bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study
Authors: Llurba Elisa , Crispi Fatima , Crovetto Francesca , Youssef Lina , Delgado Juan Luis , Puig Isabel , Mora Josefina , Krofta Ladislav , Mackova Katerina , Martinez-Varea Alicia , Tubau Albert , Ruiz Aina , Paya Antoni , Prat Maria , Chantraine Frederic , Comas Carmina , Kajdy Anna , Lopez-Tinajero Maria Fernanda , Figueras Francesc , Gratacos Eduard 
Published: June 2024

IntroductionPre-eclampsia affects ~5%–7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal–fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35–37 weeks’ gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35–37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes.Methods and analysisWe propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35–37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect).Ethics and disseminationThe study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences.Trial registration numberNCT04766866.
Finerenone cardiovascular and kidney outcomes by age and sex: FIDELITY post hoc analysis of two phase 3, multicentre, double-blind trials
Authors: Bansal Shweta , Canziani Maria E F , Birne Rita , Anker Stefan D , Bakris George L , Filippatos Gerasimos , Rossing Peter , Ruilope Luis M , Farjat Alfredo E , Kolkhof Peter , Lage Andrea , Brinker Meike , Pitt Bertram 
Published: June 2024

ObjectivesThis study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex.DesignFIDELITY post hoc analysis; median follow-up of 3 years.SettingFIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials.ParticipantsAdults with type 2 diabetes and chronic kidney disease receiving optimised renin–angiotensin system inhibitors (N=13 026).InterventionsRandomised 1:1; finerenone or placebo.Primary and secondary outcome measuresCardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes.ResultsMean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65–74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65–74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); Pinteraction=0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); Pinteraction=0.99). Effects on HHF reduction were not modified by age (Pinteraction=0.70) but appeared more pronounced in males (Pinteraction=0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65–74 but not ≥75; no heterogeneity in treatment effect was observed (Pinteraction=0.51). In sex subgroups, finerenone consistently reduced kidney events (Pinteraction=0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups.ConclusionsFinerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups.Trial registration numbersNCT02540993,NCT02545049.
A study protocol to investigate if acipimox improves muscle function and sarcopenia: an open-label, uncontrolled, before-and-after experimental medicine feasibility study in community-dwelling older adults
Authors: McDonald Claire , Alderson Craig , Birkbeck Matthew G , Brown Laura , Del Din Silvia , Gorman Grainne G , Hollingsworth Kieren , Massarella Clare , Rehman Rana , Rochester Lynn , Sayer Avan AP , Su Huizhong , Tuppen Helen , Warren Charlotte , Witham Miles D 
Published: June 2024

IntroductionSarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD concentrations are low in older people with sarcopenia, and increasing skeletal muscle NAD concentrations may offer a novel therapy for this condition. Acipimox is a licensed lipid-lowering agent known to act as an NAD precursor. This open-label, uncontrolled, before-and-after proof-of-concept experimental medicine study will test whether daily supplementation with acipimox improves skeletal muscle NAD concentrations.Methods and analysisSixteen participants aged 65 and over with probable sarcopenia will receive acipimox 250 mg and aspirin 75 mg orally daily for 4 weeks, with the frequency of acipimox administration being dependent on renal function. Muscle biopsy of the vastus lateralis and MRI scanning of the lower leg will be performed at baseline before starting acipimox and after 3 weeks of treatment. Adverse events will be recorded for the duration of the trial. The primary outcome, analysed in a per-protocol population, is the change in skeletal muscle NAD concentration between baseline and follow-up. Secondary outcomes include changes in phosphocreatine recovery rate by31P magnetic resonance spectroscopy, changes in physical performance and daily activity (handgrip strength, 4 m walk and 7-day accelerometry), changes in skeletal muscle mitochondrial respiratory function, changes in skeletal muscle mitochondrial DNA copy number and changes in NAD concentrations in whole blood as a putative biomarker for future participant selection.Ethics and disseminationThe trial is approved by the UK Medicines and Healthcare Products Regulatory Agency (EuDRACT 2021-000993-28) and UK Health Research Authority and Northeast – Tyne and Wear South Research Ethics Committee (IRAS 293565). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community.ProtocolAcipimox feasibility study Clinical Trial Protocol V.2 2/11/21.Trial registration numberThe ISRCTN trial database (ISRCTN87404878).
Evaluating a rehabilitative intervention for substance-dependent patients with and without their accompanying children in Germany (KontextSucht): study protocol for a non-randomised trial
Authors: Stullich Ananda , Hoffmann Laura , Stephan Johannes , Gehrmann Jan , Richter Matthias 
Published: June 2024

IntroductionPeople suffering from substance use disorders often live in social contexts with children or are parents themselves. Addicted parents show specific substance-related problems while raising their children, which often leads to various lifelong consequences for the children. The German rehabilitative treatment system allows bringing children to inpatient treatment centres. This mixed-methods study evaluates a newly developed intervention, called ‘KontextSucht’ or ‘AddictionContext’, for parents in rehabilitation treatment centres concerning the effectiveness of the intervention in parenting and abstinence outcome.Methods and analysisThe study uses a two-stage parallel mixed-methods design. A feasibility study (stage 1) and a benefit assessment (stage 2) will be conducted to evaluate the intervention. Both parts of the study will be carried out with qualitative and quantitative work packages. German-speaking parents of children 0–14 years will be included in this study. Qualitative data will be analysed using qualitative content analyses, whereas quantitative data will be analysed descriptively using regression analysis as well as linear mixed models.Ethics and disseminationAll participants will receive detailed information on the study and sign informed consent before data collection. The research team has obtained the approval of the Ethical Review Committee at the Technical University of Munich in Germany and will follow all legislation rules regarding data protection. The study results will be published in peer-reviewed national and international journals. Furthermore, the study results will be included in an intervention manual distributed to treatment centres.Trial registration numberDRKS00030950.
Selecting an e-cigarette for use in smoking cessation interventions and healthcare services: findings from patient and public consultation for the COSTED trial
Authors: Belderson Pippa , Ward Emma , Pope Ian , Notley Caitlin 
Published: June 2024

ObjectivesThe Cessation of Smoking Trial in the Emergency Department (COSTED) trial aims to ascertain whether brief advice, the provision of an e-cigarette starter kit and referral to stop smoking services (SSS), increases smoking cessation in people attending the emergency department. Patient and public involvement (PPI) and scoping work were undertaken to select an appropriate e-cigarette for the trial.Design and settingPPI consultation and feasibility scoping about potential devices with a professional and lay panel, all based in England. Consultation was via email, telephone or video interview. This work took place between April and July 2021, prior to recruitment commencing for the COSTED trial.ParticipantsA professional panel (n=7) including representatives from academia, SSS and the independent vaping industry, and a PPI lay panel (n=3) who smoke or vape.ResultsThe professional panel recommended a shortlist of devices which were tested by the PPI lay panel. Key criteria for selecting an appropriate e-cigarette for smoking cessation intervention include satisfaction, usability, affordability and availability. Simplicity of use was highlighted by the PPI lay panel, who found refillable devices complex, and availability of consumables was highlighted as more important than price by both panels. The pod device selected for inclusion was rated highly for satisfaction and usability and had mid-price range and consumables which were widely available.ConclusionsTo select the most appropriate device for the COSTED trial, each criterion required assessment to ensure the best fit to the intervention context and needs of the target population. There is a need for guidance to help enable decision-making about choice of vape products, tailored to service users’ needs. We propose a bespoke checklist template, based on our findings, to assist with this process. This has applicability to the recent government announcement of a ‘Swap to Stop’ programme, offering a vaping starter kit to smokers across England, allowing services flexibility to shape their own programmes and models of delivery.Trial registration numberClinical trial numberISRCTN04854616; pre-results.
Sociological determinants of adherence to continuous positive airway pressure in the management of sleep apnoea syndrome: protocol for a transdisciplinary, prospective observational study
Authors: Bailly Sebastien , Foote Alison , Mendelson Monique , Rakotovao Andry , Borel Jean Christian , Pepin Jean Louis , Tamisier Renaud , Revil Helena 
Published: June 2024

IntroductionObstructive sleep apnoea syndrome (OSAS) is a chronic multiorgan pathology that has a negative impact on quality of life. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, CPAP termination rates remain very high, and adherence to therapy is a major issue. To date, studies targeting predictive factors of CPAP adherence by OSAS patients mainly include clinical data. The social, socioeconomic, psychological, and home environment aspects have been far less studied and largely underestimated. This study aims to obtain solid quantitative results examining the relationship between the determinants of refusal, non-adherence, or termination of CPAP treatment, and in particular the pivotal role played by health literacy.Methods and analysisThis is a prospective, multicentre, observational study recruiting patients attending the sleep clinic of the Grenoble Alpes University Hospital, France. Consecutive adults (>18 years) recently diagnosed with OSAS and prescribed CPAP treatment with telemonitoring will be enrolled in the present study. They will benefit from home visits by a CPAP technician or nurse at CPAP initiation. Patients will then be followed up for 6 months through the telemonitoring platform of a home-care provider. The primary objective is to evaluate the impact of health literacy (health literacy, measured by the European Health Literacy Survey questionnaire (HLS-EU-16) on the refusal, non-adherence or termination of CPAP treatment in newly diagnosed OSAS patients, during the first 6 months after diagnosis. The target sample size is 250 participants.Ethics and disseminationThe study protocol, patient information, and the non-opposition form were approved by the French national ethics committee (CPP 2021-92, January 2022). All patients are required to have signed a written informed consent form permitting their anonymised personal and medical data to be used for clinical research purposes. We will publish the results in a peer-reviewed medical journal and on our institutional websites.Trial registration numberNCT05385302.
Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps
Authors: Hartman Terryl J , Christie Jennifer , Wilson Annette , Ziegler Thomas R , Methe Barbara , Flanders William Dana , Rolls Barbara J , Loye Eberhart Blaine , Li Jia V , Huneault Helaina , Cousineau Ben , Perez Miriam R , O'Keefe Stephen J D 
Published: June 2024

IntroductionRecently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC).Methods/designThis study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1–3 and one meal/day in months 4–6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1–2 pounds per week.Ethics and disseminationThe National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563).Trial registration numberNCT04780477.
Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation (LAA-CLIP): rationale, design and study protocol for a multicentre randomised controlled trial
Authors: Yu Chunyu , Li Haojie , Lei Chuxiang , Wang Yang , Chen Sipeng , Zhao Yan , Zheng Zhe 
Published: June 2024

IntroductionThe prevalence of atrial fibrillation (AF) is increasing globally, and stroke prevention is the key to reduce the morbidity and mortality related to AF. Currently, direct oral anticoagulants (DOACs) are the primary options for stroke prevention, while it increases risk of bleeding. Left atrial appendage (LAA) is suspected as a vital source of cerebral emboli and may lead to ischaemic stroke, and thoracoscopic LAA clipping procedure provides an alternative option for stroke prevention in high-risk patients. However, high-quality evidence comparing LAA clipping to DOACs in terms of stroke prevention is lacking. This trial is designed to assess whether the efficacy of thoracoscopic LAA clipping is superior to DOACs for stroke prevention in AF patients at high risk of thrombosis (CHA2DS2-VASc≥2 in men and ≥3 in women)[CHA2DS2-VASc stands for "congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female)”].Methods and analysisThis is a prospective, multicentre, open-labelled, randomised controlled study. This trial will randomly assign 290 patients with non-paroxysmal AF to thoracoscopic LAA clipping group or DOAC therapy group in a 1:1 randomisation. The primary endpoint is defined as a composite endpoint event consisting of stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events at 24 months after randomisation. The secondary endpoints consist of the components of the primary composite endpoint, surgery-related adverse events and minor bleeding events.Ethics and disseminationThe central ethics committee at Fuwai Hospital approved the trial entitled “Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation (LAA-CLIP trial)”. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration numberNCT06021808.
Couples motivational interviewing with mobile breathalysers to reduce alcohol use in South Africa: a pilot randomised controlled trial of Masibambisane
Authors: Msimango Lindani , Butterfield Rita , Starks Tyrel J , van Heerden Alastair , Neilands Torsten B , Hahn Judy A , Chibi Buyisile , Humphries Hilton , Conroy Amy A 
Published: June 2024

IntroductionHeavy alcohol use among people living with HIV in sub-Saharan Africa can hinder the success of HIV treatment programmes, impacting progress towards United Nations Programme on HIV/AIDS goals. Primary partners can provide critical forms of social support to reduce heavy drinking and could be included in motivational interviewing (MI) interventions to address heavy drinking; however, few studies have evaluated MI interventions for couples living with HIV in sub-Saharan Africa. We aim to evaluate the feasibility and acceptability of a couple-based MI intervention with mobile breathalyser technology to reduce heavy alcohol use and improve HIV treatment outcomes among HIV-affected couples in South Africa.Methods and analysisWe will employ a three-arm randomised controlled trial to assess the efficacy of couple-based MI (MI-only arm) and in conjunction with mobile breathalysers (MI-plus arm) to address alcohol use and HIV outcomes, as compared with enhanced usual care (control arm). We will enrol heterosexual couples aged 18–49 in a primary relationship for at least 6 months who have at least one partner reporting hazardous alcohol use and on antiretroviral therapy for 6 months. Participants in both MI arms will attend three manualised counselling sessions and those in the MI-plus arm will receive real-time feedback on blood alcohol concentration levels using a mobile breathalyser. Couples randomised in the control arm will receive enhanced usual care based on the South African ART Clinical Guidelines. Feasibility and acceptability indicators will be analysed descriptively, and exploratory hypotheses will be examined through regression models considering time points and treatment arms.Ethics and disseminationThe study was approved by the University of California, San Francisco (HRPP; protocol number 21-35034) and Human Sciences Research Council Research Ethics Committee (REC: protocol number 1/27/20/21). We will disseminate the results at local community meetings, community-level health gatherings and conferences focused on HIV and alcohol use.Trial registration numberISRCTN05756790.