International Clinical Trials Research Articles

Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications

BackgroundGenetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms.MethodsWe performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients—divided into a discovery and validation cohort—were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments.ResultsWe identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses.ConclusionsSusceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures.Trial registrationThe LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015–02-13).

P240: Sarcopenia of the lower limb on Magnetic Resonance Imaging in patients with Diabetes Mellitus – a systematic review

Abstract Introduction Sarcopenia is defined by low measures of muscle quantity and quality and physical performance. Accelerated sarcopenic changes in diabetic patients leads to biomechanical changes in the foot and limb loss. Aim To systematically review the literature on Magnetic Resonance Imaging (MRI) and sarcopenia in the lower limb in patients with diabetes. Methods A literature review was conducted in accordance with PRISMA guidelines. Embase and Medline databases were searched with Ovid interface, as well as Pubmed and Cochrane. The grey literature was also reviewed on ClinicalTrials.gov, WHO international clinical trials registry platform, Cochrane library and the NIHR journals library and ProQuest. The MeSH terms “sarcopenia” AND “diabetes mellitus” AND “magnetic resonance imaging” were employed in the primary search string. The articles were reviewed by two independent reviewers. Results 874 studies were screened. 20 articles were included in the final review. Methods of measurement included cross sectional area measurements, stereological muscle measurements, muscle volume estimation, adipose infiltration, signal intensity cut-off, Goutallier grading, semiquantitative 5-point scale. Reduction in cross-sectional area and volumes and greater intramuscular fat infiltration was noted in patients with diabetes Sarcopenia ++ in Diabetic polyneuropathy (DPN) compared to non-diabetic and diabetic but non-DPN counterparts. MRI findings correlate with neuropathy disability scores and physical tests. Single study using a semi-automated process to measure sarcopenia. Conclusion MRI has its merit in providing accurate and detailed information on skeletal muscle volume and assessment of fat infiltration in muscle. This is relevant to reducing complications associated with changes in the biomechanics of the foot.

Face-down positioning or posturing after pars plana vitrectomy for macula-involving rhegmatogenous retinal detachments.

Face-down positioning or posturing after pars plana vitrectomy for macula-involving rhegmatogenous retinal detachments.

Japan’s contribution to an ongoing global pediatric cancer clinical trial: The experience of the National Cancer Center Hospital (NCCH) in Tokyo

Compared to Europe and the United States, where the development of pediatric oncology drugs is mandated by law, Japan hosts fewer clinical trials. This can lead to a significant drug lag, especially in the case of treatments for pediatric solid tumors. Notably, regulatory authorities and the government have initiated discussions on strategies to mitigate Japan’s drug lag problem in pediatric oncology. Over the past decade, we have actively sought opportunities to participate in international collaborative clinical trials through Japan’s involvement in ACCELERATE and its predecessor organizations. This approach has aimed to address the issue above, coinciding with the ongoing centralization of medical care and advancements in genomic medicine, among other systems that support pediatric cancer care in Japan. Inspired by the ACCELERATE initiatives and in response to patient advocacy groups’ requests for new pediatric oncology drugs, Japan established its inaugural pediatric oncology support platform in 2021, the National Childhood Cancer Consortium (N3C). N3C comprises patient advocacy groups, industries, and academia. This work outlines the current status of pediatric drug development in Japan and highlights the initial successful experience of NCCH’s participation in a global clinical trial through ACCELERATE resulting in rapid preparation and patient recruitment. Participation of Asian countries including Japan in global collaborative clinical trials may benefit both pharmaceutical companies and the participating countries partnering to advance the development of pediatric oncology drugs.

Impact of pharmacist-supported transition of care services in the Middle East and North Africa: a systematic review and meta-analysis.

Transition of care (TOC) is associated with an increased risk of medication-related problems. Despite recent advancements in pharmacy practice and research in the Middle East and North Africa (MENA), the characteristics and impact of regional pharmacy-supported TOC interventions remain unclear.This systematic review and meta-analysis aimed to describe pharmacist-supported TOC interventions in the MENA region and evaluate their effectiveness. PubMed, CINAHL, EMBASE, Web of Science, World Health Organization's International Clinical Trials Registry Platform (ICTRP) were searched from their inception to March 9, 2023, for experimental studies published in English, comparing pharmacist-supported TOC interventions with usual care for adults (age ≥18 years) discharged from the hospital. The risk of bias was evaluated using Cochrane's risk-of-bias tool for randomised trials (ROB2) and the risk of bias in non-randomised studies of interventions (ROBINS-I) tool for randomised and non-randomised studies respectively. Narrative syntheses and meta-analysis methods were employed depending on the outcomes evaluated. Twelve studies (n = 2377 subjects), 10 randomised controlled trials and 2 quasi-experimental studies, were included. Most studies had high or serious risk of bias. The included studies were quite heterogeneous in terms of nature and the delivery of intervention, and assessment of outcome measures. Compared to the usual care group, pharmacist-led TOC interventions contributed to a significant reduction in preventable drug-related (N = 2) and cardiac-related healthcare utilisation (N = 1), a significant reduction in preventable adverse drug events (ADEs) (Odds ratio (OR) 0.34, 95% CI: 0.13-0.94) and an improvement in medication adherence. However, all-cause hospitalisation and medication discrepancies were not significantly reduced. Pharmacy-supported TOC interventions may improve patient outcomes in the MENA region. However, considering the limited quality of evidence and the variability in intervention delivery, future well-designed clinical trials are needed.

The evaluation study for social cognition measures in Japan: Psychometric properties, relationships with social function, and recommendations

AimPatients with schizophrenia can have significant subjective difficulties in social cognition, but few undergo testing or treatment for social cognition. The Social Cognition Psychometric Evaluation (SCOPE) study recommends six social cognitive measures; however, the reliability and validity of these measures in different cultural and linguistic areas has not been adequately examined. We examined the psychometric properties of nine social cognitive measures and the relationship to social function, with the aim of determining the level of recommendation for social cognitive measures in clinical practice in Japan. MethodsFor our test battery, an expert panel previously selected nine measures: the Bell Lysaker Emotion Recognition Task (BLERT); Facial Emotion Selection Test (FEST); Hinting Task (Hinting); Metaphor and Sarcasm Scenario Test (MSST); Intentionality Bias Task (IBT); Ambiguous Intentions and Hostility Questionnaire (AIHQ); Social Attribution Task-Multiple Choice (SAT-MC); SAT-MCII; and Biological Motion (BM) task. In total, 121 outpatients with schizophrenia and 70 healthy controls were included in the analysis, and the results were provided to an expert panel to determine the recommendations for each measure. The quantitative psychological indices of each measure were evaluated for practicality, tolerability, test-retest reliability, correlation with social function, and the incremental validity of social function. ResultsHinting and FEST received the highest recommendations for use in screening, severity assessment, and longitudinal assessment, followed by BLERT, MSST AIHQ, SAT-MC, and SAT-MCII, with IBT and BM receiving the lowest recommendations. ConclusionThis study provides a uniform assessment tool that can be used in future international clinical trials for social cognitive impairment.

Microvascular vasoregulatory dysfunction in African Americans - An enhanced opportunity for early prevention and treatment of atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease and its risk factors and precursors are a major driver of disparities in cardiovascular health. This review examines reported evidence that vascular endothelial dysfunction, and its manifestation as coronary microvascular dysfunction, underlies observed excess morbidity and mortality in African Americans. Advanced imaging insights that reveal patho-mechanisms, along with population evidence from the Jackson Heart Study, and the growing evidence emanating from national and international clinical trials and registries are presented. We examine a physiological framework that recognizes insulin-resistant cardiometabolic underpinnings of the conditions of the American Heart Associations' Life's Essential Eight construct of cardiovascular health as a unifying basis that affords early prevention. Mechanistic-based therapeutic approaches, can subsequently be implemented to interrupt progression to adverse outcomes employing layered, or personalized, treatment strategies of a well-defined set of conditions or diseases. Remaining knowledge gaps are acknowledged.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial

PurposeAdvanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group.MethodsA prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7–25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes.ConclusionThis study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden.Trial registrationThis trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452).

Emerging roles of SIRT1 activator, SRT2104, in disease treatment

Silent information regulator 1 (SIRT1) is a NAD+-dependent class III deacetylase that plays important roles in the pathogenesis of numerous diseases, positioning it as a prime candidate for therapeutic intervention. Among its modulators, SRT2104 emerges as the most specific small molecule activator of SIRT1, currently advancing into the clinical translation phase. The primary objective of this review is to evaluate the emerging roles of SRT2104, and to explore its potential as a therapeutic agent in various diseases. In the present review, we systematically summarized the findings from an extensive array of literature sources including the progress of its application in disease treatment and its potential molecular mechanisms by reviewing the literature published in databases such as PubMed, Web of Science, and the World Health Organization International Clinical Trials Registry Platform. We focuses on the strides made in employing SRT2104 for disease treatment, elucidating its potential molecular underpinnings based on preclinical and clinical research data. The findings reveal that SRT2104, as a potent SIRT1 activator, holds considerable therapeutic potential, particularly in modulating metabolic and longevity-related pathways. This review establishes SRT2104 as a leading SIRT1 activator with significant therapeutic promise.

Assessment of patients with head and neck cancer using the MD Anderson Dysphagia Inventory: Results of a study into its comprehensiveness, comprehensibility and relevance to clinical practice.

The MD Anderson Dysphagia Inventory (MDADI) is a widely used patient-reported outcome measure (PROM) which assesses dysphagia-related quality of life (QoL) in head and neck cancer (HNC). Despite its common use in HNC research and clinical practice, few of its psychometric properties have been reappraised since its inception. The aim of this study was to perform a survey-based qualitative analysis of UK HNC clinicians' perceptions of the content validity of the MDADI, evaluating it across the parameters of relevance, comprehensiveness and comprehensibility as per the COSMIN guideline for PROM assessment. Four themes relating to the content validity of the MDADI were identified: (1) MDADI items lack clarity of definition of the terms 'swallowing', 'eating' and 'dysphagia'; (2) the MDADI is perceived to be overly negative in tone including items that service users may find distressing or disempowering; (3) items in the tool are exclusory to specific subgroups of patients, such as those who are nil by mouth or socially isolated; and (4) modifications to the MDADI were suggested and encouraged to make it more clinically useful and patient-centred. This study indicates that MDADI's content validity is 'insufficient' when rated by COSMIN parameters. This has significant implications for its continued use in HNC research and clinical practice. Further re-evaluation of the content validity of the MDADI is warranted, with potential future amendment of items being indicated if the results of this study are corroborated in subsequent research. What is already known on the subject The MD Anderson Dysphagia Inventory (MDADI) patient-reported outcome measure of dysphagia-related quality of life is widely used in clinical practice and international clinical trials. Content validity is considered to be the most important property of a tool when assessing its psychometric strengths and weaknesses; however, the MDADI's content validity has not been reappraised since its initial development. What this paper adds to existing knowledge This study presents UK speech and language therapists' opinions and experience of the content validity of the MDADI and this first reappraisal of its content validity since its initial development highlights several issues with this psychometric parameter of the tool. This study highlights that further re-evaluation of the content validity of the MDADI is warranted, with potential future amendment of items being indicated if the results of this study are corroborated in subsequent research. What are the potential or actual clinical implications of this work? Clinicians cannot assume that commonly used outcomes tools have strong psychometric profiles. Consideration of the content validity of outcomes tools during selection for use in clinical and research practice should be key, as this will encourage use of tools that produce relevant, valid data that can contribute meaningfully to patient-centred care.

Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials

IntroductionMigraine headache is a significant health problem affecting patients’ psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have...

The efficacy and safety of tonifying-kidney and invigorating-blood circulation (Bushen-Huoxue) formula on renal fibrosis in patients with chronic kidney disease: A protocol for systematic review and meta-analysis

Background: The incidence of chronic kidney disease (CKD) is increasing and the progression of renal interstitial fibrosis (RIF) in end-stage renal disease is attributed to the development of various CKD. One of the treatments for RIF is an oral treatment known as Bushen-Huoxue (BSHX), which stimulates blood circulation and tonifies the kidney. Randomized controlled trials of BSHX treatment of RIF have been reported, but their efficacy and safety have not been comprehensively examined. Therefore, our study aims to describe the efficacy and safety of oral application of the traditional Chinese medicine (TCM) formula of BSHX on treating RIF in CKD by systematic analysis and meta-analysis. Methods: A total of 13 databases, including PubMed, EMBASE, MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform, Wanfang China database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and China’s Conference Papers Database and China Dissertation database will be searched from inception to July 2023. In addition, other suitable search strategies will be used as well to complete this review. All randomized controlled trials that use the BSHX formula for RIF to apply TCM treatments externally for CKD will be included. The eligible studies will be selected to enroll by 2 independent researchers following a predetermined protocol. The review manager software (Rev-Man 5.3) will be used to assess the risk of bias, reporting bias, and data synthesis. Result: We will compile and discuss the recent examples of the TCM BSHX formula treatment for RIF in CKD. Conclusion: We will provide strong evidences for evaluating the efficacy and safety of the TCM BSHX formula treatment for RIF in CKD.

Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. An individual participant data meta-analysis was carried out. Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2 = 0%). Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

Twinning to reduce research and innovation inequalities in paediatric solid tumours across Europe

Inequalities in research and innovations affect childhood cancer survival across Europe. Vilnius University Hospital Santaros Klinikos (VULSK, the coordinator) and eight research-intensive institutions from seven European countries implemented the TREL project (Twinning in Research and Education to improve survival in childhood solid tumours in Lithuania) supported by the Horizon 2020 Widening programme. TREL aimed to enhance translational, clinical, and survivorship research in paediatric CNS, neuroblastoma, and renal tumours to improve future treatment outcomes in Lithuania. From January 2021 to December 2023, 49 VULSK professionals and 55 peers from partner institutions collaborated in this twinning program. Achievements after three years were: nine educational events, the initiation of basic and clinical research on fertility preservation, ten VULSK researchers joining international research groups, six signed agreements to participate in international academic clinical trials and the implementation of the European Survivorship Passport. Thirty patients received individual treatment recommendations following multidisciplinary discussions with experts from partner institutions. Twenty-five rare genetic variants were classified by the twinning bioinformatician teams with direct consequences on patient management. In conclusion, coordination of the Horizon 2020 project enhanced VULKS’s research capacities, networking channels and attractiveness for industry and academia-initiated innovative actions that will improve survival rates in the long run.

Changing the first screening parameters for patients and their derivatives in Phase II–III clinical studies

Actuality. The search for parameters of clinical trials (CT) associated with the recruitment of patients is primarily associated with the search for parameters that can predict the recruitment — predictors of patient recruitment, since patient recruitment is an important and one of the most complex processes in clinical trials, the success of which depends on the entire study. The authors propose to use the parameters of the recruitment of patients assumed by the center, the number of exclusion criteria according to the protocol, and other simple methods that allow predicting the upcoming recruitment; however, the proposed approaches are unclaimed. The parameter of success in enrolling patients in the previous 10 or more studies proposed by the authors obviously has its drawbacks because clinical centers that did not participate in 10 successful studies are automatically excluded. However, the search for a simple parameter to predict upcoming recruitment continues; for example, the time of the first screening has its own predictor potential. We investigated changes in this parameter and its derivatives during the recruitment of patients to selected international multicenter clinical trials (IMCTs). Materials and methods. A retrospective analysis of 4 IMCTs of II–III phases was performed on the recruitment of patients and changes in the time parameters of the first screening and its derivatives. Aim. Consider changes in the time parameter of the first screening and its derivatives during patient recruitment. Statistical analysis. Descriptive statistics with typing. Results. The change in the time parameter of the first screening during the recruitment of patients for CT was considered. The time of the first screening varies depending on the type of clinical center and the experience of the principal investigator. Discussion. According to the literature, a change in the time parameter of the first screening may indicate the success of the recruitment of patients in the center. Conclusion. The changes in the time of the screening set studied by us will allow us to apply the obtained values in clinical trials.

Misleading presentations in functional food trials led by contract research organizations were frequently observed in Japan: meta-epidemiological study

ObjectivesThe functional food market has experienced significant growth, leading to an uptick in clinical trials conducted by contract research organizations (CROs). Research focusing on CRO-managed trials and the communication of trial outcomes to the consumer market remains underexplored. This metaepidemiological study aims to evaluate the quality of randomized controlled trials (RCTs) facilitated by prominent CROs in Japan and to examine the quality of the representations used to convey their results to consumers. Study Design and SettingThis study focused on the food trials that were registered in the University Hospital Medical Information Network Clinical Trial Registry or the International Clinical Trials Registry Platform by the top 5 CROs. Press releases of study results or advertisements of food products based on the study results were identified by conducting a Google search. The risk of bias in the RCT publications was independently assessed by 2 reviewers, who also evaluated the presence of “spin” in the abstracts and full texts. An assessment of “spin” in press releases/advertisements was undertaken. ResultsA total of 76 RCT registrations, 32 RCT publications, and 11 press releases/advertisements were included. Approximately 72% of the RCT publications exhibited a high risk of bias due to selective outcome reporting. “Spin” was present in the results of the abstract (72%), abstract conclusion (81%), full-text results (44%), and full-text conclusion (84%). “Spin” appeared in 73% of press releases/advertisements due to the selective outcome reporting. ConclusionFunctional food presentations in Japan frequently contained “spin.” The Japanese government should more rigorously check whether food manufacturers report outcomes selectively.

Full-thickness skin graft versus split-thickness skin graft for radial forearm free flap donor site closure: protocol for a systematic review and meta-analysis

BackgroundThe radial forearm free flap (RFFF) serves as a workhorse for a variety of reconstructions. Although there are a variety of surgical techniques for donor site closure after RFFF raising, the most common techniques are closure using a split-thickness skin graft (STSG) or a full-thickness skin graft (FTSG). The closure can result in wound complications and function and aesthetic compromise of the forearm and hand. The aim of the planned systematic review and meta-analysis is to compare the wound-related, function-related and aesthetics-related outcome associated with full-thickness skin grafts (FTSG) and split-thickness skin grafts (STSG) in radial forearm free flap (RFFF) donor site closure.MethodsA systematic review and meta-analysis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed. Electronic databases and platforms (PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI)) and clinical trial registries (ClinicalTrials.gov, the German Clinical Trials Register, the ISRCTN registry, the International Clinical Trials Registry Platform) will be searched using predefined search terms until 15 January 2024. A rerun of the search will be carried out within 12 months before publication of the review. Eligible studies should report on the occurrence of donor site complications after raising an RFFF and closure of the defect. Included closure techniques are techniques that use full-thickness skin grafts and split-thickness skin grafts. Excluded techniques for closure are primary wound closure without the use of skin graft. Outcomes are considered wound-, functional-, and aesthetics-related. Studies that will be included are randomized controlled trials (RCTs) and prospective and retrospective comparative cohort studies. Case-control studies, studies without a control group, animal studies and cadaveric studies will be excluded. Screening will be performed in a blinded fashion by two reviewers per study. A third reviewer resolves discrepancies. The risk of bias in the original studies will be assessed using the ROBINS-I and RoB 2 tools. Data synthesis will be done using Review Manager (RevMan) 5.4.1. If appropriate, a meta-analysis will be conducted. Between-study variability will be assessed using the I2 index. If necessary, R will be used. The quality of evidence for outcomes will eventually be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.DiscussionThis study's findings may help us understand both closure techniques' complication rates and may have important implications for developing future guidelines for RFFF donor site management. If available data is limited and several questions remain unanswered, additional comparative studies will be needed.Systematic review registrationThe protocol was developed in line with the PRISMA-P extension for protocols and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 17 September 2023 (registration number CRD42023351903).

Both clinical trial register and electronic bibliographic database searches were needed to identify randomized clinical trials for systematic reviews: an evaluation study

ObjectivesTo determine whether clinical trial register (CTR) searches can accurately identify a greater number of completed randomized clinical trials (RCTs) than electronic bibliographic database (EBD) searches for systematic reviews of interventions, and to quantify the number of eligible ongoing trials. Study Design and SettingWe performed an evaluation study and based our search for RCTs on the eligibility criteria of a systematic review that focused on the underrepresentation of people with chronic kidney disease in cardiovascular RCTs. We conducted a combined search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform through the Cochrane Central Register of Controlled Trials to identify eligible RCTs registered up to June 1, 2023. We searched Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE for publications of eligible RCTs published up to June 5, 2023. Finally, we compared the search results to determine the extent to which the two sources identified the same RCTs. ResultsWe included 92 completed RCTs. Of these, 81 had results available. Sixty-six completed RCTs with available results were identified by both sources (81% agreement [95% CI: 71–88]). We identified seven completed RCTs with results exclusively by CTR search (9% [95% CI: 4–17]) and eight exclusively by EBD search (10% [95% CI: 5–18]). Eleven RCTs were completed but lacked results (four identified by both sources (36% [95% CI: 15–65]), one exclusively by EBD search (9% [95% CI: 1–38]), and six exclusively by CTR search (55% [95% CI: 28–79])). Also, we identified 42 eligible ongoing RCTs: 16 by both sources (38% [95% CI: 25–53]) and 26 exclusively by CTR search (62% [95% CI: 47–75]). Lastly, we identified four RCTs of unknown status by both sources. ConclusionCTR searches identify a greater number of completed RCTs than EBD searches. Both searches missed some included RCTs. Based on our case study, researchers (eg, information specialists, systematic reviewers) aiming to identify all available RCTs should continue to search both sources. Once the barriers to performing CTR searches alone are targeted, CTR searches may be a suitable alternative.

Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity.

Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial

BackgroundDiabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN.MethodsThis study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment.DiscussionThis study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect.Trial registrationClinicalTrials.gov. NCT05521737 Registered on 30 August 2022.International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].