. Participants will be randomised into either an OLP group or a control group. The study duration will span six to nine weeks, during which all participants will aim to reduce their opioid intake. Both groups will monitor their opioid intake daily using a diary app and will receive feedback on their progress of reducing opioids. Additionally, participants in the OLP group will receive OLP tablets for the entire study period. During the first week, the OLP group will undergo a one week learning phase using a classical conditioning paradigm, where each opioid intake is paired with a placebo. In the subsequent five weeks, the OLP group will enter a dose-extension phase in which only the first opioid intake of the day is paired with a placebo, and additional placebos can be taken as desired. At the end of the study, qualitative interviews will be conducted with the first 15 participants in the OLP group. The primary outcome measure is daily opioid intake. Secondary outcomes include opioid withdrawal symptoms, pain severity, disability, anxiety, depression, opioid beliefs, intervention expectancy and qualitative data. Statistical analyses will include analysis of covariance and regression models.

Ethics and dissemination
The ethics committee of the Canton of Zurich, Switzerland, approved the study (SNCTP-nr.: SNCTP000005853/BASEC nr.: 2023–02327).
Participants will be compensated with 100 Swiss Francs for their full participation in the study. Participants who will take part in the qualitative interview will be compensated with additional 15 Swiss Francs.

Trial registration number
This study is registered at clinicaltrials.gov: NCT06350786.

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