bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed-method study to assess the feasibility, acceptability and early effectiveness of the Hospital to Home programme for follow-up of high-risk newborns in a rural district of Central Uganda: a study protocol
Authors: Kabugo Daniel , Nakamura Heidi , Magnusson Brooke , Vaughan Madeline , Niyonshaba Beatrice , Nakiganda Cornety , Otai Christine , Haddix-McKay Kimber , Seela Margaret , Nankabala Joyce , Nakakande Josephine , Ssekidde Moses , Tann Cally J , al-Haddad Benjamin J S , Nyonyintono James , Mubiri Paul , Waiswa Peter , Paudel Mohan 
Published: March 2021

IntroductionA follow-up programme designed for high-risk newborns discharged from inpatient newborn units in low-resource settings is imperative to ensure these newborns receive the healthiest possible start to life. We aim to assess the feasibility, acceptability and early outcomes of a discharge and follow-up programme, called Hospital to Home (H2H), in a neonatal unit in central Uganda.Methods and analysisWe will use a mixed-methods study design comparing a historical cohort and an intervention cohort of newborns and their caregivers admitted to a neonatal unit in Uganda. The study design includes two main components. The first component includes qualitative interviews (n=60 or until reaching saturation) with caregivers, community health workers called Village Health Team (VHT) members and neonatal unit staff. The second component assesses and compares outcomes between a prospective intervention cohort (n=100, born between July 2019 and September 2019) and a historical cohort (n=100, born between July 2018 and September 2018) of infants. The historical cohort will receive standard care while the intervention cohort will receive standard care plus the H2H intervention. The H2H intervention comprises training for healthcare workers on lactation, breast feeding and neurodevelopmentally supportive care, including cue-based feeding, and training to caregivers on recognition of danger signs and care of their high-risk infants. Infants and their families receive home visits until 6 months of age, or longer if necessary, by specially trained VHTs. Quantitative data will be analysed using descriptive statistics and regression analysis. All results will be stratified by cohort group. Qualitative data will be analysed guided by Braun and Clarke’s thematic analysis technique.Ethics and disseminationThis study protocol was approved by the relevant Ugandan ethics committees. All participants will provide written informed consent. We will disseminate through peer-reviewed publications and key stakeholders and public engagement.Trial registration numberISRCTN51636372; Pre-result.
High-dose vitamin D supplementation to prevent prostate cancer progression in localised cases with low-to-intermediate risk of progression on active surveillance (ProsD): protocol of a phase II randomised controlled trial
Authors: Nair-Shalliker Visalini , Smith David P , Gebski Val , Patel Manish I , Frydenberg Mark , Yaxley John W , Gardiner Robert , Espinoza David , Kimlin Michael G , Fenech Michael , Gillatt David , Woo Henry , Armstrong Bruce K , Rasiah Krishan , Awad Nader , Symons James , Gurney Howard 
Published: March 2021

Introduction
Active surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression.

Method and analysis
This is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS.

Ethics and dissemination
This trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals.

Trial registration number
ACTRN12616001707459.
Evaluating the contributions of strategies to prevent SARS-CoV-2 transmission in the healthcare setting: a modelling study
Authors: Qiu Xueting , Miller Joel C , MacFadden Derek R , Hanage William P 
Published: March 2021

IntroductionSince its onset, the COVID-19 pandemic has caused significant morbidity and mortality worldwide, with particularly severe outcomes in healthcare institutions and congregate settings. To mitigate spread, healthcare systems have been cohorting patients to limit contacts between uninfected patients and potentially infected patients or healthcare workers (HCWs). A major challenge in managing the pandemic is the presence of currently asymptomatic/presymptomatic individuals capable of transmitting the virus, who could introduce COVID-19 into uninfected cohorts. The optimal combination of personal protective equipment (PPE), testing and other approaches to prevent these events is unclear, especially in light of ongoing limited resources.MethodsUsing stochastic simulations with a susceptible-exposed-infected-recovered dynamic model, we quantified and compared the impacts of PPE use, patient and HCWs surveillance testing and subcohorting strategies.ResultsIn the base case without testing or PPE, the healthcare system was rapidly overwhelmed, and became a net contributor to the force of infection. We found that effective use of PPE by both HCWs and patients could prevent this scenario, while random testing of apparently asymptomatic/presymptomatic individuals on a weekly basis was less effective. We also found that even imperfect use of PPE could provide substantial protection by decreasing the force of infection. Importantly, we found that creating smaller patient/HCW-interaction subcohorts can provide additional resilience to outbreak development with limited resources.ConclusionThese findings reinforce the importance of ensuring adequate PPE supplies even in the absence of testing and provide support for strict subcohorting regimens to reduce outbreak potential in healthcare institutions.
Digital health literacy intervention to support maternal, child and family health in primary healthcare settings of Pakistan during the age of coronavirus: study protocol for a randomised controlled trial
Authors: Jafree Sara Rizvi , Bukhari Nadia , Muzamill Anam , Tasneem Faiza , Fischer Florian 
Published: March 2021

IntroductionThere is a need to continue primary healthcare services through digital communication for disadvantaged women living in underdeveloped areas of Pakistan, especially in the age of the coronavirus pandemic, social distancing and lockdown of communities. This project will be the first of its kind in aiming to implement a digital health literacy intervention, using smartphone and internet, to disadvantaged women through female community healthcare workers. Improved health literacy in women of reproductive years is known to promote maternal, child and family health overall.Methods and analysisThe study will include a baseline survey, a pre- and post-test survey and a 3-month lasting intervention on (1) hygiene and prevention and (2) coronavirus awareness and prevention. Women of reproductive years will be sampled from disadvantaged areas across the four provinces of Pakistan (Baluchistan, Khyber Pakhtunkhwa, Punjab and Sindh), and the selection criteria will be poor, semiliterate or illiterate, belonging to underdeveloped neighbourhoods devoid of universal healthcare coverage and dependent on free primary health services. A target of 1000 women will comprise the sample, with 500 women each assigned randomly to the intervention and control groups. Analysis of variance and multivariate analysis will be used for analysing the intervention’s effects compared with the control group.Ethics and disseminationEthics approval for this study has been received from the Internal Review Board of the Forman Christian College University (reference number: IRB-252/06-2020). Results will be published in academic journals of repute and dissemination to the international scientific community and stakeholders will also be planned through workshops.Trial registration numberNCT04603092.
Recent HIV testing and associated factors among people who use drugs in Cambodia: a national cross-sectional study
Authors: Eng Chee Wen , Tuot Sovannary , Chann Navy , Chhoun Pheak , Mun Phalkun , Yi Siyan 
Published: March 2021

ObjectiveTo estimate the prevalence of HIV testing and examine factors associated with recent HIV testing among people who use drugs (PWUD) in Cambodia.DesignCross-sectional study.SettingTwelve major provinces with a high burden of HIV and drug use in Cambodia.ParticipantsThis study included 1677 PWUD recruited using a peer-based social network recruitment method. Participants’ selection criteria included being at least 18 years old and using any illicit drugs via any administration routes in the past 12 months.Primary outcome measureRecent HIV testing, defined as having an HIV test in the past 6 months.ResultsThe median age of the participants was 28 (IQR 22–34) years, and 56.6% were men. The prevalence of lifetime and recent HIV testing was 70.7% and 42.9%, respectively. After adjustment in multivariable logistic regression analysis, recent HIV testing remained positively associated with being female (adjusted OR (AOR) 1.55, 95% CI 1.18 to 2.04) or third gender identity (AOR 2.06, 95% CI 1.11 to 3.80), having ever been to a drug rehabilitation centre (AOR 1.60, 95% CI 1.13 to 2.29), having used any HIV services in the past 6 months (AOR 7.37, 95% CI 5.61 to 9.69), having received HIV education in the past 3 months (AOR 3.40, 95% CI 2.63 to 4.40) and having self-perception of higher HIV risk (AOR 1.81, 95% CI 1.19 to 2.73).ConclusionsRecent HIV test uptake among PWUD in Cambodia was suboptimal. This study highlights the roles of outreach HIV education and services in promoting regular HIV testing among PWUD. Strengthening the coordinated effort of government agencies and local civil society organisations to prioritise expanding community-based peer-driven interventions to reach out to this hidden population is warranted.
Discrete choice experiment (DCE) to quantify the influence of trial features on the decision to participate in cystic fibrosis (CF) clinical trials
Authors: Dobra Rebecca Anne , Boeri Marco , Elborn Stuart , Kee Frank , Madge Susan , Davies Jane C 
Published: March 2021

IntroductionEngaging people with cystic fibrosis (CF) in clinical trials is critical to improving outcomes for this fatal disease. Following extensive exploration of engagement in CF trials we believe six key concepts require a quantitative understanding of their influence in the current CF trials landscape including how controversial issues like placebos, washouts, stipend provision and location of trial visits are viewed by the CF community and how these might be modified depending on the type of medicine being investigated and the mechanism of access to the drug on trial completion.Methods and analysisWe have designed and will administer an online discrete choice experiment to elicit and quantify preferences of people with CF for these trials’ attributes and estimate the relative importance of an attribute when choosing to participate in a trial. The cross-sectional data generated will be explored using conditional multinomial logit model. Mixed logit models such as the random-parameters logit and a latent class models will be used to explore preference heterogeneity. To determine the relative importance of an attribute, the difference between the attribute level with the highest preference weight and the level with the lowest preference weight will be calculated.Ethics and disseminationImperial College London Joint Research Compliance Office has granted ethical approval for this study. Patient consent will be sought following full explanation. No identifying information will be collected. Dissemination will be via international conferences, peer-review publication and patient accessible forums. Major CF trials networks have agreed to incorporate our findings into their review process, meaning our results can realistically influence and optimise CF trial delivery.PROSPERO registration numberCRD42020184886.
Prevalence of insufficient weight loss 5 years after Roux-en-Y gastric bypass: metabolic consequences and prediction estimates: a prospective registry study
Authors: Brissman Markus , Beamish Andrew J , Olbers Torsten , Marcus Claude 
Published: March 2021

ObjectiveThe study aimed to investigate the heterogeneity of weight loss 5 years after Roux-en-Y gastric bypass (RYGB) and the association with cardiometabolic health as well as to model prediction estimates of surgical treatment failure.DesignRetrospective analysis of prospectively collected data from the Scandinavian Obesity Surgery Registry (SOReg).Setting29 surgical units from the whole of Sweden contributed data. Inclusion was restricted to surgical units with a retention rate of >60% five years postsurgery.Participants10 633 patients were extracted from SOReg. In total 5936 participants were included in the final sample, 79.1% females. The mean age of participants before surgery was 39.4±9 years and mean body mass index (BMI) 42.9±5.1. 2322 were excluded (death before the 5-year follow-up (n=148), other types of surgery or reoperations (n=637), age at surgery <18 or >55 years (n=1329), presurgery BMI <35 kg/m2(n=208)). In total, 2375 (29%) of eligible individuals were lost to the 5-year follow-up.Main outcomeThe occurrence of surgical treatment failure 5 years after surgery was based on the three previously published definitions: per cent excess BMI loss <50%, total weight loss <20% or BMI >35 where initial BMI was <50, or >40 where initial BMI was >50. In addition, we report the association between surgical treatment failure and biochemical markers of obesity-related comorbidity. We also developed predictive models to identify patients with a high risk of surgical treatment failure 5 years postsurgery.ResultsIn total, 23.1% met at least one definition of surgical treatment failure at year 5 which was associated with (adjusted OR) with 95% CI): type 2 diabetes (T2D, OR 2.1; 95% CI 1.6 to 2.7), dyslipidaemia (OR 1.8; 95% CI 1.6 to 2.1) and hypertension (OR 1.9; 95% CI 1.6 to 2.2). Surgical treatment failure at 5 years was predicted by combined demographic and anthropometric measures from baseline, 1 and 2 years postsurgery (area under the curve=0.874).ConclusionLaparoscopic RYGB leads to a marked and sustained weight loss with improvement of obesity-related comorbidity in most patients. However, 23% met at least one definition of surgical treatment failure, which was associated with a greater risk of relapse and a higher incidence of T2D, dyslipidaemia and hypertension 5 years after surgery. Poor initial weight loss and early weight regain are strong predictors of long-term treatment failure and may be used for early identification of patients who require additional weight loss support.
Rapamycin enhances BCG-specific γδ T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study
Authors: Ji Niannian , Mukherjee Neelam , Reyes Ryan M , Gelfond Jonathan , Javors Martin , Meeks Joshua J. , McConkey David J , Shu Zhen-Ju , Ramamurthy Chethan , Dennett Ryan , Curiel Tyler J , Svatek Robert S 
Published: March 2021

BackgroundAlthough intravesical BCG is the standard treatment of high-grade non-muscle invasive bladder cancer (NMIBC), response rates remain unsatisfactory. In preclinical models, rapamycin enhances BCG vaccine efficacy against tuberculosis and the killing capacity of γδ T cells, which are critical for BCG’s antitumor effects. Here, we monitored immunity, safety, and tolerability of rapamycin combined with BCG in patients with NMIBC.MethodsA randomized double-blind trial of oral rapamycin (0.5 or 2.0 mg daily) versus placebo for 1 month was conducted in patients with NMIBC concurrently receiving 3 weekly BCG instillations (NCT02753309). The primary outcome was induction of BCG-specific γδ T cells, measured as a percentage change from baseline. Post-BCG urinary cytokines and immune cells were examined as surrogates for local immune response in the bladder. Secondary outcomes measured were adverse events (AEs) and tolerability using validated patient-reported questionnaires.ResultsThirty-one patients were randomized (11 placebo, 8 rapamycin 2.0 mg, and 12 rapamycin 0.5 mg). AEs were similar across groups and most were grade 1–2. One (12.5%) patient randomized to 2.0 mg rapamycin was taken off treatment due to stomatitis. No significant differences in urinary symptoms, bowel function, or bother were observed between groups. The median (IQR) percentage change in BCG-specific γδ T cells from baseline per group was as follows: −26% (−51% to 24%) for placebo, 9.6% (−59% to 117%) for rapamycin 0.5 mg (versus placebo, p=0.18), and 78.8% (−31% to 115%) for rapamycin 2.0 mg (versus placebo, p=0.03). BCG-induced cytokines showed a progressive increase in IL-8 (p=0.02) and TNF-α (p=0.04) over time for patients on rapamycin 2.0 mg, whereas patients receiving placebo had no significant change in urinary cytokines. Compared with placebo, patients receiving 2.0 mg rapamycin had increased urinary γδ T cells at the first week of BCG (p=0.02).ConclusionsFour weeks of 0.5 and 2.0 mg oral rapamycin daily is safe and tolerable in combination with BCG for patients with NMIBC. Rapamycin enhances BCG-specific γδ T cell immunity and boosts urinary cytokines during BCG treatment. Further study is needed to determine long-term rapamycin safety, tolerability and effects on BCG efficacy.
Electrocardiographic features of immune checkpoint inhibitor associated myocarditis
Authors: Zlotoff Daniel A , Hassan Malek Z O , Zafar Amna , Alvi Raza M , Awadalla Magid , Mahmood Syed S , Zhang Lili , Chen Carol L , Ederhy Stephane , Barac Ana , Banerji Dahlia , Jones-O'Connor Maeve , Murphy Sean P , Armanious Merna , Forrestal Brian J , Kirchberger Michael C , Coelho-Filho Otavio R , Rizvi Muhammad A , Sahni Gagan , Mandawat Anant , Tocchetti Carlo G , Hartmann Sarah , Gilman Hannah K , Zatarain-Nicolás Eduardo , Mahmoudi Michael , Gupta Dipti , Sullivan Ryan , Ganatra Sarju , Yang Eric H , Heinzerling Lucie M , Thuny Franck , Zubiri Leyre , Reynolds Kerry L , Cohen Justine V , Lyon Alexander R , Groarke John , Thavendiranathan Paaladinesh , Nohria Anju , Fradley Michael G , Neilan Tomas G 
Published: March 2021

BackgroundMyocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.MethodsFrom an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.ResultsBoth the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39).ConclusionsThe QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.
Conference panels: do they reflect the diversity of the NHS workforce?
Authors: Prathivadi Bhayankaram Kethaki , Prathivadi Bhayankaram Nuthana 
Published: March 2021

BackgroundThe number of female and black, Asian and minor ethnicity (BAME) healthcare professionals has significantly increased over the last few decades. While this highlights the National Health Service (NHS) workforce as diverse and inclusive, most senior managers and conference panellists remain mainly men from Caucasian backgrounds.MethodsWe reviewed all publicly available data for major Royal College conferences in the UK from 2015 to 2019 to examine how many of the panellists were men or women and how many were Caucasian or BAME.ResultsOur first finding was that publicly available data were available for only 20 out of 70 conferences (29%). At 60% (n=12) of conferences, there were a predominance of male speakers. The median percentage of female speakers remained between 35% and 46%. There were no all-male panels. At 20% (n=4) of conferences in the sample, there were no BAME speakers. The median percentage of BAME speakers remained between 9% and 18%.ConclusionConference panels do not yet reflect the diversity of the NHS workforce. We all have a duty to promote inclusivity and diversity in medicine. One way to do this is via conferences, through appropriate actions by conference organisers, panellists and delegates.
Precession of timelike bound orbits in Kerr spacetime
Authors: Bambhaniya Parth , Solanki Divyesh N. , Dey Dipanjan , Joshi Ashok B. , Joshi Pankaj S. , Patel Vishva 
Published: March 2021

AbstractAstrometric observations of S-stars provide a unique opportunity to probe the nature of Sagittarius-A* (Sgr-A*). In view of this, it has become important to understand the nature and behavior of timelike bound trajectories of particles around a massive central object. It is known now that whereas the Schwarzschild black hole does not allow the negative precession for the S-stars, the naked singularity spacetimes can admit the positive as well as negative precession for the bound timelike orbits. In this context, we study the perihelion precession of a test particle in the Kerr spacetime geometry. Considering some approximations, we investigate whether the timelike bound orbits of a test particle in Kerr spacetime can have negative precession. In this paper, we only consider low eccentric timelike equatorial orbits. With these considerations, we find that in Kerr spacetimes, negative precession of timelike bound orbits is not allowed.