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Background: Despite the rapid increase in research in China, little is known about the quality of clinical trials conducted there. Methods: A systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement. Results: Three hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate. Conclusion: Reporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained. [ABSTRACT FROM AUTHOR]

Background: The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods: We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results: While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions: CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response. Trial registration: This paper references experiences gained during management of three pan-European trials: EU-SolidAct's Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022). [ABSTRACT FROM AUTHOR]

Background: This paper examines the events and conditions that led to the creation of the International Clinical Trials Registry Platform (ICTRP) in 2006 by the World Health Organization (WHO), and how the WHO addressed the issue of transparency in global pharmaceutical research. Using historical textual analysis, I trace the scientific debates that advocated for the establishment of official clinical trial registries in medical journals, and the sequence of actions following the GSK Paxil scandal in 2004, identifying the major ethical and scientific arguments that led to the involvement of the WHO as a key actor in trial registration in the context of the Big Pharma business model. Results: Through the questions "Why register?" and "Why registries?" as a roadmap, I examine the issues of publication bias and selective reporting by the industry, scrutinizing two ways in which the practice of publication bias damaged transparency in industry-sponsored research. The first involved ethical concerns regarding human subject exploitation and concealing of negative results. The second addresses the deterioration of the certainty of evidence due to incomplete access to trials results. By reviewing the series of events that occurred between 2004 and 2006 –between the Paxil scandal and the launch of the ICTRP—, I analyze the actions taken by the different actors involved: (1) the International Committee of Medical Journal Editors (ICMJE) and the creation of the Ottawa Group; (2) the WHO, beginning with the Ministerial Summit on Health Research held in November of 2004, and (3) the responses of the pharmaceutical industry and specifically GSK to the call for transparency and trial registration. Conclusions: The history of trial registration through the ICTRP as a dataveillance apparatus shows the difficulty of regulating a health enterprise turned into a global business. Moreover, it shows the challenges of globalization and how easier and faster it is to globalize business compared to good practices, raising the question of why it has been so hard to undo these trends. Indeed, the history of the movement for trial registration is not a history of regulation success, or at least not yet. [ABSTRACT FROM AUTHOR]

Randomized Controlled Trials (RCTs) are the best method to determine causal effects for treatments if they are well done and well reported. Good evidence about proposed treatments for obesity is needed, and Hsieh et al. (Biomed Eng Online 17:149, 2018) are to be commended for putting moxibustion to the test. However, careful evaluation of the paper reveals inconsistencies and apparent reporting errors, which raise doubts about conclusions from the study. [ABSTRACT FROM AUTHOR]

Background: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. Methods: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. Discussion: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. Trial registration: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772) [ABSTRACT FROM AUTHOR]

Background: Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country.Methods: This observational study drew on systematic review methods. We searched six databases for published RCTs (database inception to December 2018) where ≥ 80% of participants were recruited in the Republic of Ireland. RCTs of interventions targeted at patients, providers and/or policy makers intended to improve health, healthcare or health research were included. For each study, screening, data extraction and methodological quality appraisal were conducted by one member of the author team.Results: From 17,560 titles and abstracts, 752 unique RCTs were published in 745 papers between 1968 and 2018, with a steady year-on-year increase since 1968. The number of participants was in the range of 2-8628. The majority were parallel design (86%) and classified as treatment evaluation. Of the 418 RCTs published since the introduction of mandatory clinical trial registration by the International Committee of Medical Journal Editors in 2005, 32% (n = 134) provided a trial registration number. This increased to 47% when taking studies published between 2013 and 2018 (n = 232). Since the 1996 publication of the CONSORT statement, 16% of included RCTs made specific reference to a standardised reporting guideline and this increased to 31% for more recent studies published between 2013 and 2018. Overall, 7% (n = 53) of studies referred to a published study protocol, increasing to 20% for studies published between 2013 and 2018.Conclusion: Evidence from this single-country study of RCTs published in the international literature suggests that both the number overall, the number registered and the number referencing reporting guidelines have increased steadily over time. Despite widespread endorsement of reporting standards, reporting of RCTs remains suboptimal in domains such as compliance with the CONSORT statement and prospective trial registration. Researchers, funders and journal editors, nationally and internationally, should continue to focus on improving reporting and examining avoidable waste of health research investment. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. Methods: The concept for patient-centered "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study. Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals. Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective. [ABSTRACT FROM AUTHOR]

Background: The occurrence of postoperative cognitive deficits, especially after heart surgery, has been demonstrated in several studies. These deficits can clearly be noticed by the patients and by their close relatives in daily life. Furthermore, postoperative cognitive deficits can decrease quality of life in social functioning and earning capacity. The aim of this study is to investigate whether early postoperative cognitive training can reduce subjective and objective postoperative cognitive deficits.Methods: The proposed study is a multicenter, two-arm, randomized controlled trial involving 144 elderly patients undergoing elective heart-valve surgery with extracorporeal circulation. Patients will be assigned to either a training group or a control group. The intervention involves paper-and-pencil-based cognitive training, which is conducted for 36 min over a period of 18 days. The training starts about 1 week after surgery and is carried out during the hospitalized rehabilitation phase. The control group will not receive cognitive training or a placebo intervention. A detailed assessment of psychological functions and health-related quality of life prior to surgery at discharge from rehabilitation and 3 and 12 months after discharge will be performed. The primary outcome of this trial is the training effect on objective cognitive functions at discharge from rehabilitation. Secondary outcomes are the training effect on objective and subjective cognitive functions (3 and 12 months after discharge), depression, health-related quality of life, and the impact of perioperative cerebral ischemia on the training effect. Perioperative cerebral ischemia will be measured with postoperative magnetic resonance imaging including diffusion-weighted sequences.Discussion: Should it be shown that our cognitive training can improve postoperative cognitive deficits and quality of life, one possibility could be to integrate this intervention into early rehabilitation. Furthermore, we hope that the investigation of perioperative ischemia by diffusion-weighted magnetic resonance imaging will improve our understanding of neurobiological factors influencing the course of postoperative cognitive plasticity.Trial Registration: German Clinical Trials Register (DRKS), DRKS00015512. Retrospectively registered on 21 September 2018. [ABSTRACT FROM AUTHOR]

Background: Falls are common among older people, and General Practitioners (GPs) could play an important role in implementing strategies to manage fall risk. Despite this, fall prevention is not a routine activity in general practice settings. The iSOLVE cluster randomised controlled trial aimed to evaluate implementation of a fall prevention decision tool in general practice. This paper sought to describe the strategies used and reflect on the enablers and barriers relevant to successful recruitment of general practices, GPs and their patients.Methods: Recruitment was conducted within the geographical area of a Primary Health Network in Northern Sydney, Australia. General practices and GPs were engaged via online surveys, mailed invitations to participate, educational workshops, practitioner networks and promotional practice visits. Patients 65 years or older were recruited via mailed invitations, incorporating the practice letterhead and the name(s) of participating GP(s). Observations of recruitment strategies, results and enabling factors were recorded in field notes as descriptive and narrative data, and analysed using mixed-methods.Results: It took 19 months to complete recruitment of 27 general practices, 75 GPs and 560 patients. The multiple strategies used to engage general practices and GPs were collectively useful in reaching the targeted sample size. Practice visits were valuable in engaging GPs and staff, establishing interest in fall prevention and commitment to the trial. A mix of small, medium and large practices were recruited. While some were recruited as a whole-practice, other practices had few or half of the number of GPs recruited. The importance of preventing falls in older patients, simplicity of research design, provision of resources and logistic facilitation of patient recruitment appealed to GPs. Recruitment of older patients was successfully achieved by mailed invitations which was a strategy that was familiar to practice staff and patients. Patient response rates were above the expected 10% for most practices. Many practices (n = 17) achieved the targeted number of 20 or more patients.Conclusions: Recruitment in general practice settings can be successfully achieved through multiple recruitment strategies, effective communication and rapport building, ensuring research topic and design suit general practice needs, and using familiar communication strategies to engage patients.Trial Registration: The trial was prospectively registered on 29 April 2015 with the Australian New Zealand Clinical Trial Registry www.anzctr.org.au (trial ID: ACTRN12615000401550). [ABSTRACT FROM AUTHOR]

Background: Research on clinical trials that employ stem cells to treat children's diseases is limited. The clinical trial registry database provides a unique window to us to get known about clinical trial researches with different statuses. However, few studies aimed to perform a comprehensive and thorough analysis of those registered trials in the aforementioned field based on ClinicalTrials.gov and the ICTRP portal site. Methods: Our study covered the clinical researches about stem cell therapy enrolling subjects aged under 18 years old registered on ClinicalTrials.gov and WHO ICTRP before May 18, 2021. A cross-sectional study was implemented to comprehensively describe and analyze the included trials that met the criteria. Results were available on ClinicalTrials.gov, and publications related to the included trials were identified. All analyses were performed utilizing the SPSS 25.0 software. Results: Eventually, 202 clinical trials were included and evaluated. The participant number of trials tended to be small; 71.3% were enrolled < 50. And 93.5% of the subjects were without gender restrictions. Till May 2020, 112 trials had been preliminary completed, of which only 39 trials had published papers or uploaded results. Most (73.6%) of 186 interventional trials were in phase 1 and phase 2, where 131 (70.4%) trials were conducted without masking, and 26.3% trials were randomized; 55.4% trials were performed single group assignment. Of 16 observational trials, case-only/series took up 37.5%. Hematopoietic stem cells (37.1%) and mesenchymal stem cells (36.1%) were mostly employed, while umbilical cord blood (UCB)-derived cells (24.3%) and bone marrow (BM)-derived cells (20.8%) were the major sources. Conclusions: This study provided an overall picture of utilizing stem cells for treatment and management of childhood diseases. Since clinical trials in this area are insufficient in quantity and quality, there is an urgent need of larger, better-designed trials. Increased investment in clinical research of stem cell treatment products should be carried out to achieve the transformation of results as soon as possible. Moreover, it is important to optimize the management of the registration platform and shorten the time it takes for research results to be published. [ABSTRACT FROM AUTHOR]

Background: The CONSORT Statement provides recommendations for reporting randomized controlled trials. We assessed the extent to which leading medical journals that publish reports of randomized trials incorporate the CONSORT recommendations into their journal and editorial processes. Methods: This article reports on two observational studies. Study 1: We examined the online version of 'Instructions to Authors' for 165 high impact factor medical journals and extracted all text mentioning the CONSORT Statement or CONSORT extension papers. Any mention of the International Committee of Medical Journal Editors (ICMJE) or clinical trial registration were also sought and extracted. Study 2: We surveyed the editor-in-chief, or editorial office, for each of the 165 journals about their journal's endorsement of CONSORT recommendations and its incorporation into their editorial and peer-review processes. Results: Study 1: Thirty-eight percent (62/165) of journals mentioned the CONSORT Statement in their online 'Instructions to Authors'; of these 37% (23/62) stated this was a requirement, 63% (39/62) were less clear in their recommendations. Very few journals mentioned the CONSORT extension papers. Journals that referred to CONSORT were more likely to refer to ICMJE guidelines (RR 2.16; 95% CI 1.51 to 3.08) and clinical trial registration (RR 3.67; 95% CI 2.36 to 5.71) than those journals which did not. Study 2: Thirty-nine percent (64/165) of journals responded to the on-line survey, the majority were journal editors. Eighty-eight percent (50/57) of journals recommended authors comply with the CONSORT Statement; 62% (35/56) said they would require this. Forty-one percent (22/53) reported incorporating CONSORT into their peer-review process and 47% (25/53) into their editorial process. Eighty-one percent (47/58) reported including CONSORT in their 'Instructions to Authors' although there was some inconsistency when cross checking information on the journal's website. Sixty-nine percent (31/45) of journals recommended authors comply with the CONSORT extension for cluster trials, 60% (27/45) for harms and 42% (19/45) for non-inferiority and equivalence trials. Few journals mentioned these extensions in their 'Instructions to Authors'. Conclusion: Journals should be more explicit in their recommendations and expectations of authors regarding the CONSORT Statement and related CONSORT extensions papers. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper is to describe the utility of various recruitment modalities utilized in the Working to Increase Stability through Exercise (WISE) study. WISE is a pragmatic randomized trial that is testing the impact of a 3-year, multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers or delivered via DVD on the rate of serious fall-related injuries among adults 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The modified goal was to recruit 1130 participants over 2 years in three regions of Pennsylvania.Methods: The at-risk population was identified primarily using letters mailed to patients of three health systems and those over 65 in each region, as well as using provider alerts in the health record, proactive recruitment phone calls, radio advertisements, and presentations at community meetings.Results: Over 24 months of recruitment, 209,301 recruitment letters were mailed, resulting in 6818 telephone interviews. The two most productive recruitment methods were letters (72% of randomized participants) and the research registries at the University of Pittsburgh (11%). An average of 211 letters were required to be mailed for each participant enrolled. Of those interviewed, 2854 were ineligible, 2,825 declined to enroll and 1139 were enrolled and randomized. Most participants were female (84.4%), under age 75 (64.2%), and 50% took an osteoporosis medication. Not having a prior fragility fracture was the most common reason for not being eligible (87.5%). The most common reason provided for declining enrollment was not feeling healthy enough to participate (12.6%).Conclusions: The WISE study achieved its overall recruitment goal. Bulk mailing was the most productive method for recruiting community-dwelling older adults at risk of serious fall-related injury into this long-term physical activity intervention trial, and electronic registries are important sources and should be considered. [ABSTRACT FROM AUTHOR]

Background: Vertigo and dizziness (VD) are among the most frequently seen symptoms in clinics and are important for medical students, especially for those in Chinese standardized residency training (SRT). The aim of our study was to examine the PAL method's feasibility in the clinical teaching of VD-related diseases for SRT students in China. Methods: This is a randomized, controlled, multicenter study. A total of 228 residents were invited to participate in this study, of which 198 completed the program. The students were randomized into two groups, and VD-related diseases were taught using lecture-based learning (control group) or peer-assisted learning (PAL). An examination paper and a rating scale were used to evaluate students' performance in the mastery of VD-related theoretical knowledge and clinical skills, meanwhile students' perceptions, satisfaction, and risk of burnout were also analyzed using a questionnaire. Independent-samples t-test and chi-square analysis were performed to evaluate statistical significance for continuous variables and categorical variables, respectively, using SPSS 18.0 software. Results: The PAL group performed better in mastering theoretical knowledge and clinical skills than the control group. And more students believed that PAL could help improve their personal qualities such as teamwork skills. However, more students reported that PAL increased the risk of burnout. Conclusions: PAL was a suitable and effective method in the clinical teaching of some specialized diseases, especially it was recommended for students who had gained initial knowledge and skills, such as Chinese SRT students. However, we should draw attention to the increased risk of burnout if PAL is intended to be widely used in clinical teaching. Trial registration: ISRCTN registry, ISRCTN53773239, 05/07/2021, retrospectively registered. [ABSTRACT FROM AUTHOR]

Undertaking recruitment for research in schools is an effective way to recruit young people for research participation but it is not without its challenges. Gaining access and coordinating many levels of different organisations and stakeholders whose cooperation and approval are crucial all add time and sometimes logistical challenges for the research team. In addition, recruiting around sensitive research topics can elicit additional barriers to successful research. The research team aimed to conduct a pragmatic cluster randomised controlled trial involving schools in a local government region in Victoria, Australia, to assess the effect of a vaccination-based educational card game called "Vaxcards" on vaccine consent returns. Schools were contacted via phone and email to determine which staff member would best be a contact point for a face-to-face meeting to discuss the methods and purpose of the study. Email follow-ups were scheduled to follow up non-responsive schools and consent forms. The minimum required sample size was 13. Of 31 eligible schools, 13 were recruited. The research team encountered several unanticipated challenges before achieving the recruitment target. The most common reasons for non-participation were being too busy with other commitments, concerns regarding the topic of vaccination being too sensitive, and concerns that key stakeholders in the school would not approve of the research topic of vaccination. One school required a review by a private research ethics board that rejected the study. Significant hesitancy and misinformation about vaccine science was observed that affected engagement with a small number of schools. This paper highlights the challenges of recruiting schools in the context of public anxieties about vaccines and has several important learning lessons for successful recruitment about sensitive topics. This includes navigating approval processes for research in schools, the importance of local champions, dealing with misinformation and the importance of strong relationships and organisational trust. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001753246 . Prospectively registered on 25 October 2018 8:24:21 AM. [ABSTRACT FROM AUTHOR]

Background: While high-quality meta-analyses have confirmed the effectiveness of aphasia therapy after stroke, there is limited evidence for the comparative effectiveness of different aphasia interventions. Two commonly used interventions, Constraint-induced Aphasia Therapy Plus (CIAT Plus) and Multi-modality Aphasia Therapy (M-MAT), are hypothesised to rely on diverse underlying neural mechanisms for recovery and may be differentially responsive to aphasia severity. COMPARE is a prospective randomised open-blinded end-point trial designed to determine whether, in people with chronic post-stroke aphasia living in the community, CIAT Plus and M-MAT provide greater therapeutic benefit compared to usual care, are differentially effective according to aphasia severity, and are cost-effective. This paper details the statistical analysis plan for the COMPARE trial developed prior to data analysis.Methods: Participants (n = 216) are randomised to one of three arms, CIAT Plus, M-MAT or usual care, and undertake therapy with a study trained speech pathologist in groups of three participants stratified by aphasia severity. Therapy occurs for 3 h blocks per day for 10 days across 2 weeks. The primary clinical outcome is aphasia severity as measured by the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ) immediately post intervention. Secondary outcomes include WAB-R-AQ at 12-week follow-up, and functional communication, discourse efficiency, multimodal communication, and health-related quality of life immediately post intervention and at 12-week follow-up.Results: Linear mixed models (LMMs) will be used to analyse differences between M-MAT and UC, and CIAT-Plus and UC on each outcome measure immediately and at 12 weeks post-intervention. The LMM for WAB-R-AQ will assess the differences in efficacy between M-MAT and CIAT-Plus. All analyses will control for baseline aphasia severity (fixed effect) and for the clustering effect of treatment groups (random effect).Discussion: This trial will provide relative effectiveness data for two common interventions for people with chronic post-stroke aphasia, and highlight possible differential effects based on aphasia severity. Together with the health economic analysis data, the results will enable more informed personalised prescription for aphasia therapy after stroke.Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN 12615000618550 . Registered on 15 June 2016. [ABSTRACT FROM AUTHOR]

Background: The translation of evidence from clinical trials into practice is complex. One approach to facilitating this translation is to consider the 'implementability' of trials as they are designed and conducted. Implementability of trials refers to characteristics of the design, execution and reporting of a late-phase clinical trial that can influence the capacity for the evidence generated by that trial to be implemented. On behalf of the Australian Clinical Trials Alliance (ACTA), the national peak body representing networks of clinician researchers conducting investigator-initiated clinical trials, we conducted a pragmatic literature review to develop a concept map of implementability.Methods: Documents were included in the review if they related to the design, conduct and reporting of late-phase clinical trials; described factors that increased or decreased the capacity of trials to be implemented; and were published after 2009 in English. Eligible documents included systematic reviews, guidance documents, tools or primary studies (if other designs were not available). With an expert reference group, we developed a preliminary concept map and conducted a snowballing search based on known relevant papers and websites of key organisations in May 2019.Results: Sixty-five resources were included. A final map of 38 concepts was developed covering the domains of validity, relevance and usability across the design, conduct and reporting of a trial. The concepts drew on literature relating to implementation science, consumer engagement, pragmatic trials, reporting, research waste and other fields. No single resource addressed more than ten of the 38 concepts in the map.Conclusions: The concept map provides trialists with a tool to think through a range of areas in which practical action could enhance the implementability of their trials. Future work could validate the strength of the associations between the concepts identified and implementability of trials and investigate the effectiveness of steps to address each concept. ACTA will use this concept map to develop guidance for trialists in Australia.Trial Registration: This review did not include health-related outcomes and was therefore not eligible for registration in the PROSPERO register. [ABSTRACT FROM AUTHOR]

Background: Although current guidelines make consensus recommendations for the early resumption of oral intake after surgery, a recent comprehensive meta-analysis failed to identify any patient-centered benefits. We hypothesized this finding was attributable to pooling studies providing effective protein-containing diets with ineffective non-protein liquid diets. Therefore, the aim of this paper was to investigate the safety and efficacy of early oral protein-containing diets versus later (traditional) feeding after elective lower gastrointestinal tract surgery in adults. Methods: PubMed, Embase, and the China National Knowledge Infrastructure databases were searched from inception until 1 August 2019. Reference lists of retrieved studies were hand searched to identify randomized clinical trials reporting mortality. No language restrictions were applied. Study selection, risk of bias appraisal and data abstraction were undertaken independently by two authors. Disagreements were settled by obtaining an opinion of a third author. Majority decisions prevailed. After assessment of underlying assumptions, a fixed-effects method was used for analysis. The primary outcome was mortality. Secondary outcomes included surgical site infections, postoperative nausea and vomiting, serious postoperative complications and other key measures of safety and efficacy. Results: Eight randomized clinical trials recruiting 657 patients were included. Compared with later (traditional) feeding, commencing an early oral protein-containing diet resulted in a statistically significant reduction in mortality (odds ratio [OR] 0.31, P = 0.02, I2 = 0%). An early oral protein-containing diet also significantly reduced surgical site infections (OR 0.39, P = 0.002, I2 = 32%), postoperative nausea and vomiting (OR 0.62, P = 0.04, I2 = 37%), serious postoperative complications (OR 0.60, P = 0.01, I2 = 25%), and significantly improved other major outcomes. No harms attributable to an early oral protein-containing diet were identified. Conclusions: The results of this systematic review can be used to upgrade current guideline statements to a grade A recommendation supporting an oral protein-containing diet commenced before the end of postoperative day 1 after elective lower gastrointestinal surgery in adults. [ABSTRACT FROM AUTHOR]

Background: The presence of hereditary cancer syndromes in cancer patients can have an impact on current clinical care and post-treatment prevention and surveillance measures. Several barriers inhibit identification of hereditary cancer syndromes in routine practice. This paper describes the impact of using a patient-facing family health history risk assessment platform on the identification and referral of breast cancer patients to genetic counselling services. Methods: This was a hybrid implementation-effectiveness study completed in breast cancer clinics. English-literate patients not previously referred for genetic counselling and/or gone through genetic testing were offered enrollment. Consented participants were provided educational materials on family health history collection, entered their family health history into the platform and completed a satisfaction survey. Upon completion, participants and their clinicians were given personalized risk reports. Chart abstraction was done to identify actions taken by patients, providers and genetic counsellors. Results: Of 195 patients approached, 102 consented and completed the study (mean age 55.7, 100 % women). Sixty-six (65 %) met guideline criteria for genetic counseling of which 24 (36 %) were referred for genetic counseling. Of those referred, 13 (54 %) participants attended and eight (33 %) completed genetic testing. On multivariate logistic regression, referral was not associated with age, cancer stage, or race but was associated with clinical provider (p = 0.041). Most providers (71 %) had higher referral rates during the study compared to prior. The majority of participants found the experience useful (84 %), were more aware of their health risks (83 %), and were likely to recommend using a patient-facing platform to others (69 %). Conclusions: 65 % of patients attending breast cancer clinics in this study are at-risk for hereditary conditions based on current guidelines. Using a patient-facing risk assessment platform enhances the ability to identify these patients systematically and with widespread acceptability and recognized value by patients. As only a third of at-risk participants received referrals for genetic counseling, further understanding barriers to referral is needed to optimize hereditary risk assessment in oncology practices. Trial Registration: NIH Clinical Trials registry, NCT04639934. Registered Nov 23, 2020 -- Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol.Methods: Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia's peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outcome measures before randomisation and 1, 3 and 6 months after study consent.Discussion: The Navigate online decision aid has the potential to increase the choice of AS in LRPC, avoiding or delaying unnecessary radical treatments and associated side effects. In addition, Navigate is likely to reduce patients' and partners' confusion and distress in management decision-making and increase their quality of life.Trial Registration: Australian and New Zealand Clinical Trial Registry ACTRN12616001665426 . Registered on 2 December 2016. All items from the WHO Trial Registration Data set can be found in this manuscript. [ABSTRACT FROM AUTHOR]

Rationale: Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium.Methods and Design: The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium.Results: This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications.Discussion: The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium.Trial Registration: Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number - U1111-1175-1814. [ABSTRACT FROM AUTHOR]

Background: Peer-led support models have gained increasing popularity in suicide prevention. While previous reviews show positive effects of peer-led support for people with mental health problems and those bereaved by suicide, little is known about the types of lived experience peer support programs in suicide prevention and whether these are effective in improving the health and wellbeing of people at risk of suicide. The aim of this paper is to provide an overview of peer support programs that aim to reduce suicidality and are led by people with lived experience of suicide. Method: We conducted a systematic scoping review, involving a search of three academic (Medline, PsycINFO, Embase) and selected grey literature databases (Google Scholar, WHO Clinical Trials Registry) for publications between 2000 and 2019. We also contacted suicide prevention experts and relevant internet sites to identify peer support programs that exist but have not been evaluated. The screening of records followed a systematic two-stage process in alignment with PRISMA guidelines. Results: We identified 8 records accounting for 7 programs focussed on peer-led support programs in suicide prevention. These programs employed a range of different designs and included a variety of settings (schools, communities, rural and online). Only 3 of the 7 programs contained data on effectiveness. With the small number of eligible programs the findings from this review are limited and must be interpreted with caution. Conclusions: Despite the increased focus of policymakers on the importance of peer support programs in suicide prevention, our scoping review confirms an evidence gap in research knowledge regarding program design, implementation, and effectiveness. More rigour is required in reporting peer-led support initiatives to clarify the underlying definition of peer support and lived experience and to enhance our understanding of the types of current peer support programs available to those experiencing suicidality. Further, we need formal and high-quality evaluations of peer support suicide prevention programs led by people with lived experience to better understand their effectiveness on participant health across different settings and delivery modalities and to allow for comprehensive systematic reviews and meta-analysis in future. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest among older people in moving into retirement villages (RVs), an attractive option for those seeking a supportive community as they age, while still maintaining independence. Currently in New Zealand there is limited knowledge of the medical, service supports, social status and needs of RV residents. The objective of this study is to explore RV facilities and services, the health and functional status of RV residents, prospectively study their healthcare trajectories and to implement a multidisciplinary team intervention to potentially decrease dependency and impact healthcare utilization.Methods: All RVs located in two large district health boards in Auckland, New Zealand were eligible to participate. This three-year project comprised three phases: The survey phase provided a description of RVs, residents' characteristics and health and functional status. RV managers completed a survey of size, facilities and recreational and healthcare services provided in the village. Residents were surveyed to establish reasons for entry to the village and underwent a Gerontology Nurse Specialist (GNS) assessment providing details of demographics, social engagement, health and functional status. The cohort study phase examines residents' healthcare trajectories and adverse outcomes, over three years. The final phase is a randomised controlled trial of a multidisciplinary team intervention aimed to improve health outcomes for more vulnerable residents. Residents who triggered potential unmet health needs during the assessment in the survey phase were randomised to intervention or usual care groups. Multidisciplinary team meetings included the resident and support person, a geriatrician or gerontology nurse practitioner, GNS, pharmacist and General Practitioner. The primary outcome of the randomised controlled trial will be first acute hospitalization. Secondary outcomes include all acute hospitalizations, long-term care admissions, and all-cause mortality.Discussion: This paper describes the study protocol of this complex study. The study aims to inform policies and practices around health care services for residents in retirement villages. The results of this trial are expected early 2020 with publication subsequently.Trial Registration: Australia and New Zealand Clinical Trials Registry: ACTRN12616000685415 . Registered 25.5.2016. Universal Trial Number (UTN): U111-1173-6083. [ABSTRACT FROM AUTHOR]

Background: We are performing a combined randomised and observational study comparing internal fixation to non-surgical management for common wrist fractures in older patients. This paper describes the statistical analysis plan.Methods/design: A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE) is a randomised controlled trial comparing two types of usual care for treating wrist fractures in older patients, surgical fixation using volar locking plates and non-surgical treatment using closed reduction and plaster immobilisation. The primary aim of this comparative-effectiveness study is to determine whether surgery is superior to non-surgical treatment with respect to patient-reported wrist function at 12 months post treatment. The secondary outcomes include radiographic outcomes, complication rates and patient-reported outcomes including quality of life, pain, treatment success and cosmesis. Primary analysis will use a two-sample t test and an intention-to-treat analysis using the randomised arm of the study. Statistical analyses will be two-tailed and significance will be determined by p < 0.05. Sensitivity analyses will be conducted to assess for differences in intention-to-treat, per-protocol and as-treated analyses. Sensitivity analyses will also be conducted to assess selection bias by evaluating differences in participants between the randomised and observational study arms, and for bias relating to any missing data. An economic analysis will be conducted separately if surgery is shown to provide superior outcomes to a level of clinical significance.Discussion: This statistical analysis plan describes the analysis of the CROSSFIRE study which aims to provide evidence to aid clinical decision-making in the treatment of distal radius fractures in older patients.Trial Registration: CROSSFIRE was approved by The Hunter New England Human Research Ethics Committee (HNEHREC Reference No: 16/02/17/3.04). Registered on 22 July 2016 with The Australian and New Zealand Clinical Trials Registry (ANZCTR Number; ACTRN12616000969460 ). This manuscript is based on v.11 of the statistical analysis plan. A copy of v.11, signed by the chief investigator and the senior statistician is kept at the administering institution. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders are a risk factor for developing a variety of mental disorders, have a negative impact on their remission rates and increase the risk of relapse. Early identification and treatment of sleep disorders is therefore of paramount importance. Unfortunately, in mental health care sleep disorders are often poorly recognized and specific treatment frequently occurs late or not at all. This protocol-paper presents a randomized controlled trial investigating the clinical relevance of early detection and treatment of sleep disorders in mental health care. The two aims of this project are 1) to determine the prevalence of sleep disorders in different mental disorders, and 2) to investigate the contribution of early identification and adequate treatment of sleep disorders in individuals with mental disorders to their sleep, mental disorder symptoms, general functioning, and quality of life. Methods: Patients newly referred to a Dutch mental health institute for psychiatric treatment will be screened for sleep disorders with the self-assessment Holland Sleep Disorders Questionnaire (HSDQ). Patients scoring above the cut-off criteria will be invited for additional diagnostic evaluation and, treatment of the respective sleep disorder. Participants will be randomly assigned to two groups: Immediate sleep diagnostics and intervention (TAU+SI-T0), or delayed start of sleep intervention (TAU+SI-T1; 6 months after inclusion). The effect of sleep treatment as add-on to treatment as usual (TAU) will be tested with regard to sleep disorder symptoms, general functioning, and quality of life (in collaboration with a psychiatric sleep centre). Discussion: This trial will examine the prevalence of different sleep disorders in a broad range of mental disorders, providing information on the co-occurrence of specific sleep and mental disorders. Further, this study is the first to investigate the impact of early treatment of sleep disorders on the outcome of many mental disorders. Moreover, standard sleep interventions will be tailored to specific mental disorders, to increase their efficacy. The results of this trial may contribute considerably to the improvement of mental health care. Trial registration: This clinical trial has been retrospectively registered in the Netherlands Trial Register (NL8389; https://www.trialregister.nl/trial/8389) on February 2th, 2020. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity and unhealthy eating are two leading behavioral risk factors contributing to preventable non-communicable diseases (NCDs). Evidence-based interventions (EBI) using community-engaged approaches to address these risks abound in high-income countries. Comparatively, evidence of such interventions is sparse in low- and middle-income countries, where NCD mortality is greater. This paper describes the protocol for the development of the cultural adaptation and pilot testing of a combination of two EBI (i.e., Body and Soul and the Healthy Body Healthy Spirit), in church-based settings in Lagos, Nigeria. In addition, we describe the development of the inclusion of an additional component, i.e., faith-based text messages, into one of the treatment arms. Our objective is to assess the feasibility of developing and implementing the adapted interventions with the ultimate aim of developing a fully powered trial. Methods: This pilot study will assess the design and implementation of a three-arm cluster-randomized pilot trial in 12 randomly selected Anglican churches (4 in each arm). First, we will design a cultural adaptation of the two EBI's to form a multifaceted combined intervention known as the Body Soul and Spirit. The second treatment arm, i.e., Body Soul and Spirit Plus, will retain all the components of Body Soul and Spirit with the inclusion of faith-based text messages using mobile phones. Participants in the control arm will receive information leaflets designed to increase physical activity and healthy food consumption. The outcome measures include participant recruitment and retention, program participation and satisfaction, and data collection completion rates. The outcomes for the proposed definitive trial will be the number of servings of fruit and vegetables and minutes of moderate to vigorous physical activity per day will be assessed at baseline, 3 and 6-month follow-up. Implementation outcomes will be assessed using qualitative and quantitative methods. Discussion: The study will enhance the understanding of how best to design and implement behavioral interventions in church-based settings using community-based participatory approaches. It will also inform the development of a definitive randomized controlled trial. Trial registration: Pan African Clinical Trials Registry on 12th July 2018. PACTR201807136835945. Available at https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3481 [ABSTRACT FROM AUTHOR]

Background: Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a condition characterized by clinical and laboratory evidence of acute or sub-acute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow. HIE is a common and devastating clinical condition in resource-poor countries with poor treatment outcome. This paper describes the protocol for an ongoing study that aims to evaluate the neuroprotective effects of Erythropoietin (EPO) as compared to routine care in the management of moderate to severe HIE among term infants.Methods: This study is a double-blind randomized controlled trial that will be conducted in the neonatal wards of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, over a two-year period after ethical approvals and consents. One hundred and twenty-eight term newborns (≥ 37 weeks gestation) diagnosed with moderate/ severe HIE at admission will be allocated by randomization to receive either EPO or normal saline. All the participants will be offered standard care according to the unit protocol for HIE. Baseline investigations and close monitoring of the babies are done until discharge. Participants are followed up for 2 years to monitor their outcome (death or neurological development) using standard instruments.Discussion: Previous trials had shown that EPO confers neuroprotective benefits and improve neurological and behavioral outcome in infants with HIE both singly or as an adjuvant to therapeutic hypothermia. This study hypothesized that administering EPO to newborns with moderate /severe HIE can positively influence their clinical and neurological outcomes and will provide evidence to either support or disprove the usefulness of Erythropoietin as a sole agent in the treatment of HIE, especially in resource-limited environment with the highest burden of the disease.Trial Registration: The study has been registered with the Pan African Clinical trials registry on the 2nd of December 2018, with registration number PACTR201812814507775. [ABSTRACT FROM AUTHOR]

Background: Parkinson disease (PD) is a debilitating and chronic neurodegenerative disease resulting in ambulation difficulties. Natural walking activity often declines early in disease progression despite the relative stability of motor impairments. In this study, we propose a paradigm shift with a "connected behavioral approach" that targets real-world walking using cognitive-behavioral training and mobile health (mHealth) technology.Methods/design: The Walking and mHealth to Increase Participation in Parkinson Disease (WHIP-PD) study is a twelve-month, dual site, two-arm, randomized controlled trial recruiting 148 participants with early to mid-stage PD. Participants will be randomly assigned to connected behavioral or active control conditions. Both conditions will include a customized program of goal-oriented walking, walking-enhancing strengthening exercises, and eight in-person visits with a physical therapist. Participants in the connected behavioral condition also will (1) receive cognitive-behavioral training to promote self-efficacy for routine walking behavior and (2) use a mHealth software application to manage their program and communicate remotely with their physical therapist. Active control participants will receive no cognitive-behavioral training and manage their program on paper. Evaluations will occur at baseline, three-, six-, and twelve-months and include walking assessments, self-efficacy questionnaires, and seven days of activity monitoring. Primary outcomes will include the change between baseline and twelve months in overall amount of walking activity (mean number of steps per day) and amount of moderate intensity walking activity (mean number of minutes per day in which > 100 steps were accumulated). Secondary outcomes will include change in walking capacity as measured by the six-minute walk test and ten-meter walk test. We also will examine if self-efficacy mediates change in amount of walking activity and if change in amount of walking activity mediates change in walking capacity.Discussion: We expect this study to show the connected behavioral approach will be more effective than the active control condition in increasing the amount and intensity of real-world walking activity and improving walking capacity. Determining effective physical activity interventions for persons with PD is important for preserving mobility and essential for maintaining quality of life. Clinical trials registration NCT03517371, May 7, 2018.Trial Registration: ClinicalTrials.gov: NCT03517371. Date of registration: May 7, 2018. Protocol version: Original. [ABSTRACT FROM AUTHOR]

Background: Regulatory agencies, such as the European Medicines Agency and Health Canada, are requiring the public sharing of clinical trial reports that are used to make drug approval decisions. Both agencies have provided guidance for the quantitative anonymization of these clinical reports before they are shared. There is limited empirical information on the effectiveness of this approach in protecting patient privacy for clinical trial data.Methods: In this paper we empirically test the hypothesis that when these guidelines are implemented in practice, they provide adequate privacy protection to patients. An anonymized clinical study report for a trial on a non-steroidal anti-inflammatory drug that is sold as a prescription eye drop was subjected to re-identification. The target was 500 patients in the USA. Only suspected matches to real identities were reported.Results: Six suspected matches with low confidence scores were identified. Each suspected match took 24.2 h of effort. Social media and death records provided the most useful information for getting the suspected matches.Conclusions: These results suggest that the anonymization guidance from these agencies can provide adequate privacy protection for patients, and the modes of attack can inform further refinements of the methodologies they recommend in their guidance for manufacturers. [ABSTRACT FROM AUTHOR]

Background: Nurses' recognition of clinical deterioration is crucial for patient survival. Evidence for the effectiveness of modified early warning scores (MEWS) is derived from large observation studies in developed countries.Methods: We tested the effectiveness of the paper-based Cape Town (CT) MEWS vital signs observation chart and situation-background-assessment-recommendation (SBAR) communication guide. Outcomes were: proportion of appropriate responses to deterioration, differences in recording of clinical parameters and serious adverse events (SAEs) in intervention and control trial arms. Public teaching hospitals for adult patients in Cape Town were randomised to implementation of the CT MEWS/SBAR guide or usual care (observation chart without track-and-trigger information) for 31 days on general medical and surgical wards. Nurses in intervention wards received training, as they had no prior knowledge of early warning systems. Identification and reporting of patient deterioration in intervention and control wards were compared. In the intervention arm, 24 day-shift and 23 night-shift nurses received training. Clinical records were reviewed retrospectively at trial end. Only records of patients who had given signed consent were reviewed.Results: We recruited two of six CT general hospitals. We consented 363 patients and analysed 292 (80.4%) patient records (n = 150, 51.4% intervention, n = 142, 48.6% control arm). Assistance was summoned for fewer patients with abnormal vital signs in the intervention arm (2/45, 4.4% versus (vs) 11/81, 13.6%, OR 0.29 (0.06-1.39)), particularly low systolic blood pressure. There was a significant difference in recording between trial arms for parameters listed on the MEWS chart but omitted from the standard observations chart: oxygen saturation, level of consciousness, pallor/cyanosis, pain, sweating, wound oozing, pedal pulses, glucose concentration, haemoglobin concentration, and "looks unwell". SBAR was used twice. There was no statistically significant difference in SAEs (5/150, 3.3% vs 3/143, 2.1% P = 0.72, OR 1.61 (0.38-6.86)).Conclusions: The revised CT MEWS observations chart improved recording of certain parameters, but did not improve nurses' ability to identify early signs of clinical deterioration and to summon assistance. Recruitment of only two hospitals and exclusion of patients too ill to consent limits generalisation of results. Further work is needed on educational preparation for the CT MEWS/SBAR and its impact on nurses' reporting behaviour.Trial Registration: Pan African Clinical Trials Registry, PACTR201406000838118. Registered on 2 June 2014, www.pactr.org. [ABSTRACT FROM AUTHOR]

Background: There has been little research to investigate whether the appearance of paper patient information leaflets (PILs) used to describe research studies to potential participants influences their decision to take part. Embedding a study within a trial (SWAT) is an efficient way of answering this type of methodological question. We included a randomised SWAT within a large cohort study, Outcome Monitoring after Cardiac Surgery (OMACS), to address this question.Methods: Potential participants for the OMACS study were randomised to receive one of three PILs, which were identical in content but with varying formatting and use of colour: PIL A (enhanced format), PIL B (hybrid format) and PIL C (standard format). Consent to OMACS was the primary outcome. Consent rates using the three different PIL formats were collected and compared. Qualitative feedback on the different formats was obtained from a public and patient involvement (PPI) group.Results: For the SWAT, 1517 PILs were sent to potential participants, of whom 640 (42%) consented to take part in OMACS. PIL B had the highest recruitment rate, with 45% of patients consenting to participation; 40% and 41% of patients consented to participation after receiving PILs A and C, respectively. Compared to PIL C, the consent rate was 4% higher with PIL B (45% versus 41%, 95% confidence interval (CI) -2% to + 10%, p = 0.16) and 1% lower with PIL A (40% versus 41%, 95% CI - 7% to + 5%, p = 0.72).Conclusions: Consent rates were similar for all three PIL formats. PIL B is being used for the remainder of the host study and will be used to inform the design of PILs for other research studies, as it was the preferred format of the PPI group.Trial Registration: International Clinical Trials Registry, ISRCTN90204321. Registered on 21 January 2015. [ABSTRACT FROM AUTHOR]

Background: The integration of Virtual Reality (VR) with Case-Based Learning (CBL) has the potential to revolutionise undergraduate medical education, particularly in complex subjects such as the anatomy and rehabilitation of the shoulder joint. This study aimed to explore the effectiveness of this innovative approach in enhancing learning outcomes and knowledge retention. Methods: This study employed a parallel-group, assessor-blinded randomised controlled trial (RCT) design. A comprehensive five-week educational programme was developed, combining traditional lecture-based learning with VR-enhanced CBL. The study involved 82 undergraduate students from China Medical University, who were divided into groups receiving different combinations of VR and CBL. Student performance was evaluated through tests and questionnaires. Results: In the anatomy-related courses, the integration of VR technology with CBL yielded significantly higher results (87.71 ± 5.60) compared to traditional methods (82.59 ± 6.64), with a statistically significant difference (P < 0.05). This provides compelling evidence of VR's potential to enhance student engagement and knowledge retention. In the context of physiotherapy-related courses, however, while the test scores of the VR-combined CBL group (81.85 ± 5.99) were marginally higher than those of the traditional CBL group (79.02 ± 7.57), this difference was not statistically significant (P > 0.05). Conclusion: The present study provides preliminary evidence for the benefits of incorporating VR into medical education, particularly in anatomy. While the results are promising, further research is needed to explore the optimal integration of VR and CBL in rehabilitation studies and to assess their long-term impact on student learning and clinical performance. Trial registration: The study was registered with Chinese Clinical Trials Registry (Registration Number: ChiCTR2400089295) on 05/09/2024. [ABSTRACT FROM AUTHOR]

The current research ethics review systems are composed of isolated institutional Research Ethics Committees (RECs) that develop their own standard operating procedures (SOPs), templates and so on, with low adoption of digital solutions to manage submission and review processes. This poses several challenges, such as delays, higher costs, and hindering multi-site research. We propose an online national research ethics platform that all RECs can use, with common review processes and documentation requirements following national policy. The system will scale up adoption of digital solutions to all RECs. It will reduce administrative burden and harmonize review procedures. It will also obviate the need for separate and isolated interventions such as national REC registries or clinical trial registries, as these can be generated as transactional outputs of the system. The harmonized procedures and possibility of single submission will facilitate multi-site research. Sharing of resources and expertise among RECs on the platform will enhance resilience. An e-EC system developed in India and a Regional Health research portal developed by the WHO South-East Asia office offer proof of concepts to demonstrate the feasibility of developing and using such systems. The proposed solution is ambitious but feasible. Developing the proposed system will be a vital cost-effective investment in national health infrastructure to strengthen the research ecosystem and accelerate delivery of improved healthcare innovations by reducing unnecessary delays in conducting research. To maximize benefits, concurrent efforts are needed to build researchers' capacity and enhance the quality and efficiency of human reviews of the research proposals by REC. [ABSTRACT FROM AUTHOR]

Background: Modern housing has been shown to reduce the risk of malaria infections compared to traditional houses; however, it is unclear if the effects differ in different malaria transmission settings. This study evaluated the effects of modern housing on malaria among different endemic areas. Methods: Electronic databases, clinical trial registries and grey literature were searched for randomized controlled trials, cohort studies, case–control studies, and cross-sectional surveys on housing done between 1987 and 2022. Forest plots were done, and the quality of evidence was assessed using the Grading of Recommendations, Assessments, Development and Evaluation Framework. Results: Twenty-one studies were included; thirteen were cross-sectional, four were case–control and four were cohort studies. Cohort studies showed an adjusted risk ratio of 0.68 (95% CI 0.48–0.96), and cross-sectional studies indicated an adjusted odds ratio (aOR) of 0.79 (95%CI 0.75–0.83). By endemic transmission regions, the adjusted odds ratio in the high endemic settings was 0.80 (95%CI 0.76–085); in the moderate transmission regions, aOR = 0.76 (95%CI 0.67–0.85) and in the low transmission settings, aOR = 0.67 (95%CI 0.48–0.85). Conclusions: The evidence from observational studies suggests that there are no differences in the protective effects of modern houses compared to traditional houses on malaria by endemicity level. This implies that good quality modern housing protects against malaria regardless of the malaria transmission settings. [ABSTRACT FROM AUTHOR]

Background: Adequate reporting of adaptive designs (ADs) maximises their potential benefits in the conduct of clinical trials. Transparent reporting can help address some obstacles and concerns relating to the use of ADs. Currently, there are deficiencies in the reporting of AD trials. To overcome this, we have developed a consensus-driven extension to the CONSORT statement for randomised trials using an AD. This paper describes the processes and methods used to develop this extension rather than detailed explanation of the guideline.Methods: We developed the guideline in seven overlapping stages: 1) Building on prior research to inform the need for a guideline; 2) A scoping literature review to inform future stages; 3) Drafting the first checklist version involving an External Expert Panel; 4) A two-round Delphi process involving international, multidisciplinary, and cross-sector key stakeholders; 5) A consensus meeting to advise which reporting items to retain through voting, and to discuss the structure of what to include in the supporting explanation and elaboration (E&E) document; 6) Refining and finalising the checklist; and 7) Writing-up and dissemination of the E&E document. The CONSORT Executive Group oversaw the entire development process.Results: Delphi survey response rates were 94/143 (66%), 114/156 (73%), and 79/143 (55%) in rounds 1, 2, and across both rounds, respectively. Twenty-seven delegates from Europe, the USA, and Asia attended the consensus meeting. The main checklist has seven new and nine modified items and six unchanged items with expanded E&E text to clarify further considerations for ADs. The abstract checklist has one new and one modified item together with an unchanged item with expanded E&E text. The E&E document will describe the scope of the guideline, the definition of an AD, and some types of ADs and trial adaptations and explain each reporting item in detail including case studies.Conclusions: We hope that making the development processes, methods, and all supporting information that aided decision-making transparent will enhance the acceptability and quick uptake of the guideline. This will also help other groups when developing similar CONSORT extensions. The guideline is applicable to all randomised trials with an AD and contains minimum reporting requirements. [ABSTRACT FROM AUTHOR]

Background: Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer).Methods: A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised controlled trials (more than 1000 adult participants) published from March 2006 to April 2017 were evaluated. Two reviewers screened and extracted data attaining > 95% concordance of papers checked. Assessment of bias in the trials was evaluated using the Cochrane Risk of Bias tool.Results: Fifty-seven thousand three hundred and fifty-two papers were identified and 65 trials which had post-trial follow-up (PTFU) were included in the analysis. The majority of trials used more than one type of follow-up. There was no evidence of an association between the retention rates of participants in the PTFU period and the type of follow-up used. Costs of PTFU varied widely with data linkage being the most economical. It was not possible to assess associations between risk of bias during the in-trial period and proportions lost to follow-up during the PTFU period.Discussion: Data captured during the post-trial follow-up period can add scientific value to a trial. However, there are logistical and financial barriers to overcome. Where available, data linkage via electronic registries and records is a cost-effective method which can provide data on a range of endpoints.Systematic Review Registration: Not applicable for PROSPERO registration. [ABSTRACT FROM AUTHOR]

Background: Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes implemented during the study. We present a process evaluation protocol of a home-based gait, balance, and resistance exercise intervention to ameliorate persistent taxane-induced neuropathy study according to 7 key elements of process evaluation. Methods: The process evaluation is conducted parallel to the longitudinal, randomized control clinical trial examining the effects of the home-based gait, balance, and resistance exercise program for women with persistent peripheral neuropathy following treatment with taxanes for breast cancer (IRB approval: Pro00040035). The flowcharts clarify how the intervention should be implemented in comparable settings, fidelity procedures help to ensure the participants are comfortable and identify their individual needs, and the process evaluation allows for the individual attention tailoring and focus of the research to avoid protocol deviation. Conclusions: The publication of the evaluation protocol plan adds transparency to the findings of clinical trials and favors process replication in future studies. The process evaluation enables the team to systematically register information and procedures applied during recruitment and factors that impact the implementation of the intervention, thereby allowing proactive approaches to prevent deviations from the protocol. When tracking an intervention continuously, positive or negative intervention effects are revealed early on in the study, giving valuable insight into inconsistent results. Furthermore, a process evaluation adds a participant-centered element to the research protocols, which allows a patient-centered approach to be applied to data collection. Trial registration: ClinicalTrials.gov NCT04621721, November 9, 2020, registered prospectively. Protocol version: April 27, 2020, v2. [ABSTRACT FROM AUTHOR]

Background: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. Methods: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel–Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. Discussion: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. Systematic review registration: PROSPERO-ID CRD42023410645. [ABSTRACT FROM AUTHOR]

Background: Hearing impairments are a rising burden in our aging society. Hearing loss is associated with reduced cognitive performance as well as decrements in balance and gait. Therefore, impaired hearing affects also dual tasking (DT). The aim of this review is to summarize the evidence for DT performance decrements of older adults with hearing impairments during maintaining balance or walking. Methods: The systematic literature research according to PRISMA guidelines was conducted using MEDLINE, APA Psych-Info, and Web of Science. Inclusion criteria were: Independent living older people ≥ 60 years with hearing impairments, use of a DT paradigm to test hearing impaired older adults within a balance or walking condition. Results: N = 57 studies were found within the databases. Eight studies were included (N = 456 participants (58% women), including n = 200 older hearing-impaired persons with different levels of hearing loss). Most of the included studies oriented their inclusion criteria for hearing-impairments at thresholds for mild hearing loss with Pure Tone Average (0.5-4 kHz) ≥ 25 and < 40 dB. Three of the studies focused on DT balance performance and five used DT walking comparing participants with and without hearing loss. For DT balance and gait performance, higher decrements for the hearing-impaired group were observed compared to healthy older adults. Performance decrements were accompanied by reduced compensatory strategies in balance performance. Conclusion: More pronounced decrements in DT performance were observed for participants with hearing impairments compared to those without. This implies that hearing-impaired older adults might need specific interventions to reduce the cognitive-motor interference (CMI) to maintain balance control or walking stability in daily situations that require managing of cognitive and motor tasks simultaneously. However, taking all results into account the underlying mechanisms of CMI for this target group needs to be further examined. Trial registration: This review was registered at Prospero with the ID CRD42022340232. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to create a machine learning architecture capable of identifying obstructive sleep apnea (OSA) patterns in single-lead electrocardiography (ECG) signals, exhibiting exceptional performance when utilized in clinical data sets. Methods: We conducted our research using a data set consisting of 1656 patients, representing a diverse demographic, from the sleep center of China Medical University Hospital. To detect apnea ECG segments and extract apnea features, we utilized the EfficientNet and some of its layers, respectively. Furthermore, we compared various training and data preprocessing techniques to enhance the model's prediction, such as setting class and sample weights or employing overlapping and regular slicing. Finally, we tested our approach against other literature on the Apnea-ECG database. Results: Our research found that the EfficientNet model achieved the best apnea segment detection using overlapping slicing and sample-weight settings, with an AUC of 0.917 and an accuracy of 0.855. For patient screening with AHI > 30, we combined the trained model with XGBoost, leading to an AUC of 0.975 and an accuracy of 0.928. Additional tests using PhysioNet data showed that our model is comparable in performance to existing models regarding its ability to screen OSA levels. Conclusions: Our suggested architecture, coupled with training and preprocessing techniques, showed admirable performance with a diverse demographic dataset, bringing us closer to practical implementation in OSA diagnosis. Trial registration The data for this study were collected retrospectively from the China Medical University Hospital in Taiwan with approval from the institutional review board CMUH109-REC3-018. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials (RCTs) are usually the basis of evidence-based medicine, but whether the results of RCTs can be correctly translated into clinical practice depends on the quality of the literature reported. In this study, we evaluated the general characteristics and quality of paediatric RCTs published in China to provide evidence for the reporting of paediatric RCTs and their application in clinical practice. Methods: We conducted a cross-sectional observational study of paediatric RCTs published in paediatric journals in China between January 1, 1999, and December 30, 2022. All RCTs that included children (younger than 18 years old) were retrieved, and the general characteristics of the RCTs were extracted and analysed. The quality of the RCTs was assessed by the Cochrane quality assessment protocol. Results: After screening 20 available paediatric journals, 3545 RCTs were included for analysis. The average annual growth rate of the number of published paediatric RCTs from 1999 to 2022 was 7.8% (P = 0.005, R2 = 0.311). Most of the studies were carried out in East China [1148 (32.4%]; the centres of the RCTs were mainly single-centre [3453 (97.4%], and the interventions were mainly medication [2442 (68.9%)]. Comparing RCTs published in 2017–2022 with RCTs published in 1999–2004, the quality of RCTs significantly improved in terms of random sequence generation, allocation concealment, blinding participants and personnel, incomplete outcome data and selective outcome reporting. RCTs published in multiple centres from the Chinese Science Citation Database were identified, and the approval of the ethics committee was of better quality for all the analysed risk of bias items. Conclusion: The number and quality of paediatric RCTs reported in China have improved in recent years, but the overall quality was relatively low. Special attention should be given to allocation concealment and blinding outcome assessment, and dropouts, adverse effects and sample size calculations should be reported. Promoting government policies, strengthening the standardization of journal publishing and advancing the registration of clinical trials are feasible measures. [ABSTRACT FROM AUTHOR]

Background: Acute Coronary Syndrome is the most common heart disease and the most significant cause of death and disability-adjusted life years worldwide. Teaching a healthy eating style is one preventive measure to prevent the disease's recurrence. This study aimed to determine the effect of healthy nutrition education with the help of traffic light labels on food selection, preference, and consumption in patients with acute coronary syndrome. Methods: This randomized, single-blinded clinical trial was conducted with 139 participants (66 in the intervention group and 73 in the control group) from January 2021 to August 2021 in Shaheed Rajaie Hospital, Tehran, Iran. The control group received standard training. The intervention group, besides this, received additional bedside training with an educational poster on traffic light labels from the research team during their final hospitalization days. Data were collected using a researcher-made questionnaire on food selection, preference, and consumption. Results: The Brunner-Munzel test showed no significant difference between the two groups in terms of selection (P = 0.127), preference (P = 0.852), and food consumption (P = 0.846) in the baseline, while after the intervention, there were significant differences in selection (P > 0.001), preference (P > 0.001), and consumption (p < 0.004). Comparing the difference between the two groups in the difference between the before and after scores for selection (p < 0.001), preference (p < 0.001), and food consumption (p = 0.011) with the Brunner-Munzel test indicated a significant difference in all outcome variables. Conclusions: Teaching healthy eating styles with the help of traffic light labels affected food selection, preference, and consumption and led to healthier diets in these patients. Clinical trial registration number: Clinical trial registration: It was prospectively registered in the Iran Clinical Trials Registration Center on this date 30/10/2020 (IRCT20200927048857N1). [ABSTRACT FROM AUTHOR]

Background: For the purpose of epidemiological surveillance, the Hospital University Institute Méditerranée infection has implemented since 2013 a system named MIDaS, based on the systematic collection of routine activity materials, including MALDI-TOF spectra, and results. The objective of this paper is to present the pipeline we use for processing MALDI-TOF spectra during epidemiological surveillance in order to disclose proteinic cues that may suggest the existence of epidemic processes in complement of incidence surveillance. It is illustrated by the analysis of an alarm observed for Streptococcus pneumoniae.Methods: The MALDI-TOF spectra analysis process looks for the existence of clusters of spectra characterized by a double time and proteinic close proximity. This process relies on several specific methods aiming at contrasting and clustering the spectra, presenting graphically the results for an easy epidemiological interpretation, and for determining the discriminating spectra peaks with their possible identification using reference databases.Results: The use of this pipeline in the case of an alarm issued for Streptococcus pneumoniae has made it possible to reveal a cluster of spectra with close proteinic and temporal distances, characterized by the presence of three discriminant peaks (5228.8, 5917.8, and 8974.3 m/z) and the absence of peak 4996.9 m/z. A further investigation on UniProt KB showed that peak 5228.8 is possibly an OxaA protein and that the absent peak may be a transposase.Conclusion: This example shows this pipeline may support a quasi-real time identification and characterization of clusters that provide essential information on a potentially epidemic situation. It brings valuable information for epidemiological sensemaking and for deciding on the continuation of the epidemiological investigation, in particular the involving of additional costly resources to confirm or invalidate the alarm.Clinical Trials Registration: NCT03626987. [ABSTRACT FROM AUTHOR]

Background: Health systems globally are investing in integrating secure messaging platforms for virtual care in clinical practice. Implementation science is essential for adoption, scale-up, spread and maintenance of complex evidence-based solutions in clinics with evolving priorities. In response, the mobile Health (mHealth) Research Group modified the existing consolidated framework for implementation research (CFIR) to evaluate implementation of virtual health tools in clinical settings. WelTel® is an evidence-based digital health platform widely deployed in various geographical and health contexts. The objective is to identify the facilitators and barriers for implementing WelTel and to assess the application of the mCFIR tool in facilitating focus groups in different geographical and health settings.Methods: Both qualitative and descriptive quantitative approaches were employed. Six mCFIR sessions were held in three countries with 51 key stakeholders. The mCFIR tool consists of 5 Domains and 25 constructs and was distributed through Qualtrics Experience Management (XM). "Performance" and "Importance" scores were valued on a scale of 0 to 10 (Mean ± SD). Descriptive analysis was conducted using R computing software. NVivo 12 Pro software was used to analyze mCFIR responses and to generate themes from the participants' input.Results: We observed a parallel trend in the scores of Importance and Performance. Of the five Domains, Domain 4 (End-user Characteristics) and Domain 3 (Inner Settings) scored highest in Importance (8.9 ± 0.5 and 8.6 ± 0.6, respectively) and Performance (7.6 ± 0.7 and 7.2 ± 1.3, respectively) for all sites. Domain 2 (Outer Setting) scored the lowest in both Importance and Performance for all sites (7.6 ± 0.4 and 5.6 ± 1.8). The thematic analysis produced the following themes: for areas of strengths, the themes brought up were timely diagnosis and response, cost-effectiveness, and user-friendliness. As for areas for improvement, the themes discussed were training, phone accessibility, stakeholder engagement, and literacy.Conclusion: The mCFIR tool allowed for a comprehensive understanding of the barriers and facilitators to the implementation, reach, and scale-up of digital health tools. Amongst several important findings, we observed the value of bringing the perspectives of both end users (HCPs and patients) to the table across Domains.Trial Registration: NCT02603536 - November 11, 2015: WelTelOAKTREE: Text Messaging to Support Patients With HIV/AIDS in British Columbia (WelTelOAKTREE). NCT01549457 - March 9, 2012: TB mHealth Study-Use of Cell Phones to Improve Compliance in Patients on LTBI Treatment. [ABSTRACT FROM AUTHOR]

Background: Discrepancies between pre-specified and reported outcomes are an important and prevalent source of bias in clinical trials. COMPare (Centre for Evidence-Based Medicine Outcome Monitoring Project) monitored all trials in five leading journals for correct outcome reporting, submitted correction letters on all misreported trials in real time, and then monitored responses from editors and trialists. From the trialists' responses, we aimed to answer two related questions. First, what can trialists' responses to corrections on their own misreported trials tell us about trialists' knowledge of correct outcome reporting? Second, what can a cohort of responses to a standardised correction letter tell us about how researchers respond to systematic critical post-publication peer review?Methods: All correspondence from trialists, published by journals in response to a correction letter from COMPare, was filed and indexed. We analysed the letters qualitatively and identified key themes in researchers' errors about correct outcome reporting, and approaches taken by researchers when their work was criticised.Results: Trialists frequently expressed views that contradicted the CONSORT (Consolidated Standards of Reporting Trials) guidelines or made inaccurate statements about correct outcome reporting. Common themes were: stating that pre-specification after trial commencement is acceptable; incorrect statements about registries; incorrect statements around the handling of multiple time points; and failure to recognise the need to report changes to pre-specified outcomes in the trial report. We identified additional themes in the approaches taken by researchers when responding to critical correspondence, including the following: ad hominem criticism; arguing that trialists should be trusted, rather than follow guidelines for trial reporting; appealing to the existence of a novel category of outcomes whose results need not necessarily be reported; incorrect statements by researchers about their own paper; and statements undermining transparency infrastructure, such as trial registers.Conclusions: Researchers commonly make incorrect statements about correct trial reporting. There are recurring themes in researchers' responses when their work is criticised, some of which fall short of the scientific ideal. Research on methodological shortcomings is now common, typically in the form of retrospective cohort studies describing the overall prevalence of a problem. We argue that prospective cohort studies which additionally issue correction letters in real time on each individual flawed study-and then follow-up responses from trialists and journals-are more impactful, more informative for those consuming the studies critiqued, more informative on the causes of shortcomings in research, and a better use of research resources. [ABSTRACT FROM AUTHOR]

Background: Endodontic therapy in pediatric dentistry is a challenging procedure, especially for special needs, uncooperative, and very young patients. A new conservative approach which is the non-instrumental endodontic treatment (NIET) has been developed to simplify the management of primary teeth requiring pulpectomy. This review aimed to compare the efficiency of NIET and conventional endodontic treatment in primary teeth. Methods: Electronic databases including MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Scopus without restrictions on publication year or publication language were searched. Only randomized clinical trials reporting clinical and radiographical outcomes of NIET and conventional pulpectomy on primary teeth were considered eligible. Two reviewers extracted the data according to the PRISMA statement and assessed the bias risk using the revised Cochrane risk-of-bias tool and a meta-analysis was performed. Results: From 3322 screened articles, seven articles meeting the inclusion criteria were included. The selected studies included 283 primary molars, of 213 children aged between 3 and 9 years, treated by NIET and conventional pulpectomy, and had follow-up periods ranging from 1 month to tooth exfoliation. Two studies reported good success rates for both the NIET technique and endodontic therapy with no statistically significant difference while three studies showed radiographical significant differences with a low success rate for the NIET technique. Only one study reported better outcomes in the pulpectomy group with statistically significant differences. The quantitative grouping of the included studies showed no significant differences between NIET and conventional endodontic therapy regarding clinical and radiographical success (p value > 0.05). Conclusion: No difference between the NIET technique and the conventional endodontic therapy in primary molars requiring pulpectomy could be confirmed. Results of the present review need to be interpreted with caution since the quality of evidence according to the GRADE was considered as moderate to very low. Therefore, additional clinical trials on the NIET technique are recommended. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. Methods: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. Results: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. Conclusions: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. Trial registration: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829. [ABSTRACT FROM AUTHOR]

Background: n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions. Methods: Databases and clinical trials registries were searched for articles including "n-of-1" in the title between 2011 and 2023. The reference lists of reviews identified by the searches were searched for any additional eligible articles. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables. Results: We identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare conditions. They were conducted in a range of clinical areas with the most common being neurological conditions (n = 16, 21.6%). The median (Q1, Q3) number of participants randomised was 9 (4, 20) and 12 trials (16.2%) involved a single patient only. Forty-six (62.2%) trials evaluated pharmaceutical interventions and 49 (66.2%) trials were placebo controlled. Trials had a median (Q1, Q3) of six (4, 8) periods and 61 (82.4%) compared two health technologies. Fifty-seven (77.0%) trials incorporated blinding and 32 (43.2%) had a washout period. Forty-nine trials (66.2%) used patient-reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 48 (64.9%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare conditions were generally consistent with those in non-rare conditions. Conclusions: n-of-1 trials are still underused and the application of the n-of-1 design for the evaluation of health technologies for rare diseases has been particularly limited. We have summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 studies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Premenstrual syndrome (PMS) is prevalent among women of reproductive age, but most do not seek medical advice. We hypothesized that building PMS awareness could promote medical help-seeking for PMS and thus reduce menstrual symptoms and improve work productivity. Methods: In January 2020, women aged between 25 and 44 years, having paid work, and not currently consulting with an obstetrics and gynecology doctor (n = 3090) responded to the Menstrual Distress Questionnaire (MDQ), the Premenstrual Symptoms screening tool, and the World Health Organisation Health and Work Performance Questionnaire. In addition, they received checklist-based online education for PMS. Of 3090 participants, 2487 (80.5%) participated in a follow-up survey in September 2020. We conducted multiple logistic regression analyses and text analyses to explore factors that encouraged and discouraged medical help-seeking. We also evaluated changes in menstrual symptoms and work productivity, using generalized estimating equations with interactions between the severity of PMS, help-seeking, and time. Results: During the follow-up period, 4.9% of the participants (121/2487) sought medical help. Those having high annual income (adjusted odds ratio [aOR] = 2.07, 95% confidence interval [CI]: 1.21–3.53) and moderate-to-severe PMS (aOR = 2.27, 95% CI: 1.49–3.46) were more likely to have sought medical help. Those who did not seek medical help despite their moderate-to-severe PMS reported normalization of their symptoms (36%), time constraints (33%), and other reasons for not seeking medical help. Participants with moderate-to-severe PMS who had sought medical help showed a significant improvement of − 8.44 points (95% CI: − 14.73 to − 2.15 points) in intermenstrual MDQ scores during the follow-up period. However, there were no significant improvements in premenstrual and menstrual MDQ scores or absolute presenteeism. Conclusion: Medical help-seeking alleviated intermenstrual symptoms in women with moderate-to-severe PMS, but only a small proportion of them sought medical help after PMS education. Further research should be conducted to benefit the majority of women who are reluctant to seek medical help, including the provision of self-care information. Trial registration: UMIN Clinical Trials Registry number: UMIN000038917. [ABSTRACT FROM AUTHOR]

Background: Coronavirus 2019 (COVID-19) is an epidemic condition that compromises various consequences. The goal of this study was to investigate the effect of home-based pulmonary rehabilitation on exercise capacity in patients with post COVID-19 syndrome. Methods: The study was designed as a randomized control trial. A total of sixty-eight patients with post COVID-19 syndrome complaining of fatigue, dyspnea, and exercise intolerance participated in this study. Their ages ranged from 40 to 70 years old. The patients were randomly classified into two equal groups. The control group received usual medical care only, whereas the rehabilitation group received a selected home-based pulmonary rehabilitation exercise program plus the same usual medical care. The Physical Fitness Index (PFI), Chalder fatigue index, SF-36 questionnaire, dyspnea scale, and six-minute walk test (6 MWT) were measured before and after 12 weeks of intervention. Results: The rehabilitation group showed a significant lower mean of Chalder fatigue (11.1 ± 0.94) and a higher mean of 6MWT (439.7 ± 25.3) and PFI (52.3 ± 10.2), in addition to a higher mean of the SF-36 Questionnaire (66.4 ± 3.7) and a significant improvement of dyspnea in the mMRC score (26.7%), grade 2, (63.3%), grade 1 (10%), and grade 0 with a p-value < 0.001 when compared to the control group. Conclusion: Home-based pulmonary rehabilitation (HBPR) for patients with post COVID-19 syndrome is effective and has a potential direct influence on exercise capacity, fatigue, dyspnea, and quality of life. HBPR could be considered an adjunctive, applicable, and low-cost therapy for patients with post COVID-19 syndrome. Trial registration: The study was registered in Pan African Clinical Trial Registry as a clinical trial ID (PACTR202111640499636), November 2021. [ABSTRACT FROM AUTHOR]