bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhaled and intranasal ciclesonide for the treatment of covid-19 in adult outpatients: CONTAIN phase II randomised controlled trial
Authors: Ezer Nicole , Belga Sara , Daneman Nick , Chan Adrienne , Smith Benjamin M , Daniels Shay-Anne , Moran Kristen , Besson Charlotte , Smyth Louisa Y , Bartlett Susan J , Benedetti Andrea , Martin James G , Lee Todd C , McDonald Emily G 
Published: November 2021

Abstract

Objective
To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19.

Design
Randomised, double blind, placebo controlled trial.

Setting
Three Canadian provinces (Quebec, Ontario, and British Columbia).

Participants
203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea.

Intervention
Participants were randomised to receive either inhaled ciclesonide (600 μg twice daily) and intranasal ciclesonide (200 μg daily) or metered dose inhaler and nasal saline placebos for 14 days.

Main outcome measures
The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex.

Results
The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval −7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered.

Conclusion
Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed.

Trial registration

ClinicalTrials.gov
NCT04435795
.
Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials
Authors: Hunter Jennifer , Arentz Susan , Goldenberg Joshua , Yang Guoyan , Beardsley Jennifer , Myers Stephen P , Mertz Dominik , Leeder Stephen 
Published: November 2021

ObjectiveTo evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults.MethodSeventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.ResultsTwenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD −1.20 points, 95% CI −0.66 to −1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD −0.15, 95% CI −0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality).ConclusionsIn adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted.PROSPERO registration numberCRD42020182044.
Effect of Pudilan Keyanning antibacterial mouthwash on dental plaque and gingival inflammation in patients during periodontal maintenance phase: study protocol for double-blind, randomised clinical trial
Authors: Liu Jianru , Huang Yan , Lou Xinzhe , Liu Bei , Liu Wenyi , An Na , Wu Rong , Ouyang Xiangying 
Published: November 2021

IntroductionPlaque control plays a critical role in the prevention and treatment of periodontitis. Antibacterial mouthwash is one of the most important tools for plaque control. Pudilan, including extracts ofScutellaria baicalensisroot,Taraxacum mongolicum, Bunge corydalis herb andIsatis indigotica, was reported playing the role of anti-inflammatory and anti-bacterial. However, its effect on dental plaque and periodontal inflammation remains unknown. We aimed to assess the efficacy of Pudilan Keyanning antibacterial mouthwash which contains the active essence of Pudilan and 0.03%–0.06% cetylpyridinium chloride, as well as Pudilan active essence for plaque control and gingival anti-inflammation in patients during periodontal maintenance phase.Methods and analysisIn this double-blind, randomised, placebo-controlled clinical trial, a total of 120 participants during periodontal maintenance phase will be enrolled. After supragingival scaling, they will be randomly assigned into three groups in a 1:1:1 ratio: the Pudilan Keyanning antibacterial mouthwash group, a chlorhexidine acetate mouthwash (0.12%) group or a placebo group with mouthwash containing the same components as the Pudilan Keyanning mouthwash except for Pudilan active ingredients. They will rinse with mouthwash, respectively, two times per day for 6 weeks. Clinical parameters (such as plaque index, bleeding index) and the level of volatile sulfide in the breath will be measured and analysed. The subgingival plaque will be collected and analysed microbiologically. Questionnaire feedback will be analysed.Ethics and disseminationThe study protocol (V.4) was reviewed and approved by the Medical Ethical Committee of Peking University School and Hospital of Stomatology (Ethics Approval No. PKUSSIRB-201950153b). All participants signed a written consent form.Trial registration numberChiCTR2000041253.
MyPal ADULT study protocol: a randomised clinical trial of the MyPal ePRO-based early palliative care system in adult patients with haematological malignancies
Authors: Scarfò Lydia , Karamanidou Christina , Doubek Michael , Garani-Papadatos Tina , Didi Jana , Pontikoglou Charalampos , Ling Julie , Payne Cathy , Papadaki Helen Α , Rosenquist Richard , Stavroyianni Niki , Payne Sheila , Ghia Paolo , Natsiavas Pantelis , Maramis Christos , Stamatopoulos Kostas 
Published: November 2021

IntroductionThe systematic collection of electronic patient-reported outcome (ePRO) in the routine care of patients with chronic haematological malignancies such as chronic lymphocytic leukaemia (CLL) and myelodysplasia syndromes (MDS) can constitute a very ambitious but worthwhile challenge. MyPal is a Horizon 2020 Research & Innovation Action aiming to meet this challenge and foster palliative care for patients with CLL or MDS by leveraging ePRO systems to adapt to the personal needs of patients and caregiver(s).Methods and analysisIn this interventional randomised trial, 300 patients with CLL or MDS will be recruited across Europe. Patients will be randomly allocated to early palliative care using the MyPal system (n=150) versus standard care including general palliative care if needed (n=150). Patients in the experimental arm will be given access to the MyPal digital health platform which consists of purposely designed software available on smartphones and/or tablets. The platform entails different functionalities including physical and psychoemotional symptom reporting via regular questionnaire completion, spontaneous self-reporting, motivational messages, medication management and a personalised search engine for health information. Data on patients’ activity (daily steps and sleep quality) will be automatically collected via wearable devices.Ethics and disseminationThe integration of ePROs via mobile applications has raised ethical concerns regarding inclusion criteria, information provided to participants, free and voluntary consent, and respect for their autonomy. These have been carefully addressed by a multidisciplinary team. Data processing, dissemination and exploitation of the study findings will take place in full compliance with European Union data protection law. A participatory design was adopted in the development of the digital platform involving focus groups and discussions with patients to identify needs and preferences. The protocol was approved by the ethics committees of San Raffaele (8/2020), Thessaloniki ‘George Papanikolaou’ Hospital (849), Karolinska Institutet (20.10.2020), University General Hospital of Heraklion (07/15.4.2020) and University of Brno (01-120220/EK).Trial registration numberNCT04370457.
Gender differences in faculty rank among academic physicians: a systematic review and meta-analysis
Authors: Li Ben , Jacob-Brassard Jean , Dossa Fahima , Salata Konrad , Kishibe Teruko , Greco Elisa , Baxter Nancy N , Al-Omran Mohammed 
Published: November 2021

ObjectiveMany studies have analysed gender bias in academic medicine; however, no comprehensive synthesis of the literature has been performed. We conducted a pooled analysis of the difference in the proportion of men versus women with full professorship among academic physicians.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, Embase, Cochrane Central Register of Controlled Trials, Education Resources Information Center and PsycINFO were searched from inception to 3 July 2020.Study selectionAll original studies reporting faculty rank stratified by gender worldwide were included.Data extraction and synthesisStudy screening, data extraction and quality assessment were performed by two independent reviewers, with a third author resolving discrepancies. Meta-analysis was conducted using random-effects models.ResultsOur search yielded 5897 articles. 218 studies were included with 991 207 academic physician data points. Men were 2.77 times more likely to be full professors (182 271/643 790 men vs 30 349/251 501 women, OR 2.77, 95% CI 2.57 to 2.98). Although men practised for longer (median 18 vs 12 years, p<0.00002), the gender gap remained after pooling seven studies that adjusted for factors including time in practice, specialty, publications, h-index, additional PhD and institution (adjusted OR 1.83, 95% CI 1.04 to 3.20). Meta-regression by data collection year demonstrated improvement over time (p=0.0011); however, subgroup analysis showed that gender disparities remain significant in the 2010–2020 decade (OR 2.63, 95% CI 2.48 to 2.80). The gender gap was present across all specialties and both within and outside of North America. Men published more papers (mean difference 17.2, 95% CI 14.7 to 19.7), earned higher salaries (mean difference $33 256, 95% CI $25 969 to $40 542) and were more likely to be departmental chairs (OR 2.61, 95% CI 2.19 to 3.12).ConclusionsGender inequity in academic medicine exists across all specialties, geographical regions and multiple measures of success, including academic rank, publications, salary and leadership. Men are more likely than women to be full professors after controlling for experience, academic productivity and specialty. Although there has been some improvement over time, the gender disparity in faculty rank persists.PROSPERO registration numberCRD42020197414.
Preterm birth among Pacific Islander women and related perinatal outcomes: a scoping review protocol
Authors: Wu Bohao , Arslanian Kendall J , Nyhan Kate , Taylor Sarah , Shabanova Veronika , Muasau-Howard Bethel , Hawley Nicola L 
Published: November 2021

IntroductionInfants born alive <37 weeks are classified as premature. The global estimate of preterm birth in 2014 was 10.6%, and it is the leading cause of death of children under the age of 5 years. Preterm birth disproportionately affects women of minority populations, yet knowledge about the incidence and associated outcomes among Pacific Islanders is limited. The objectives of this scoping review are to identify studies that describe risk factors, maternal-child health outcomes and existing interventions to prevent preterm birth among Pacific Islanders, and to summarise the barriers and facilitators to decrease the burden.Methods and analysisWe will follow the Joanna Briggs Institute Manual for Evidence Synthesis for scoping reviews and the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) to conduct this scoping review. The Covidence web application will be used for data management and consensus review. We will search on MEDLINE ALL (Ovid), EMBASE (Ovid), Web of Science Core Collection (as licensed at Yale), the Cochrane Library, CINAHL (EBSCOhost) and two non-indexed regional journals (Pacific Journal of Reproductive HealthandPacific Health Dialog). Title-abstract and full-text screening of eligible studies will be performed by two authors, and data will be extracted by the first author. Outcomes extracted will be presented using evidence mapping.Ethics and disseminationFindings will drive suggestions for new data collection needed to fill knowledge gaps and improve future study designs to decrease the burden of preterm birth among Pacific Islanders. There are no ethical concerns. This protocol will be disseminated in related peer-reviewed journals.
Impact of disease-modifying therapies on MRI and neurocognitive outcomes in relapsing–remitting multiple sclerosis: a protocol for a systematic review and network meta-analysis
Authors: Lees Samuel , Dicker Mathew , Ku Jie En , Chaganti Varun , Mew-Sum Matthew , Wang Nick , Smith Angela , Oldmeadow Christopher , Goon Wooi Lynn , Bevan Marc , Lang Danielle , Hinwood Madeleine 
Published: November 2021

IntroductionDisease-modifying therapies (DMTs) are the mainstay of treatment for relapsing–remitting multiple sclerosis (RRMS). There is established evidence that DMTs are effective at reducing relapse rate and disease progression in RRMS, but there has been less consideration to the synthesis of MRI and neurocognitive outcomes, which play an increasingly important role in treatment decisions. The aim of this systematic review and network meta-analysis is to examine the relative efficacy, acceptability and tolerability of DMTs for RRMS, using MRI and neurocognitive outcomes.Methods and analysisWe will search electronic databases, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, with no date restrictions. We will also search the websites of international regulatory bodies for pharmaceuticals and international trial registries. We will include parallel group randomised controlled trials of DMTs including interferon beta-1a intramuscular, interferon beta-1a subcutaneous, interferon beta-1b, peginterferon beta-1a, glatiramer acetate, natalizumab, ocrelizumab, alemtuzumab, dimethyl fumarate, teriflunomide, fingolimod, cladribine, ozanimod, mitoxantrone and rituximab, either head-to-head or against placebo in adults with RRMS. Primary outcomes include efficacy (MRI outcomes including new T1/hypointense lesions and T2/hyperintense lesions) and acceptability (all-cause dropouts). Secondary outcomes include gadolinium-enhancing lesions, cerebral atrophy and tolerability (dropouts due to adverse events). Neurocognitive measures across three domains including processing speed, working memory and verbal learning will be included as exploratory outcomes. Data will be analysed using a random-effects pairwise meta-analysis and a Bayesian hierarchical random effects network meta-analysis to evaluate the efficacy, acceptability and tolerability of the included DMTs. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses statement.Ethics and disseminationThis protocol does not require ethics approval. Results will be disseminated in a peer-reviewed academic journal.PROSPERO registration numberCRD42021239630.
Predicting patient-level new-onset atrial fibrillation from population-based nationwide electronic health records: protocol of FIND-AF for developing a precision medicine prediction model using artificial intelligence
Authors: Nadarajah Ramesh , Wu Jianhua , Frangi Alejandro F , Hogg David , Cowan Campbell , Gale Chris 
Published: November 2021

IntroductionAtrial fibrillation (AF) is a major cardiovascular health problem: it is common, chronic and incurs substantial healthcare expenditure because of stroke. Oral anticoagulation reduces the risk of thromboembolic stroke in those at higher risk; but for a number of patients, stroke is the first manifestation of undetected AF. There is a rationale for the early diagnosis of AF, before the first complication occurs, but population-based screening is not recommended. Previous prediction models have been limited by their data sources and methodologies. An accurate model that uses existing routinely collected data is needed to inform clinicians of patient-level risk of AF, inform national screening policy and highlight predictors that may be amenable to primary prevention.Methods and analysisWe will investigate the application of a range of deep learning techniques, including an adapted convolutional neural network, recurrent neural network and Transformer, on routinely collected primary care data to create a personalised model predicting the risk of new-onset AF over a range of time periods. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the CPRD-AURUM dataset will be used for external geographical validation. Both comprise a sizeable representative population and are linked at patient-level to secondary care databases. The performance of the deep learning models will be compared against classic machine learning and traditional statistical predictive modelling methods. We will only use risk factors accessible in primary care and endow the model with the ability to update risk prediction as it is presented with new data, to make the model more useful in clinical practice.Ethics and disseminationPermissions for CPRD-GOLD and CPRD-AURUM datasets were obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences.Trial registration detailsA systematic review to incorporate within the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT04657900).
Mechanical thrombectomy versus intravenous alteplase alone in acute isolated posterior cerebral artery occlusion: a systematic review
Authors: Monteiro Andre , Khan Slah , Waqas Muhammad , Dossani Rimal H , Ruggiero Nicco , Siddiqi Nehaal M , Baig Ammad A , Rai Hamid H , Cappuzzo Justin M , Levy Elad I , Siddiqui Adnan H 
Published: November 2021

BackgroundAcute isolated posterior cerebral artery occlusions (aPCAOs) were excluded or under-represented in major randomized trials of mechanical thrombectomy (MT). The benefit of MT in comparison to intravenous tissue plasminogen activator (alteplase; IV-tPA) alone in these patients remains controversial and uncertain.MethodsWe performed a systematic search of PubMed, MEDLINE, and EMBASE databases for articles comparing MT with or without bridging IV-tPA and IV-tPA alone for aPCAO using keywords (‘posterior cerebral artery’, ‘thrombolysis’ and ‘thrombectomy’) with Boolean operators. Extracted data from patients reported in the studies were pooled into groups (MT vs IV-tPA alone) for comparison. Estimated rates for favorable outcome (modified Rankin scale score 0–2), symptomatic intracranial hemorrhage (sICH), and mortality were extracted.ResultsSeven articles (201 MT patients, 64 IV-tPA) were included, all retrospective. There was no statistically significant difference between pooled groups in median age, median presentation National Institutes of Health Stroke Scale (NIHSS) score, PCAO segment, and median time from symptom onset to puncture or needle. The recanalization rate was significantly higher in the MT group than the IV-tPA group (85.6% vs 53.1%, p<0.00001). Odds ratios for favorable outcome (OR 1.5, 95% CI 0.8 to 2.5), sICH (OR 1.1, 95% CI 0.2 to 5.5), and mortality (OR 1.4, 95% CI 0.5 to 3.6) did not significantly favor any modality.ConclusionsWe found no significant differences in odds of favorable outcome, sICH, and mortality in MT and IV-tPA in comparable aPCAO patients, despite superior MT recanalization rates. Equipoise remains regarding the optimal treatment modality for these patients.
Strong cosmic censorship in near-extremal Kerr-Sen-de Sitter spacetime
Authors: Zhang Ming , Jiang Jie 
Published: November 2021

AbstractIn this work, we first calculate equations of motion for particles in the Kerr-Sen-de Sitter black hole spacetime. Then, in the eikonal regime, we analytically obtain the quasi-normal resonant modes of massless neutral scalar field perturbation and find its imaginary part to be characterized by the surface gravity of a near-extremal Kerr-Sen-de Sitter black hole with the Cauchy horizon approaching the event horizon. We further show that the Penrose strong cosmic censorship conjecture is thus respected in this spacetime with dilaton scalar field and axion pseudoscalar field.
Prospects on searches for baryonic Dark Matter produced in $${\varvec{b}}$$-hadron decays at LHCb
Authors: Brea Rodríguez Alexandre , Chobanova Veronika , Cid Vidal Xabier , López Soliño Saúl , Martínez Santos Diego , Mombächer Titus , Prouvé Claire , Rodríguez Fernández Emilio Xosé , Vázquez Sierra Carlos 
Published: November 2021

AbstractA model that can simultaneously explain Dark Matter relic density and the apparent matter anti-matter imbalance of the universe has been recently proposed. The model requires b-hadron branching fractions to Dark Matter at the per mille level. The b-hadrons decay to a dark sector baryon, $$\psi _{\mathrm{DS}}$$

ψ
DS

, which has a mass in the region $$940 ~\mathrm{MeV}/c^2\le m_{\psi _{\mathrm{DS}}}\le 4430~\mathrm{MeV}/c^2$$

940

MeV
/

c
2

≤

m

ψ
DS

≤
4430

MeV
/

c
2

. In this paper, we discuss the sensitivity of the LHCb experiment to search for this dark baryon, covering different types of topology and giving prospects for Runs 3 and 4 of the LHC, as well as for the proposed Upgrade II. We show that the LHCb experiment can cover the entire mass range of the hypothetical dark baryon.