bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a novel stratified PAthway of CarE for common musculoskeletal (MSK) conditions in primary care: protocol for a multicentre pragmatic randomised controlled trial (the PACE MSK trial)
Authors: Rebbeck Trudy , Evans Kerrie , Ferreira Paulo , Beales Darren , Sterling Michele , Bennell Kim L , Cameron Ian , Nicholas Michael , Ritchie Carrie , Jull Gwen , Treleaven Julia , Trevena Lyndal , Refshauge Kathryn , Connelly Luke , Foster Nadine , Black Deborah , Hodges Paul , Ferreira Manuela , Shaw Tim J , Simic Milena 
Published: December 2021

IntroductionMusculoskeletal (MSK) conditions constitute the highest burden of disease globally, with healthcare services often utilised inappropriately and overburdened. The aim of this trial is to evaluate the effectiveness of a novel clinical PAthway of CarE programme (PACE programme), where care is provided based on people’s risk of poor outcome.Methods and analysisMulticentre randomised controlled trial. 716 people with MSK conditions (low back pain, neck pain or knee osteoarthritis) will be recruited in primary care. They will be stratified for risk of a poor outcome (low risk/high risk) using the Short Form Örebro Musculoskeletal Pain Screening Questionnaire (SF-ÖMSPQ) then randomised to usual care (n=358) or the PACE programme (n=358). Participants at low risk in the PACE programme will receive up to 3 sessions of guideline based care from their primary healthcare professional (HCP) supported by a custom designed website (mypainhub.com). Those at high risk will be referred to an allied health MSK specialist who will conduct a comprehensive patient-centred assessment then liaise with the primary HCP to determine further care. Primary outcome (SF 12-item PCS) and secondary outcomes (eg, pain self-efficacy, psychological health) will be collected at baseline, 3, 6 and 12 months. Cost-effectiveness will be measured as cost per quality-adjusted life-year gained. Health economic analysis will include direct and indirect costs. Analyses will be conducted on an intention-to-treat basis. Primary and secondary outcomes will be analysed independently, using generalised linear models. Qualitative and mixed-methods studies embedded within the trial will evaluate patient experience, health professional practice and interprofessional collaboration.Ethics and disseminationEthics approval has been received from the following Human Research Ethics Committees: The University of Sydney (2018/926), The University of Queensland (2019000700/2018/926), University of Melbourne (1954239), Curtin University (HRE2019-0263) and Northern Sydney Local Health District (2019/ETH03632). Dissemination of findings will occur via peer-reviewed publications, conference presentations and social media.Trial registration numberACTRN12619000871145.
Time to inclusion in clinical guidance documents for non-oncological orphan drugs and biologics with expedited FDA designations: a retrospective survival analysis
Authors: Rodriguez Ryan , Brunner Rachel , Spencer Samantha , Qato Dima M 
Published: December 2021

ObjectivesDrug and biological products that treat rare, serious or life-threatening conditions can receive US Food and Drug Administration (FDA) orphan designation and expedited programme designations (accelerated approval, breakthrough therapy, fast track or priority review) meant to incentivise development. Timely recommendations from guidance documents may encourage more rapid and appropriate use and access to these medicines for serious conditions. We sought to determine time between FDA approval and inclusion in guidance documents for non-oncological orphan products overall and by number and type of expedited programme designations.Design and settingRetrospective survival analysis of non-oncological orphan products with ≥1 expedited designation approved since 1992. In June 2020, PubMed, Turning Research into Practice and Guideline Central databases were searched to identify guidance documents influencing US practice that included each product.Main outcomes and measuresThe primary outcome was time to guidance inclusion, defined as any recommendation on use provided within the recommendation framework used by the guidance document.ResultsAmong 135 included non-oncological orphan products, 97.0% (n=131) were designated with priority review, 49.6% (n=67) fast track, 16.3% (n=22) breakthrough therapy and 14.1% (n=19) accelerated approval. Sixty per cent of products (n=81) received ≥2 designations. Overall, 74.1% (n=100) were included in a guidance document. The median time to inclusion was 2.87 years (IQR 2.21–4.18) for the entire cohort. In survival analyses, guidance inclusion was more likely to occur earlier for products with ≥2 designations (HR, 1.84; 95% CI 1.21 to 2.79) and for those with fast-track designation compared with priority review (HR 1.40; 95% CI 1.02 to 2.0). Of 35 products not included in a guidance document, 54.3% (n=19) were approved in 2018 or later.ConclusionsAmong non-oncological orphan products with priority designations, nearly 3 years had passed between FDA approval and inclusion in any guidance document. These findings suggest that despite efforts to expedite availability, appropriate access to these treatments may be delayed because of the lack of timely guidance on their use in clinical practice.
Prospective comparison of AMB, GAP AND START scores and triage nurse clinical judgement for predicting admission from an ED: a single-centre prospective study
Authors: Salvato Mauro , Solbiati Monica , Bosco Paola , Casazza Giovanni , Binda Filippo , Iotti Marco , Calegari Jessica , Laquintana Dario , Costantino Giorgio 
Published: December 2021

BackgroundIt is postulated that early determination of the need for admission can improve flow through EDs. There are several scoring systems which have been developed for predicting patient admission at triage, although they have not been directly compared. In addition, it is not known if these scoring systems perform better than clinical judgement. Therefore, the aim of this study was to validate existing tools in predicting hospital admission during triage and then compare them with the clinical judgement of triage nurses.MethodsTo conduct this prospective, single-centre observational study, we enrolled consecutive adult patients who presented between 30 September 2019 and 25 October 2019 at the ED of a large teaching hospital in Milan, Italy. For each patient, triage nurses recorded all of the variables needed to perform Ambulatory (AMB), Glasgow Admission Prediction (GAP) and Sydney Triage to Admission Risk Tool (START) scoring. The probability of admission was estimated by the triage nurses using clinical judgement and expressed as a percentage from 0 to 100 with intervals of 5. Nurse estimates were dichotomised for analysis, with ≥50% likelihood being a prediction of admission. Receiver operating characteristic curves were generated for accuracy of the predictions. Area under the curve (AUC) with 95% CI for each of the scores and for the nursing judgements was also calculated.ResultsA total of 1710 patients (844 men; median age, 54 years (IQR: 34–75)) and 35 nurses (15 men; median age, 37 years (IQR: 33–48)) were included in this study. Among these patients, 310 (18%) were admitted to hospital from the ED. AUC values for AMB, GAP and START scores were 0.77 (95% CI: 0.74 to 0.79), 0.72 (95% CI: 0.69 to 0.75) and 0.61 (95% CI: 0.58 to 0.64), respectively. The AUC for nurse clinical judgement was 0.86 (95% CI: 0.84 to 0.89).ConclusionAMB, GAP and START scores provided moderate accuracy in predicting patient admission. However, all of the scores were significantly worse than the clinical judgement of the triage nurses.
Occupational injury among paramedics: a systematic review
Authors: Kearney Jason , Muir Carlyn , Smith Karen 
Published: December 2021

IntroductionParamedics are frequently exposed to acute and/or chronic environmental, operational and patient-related factors that increase their risk of physical and psychological injury. However, there has been wide variation in reported paramedic injury rates. This systematic review aims to synthesise the evidence to examine the incidence and nature of occupational injury among paramedics.MethodsThis systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO 2020: CRD42020164556). A systematic search of four electronic databases was conducted for the years 2004–2019. Peer-reviewed studies examining the incidence and proportions of paramedic occupational injury within civilian emergency medical services (EMS) were included. Injury types, mechanisms, contributing factors and incidence of injury were synthesised narratively.ResultsTwelve studies met the inclusion criteria. The incidence of injury ranged from 29.7 to 345.6 injuries per 1000 workers per year. Sprains and strains were the most reported injury types, and the trunk and upper limbs were the main sites. Body motion was the most frequently reported mechanism of injury, accounting for 35%–55% of all injuries. Female paramedics had a proportionally higher rate of injury compared with male paramedics. Paramedics aged 25–34 years accounted for the majority of fatal (mean 34.0%) and non-fatal (mean 51.7%) injuries.ConclusionThis review highlights the increased risk of occupational injury among paramedics and provides further insight into their overall injury profile.
Development of a working core outcome set for cutaneous lupus erythematosus: a practical approach to an urgent unmet need
Authors: Guo Lisa N , Perez-Chada Lourdes M , Borucki Robert , Nambudiri Vinod E , Werth Victoria P , Merola Joseph F 
Published: December 2021

ObjectiveThe lack of standardised outcomes and outcome measures for cutaneous lupus erythematosus (CLE) represents a substantial barrier to clinical trial design, comparative analysis and approval of novel investigative treatments. We aimed to develop a working core outcome set (COS) for CLE randomised controlled trials and longitudinal observational studies.MethodsWe conducted a multistage literature review of CLE and SLE studies to generate candidate domains and outcome measures. Domains were narrowed to a working core domain set. Outcome measures for core domains were identified and examined.ResultsProposed core domains include skin-specific disease activity and damage, investigator global assessment (IGA) of disease activity, symptoms (encompassing itch, pain and photosensitivity), health-related quality of life (HRQoL) and patient global assessment (PtGA) of disease activity. Recommended physician-reported outcome measures include the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and Cutaneous Lupus Activity IGA (CLA-IGA). For the domains of symptoms, HRQoL and PtGA of disease activity, we were unable to recommend one clearly superior instrument.ConclusionThis work represents a starting point for further refinement pending formal consensus activities and more rigorous evaluations of outcome measure quality. In the interim, the proposed working COS can serve as a much-needed guide for upcoming CLE clinical trials.
Effect of occupational exposure to antineoplastic drugs on DNA damage in nurses: a cross-sectional study
Authors: Huang Xiaohong , Gao Chaoxian , Cai Wenzhi , Tao Yanling , Zhong Xiao , Liu Haiying , Hong Xiaodan , Ding Xiaorong , Lu Hong , Lai Wenjuan , Yi Xiaoqing , Gu Yeqing 
Published: December 2021

BackgroundAlthough the therapeutic effect of antineoplastic drugs is incontestable, these agents can also potentially act as carcinogens, mutagens and/or teratogens in people. The aim of this study was to assess the effect of occupational exposure to antineoplastic drugs on DNA damage, assessed by the comet assay and cytokinesis-block micronucleus (CBMN) assay, in nurses.MethodsThe cross-sectional study enrolled 305 nursing staff members from 7 public hospitals in Shenzhen who handled antineoplastic drugs, and 150 healthy nursing staff members who were not exposed to antineoplastic drugs as the control group. DNA damage was assessed by the comet and CBMN assay. Multiple linear regressions and logistic regressions models were used to analyse the effect of occupational exposure to antineoplastic drugs on DNA damage.ResultsAfter adjustment for confounding factors, compared with non-exposure to antineoplastic drugs, exposure to antineoplastic drugs was positively related to tail moment, olive moment, tail length and tail DNA per cent, and adjusted β or OR (95% CI) was 0.17 (0.08 to 0.26), 0.18 (0.10 to 0.27), 1.03 (0.47 to 1.60) and 1.16 (1.04 to 1.29) (all p<0.05). Moreover, similar significant relationships were observed for the biomarkers of the CBMN assay. Additionally, other than age, there was no interaction between antineoplastic drug exposure and other variables for the levels of biomarkers of the CBMN assay and the comet assay.ConclusionsThe present results showed that exposure to antineoplastic drugs was positively related to the risk of DNA damage in nurses. The results imply that occupational exposure to antineoplastic agents is an important global public health problem that requires urgent attention.
Nonassociative black ellipsoids distorted by R-fluxes and four dimensional thin locally anisotropic accretion disks
Authors: Bubuianu Laurenţiu , Vacaru Sergiu I. , Veliev Elşen Veli 
Published: December 2021

AbstractWe construct nonassociative quasi-stationary solutions describing deformations of Schwarzschild black holes, BHs, to ellipsoid configurations, which can be black ellipsoids, BEs, and/or BHs with ellipsoidal accretion disks. Such solutions are defined by generic off-diagonal symmetric metrics and nonsymmetric components of metrics (which are zero on base four dimensional, 4-d, Lorentz manifold spacetimes but nontrivial in respective 8-d total (co) tangent bundles). Distorted nonassociative BH and BE solutions are found for effective real sources with terms proportional to $$\hbar \kappa $$

ħ
κ

(for respective Planck and string constants). These sources and related effective nontrivial cosmological constants are determined by nonlinear symmetries and deformations of the Ricci tensor by nonholonomic star products encoding R-flux contributions from string theory. To generate various classes of (non) associative /commutative distorted solutions we generalize and apply the anholonomic frame and connection deformation method for constructing exact and parametric solutions in modified gravity and/or general relativity theories. We study properties of locally anisotropic relativistic, optically thick, could and thin accretion disks around nonassociative distorted BHs, or BEs, when the effects due to the rotation are negligible. Such configurations describe angular anisotropic deformations of axially symmetric astrophysical models when the nonassociative distortions are related to the outer parts of the accretion disks.
Immediate effect of stabilization exercises versus conventional exercises of the trunk on dynamic balance among trained soccer players
Authors: D’souza Cyanna Joseph , Santhakumar Haripriya , Bhandary Bhaskara , Rokaya Abhishek 
Published: December 2021

Background: Trunk stability is key in controlling body balance and movements. Trunk Stabilization Exercises (TSE) and Conventional Trunk Exercises (CTE) are performed to improve dynamic balance. The authors have previously reported that dynamic balance was improved by a 12-week and 6-week TSE program. However, there is a dearth of research on its immediate effect on dynamic balance in trained soccer players. Objective: To compare the immediate effect of TSE with that of CTE on dynamic balance in trained soccer players. Methods: Forty-eight male soccer players (24.60 ± 1.38 years) participated in this crossover study, wherein each participant took part in three exercise sessions: TSE, CTE, and No Exercise control (NE), each consisting of three steps: pre-test, intervention and post-test, with an interval of one week between each exercise condition. To assess dynamic balance, the Y Balance Test-Lower Quarter (YBT-LQ) score in the anterior, posteromedial, and posterolateral directions was measured before and 5 minutes after each intervention. Results: The YBT-LQ composite score was significantly improved after TSE (0.51) as compared to CTE (0.22) and NE (0.04) (p<0.05). Furthermore, in TSE and CTE conditions, YBT-LQ scores of the posterolateral and posteromedial directions significantly improved at the post-test (p<0.05). Conclusion: Both TSE and CTE are effective in immediately improving dynamic balance; however, TSE showed greater improvement as compared to the latter. Immediate improvements in the posteromedial and posterolateral directions of the YBT-LQ were demonstrated after performing the TSE and CTE.
Examining the Development of Chronic Thromboembolic Pulmonary Hypertension at the Single-Cell Level
Authors: Miao Ran , Dong Xingbei , Gong Juanni , Li Yidan , Guo Xiaojuan , Wang Jianfeng , Huang Qiang , Wang Ying , Li Jifeng , Yang Suqiao , Kuang Tuguang , Liu Min , Wan Jun , Zhai Zhenguo , Zhong Jiuchang , Yang Yuanhua 
Published: December 2021

Background:
The mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is known to be multifactorial but remains incompletely understood.

Methods:
In this study, single-cell RNA sequencing, which facilitates the identification of molecular profiles of samples on an individual cell level, was applied to investigate individual cell types in pulmonary endarterectomized tissues from 5 patients with CTEPH. The order of single-cell types was then traced along the developmental trajectory of CTEPH by trajectory inference analysis, and intercellular communication was characterized by analysis of ligand-receptor pairs between cell types. Finally, comprehensive bioinformatics tools were used to analyze possible functions of branch-specific cell types and the underlying mechanisms.

Results:
Eleven cell types were identified, with immune-related cell types (T cells, natural killer cells, macrophages, and mast cells) distributed in the left (early) branch of the pseudotime tree, cancer stem cells, and CRISPLD2+ cells as intermediate cell types, and classic disease-related cell types (fibroblasts, smooth muscle cells, myofibroblasts, and endothelial cells) in the right (later) branch. Ligand-receptor interactions revealed close communication between macrophages and disease-related cell types as well as between smooth muscle cells and fibroblasts or endothelial cells. Moreover, the ligands and receptors were significantly enriched in key pathways such as the PI3K/Akt signaling pathway. Furthermore, highly expressed genes specific to the undefined cell type were significantly enriched in important functions associated with regulation of endoplasmic reticulum stress.

Conclusions:
This single-cell RNA sequencing analysis revealed the order of single cells along a developmental trajectory in CTEPH as well as close communication between different cell types in CTEPH pathogenesis.
Association Between Arousals During Sleep and Hypertension Among Patients With Obstructive Sleep Apnea
Authors: Ren Rong , Zhang Ye , Yang Linghui , Somers Virend K. , Covassin Naima , Tang Xiangdong 
Published: December 2021

Background
Sleep fragmentation induced by repetitive arousals is a hallmark of obstructive sleep apnea (OSA). Sleep fragmentation has been linked to hypertension in community‐based studies, but it is unclear if this association is manifest in OSA. We aimed to explore whether frequent arousals from sleep modify the relationship between OSA and prevalent hypertension.

Methods and Results

A total of 10 102 patients with OSA and 1614 primary snorers were included in the study. Hypertension was defined on either direct blood pressure measures or diagnosis by a physician. Spontaneous, respiratory, and movement arousals were derived by polysomnography. Logistic regression models were used to estimate the associations between arousals and prevalent hypertension in patients with OSA and primary snorers. For every 10‐unit increase of total arousal index, odds of hypertension significantly increased in both the total sample (odds ratio [OR], 1.08; 95% CI, 1.03–1.14;
P
=0.002) and patients with OSA (OR, 1.10; 95% CI, 1.04–1.16;
P
<0.001), but not in the primary snoring group. Total arousal index was significantly associated with systolic blood pressure and diastolic blood pressure in the total sample (β=0.05 and β=0.06;
P
<0.001) and in patients with (β=0.05 and β=0.06;
P
<0.01), but not in primary snorers. In addition, a greater influence of respiratory events with arousals than respiratory events without arousals on blood pressure in OSA was also noted. Results were independent of confounders, including apnea‐hypopnea index and nocturnal hypoxemia.

Conclusions
We conclude that repetitive arousals from sleep are independently associated with prevalent hypertension in patients with OSA.
Trend and Outcomes for Surgical Versus Transcatheter Patent Ductus Arteriosus Closure in Neonates and Infants at US Children’s Hospitals
Authors: Kuntz Michael T. , Staffa Steven J. , Graham Dionne , Faraoni David , Levy Philip , DiNardo James , Maschietto Nicola , Nasr Viviane G. 
Published: December 2021

Background
Pharmacologic therapy for patent ductus arteriosus closure is not consistently successful. Surgical ligation (SL) or transcatheter closure (TC) may be needed. Large multicenter analyses comparing outcomes and resource use between SL and TC are lacking. We hypothesized that patients undergoing TC have improved outcomes compared with SL, including mortality, hospital and intensive care unit length of stay, and mechanical ventilation.

Methods and Results

Using the 2016 to 2020 Pediatric Health Information System database, characteristics, outcomes, and charges of patients aged <1 year who underwent TC or SL were analyzed. A total of 678 inpatients undergoing TC (n=503) or SL (n=175) were identified. Surgical patients were younger (0.1 versus 0.53 years;
P
<0.001) and more premature (60% versus 20.3%;
P
<0.001). Surgical patients had higher mortality (1.7% versus 0%;
P
=0.02). Using inverse probability of treatment weighting by the propensity score, multivariable‐adjusted analyses demonstrated favorable outcomes in TC: intensive care unit admission rates (adjusted odds ratio [OR], 0.2; 95% CI, 0.11–0.32;
P
<0.001); mechanical ventilation rates (adjusted OR, 0.3; 95% CI, 0.19–0.56;
P
<0.001); and shorter hospital (adjusted coefficient, 2 days shorter; 95% CI, 1.3–2.7;
P
<0.001) and postoperative (adjusted coefficient, 1.2 days shorter; 95% CI, 0.1–2.3;
P
=0.039) stays. Overall charges and readmission rates were similar. Among premature neonates and infants, hospital (adjusted difference in medians, 4 days; 95% CI, 1.7–6.3 days;
P
<0.001) and postoperative stays (adjusted difference in medians, 3 days; 95% CI, 1.1–4.9 days;
P
=0.002) were longer for SL.

Conclusions
TC is associated with lower mortality and reduced length of stay compared with SL. Rates of TC continue to increase compared with SL.