bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in type 2 diabetes: study protocol for a randomised clinical trial
Authors: Balducci Stefano , Conti Francesco , Sacchetti Massimo , Russo Cosimo R , Argento Giuseppe , Haxhi Jonida , Orlando Giorgio , Rapisarda Gianvito , D'Errico Valeria , Cardelli Patrizia , Pugliese Luca , Laghi Andrea , Vitale Martina , Bollanti Lucilla , Zanuso Silvano , Nicolucci Antonio , Pugliese Giuseppe 
Published: April 2023

IntroductionType 2 diabetes (T2D) is associated with an increased fracture risk despite normal-to-increased bone mineral density, suggesting reduced bone quality. Exercise may be effective in reducing fracture risk by ameliorating muscle dysfunction and reducing risk of fall, though it is unclear whether it can improve bone quality.Methods and analysisThe ‘Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in T2D’ is an open-label, assessor-blinded, randomised clinical trial comparing an exercise training programme of 2-year duration, specifically designed for improving bone quality and strength, with standard care in T2D individuals. Two hundred T2D patients aged 65–75 years will be randomised 1:1 to supervised exercise training or standard care, stratified by gender, age ≤ or >70 years and non-insulin or insulin treatment. The intervention consists of two weekly supervised sessions, each starting with 5 min of warm-up, followed by 20 min of aerobic training, 30 min of resistance training and 20 min of core stability, balance and flexibility training. Participants will wear weighted vests during aerobic and resistance training. The primary endpoint is baseline to end-of-study change in trabecular bone score, a parameter of bone quality consistently shown to be reduced in T2D. Secondary endpoints include changes in other potential measures of bone quality, as assessed by quantitative ultrasound and peripheral quantitative CT; bone mass; markers of bone turnover; muscle strength, mass and power; balance and gait. Falls and asymptomatic and symptomatic fractures will be evaluated over 7 years, including a 5-year post-trial follow-up. The superiority of the intervention will be assessed by comparing between-groups baseline to end-of-study changes.Ethics and disseminationThis study was approved by the institutional ethics committee. Written informed consent will be obtained from all participants. The study results will be submitted for peer-reviewed publication.Trial registration numberNCT02421393.
Proactive community case management and child survival: protocol for a cluster randomised controlled trial
Authors: Whidden Caroline , Treleaven Emily , Liu Jenny , Padian Nancy , Poudiougou Belco , Bautista-Arredondo Sergio , Fay Michael P , Samaké Salif , Cissé Amadou B , Diakité Djoumé , Keita Youssouf , Johnson Ari D , Kayentao Kassoum 
Published: April 2023

IntroductionCommunity health workers (CHWs)—shown to improve access to care and reduce maternal, newborn, and child morbidity and mortality—are re-emerging as a key strategy to achieve health-related Sustainable Development Goals (SDGs). However, recent evaluations of national programmes for CHW-led integrated community case management (iCCM) of common childhood illnesses have not found benefits on access to care and child mortality. Developing innovative ways to maximise the potential benefits of iCCM is critical to achieving the SDGs.Methods and analysisAn unblinded, cluster randomised controlled trial in rural Mali aims to test the efficacy of the addition of door-to-door proactive case detection by CHWs compared with a conventional approach to iCCM service delivery in reducing under-five mortality. In the intervention arm, 69 village clusters will have CHWs who conduct daily proactive case-finding home visits and deliver doorstep counsel, care, referral and follow-up. In the control arm, 68 village clusters will have CHWs who provide the same services exclusively out of a fixed community health site. A baseline population census will be conducted of all people living in the study area. All women of reproductive age will be enrolled in the study and surveyed at baseline, 12, 24 and 36 months. The survey includes a life table tracking all live births and deaths occurring prior to enrolment through the 36 months of follow-up in order to measure the primary endpoint: under-five mortality, measured as deaths among children under 5 years of age per 1000 person-years at risk of mortality.Ethics and disseminationThe trial has received ethical approval from the Ethics Committee of the Faculty of Medicine, Pharmacy and Dentistry, University of Bamako. The results will be disseminated through peer-reviewed publications, national and international conferences and workshops, and media outlets.Trial registration numberNCT02694055; Pre-results.
Rituximab versus steroids and cyclophosphamide for the treatment of primary membranous nephropathy: protocol of a pilot randomised controlled trial
Authors: Scolari Francesco , Dallera Nadia , Gesualdo Loreto , Santoro Domenico , Pani Antonello , Santostefano Marisa , Feriozzi Sandro , Mani Laila-Yasmin , Boscutti Giuliano , Messa Piergiorgio , Magistroni Riccardo , Quaglia Marco , Ponticelli Claudio , Ravani Pietro 
Published: April 2023

IntroductionPrimary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease may have different long-term outcomes. After 10 years of follow-up, 35%–50% of the untreated patients with persistent nephrotic syndrome may die or progress to end stage renal disease. The 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend that initial therapy should consist of alternating steroids and an alkylating agent for 6 months. Recent observational studies showed that the anti-CD20 antibody rituximab may be effective in inducing remission. We designed a pilot multicentre randomised trial to inform the design of a larger trial testing the efficacy and safety of treatment with steroids and cyclophosphamide versus rituximab in patients with primary MN and heavy proteinuria (>3.5 g/24 hours).Methods and analysisThis pilot, open-label, two-parallel-arm, randomised clinical trial will enrol 70 patients with primary MN and heavy proteinuria. Patients will be randomised in a 1:1 ratio to either the intervention arm (rituximab) or the active comparator arm (corticosteroid/alkylating-agent therapy). The study will provide estimates of the probability of complete remission of proteinuria and risk of serious side effects at 12 months to inform the design of a larger trial. We will also assess the recruitment potential of each participating centre to address study feasibility.Ethics and disseminationThe trial received ethics approval from the local ethics boards. We will publish pilot data to inform the design of a larger clinical trial.Trial registration numbersNCT03018535; 2011-006115-59.
TurnerFertility trial: PROTOCOL for an observational cohort study to describe the efficacy of ovarian tissue cryopreservation for fertility preservation in females with Turner syndrome
Authors: Schleedoorn Myra , van der Velden Janielle , Braat Didi , Beerendonk Ina , van Golde Ron , Peek Ron , Fleischer Kathrin 
Published: April 2023

ObjectiveTo investigate the occurrence of live birth in women with Turner syndrome (TS) after ovarian tissue cryopreservation in childhood followed by auto transplantation in adulthood and to find reliable prognostic markers for estimating the ovarian reserve in girls with TS in the future.SettingAn observational cohort study with long-term follow-up in a tertiary fertility clinic in the Netherlands. Patients recruitment between January 2018 and December 2021.Participants100 females aged 2 through 18 years with classical Turner (ie, 45,X0) or Turner variants (ie, 45,X mosaicism or structural anomalies). Girls with Y chromosomal content, minor X deletions with marginal impact on fertility, active HIV, hepatitis B or hepatitis C infection, and/or an absolute contra indication for surgery, anaesthesia or future pregnancy will be excluded.InterventionsOvarian cortical tissue will be harvested by performing a unilateral oophorectomy via laparoscopic approach. Ovarian cortex fragments will be prepared and cryopreserved. One fragment per patient will be used to determine follicular density by conventional histology, and to perform fluorescence in situ hybridisation analysis of ovarian cells. Routine chromosome analysis will be performed on both lymphocytes and buccal cells. A blood sample will be taken for hormonal analysis and all subjects will undergo a transabdominal ultrasound to determine the uterine and ovarian size. Patient characteristics, pregnancy rates and pregnancy outcomes will be collected from the patient’s medical record.Ethics and disseminationThe study protocol has been approved by the Central Committee on Research Involving Human Subjects in November 2017 (CCMO NL57738.000.16).Trial registration numberNCT03381300.
Testing a digital system that ranks the risk of unplanned intensive care unit admission in all ward patients: protocol for a prospective observational cohort study
Authors: Malycha James , Redfern Oliver C , Ludbrook Guy , Young Duncan , Watkinson Peter J 
Published: April 2023

IntroductionTraditional early warning scores (EWSs) use vital sign derangements to detect clinical deterioration in patients treated on hospital wards. Combining vital signs with demographics and laboratory results improves EWS performance. We have developed the Hospital Alerting Via Electronic Noticeboard (HAVEN) system. HAVEN uses vital signs, as well as demographic, comorbidity and laboratory data from the electronic patient record, to quantify and rank the risk of unplanned admission to an intensive care unit (ICU) within 24 hours for all ward patients. The primary aim of this study is to find additional variables, potentially missed during development, which may improve HAVEN performance. These variables will be sought in the medical record of patients misclassified by the HAVEN risk score during testing.MethodsThis will be a prospective, observational, cohort study conducted at the John Radcliffe Hospital, part of the Oxford University Hospitals NHS Foundation Trust in the UK. Each day during the study periods, we will document all highly ranked patients (ie, those with the highest risk for unplanned ICU admission) identified by the HAVEN system. After 48 hours, we will review the progress of the identified patients. Patients who were subsequentlyadmittedto the ICU will be removed from the study (as they will have been correctly classified by HAVEN). Highly ranked patientsnot admittedto ICU will undergo a structured medical notes review. Additionally, at the end of the study periods, all patients who had an unplanned ICU admission but whom HAVENfailed to rank highlywill have a structured medical notes review. The review will identify candidate variables, likely associated with unplanned ICU admission, not included in the HAVEN risk score.Ethics and disseminationApproval has been granted for gathering the data used in this study from the South Central Oxford C Research Ethics Committee (16/SC/0264, 13 June 2016) and the Confidentiality Advisory Group (16/CAG/0066).DiscussionOur study will use a clinical expert conducting a structured medical notes review to identify variables, associated with unplanned ICU admission, not included in the development of the HAVEN risk score. These variables will then be added to the risk score and evaluated for potential performance gain. To the best of our knowledge, this is the first study of this type. We anticipate that documenting the HAVEN development methods will assist other research groups developing similar technology.Trial registration numberNCT12518261
Cohort profile: the Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) cohort, a prospective preterm birth cohort in New York City
Authors: Stroustrup Annemarie , Bragg Jennifer B , Spear Emily A , Aguiar Andrea , Zimmerman Emily , Isler Joseph R , Busgang Stefanie A , Curtin Paul C , Gennings Chris , Andra Syam S , Arora Manish 
Published: April 2023

PurposeThe Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) longitudinal preterm birth cohort studies the impact of the NICU exposome on early-life development. NICU-HEALTH collects multiple biospecimens, complex observational and survey data and comprehensive multisystem outcome assessments to allow measurement of the impact of modifiable environmental exposures during the preterm period on neurodevelopmental, pulmonary and growth outcomes.ParticipantsModerately preterm infants without genetic or congenital anomalies and their mothers are recruited from an urban academic medical centre level IV NICU in New York City, New York, USA. Recruitment began in 2011 and continues through multiple enrolment phases to the present with goal enrolment of 400 infants. Follow-up includes daily data collection throughout the NICU stay and six follow-up visits in the first 2 years. Study retention is 77% to date, with the oldest patients turning age 8 in 2019.Findings to dateNICU-HEALTH has already contributed significantly to our understanding of phthalate exposure in the NICU. Phase I produced the first evidence of the clinical impact of phthalate exposure in the NICU population. Further study identified specific sources of exposure to clinically relevant phthalate mixtures in the NICU.Future plansFollow-up from age 3 to 12 is co-ordinated through integration with the Environmental Influences on Child Health Outcomes (ECHO) programme. The NICU-HEALTH cohort will generate a wealth of biomarker, clinical and outcome data from which future studies of the impact of early-life chemical and non-chemical environmental exposures can benefit. Findings from study of this cohort and other collaborating environmental health cohorts will likely translate into improvements in the hospital environment for infant development.Trial registration numbersThis observational cohort is registered with ClinicalTrials.gov (NCT01420029andNCT01963065).
Oral switch versus standard intravenous antibiotic therapy in left-sided endocarditis due to susceptible staphylococci, streptococci or enterococci (RODEO): a protocol for two open-label randomised controlled trials
Authors: Lemaignen Adrien , Bernard Louis , Tattevin Pierre , Bru Jean-Pierre , Duval Xavier , Hoen Bruno , Brunet-Houdard Solène , Mainardi Jean-Luc , Caille Agnes 
Published: April 2023

IntroductionLeft-sided infective endocarditis (IE) is a serious infection with a heavy burden for patients and healthcare system. Oral switch after initial intravenous antibiotic therapy may reduce costs and improve patients’ discomfort without increasing unfavourable outcomes. We describe the methodology of two simultaneously conducted open-label randomised trials aiming to assess non-inferiority of oral switch as compared with entirely intravenous antibiotic therapy for the treatment of left-sided IE.Methods and analysisTwo simultaneous multicentre open-label prospective randomised trials assessing non-inferiority of oral switch during antibiotic treatment as compared with entirely intravenous therapy in patients with left-sided IE are ongoing. One trial is dedicated to left-sided IE caused by multisusceptible staphylococci (Relais Oral Dans le traitement des Endocardites à staphylocoques ou streptOcoques (RODEO)-1) and the other is dedicated to left-sided IE caused by susceptible streptococci or enterococci (RODEO-2). It is planned to randomise 324 patients in each trial after an initial course of at least 10 days of intravenous antibiotic therapy either to continue intravenous antibiotic therapy or to switch to oral antibiotic therapy. The primary outcome is treatment failure within 3 months after the end of antibiotic treatment, a composite outcome defined by all-cause death and/or symptomatic embolic events and/or unplanned valvular surgery and/or microbiological relapse (with the primary pathogen). Secondary outcomes include patient quality of life, echocardiographic outcome, costs and efficiency associated with IE care. Statistical analysis will be performed with a non-inferiority margin of 10% and a one-sided 2.5% type I error.Ethics and disseminationWritten informed consent will be obtained from all participants. This study was approved by Tours Research ethics committee (CPP TOURS-Region Centre-Ouest 1, 2015-R26, 23 February 2016). Study findings will be published in peer-reviewed journals and disseminated through presentation at relevant national and international conferences.Trial registration numberEudraCT Number: 2015-002371-16 andNCT02701608NCT02701595.
Assessment of the impact of a new sequential approach to antimicrobial use in young febrile children in the emergency department (DIAFEVERCHILD): a French prospective multicentric controlled, open, cluster-randomised, parallel-group study protocol
Authors: Hubert Gaelle , Launay Elise , Feildel Fournial Cécile , Chauvire-Drouard Anne , Lorton Fleur , Tavernier Elsa , Giraudeau Bruno , Gras Le Guen Christele 
Published: April 2023

IntroductionFever is one of the most common reasons for consultation in the paediatric emergency department (ED). Because of fear of bacterial infection in parents and caregivers, clinicians often overprescribe laboratory tests and empirical antibiotic treatment. The aims of this study are to demonstrate that using a procalcitonin (PCT) rapid test-based prediction rule (1) would not be inferior to usual practice in terms of morbidity and mortality (non-inferiority objective) and (2) would result in a significant reduction in antibiotic use (superiority objective).Methods and analysisThis prospective multicentric cluster-randomised study aims to include 7245 febrile children aged 6 days to 3 years with a diagnosis of fever without source in 26 participating EDs in France and Switzerland during a 24-month period. During first period, all children will receive usual care. In a second period, a point-of-care PCT-based algorithm will be used in half of the clusters. The primary endpoints collected on day 15 after ED consultation will be a composite outcome of death or intensive care unit admission for any reason, disease-specific complications, diagnosis of bacterial infection after discharge from the ED for the non-inferiority objective and proportion of children with antibiotic treatment administered for the superiority objective. The endpoints will be compared between the two groups (experimental and control) by using a mixed logistic regression model adjusted on clustering of participants within centres and period within centres.DiscussionIf the algorithm is validated, a new strategy will be discussed with medical societies to safely manage fever in young children without the need for invasive procedures for microbiological testing or empirical antibiotics.Ethics and disseminationThis study was submitted to an independent ethics committee on 17 May 2018 (no. 2018-A00252-53). Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration numberNCT03607162.
Economic evaluation protocol of a short, all-oral bedaquiline-containing regimen for the treatment of rifampicin-resistant tuberculosis from the STREAM trial
Authors: Rosu Laura , Madan Jason , Worrall Eve , Tomeny Ewan , Squire Bertel 
Published: April 2023

IntroductionA December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9–11-month MDR-TB treatment regimens.Methods and analysisHealth system costs of delivering a 9-month injectable-containing regimen and a 9-month all-oral bedaquiline-containing regimen will be collected in Ethiopia, India, Moldova and Uganda, using ‘bottom-up’ and ‘top-down’ costing approaches. Patient costs will be collected using questionnaires that have been developed based on the STOP-TB questionnaire. The primary objective of the study is to estimate the cost utility of the two regimens, from a health system perspective. Secondary objectives include estimating the cost utility from a societal perspective as well as evaluating the cost-effectiveness of the regimens, using both health system and societal perspectives. The effect measure for the cost–utility analysis will be the quality-adjusted life years (QALY), while the effect measure for the cost-effectiveness analysis will be the efficacy outcome from the clinical trial.Ethics and disseminationThe study has been evaluated and approved by the Ethics Advisory Group of theInternational Union Against Tuberculosis and Lung Diseaseand also approved by ethics committees in all participating countries. All participants have provided written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal.Trial registration numberNCT18148631.
Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases
Authors: Yang Annie , Zhang Zhifang , Chaurasiya Shyambabu , Park Anthony K , Jung Audrey , Lu Jianming , Kim Sang-In , Priceman Saul , Fong Yuman , Woo Yanghee 
Published: April 2023

BackgroundGastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors (NCT05346484) and triple-negative breast cancer (NCT05081492). Here, we investigated the antitumor activity of CF33-oncolytic viruses (OVs) against GC and CF33-hNIS-antiPDL1 in the intraperitoneal (IP) treatment of GC peritoneal metastases (GCPM).MethodsWe infected six human GC cell lines AGS, MKN-45, MKN-74, KATO III, SNU-1, and SNU-16 with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities of infection (0.01, 0.1, 1.0, and 10.0), and performed viral proliferation and cytotoxicity assays. We used immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression. We evaluated the antitumor activity of CF33-hNIS-antiPDL1 following IP treatment (3×105pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging.ResultsCF33-OVs showed dose-dependent infection, replication, and killing of both diffuse and intestinal subtypes of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 antibody scFv expression in CF33-OV-infected GC cells. We confirmed GC cell surface PD-L1 blockade by virus-encoded anti-PD-L1 scFv using flow cytometry. In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×105pfu × 3 doses) treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p<0.01).ConclusionsOur results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.