bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-MannosE to prevent Recurrent urinary tract InfecTions (MERIT): protocol for a randomised controlled trial
Authors: Franssen Marloes , Cook Johanna , Robinson Jared , Williams Nicola , Glogowska Margaret , Yang Yaling , Allen Julie , Butler Christopher C , Thomas Nick , Hay Alastair , Moore Michael , Hayward Gail 
Published: January 2021

IntroductionRecurrent urinary tract infections (RUTIs) have a significant negative impact on quality of life and healthcare costs. To date, daily prophylactic antibiotics are the only treatment which have been shown to help prevent RUTIs. D-mannose is a type of sugar which is believed to inhibit bacterial adherence to uroepithelial cells, and is already being used by some women in an attempt to prevent RUTIs. There is currently insufficient rigorous evidence on which to base decisions about its use. The D-mannose to prevent recurrent urinary tract infections (MERIT) study will evaluate whether D-mannose is clinically and cost-effective in reducing frequency of infection and symptom burden for women presenting to UK primary care with RUTI.Methods and analysisMERIT will be a two-arm, individually randomised, double blind placebo controlled, pragmatic trial. Participants will be randomised to take D-mannose powder or placebo powder daily for 6 months. The primary outcome will be the number of medical attendances attributable to symptoms of RUTI. With 508 participants we will have 90% power to detect a 50% reduction in the chance of a further clinically suspected UTI, assuming 20% lost to follow-up. Secondary outcomes will include: number of days of moderately bad symptoms of UTI; time to next consultation; number of clinically suspected UTIs; number of microbiologically proven UTIs; number of antibiotic courses for UTI; quality of life and healthcare utilisation related to UTI. A within trial economic evaluation will be conducted to examine cost-effectiveness of D-mannose in comparison with placebo. A nested qualitative study will explore participants’ experiences and perceptions of recruitment to, and participation in a study requiring a daily treatment.Ethics and disseminationEthical approval has been obtained from South West-Central Bristol Research Ethics Committee. Publication of the MERIT study is anticipated to occur in 2021.Trial registration numberISRCTN 13283516.
Evaluation of an automated feedback intervention to improve antimicrobial prescribing among primary care physicians (OPEN Stewardship): protocol for an interrupted time-series and usability analysis in Ontario, Canada and Southern Israel
Authors: Soucy Jean-Paul R , Low Marcelo , Acharya Kamal Raj , Ellen Moriah , Hulth Anette , Löfmark Sonja , Garber Gary E , Watson William , Moran-Gilad Jacob , Fisman David N , MacFadden Derek R 
Published: January 2021

IntroductionAntimicrobial resistance undermines our ability to treat bacterial infections, leading to longer hospital stays, increased morbidity and mortality, and a mounting burden to the healthcare system. Antimicrobial stewardship is increasingly important to safeguard the efficacy of existing drugs, as few new drugs are in the developmental pipeline. While significant progress has been made with respect to stewardship in hospitals, relatively little progress has been made in the primary care setting, where the majority of antimicrobials are prescribed. OPEN Stewardship is an international collaboration to develop an automated feedback platform to improve responsible antimicrobial prescribing among primary care physicians and capable of being deployed across heterogeneous healthcare settings. We describe the protocol for an evaluation of this automated feedback intervention with two main objectives: assessing changes in antimicrobial prescribing among participating physicians and determining the usability and usefulness of the reports.Methods and analysisA non-randomised evaluation of the automated feedback intervention (OPEN Stewardship) will be conducted among approximately 150 primary care physicians recruited from Ontario, Canada and Southern Israel, based on a series of targeted stewardship messages sent using the platform. Using a controlled interrupted time-series analysis and multilevel negative binomial modelling, we will compare the antimicrobial prescribing rates of participants before and after the intervention, and also to the prescribing rates of non-participants (from the same healthcare network) during the same period. We will examine outcomes targeted by the stewardship messages, including prescribing for antimicrobials with duration longer than 7 days and prescribing for indications where antimicrobials are typically unnecessary. Participants will also complete a series of surveys to determine the usability and usefulness of the stewardship reports.Ethics and disseminationAll sites have obtained ethics committee approval to recruit providers and access anonymised prescribing data. Dissemination will occur through open-access publication, stakeholder networks and national/international meetings.
Symptom heterogeneity and patient subgroup classification among US patients with post-treatment Lyme disease: an observational study
Authors: Rebman Alison W , Yang Ting , Aucott John N 
Published: January 2021

ObjectivesTo identify underlying subgroups with distinct symptom profiles, and to characterise and compare these subgroups across a range of demographic, clinical and psychosocial factors, within a heterogeneous group of patients with well-defined post-treatment Lyme disease (PTLD).DesignA clinical case series of patents.SettingParticipants were recruited from a single-site, Lyme disease referral clinic patient population and were evaluated by physical exam, clinical laboratory testing and standardised questionnaires.ParticipantsTwo hundred and twelve participants met study criteria for PTLD, with medical record-confirmed prior Lyme disease as well as current symptoms and functional impact.ResultsExploratory factor analysis classified 30 self-reported symptoms into 6 factors: ‘Fatigue Cognitive’, ‘Ocular Disequilibrium’, ‘Infection-Type’, ‘Mood-Related’, ‘Musculoskeletal Pain’ and ‘Neurologic’. A final latent profile analysis was conducted using ‘Fatigue Cognitive’, ‘Musculoskeletal Pain’ and ‘Mood-Related’ factor-based scores, which produced three emergent symptom profiles, and participants were classified into corresponding subgroups with 59.0%, 18.9% and 22.2% of the sample, respectively. Compared with the other two groups, subgroup 1 had similarly low levels across all factors relative to the sample as a whole, and reported lower rates of disability (1.6% vs 10.0%, 12.8%; q=0.126, 0.035) and higher self-efficacy (median: 7.5 vs 6.0, 5.3; q=0.068,<0.001). Subgroup 2 had the highest ‘Musculoskeletal Pain’ factor-based scores (q≤0.001). Subgroup 3 was characterised overall by higher symptom factor-based scores, and reported higher depression (q≤0.001).ConclusionsThis analysis identified six symptom factors and three potentially clinically relevant subgroups among patients with well-characterised PTLD. We found that these subgroups were differentiated not only by symptom phenotype, but also by a range of other factors. This may serve as an initial step towards engaging with the symptom heterogeneity that has long been observed among patients with this condition.
Government’s subsidisation policy and utilisation of smoking cessation treatments: a population-based cross-sectional study in Taiwan
Authors: Wang Sheng-Kuang , Kao Chi-Wen , Chuang Hui-Wan , Tseng Yi-Kai , Chen Wan-Chun , Yeh Chien-Chih , Lai Chung-Yu , Yen Li-Chen , Chiu Yu-Lung 
Published: January 2021

ObjectivesThis study examined the associations between the Second-Generation Cessation Payment Scheme (SCPS) and the use of smoking cessation treatments. Furthermore, these associations were compared between light and heavy smokers in Taiwan.DesignThis study had a cross-sectional design.SettingData were obtained from the Taiwan Adult Smoking Behaviour Surveillance System 2010–2011 and 2013–2014; data for each year consisted of a nationally representative sample of adults aged 18 years and older.ParticipantsCurrent smokers who had either quit or made a serious attempt to quit smoking were selected for the analysis.Primary outcome measureThe primary outcome measure was the use of a smoking cessation clinic or pharmacy in a twice daily to quit smoking.ResultsAccording to multivariate analysis, the SCPS was positively associated with the combined use of a smoking cessation clinic and a pharmacy (OR=3.947; 95% CI: 1.359 to 11.463) when individual-level predictors (gender, age, education level, marital status, monthly household income, daily cigarette consumption, smoking status and self-reported health) were controlled. Heavy smokers showed a signiﬁcant increase in the sole use of a pharmacy (OR=1.676; 95% CI: 1.094 to 2.569) and combined use of a smoking cessation clinic and pharmacy (OR=8.984; 95% CI: 1.914 to 42.173) after the SCPS was introduced. In addition, when related factors were controlled, the use of smoking cessation services was more frequent among heavy smokers than light smokers, including any treatment (OR=1.594; 95% CI: 1.308 to 1.942), a smoking cessation clinic (OR=1.539; 95% CI: 1.232 to 1.922), a pharmacy (OR=1.632; 95% CI: 1.157 to 2.302) and the combination of a smoking cessation clinic and pharmacy (OR=4.608; 95% CI: 1.331 to 15.949) .ConclusionsThe SCPS subsidisation policy increased the use of smoking cessation treatments, particularly among heavy smokers.
Study protocol for COVID-RV: a multicentre prospective observational cohort study of right ventricular dysfunction in ventilated patients with COVID-19
Authors: Willder Jennifer Mary , McCall Philip , Messow Claudia-Martina , Gillies Mike , Berry Colin , Shelley Benjamin 
Published: January 2021

IntroductionCOVID-19 can cause severe acute respiratory failure requiring management in intensive care unit with invasive ventilation and a 40% mortality rate. Cardiovascular manifestations are common and studies have shown an increase in right ventricular (RV) dysfunction associated with mortality. These studies, however, comprise heterogeneous patient groups with few requiring invasive ventilation. This study will investigate the prevalence and prognostic significance of RV dysfunction in ventilated patients with COVID-19 which may lead to targeted interventions to improve patient outcomes.Methods and analysisThis prospective multicentre observational cohort study will perform transthoracic echocardiography (TTE) in 150 patients with COVID-19 requiring invasive ventilation for more than 48 hours. RV dysfunction will be defined as TTE evidence of RV dilatation along with the presence of septal flattening. Baseline demographics, disease severity data and clinical information relating to proposed aetiological mechanisms of RV dysfunction (acute respiratory distress syndrome (ARDS), disordered coagulation, direct myocardial injury and ventilation) will be collected and analysed.Primary outcome measures include the prevalence of RV dysfunction and its association with 30-day mortality. Exploratory outcome measures will investigate the association of the proposed aetiological mechanisms of RV dysfunction to the primary outcomes.Prevalence of RV dysfunction will be determined along with 95% Clopper-Pearson CIs and 30-day survival will be analysed using logistic regression adjusting for patient demographics, phase of disease and baseline severity of illness. The role of potential aetiological factors (ARDS, disordered coagulation, direct myocardial injury and ventilation) in relation to the primary outcomes will be analysed using logistic regression.Ethics and disseminationApproval was gained from Scotland A Research Ethics Committee (REC reference 20/SS/0059). Findings will be disseminated by various methods including webinars, international presentations and publication in peer-reviewed journals.
Protocol for the process evaluation of a complex intervention delivered in schools to prevent adolescent depression: the Future Proofing Study
Authors: Beames Joanne R , Lingam Raghu , Boydell Katherine , Calear Alison L , Torok Michelle , Maston Kate , Zbukvic Isabel , Huckvale Kit , Batterham Philip J , Christensen Helen , Werner-Seidler Aliza 
Published: January 2021

IntroductionProcess evaluations provide insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a cluster randomised trial of a digital depression prevention intervention delivered to secondary school students (the Future Proofing Study). The purpose is to describe the methods that will be used to capture process evaluation data within this trial.Methods and analysisUsing a hybrid type 1 design, a mixed-methods approach will be used with data collected in the intervention arm of the Future Proofing Study. Data collection methods will include semistructured interviews with school staff and study facilitators, automatically collected intervention usage data and participant questionnaires (completed by school staff, school counsellors, study facilitators and students). Information will be collected about: (1) how the intervention was implemented in schools, including fidelity; (2) school contextual factors and their association with intervention reach, uptake and acceptability; (3) how school staff, study facilitators and students responded to delivering or completing the intervention. How these factors relate to trial effectiveness outcomes will also be assessed. Overall synthesis of the data will provide school cluster-level and individual-level process outcomes.Ethics and disseminationEthics approval was obtained from the University of New South Wales (NSW) Human Research Ethics Committee (HC180836; 21st January 2019) and the NSW Government State Education Research Applications Process (SERAP 2019201; 19th August 2019). Results will be submitted for publication in peer-reviewed journals and discussed at conferences. Our process evaluation will contextualise the trial findings with respect to how the intervention may have worked in some schools but not in others. This evaluation will inform the development of a model for rolling out digital interventions for the prevention of mental illness in schools.Trial registration numberANZCTRN12619000855123;https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377664&isReview=true.
Efficacy, safety and response predictors of adjuvant astragalus for diabetic kidney disease (READY): study protocol of an add-on, assessor-blind, parallel, pragmatic randomised controlled trial
Authors: Chan Kam Wa , Kwong Alfred Siu Kei , Tsui Pun Nang , Cheung Simon Chi Yuen , Chan Gary Chi Wang , Choi Wing Fai , Yiu Wai Han , Zhang Yanbo , Wong Michelle Man-Ying , Zhang Zhang-Jin , Tan Kathryn Choon Beng , Lao Lixing , Tang Sydney Chi Wai 
Published: January 2021

IntroductionDiabetic kidney disease (DKD) is a prevalent and costly complication of diabetes with limited therapeutic options, being the leading cause of end-stage kidney disease in most developed regions. Recent big data studies showed that add-on Chinese medicine (CM) led to a reduced risk of end-stage kidney disease and mortality among patients with chronic kidney disease (CKD) and diabetes. Astragalus, commonly known as huang-qi, is the most prescribed CM or used dietary herb in China for diabetes and DKD.In vivoandin vitrostudies showed that astragalus ameliorated podocyte apoptosis, foot process effacement, mesangial expansion, glomerulosclerosis and interstitial fibrosis. Nevertheless, the clinical effect of astragalus remains uncharacterised. This pragmatic clinical trial aims to evaluate the effectiveness of add-on astragalus in patients with type 2 diabetes, stage 2–3 CKD and macroalbuminuria, and to identify related response predictors.Methods and analysisThis is an add-on, assessor-blind, parallel, pragmatic randomised controlled clinical trial. 118 patients diagnosed with DKD will be recruited and randomised 1:1 to receive 48 weeks of add-on astragalus or standard medical care. Primary endpoints are the changes in estimated glomerular filtration rate and urine albumin-to-creatinine ratio between baseline and treatment endpoint. Secondary endpoints include adverse events, fasting blood glucose, glycated haemoglobin, lipids and other biomarkers. Adverse events are monitored through self-complete questionnaire and clinical visits. Outcomes will be analysed by regression models. Subgroup and sensitivity analyses will be conducted for different epidemiological subgroups and statistical analyses. Enrolment started in July 2018.Ethics and disseminationThis study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West/East/Kowloon Central clusters (UW 16-553/HKEC-2019-026/REC (KC/KE)-19-0049/ER-4). We will report the findings in medical journals and conferences. The dataset will be available on reasonable request.Trial registration numberNCT03535935
Study protocol: randomised controlled trial evaluating exercise therapy as a supplemental treatment strategy in early multiple sclerosis: the Early Multiple Sclerosis Exercise Study (EMSES)
Authors: Riemenschneider Morten , Hvid Lars G , Ringgaard Steffen , Nygaard Mikkel K E , Eskildsen Simon F , Petersen Thor , Stenager Egon , Dalgas Ulrik 
Published: January 2021

IntroductionIn the relapsing remitting type of multiple sclerosis (MS) reducing relapses and neurodegeneration is crucial in halting the long-term impact of the disease. Medical disease-modifying treatments have proven effective, especially when introduced early in the disease course. However, patients still experience disease activity and disability progression, and therefore, supplemental early treatment strategies are warranted. Exercise appear to be one of the most promising supplemental treatment strategies, but a somewhat overlooked ‘window of opportunity’ exist early in the disease course. The objective of this study is to investigate exercise as a supplementary treatment strategy early in the disease course of MS.Methods and analysisThe presented Early Multiple Sclerosis Exercise Study is a 48-week (plus 1-year follow-up) national multicentre single-blinded parallel group randomised controlled trial comparing two groups receiving usual care plus supervised high-intense exercise or plus health education (active control). Additionally, data will be compared with a population-based control group receiving usual care only obtained from the Danish MS Registry. The primary outcomes are annual relapse rate and MRI derived global brain atrophy. The secondary outcomes are disability progression, physical and cognitive function, MS-related symptoms, and exploratory MRI outcomes. All analyses will be performed as intention to treat.Ethics and disseminationThe study is approved by The Central Denmark Region Committees on Health Research Ethics (1-10-72-388-17) and registered at the Danish Data Protection Agency (2016-051-000001 (706)). All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.Trial registration numberNCT03322761.
One-stop shop for variceal surveillance: integration of unsedated ultrathin endoscopy into the routine clinic visit
Authors: Eqbal Ali , Wickremeratne Tehara , Turner Stephanie , Higgins Sarah Elizabeth , Sloss Andrew , Mitchell Jonathan , O'Beirne James 
Published: January 2021

BackgroundThe endoscopic appearance of oesophageal varices determines the need for prophylaxis. However, as the point prevalence of varices is low (25%), the majority of surveillance endoscopies are unnecessary and costly. Narrow diameter,ultrathin (UT) endoscopes are more tolerable than conventional upper gastrointestinal (UGI) endoscopes and can be used without sedation. We hypothesised that unsedated UT endoscopy for variceal surveillance could be implemented during the routine outpatient clinic visit allowing accurate diagnosis of varices and the timely provision of prophylaxis.MethodsPatients with cirrhosis awaiting surveillance endoscopy were identified. UT endoscopy was scheduled during routine clinic review at the same time as ultrasound surveillance for hepatocellular carcinoma. UGI endoscopy was performed unsedated using the E.G Scan II disposable endoscope. Varices were graded using the modified Paquet classification. Video recordings of procedures were reviewed by blinded assessors and agreement was assessed using the kappa statistic.Results40 patients (80% male) underwent unsedated UT endoscopy. All procedures were successful and tolerated well in 98% of cases. Median procedure time was 2 min (IQR 1–3). Varices were found in 37.5% (17.5% grade 1 and 20% grade 2). Patients with grade 2 varices were prescribed non-selective beta blockers at the clinic appointment. Kappa statistic for the finding of any varices was 0.636 (p=0.001) and 0.8–1.0 for diagnosis of grade 2 varices (p<0.0001).ConclusionsOutpatient unsedated ultrathin endoscopy in patients with cirrhosis is accurate, safe and feasible. This integrative care model is convenient, particularly for regional communities, and is likely to result in significant cost savings associated with variceal surveillance.
Association of sleep duration with all-cause and disease-specific mortality in US adults
Authors: Yang Lili , Xi Bo , Zhao Min , Magnussen Costan G 
Published: January 2021

BackgroundPrevious studies revealed inconsistent findings regarding the association between sleep duration and all-cause and disease-specific mortality. This study aimed to clarify the association of sleep duration with mortality using a large population-based prospective cohort study from the USA.MethodsWe used data from the National Health Interview Survey (2004–2014) linked to National Death Index records to 31 December 2015. A total of 284 754 participants aged ≥18 years were included. Self-reported sleep duration (average time slept in a 24-hour period) was categorised into seven groups: ≤4 hours, 5 hours, 6 hours, 7 hours (reference), 8 hours, 9 hours and ≥10 hours. Study outcomes included all-cause, cardiovascular disease-specific and cancer-specific mortality. Cox proportional hazards models were used to examine the association between sleep duration and mortality.ResultsDuring a median follow-up of 5.25 years, we identified 20 872 deaths, of which 4 129 were cardiovascular disease-related and 5 217 were cancer-related. Compared with 7 hours/day of sleep, both short and long sleep durations were associated with an increased risk of all-cause mortality (≤4 hours: HR=1.46, 95% CI=1.33–1.61; 5 hours: HR=1.22, 95% CI=1.13–1.32; 6 hours: HR=1.10, 95% CI=1.05–1.17; 8 hours: HR=1.22, 95% CI=1.17–1.28; 9 hours: HR=1.41, 95% CI=1.31–1.51; ≥10 hours: HR=2.00, 95% CI=1.88–2.13). Similar results were observed for cardiovascular disease-specific and cancer-specific mortality.ConclusionsOur study indicates that both short (≤6 hours/day) and long (≥8 hours/day) sleep durations increase the risk of mortality compared with sleep of 7 hours/day. A normal sleep duration (about 7 hours) every day is recommended for health benefits.