BMJ Open最新文献

Objective: This post hoc analysis compared the immunogenicity of the biosimilar adalimumab-adbm (Cyltezo) with the adalimumab reference product (RP; Humira) across indications, including rheumatoid arthritis (RA), Crohn's disease (CD) and plaque psoriasis (PsO), and by patient sex in the VOLTAIRE trials programme.

Methods: In each active-comparator randomised controlled trial (RCT), immunogenicity was assessed at various time points by the proportion of patients with antidrug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by electrochemiluminescence assay. Assay sensitivity was 50 ng/mL, and drug tolerance was ≥30 µg/mL (free drug) at the low positive control level.

Results: Minor differences in immunogenicity parameters (ADAs, ADA titres and nAbs) were evident between adalimumab-adbm and adalimumab RP across these three immune-mediated inflammatory diseases (IMIDs). The proportion of ADA-positive and nAb-positive patients increased from baseline over time in all three RCTs, as expected, and was similar in the RA and CD RCTs but with higher numbers of ADA-positive and nAb-positive patients reported in the PsO trial. Subgroup analysis by patient sex showed the same trend.

Conclusions: Differences among the RCTs may partially be explained by concomitant background therapy (methotrexate) in the RA trial, stable doses of azathioprine, 6-mercaptopurine or methotrexate in 36% of patients with CD and absence of background therapy in the PsO RCT. The analyses further confirm the biosimilarity of adalimumab-adbm with the adalimumab RP across IMIDs and provide supporting evidence that adalimumab-adbm is an interchangeable biosimilar with consistent clinical results in patients originally treated with the RP.

Trial registration numbers: VOLTAIRE-RA (NCT02137226; EudraCT 2012-002945-40); VOLTAIRE-CD (NCT02871635; EudraCT 2016-000612-14); VOLTAIRE-PsO (NCT02850965; EudraCT 2016-000613-79).

Introduction: Teleworking is one of the most significant legacies of the pandemic. Great attention is now being paid to its effects on workers' health. One of the arguments that emerged on this issue is that 'working away from the office' affects the time we spend with significant others. This calls into question all those processes that make relatives and colleagues important to our health, such as forms of mentoring and social support, but also conflicts, work interruptions or control over workers' activities. So far, no study has evaluated the impact that teleworking has on these processes using data on personal networks. The Empty Office is the first study to use social network analysis to measure the impact that telework has on social relations and, in turn, workers' health and well-being.

Methods and analysis: The project draws on a total sample of 4400 participants from Switzerland, the Netherlands, Spain and Germany (n=1100 per country). The choice of these countries is due to their specificity and diversity in socioeconomic features, which make them particularly interesting for studying teleworking from a comparative point of view. The research is conceived as a sequential mixed-method design. First, quantitative data collection will administer an online questionnaire to gather information on telework modalities, health and well-being markers, and data on personal networks collected by a name generator. A qualitative module, administered one year later, will consist of in-depth interviews with a subsample (n=32) of teleworkers selected for delving narratively into the mechanisms identified with the quantitative analyses.

Ethics and dissemination: This study has obtained 2 years of funding from the Swiss Network for International Study and was approved by the Ethics Committee of the University of Geneva (CUREG-20230920-292-2). All participants will be asked to provide informed consent to participate in this study. The results will be shared with international organisations and disseminated in scientific journals and conferences. Fully anonymised data will be made available on the Open Science Framework (OSF) data-repository platform.

Introduction: Postoperative delirium (POD) is a common neurological complication after surgery among older patients, characterised by acute disturbances in consciousness, attention and cognition, usually occurring within 24-72 hours after surgery. POD has a significant impact on the prognosis of older patients undergoing major cardiovascular surgery, including increased length of hospital stay, hospital costs and readmission rates, with an incidence rate as high as 26%-52%. Computerised cognitive training (CCT) refers to difficulty-adaptive training in cognitive domains such as attention, memory and logical reasoning, using systematically designed tasks. Existing studies have shown that CCT has reduced the risk of delirium in non-cardiac surgery patients with at least minimal compliance. The purpose of this study is to investigate the effects of preoperative CCT on the incidence of POD in older patients undergoing elective cardiac surgery, to clarify the dose-effect relationship between different training time of preoperative CCT and POD and to explore the minimum effective time target that can significantly lower the incidence of POD.

Methods and analysis: This is a prospective, single-blind, randomised controlled trial that aims to enrol 261 older patients scheduled for elective cardiac surgery at the Affiliated Hospital of Xuzhou Medical University. The patients will be randomised into three groups: group C will be the routine care group (no CCT prior to surgery); group L will be the low-dose time group (with a total of 5 hours of CCT prior to surgery) and group H will be the high-dose time group (with a total of 10 hours of CCT prior to surgery). The primary outcome is the incidence of delirium within 7 days after surgery. Secondary outcomes include postoperative mild neurocognitive disorder (NCD) and postoperative major NCD (30 days up to 1 year), time of onset and duration and severity of delirium, and all-cause mortality within 1 year after surgery. The results of this study are of significant importance for establishing effective, patient-centred and low-risk prevention strategies for POD/postoperative NCD.

Ethics and dissemination: This study protocol has been approved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (Ethics Number: XYFY2023-KL149-01). All participants will provide written informed consent, and the results of the study will be published in international peer-reviewed academic journals and presented at academic conferences.

Trial registration number: ChiCTR2300072806.

Background: Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration.

Methods: We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching <90% of target enrolment), and whether the primary outcome had been changed as compared with the initial protocol registration.

Results: The 775 clinical trials included in the analysis planned to enrol 238 933 (median (IQR) 120 (60, 304) patients; 355 (46%) of the trials had reported results, and 283 (36%) were published in a scientific journal. In the reported trials, the total enrolment was 95 332 (median (IQR) 105 (45, 222) patients. 186 (24%) trials were completed, and 169 (22%) trials were discontinued, with slow recruitment being the most stated reason for discontinuation (9% of all trials, although 30% of the discontinued trials did not report a reason). 117 (33%) of the reported trials had changed their primary outcome. In total, 157 (20%) trials were completed and published in a scientific journal, of which 105 enrolled ≥100 patients and 103 had not changed the primary outcome. 63 completed and published trials enrolled ≥100 patients and had not changed the primary outcome.

Conclusions: Most clinical trials of COVID-19 registered at ClinicalTrials.gov during the first 6 months of the pandemic remained unreported or had been discontinued. Many of the trials whose results had been reported enrolled few patients and changed the primary outcome after trial registration.

Objectives: Serrated polyps (SPs) with synchronous advanced adenoma (AA) may increase the incidence of colorectal cancer. However, current studies do not address this combination of SPs and AAs in detail with regard to their clinical characteristics in different age groups. The aim was to assess clinical characteristics and risk factors for SPs with synchronous AA in different age groups.

Design: Retrospective cohort study.

Setting: Electronic medical record data from January 2011 to January 2022 at three grade III class A hospitals were enrolled in the study.

Participants: A total of 1605 patients with SPs with synchronous AA, including 484 patients in the elderly group and 1121 patients in the non-elderly group, were studied.

Main exposure measure: The elderly group and the non-elderly group.

Main outcome measure: Sex, smoking history, drinking history, body mass index (BMI), SP location, size, morphology and pathology.

Results: The incidence of hyperplastic polyps (HPs) with synchronous AA in the elderly group was higher than that in the non-elderly group, while the incidence of sessile serrated adenomas/polyps (SSAs/Ps) with synchronous AA in the non-elderly group was higher than that in the elderly group. Male sex, drinking history and HP size (≤20 mm) were independent risk factors for HPs with synchronous AA in the non-elderly group, while drinking history and HP size (≤15 mm) were independent risk factors in the elderly group. For SSAs/Ps with synchronous AA, male sex, smoking history, drinking history, and SSA size (≥16 mm) were independent risk factors in the non-elderly group; high BMI was an independent risk factor in the elderly group.

Conclusions: SPs with synchronous AA showed different clinical characteristics and risk factors in different age groups.

Introduction: Knee osteoarthritis (OA) represents a leading cause of disability globally. Exercise has been demonstrated to improve pain and function in people with knee OA. However, when in pain, commencement of exercise is difficult, and clinical effects with such interventions are often modest. Recently, transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, has been shown to bolster the pain-relieving effect of exercise in experimental settings. While promising, the utility of employing this approach beyond the research environment is yet to be elucidated. Therefore, this pilot study aims to investigate the feasibility, safety, adherence, tolerability and preliminary efficacy of tDCS and exercise in home-based settings to improve pain and function in people with knee OA.

Methods and analysis: This protocol is for a pilot randomised, double-blinded, sham-controlled trial. 24 individuals with idiopathic knee OA will be randomised to receive either active tDCS+exercise (Intervention) or sham tDCS+exercise (Control) at home. Participants will receive 20 min of tDCS 5 days per week for the first 2 weeks of this 8-week trial. Participants in both groups will complete a lower limb strengthening programme 3 days per week for the entire 8 weeks. Outcome measures of feasibility (acceptability, satisfaction, retention), safety, adherence and tolerability will be assessed throughout the trial period, with clinical outcomes of pain and function assessed before and following the intervention. Feasibility, safety, adherence and tolerability outcomes will be explored descriptively using frequencies and percentages. To examine preliminary efficacy, within-group and between-group changes in pain and functional measures will be analysed.

Ethics and dissemination: This protocol obtained ethical approval from the Queensland University of Technology Human Research Ethics Committee (HREA 2024-8302-20200). All participants will provide written informed consent. The findings of the study will be disseminated via journal publications and international conference proceedings.

Trial registration number: ACTRN12624000397516p.

Introduction: Globally, long-distance truck drivers' (LDTDs) risk of exposure to HIV infections is higher compared with other populations in transit. Thus, several HIV prevention interventions have been implemented, though to a narrower extent compared with other most at-risk populations. Consequently, the effectiveness of such interventions is not well understood. Therefore, a review is warranted to inform policymakers on the most effective HIV prevention interventions targeted for LDTDs.

Methods and analysis: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines were followed. Original peer-reviewed interventional studies involving LDTDs of either gender aged above 18 years, and reporting findings on HIV prevention interventions from any part of the world will be included. Non-empirical research studies like systematic reviews, literature reviews and scoping reviews will be excluded. A comprehensive search will be done from PubMed, Cumulated Index to Nursing and Allied Health Literature and other five databases to identify eligible studies. The Rayyan online platform will be used for the screening of titles and abstracts. For the meta-analysis, a random-effects meta-analysis using the 'metafor' package in R software will be done. Where specific studies may not report adequate data for meta-analysis, their findings will be presented qualitatively. The Cochrane Collaboration tool and Joanna Brigs Checklist will be used to assess the quality and risk of bias in the included studies.

Ethics and dissemination: A formal ethical approval is not required for this systematic review and meta-analysis. The findings will be presented at scientific conferences and published in open-access peer-reviewed journals to reach policymakers, stakeholders and the scientific community.

Prospero registration number: CRD42024505542.

Objective: This study aimed to assess the determinants of underweight among returnees lactating mothers in governmental health facilities of Gedeo zone, Southern Ethiopia.

Design: Case-control study.

Setting: Gedeb District governmental health facilities.

Participants: A total of 264 returnees lactating mothers (88 cases and 176 controls) were randomly selected from four health institutions of Gedeb District.

Outcome measures: Underweight was measured by anthropometric measurement weight/height². An institutional-based unmatched case-control study was conducted from 11 July 2022 to 20 September 2022. The study involved 264 returnee lactating mothers, with 88 classified as cases (body mass index, BMI<18.5 kg/m²) and 176 as controls (BMI 18.5-24.9 kg/m²). Participants were selected through simple random sampling from public health institutions. Data were collected on sociodemographic, reproductive and nutritional factors using structured questionnaires and anthropometric measurements. Bivariate and multivariable logistic regression analyses were performed to identify significant determinants of maternal underweight.

Result: The study identified several key determinants of underweight. Returnee lactating mothers with a short birth interval (<24 months) were significantly more likely to be underweight (adjusted OR (AOR) 4.04, 95% CI 1.68 to 9.74). Unplanned pregnancies (AOR 7.60, 95% CI 3.14 to 18.41), home deliveries (AOR 5.81, 95% CI 2.09 to 16.14) and meals frequency <3 per day (AOR 2.51, 95% CI 1.12 to 5.63) were also strongly associated with increased risk of underweight. Inadequate dietary diversity (AOR 3.92, 95% CI 1.52 to 10.15) and food insecurity (AOR 4.72, 95% CI 1.77 to 12.61) further contributed to the risk. Poor socioeconomic status was associated with a higher likelihood of being underweight (AOR 4.38, 95% CI 1.49 to 12.82).

Conclusion: The study highlights significant factors contributing to maternal underweight among returnee lactating mothers. Addressing short birth intervals, unplanned pregnancies, dietary diversity and food insecurity is crucial. Policy-makers should focus on targeted interventions to improve maternal health, with special emphasis on returnee lactating mothers. Enhanced healthcare access, nutritional support and socioeconomic development are essential for mitigating underweight and improving overall health outcomes.

Introduction: Early detection of colorectal cancer (CRC) and clinically relevant (advanced) adenomas leads to a significant reduction of CRC-related mortality and morbidity. However, the faecal immunochemical test (FIT) suffers from a high number of false-positive results and is insensitive to detecting advanced adenomas, resulting in false-negative results for these premalignant lesions. Therefore, more accurate, non-invasive screening tools are needed for the detection and prognostication of colorectal neoplasia. Previous research on volatile organic compounds (VOCs) analysis in breath and faeces has shown to be promising potential biomarkers for this purpose. Several VOC-sampling methods, including breath sampling, have improved significantly over the recent years resulting in an increased reliability of measurements. Therefore, we aim to identify relevant VOC profiles in exhaled breath and faeces for the diagnosis of colorectal neoplasia while taking into account relevant confounding factors. Follow-up data will be used to identify relevant VOC profiles in exhaled breath and faeces for the prognostication of colorectal neoplasia. Finally, a biobank will be set up for future research questions on this topic.

Methods and analysis: Subjects with positive FIT within the Dutch national CRC cancer screening programme are included. Subjects are asked to fill in questionnaires and exhaled breath, faeces and blood are sampled prior to colonoscopy. All subjects are asked to fill in follow-up questionnaires at years 1 and 5 of the study. In case of surveillance colonoscopies, subjects are asked to provide exhaled breath, faeces and blood prior to the colonoscopy again. Breath sampling is performed using the ReCIVA breath sampler. VOCs in breath and faeces are analysed using gas-chromatography-mass spectrometry (GC-MS). Raw GC-MS data is preprocessed and analysed using machine learning techniques.

Ethics and dissemination: The study is approved by the medical ethics committee at the Maastricht University Medical Center (NL74844.068.20) in November 2021 and started inclusion in January 2022.

Background: Splitting or crushing medications are used for dosage administration when a certain dose is not easily accessible. Understanding the splitting or crushing of medications is essential to guarantee safe medication administration since inappropriate handling might impact therapeutic efficacy, safety and patient outcomes.

Objectives: This study intends to examine the practices, attitudes and knowledge of the Jordanian population regarding the splitting/crushing of medications.

Study design and setting: This is a cross-sectional survey study conducted in Jordan between November 2022 and March 2023. The questionnaire tool was adapted from previous literature, and binary logistic regression analysis was used, to identify the predictors of participants' knowledge concerning medication splitting/crushing.

Participants: A total of 1259 participants from the general public were involved, without restrictions on gender or age.

Results: Around 22.2% of participants confirmed that tablet splitting/crushing is a useful way to reduce medication costs. 67.0% reported that they are not sure whether tablets are suitable for splitting/crushing/crushing. 75.8% reported that they refer to package leaflet information to check whether tablets are suitable for splitting/crushing. 84.8% correctly believed that scored tablets can be split, while unscored tablets cannot. 72.0% identified correctly that not all types of tablets and capsules can be split/crushed or dissolved. The mean knowledge score of study participants was 2.7 (SD: 1.5) out of 6, which is equal to 45% of the maximum attainable score and reflects a weak level of knowledge about tablet crushing. Those who hold a bachelor's degree and have an income level of JD500-JD1000 (which is equal to US$715-US$1428) were more likely to have knowledge about tablet crushing. Around 39.2% of the participants reported that they had split or crushed tablets to reach their desired dose, of which the vast majority (82.9%) were using scored tablets.

Conclusion: Understanding of tablet-splitting and crushing techniques ought to be enhanced while encouraging prescribing practices that stress safety and well-informed decision-making. Patients should actively seek reliable sources of information, have an awareness of which tablets can be safely divided and actively engage with healthcare experts to receive appropriate guidance.