bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing relative COVID-19 mortality during the second wave: a prospective Swiss population-based study
Authors: Siegfried Sandra , Bopp Matthias , Günthard Huldrych , Keiser Olivia , Weibull Caroline E , Crowther Michael , Hothorn Torsten 
Published: October 2021

ObjectiveDuring the first COVID-19 wave in Switzerland, relative mortality was at least eight times higher compared with the uninfected general population. We aimed to assess sex-specific and age-specific relative mortality associated with a SARS-CoV-2 diagnosis during the second wave.DesignProspective population-based study.SettingIndividuals testing positive for SARS-CoV-2 after the start of the second wave on 1 October 2020 were followed up until death or administrative censoring on 31 December 2020.Participants5 179 740 inhabitants of Switzerland in fall 2018 aged 35–95 years (without COVID-19) and 257 288 persons tested positive for SARS-CoV-2 by PCR or antigen testing during the second wave.Primary and secondary outcome measuresThe planned outcome measure was time to death from any cause, measured from the date of a SARS-CoV-2 diagnosis or 1 October in the general population. Information on confirmed SARS-CoV-2 diagnoses and deaths was matched by calendar time with the all-cause mortality of the general Swiss population of 2018. Proportional hazards models were used to estimate sex-specific and age-specific mortality rates and probabilities of death within 60 days.ResultsThe risk of death for individuals tested positive for SARS-CoV-2 in the second wave in Switzerland increased at least sixfold compared with the general population. HRs, reflecting the risk attributable to a SARS-CoV-2 infection, were higher for men (1.40, 95% CI 1.29 to 1.52) and increased for each additional year of age (1.01, 95% CI 1.01 to 1.02). COVID-19 mortality was reduced by at least 20% compared with the first wave in spring 2020.ConclusionGeneral mortality patterns, increased for men and older persons, were similar in spring and in fall. Absolute and relative COVID-19 mortality was smaller in fall.Trial registrationThe protocol for this study was registered on 3 December 2020 athttps://osf.io/gbd6r.
Recovery, rehabilitation and follow-up services following critical illness: an updated UK national cross-sectional survey and progress report
Authors: Connolly Bronwen , Milton-Cole Rhian , Adams Claire , Battle Ceri , McPeake Joanne , Quasim Tara , Silversides Jon , Slack Andrew , Waldmann Carl , Wilson Elizabeth , Meyer Joel 
Published: October 2021

ObjectiveTo comprehensively update and survey the current provision of recovery, rehabilitation and follow-up services for adult critical care patients across the UK.DesignCross-sectional, self-administered, predominantly closed-question, electronic, online survey.SettingInstitutions providing adult critical care services identified from national databases.ParticipantsMultiprofessional critical care clinicians delivering services at each site.ResultsResponses from 176 UK hospital sites were included (176/242, 72.7%). Inpatient recovery and follow-up services were present at 127/176 (72.2%) sites, adopting multiple formats of delivery and primarily delivered by nurses (n=115/127, 90.6%). Outpatient services ran at 130 sites (73.9%), predominantly as outpatient clinics. Most services (n=108/130, 83.1%) were co-delivered by two or more healthcare professionals, typically nurse/intensive care unit (ICU) physician (n=29/130, 22.3%) or nurse/ICU physician/physiotherapist (n=19/130, 14.6%) teams. Clinical psychology was most frequently lacking from inpatient or outpatient services. Lack of funding was consistently the primary barrier to service provision, with other barriers including logistical and service prioritisation factors indicating that infrastructure and profile for services remain inadequate. Posthospital discharge physical rehabilitation programmes were relatively few (n=31/176, 17.6%), but peer support services were available in nearly half of responding institutions (n=85/176, 48.3%). The effects of the COVID-19 pandemic resulted in either increasing, decreasing or reformatting service provision. Future plans for long-term service transformation focus on expansion of current, and establishment of new, outpatient services.ConclusionOverall, these data demonstrate a proliferation of recovery, follow-up and rehabilitation services for critically ill adults in the past decade across the UK, although service gaps remain suggesting further work is required for guideline implementation. Findings can be used to enhance survivorship for critically ill adults, inform policymakers and commissioners, and provide comparative data and experiential insights for clinicians designing models of care in international healthcare jurisdictions.
Protocol for a prospective multisite cohort study investigating hysterectomy versus uterine preservation for pelvic organ prolapse surgery: the HUPPS study
Authors: Scime Natalie V , Ramage Kaylee , Brennand Erin A 
Published: October 2021

IntroductionPelvic organ prolapse (POP) is the descent of pelvic organs into the vagina resulting in bulge symptoms and occurs in approximately 50% of women. Almost 20% of women will elect surgical correction of this condition by age 85. Removal of the uterus (hysterectomy) with concomitant vaginal vault suspension is a long-standing practice in POP surgery to address apical (uterine) prolapse. Yet, contemporary evidence on the merits of this approach relative to preservation of the uterus through suspension is needed to better inform surgical decision making by patients and their healthcare providers. The objective of this study is to evaluate POP-specific health outcomes and service utilisation of women electing uterine suspension compared with those electing hysterectomy and vaginal vault suspension for POP surgery up to 1-year postsurgery.Methods and analysisThis is a prospective cohort study planning to enrol 321 adult women with stage ≥2 POP from multiple sites in Alberta, Canada. Following standardised counselling from study surgeons, participants self-select either a hysterectomy based or uterine preservation surgical group. Data are being collected through participant questionnaires, medical records and administrative data linkage at four time points spanning from the presurgical consultation to 1-year postsurgery. The primary outcome is anatomic failure to correct POP, and secondary outcomes include changes in positioning of pelvic structures, retreatment, subjective report of bulge symptoms, pelvic floor distress and impact, sexual function and health service use. Data will be analysed using inverse probability weighting of propensity scores and generalised linear models.Ethics and disseminationThis study is approved by the Conjoint Health Research Ethics Board at the University of Calgary (REB19-2134). Results will be disseminated via peer-reviewed publications, presentations at national and international conferences, and educational handouts for patients.Trial registration numberNCT04890951.
Quantifying healthcare and welfare sector workers’ preferences around COVID-19 vaccination: a cross-sectional, single-profile discrete-choice experiment in France
Authors: Díaz Luévano Carolina , Sicsic Jonathan , Pellissier Gerard , Chyderiotis Sandra , Arwidson Pierre , Olivier Cyril , Gagneux-Brunon Amandine , Botelho-Nevers Elisabeth , Bouvet Elisabeth , Mueller Judith 
Published: October 2021

ObjectivesTo analyse preferences around promotion of COVID-19 vaccination among workers in the healthcare and welfare sector in Fance at the start of the vaccination campaign.DesignSingle-profile discrete-choice experiment. Respondents in three random blocks chose between accepting or rejecting eight hypothetical COVID-19 vaccination scenarios.Setting4346 healthcare and welfare sector workers in France, recruited through nation-wide snowball sampling, December 2020 to January 2021.OutcomeThe primary outcomes were the effects of attributes’ levels on hypothetical acceptance, expressed as ORs relative to the reference level. The secondary outcome was vaccine eagerness as certainty of decision, ranging from −10 to +10.ResultsAmong all participants, 61.1% made uniform decisions, including 17.2% always refusing vaccination across all scenarios (serial non-demanders). Among 1691 respondents making variable decisions, a strong negative impact on acceptance was observed with 50% vaccine efficacy (compared with 90% efficacy: OR 0.05, 95% CI 0.04 to 0.06) and the mention of a positive benefit–risk balance (compared with absence of severe and frequent side effects: OR 0.40, 0.34 to 0.46). The highest positive impact was the prospect of safely meeting older people and contributing to epidemic control (compared with no indirect protection: OR 4.10, 3.49 to 4.82 and 2.87, 2.34 to 3.50, respectively). Predicted acceptance was 93.8% for optimised communication on messenger RNA vaccines and 16.0% for vector-based vaccines recommended to ≥55-year-old persons. Vaccine eagerness among serial non-demanders slightly but significantly increased with the prospect of safely meeting older people and epidemic control and reduced with lower vaccine efficacy.DiscussionVaccine promotion towards healthcare and welfare sector workers who hesitate or refuse vaccination should avoid the notion of benefit–risk balance, while collective benefit communication with personal utility can lever acceptance. Vaccines with limited efficacy will unlikely achieve high uptake.
Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects
Authors: Suarez-Carmona Meggy , Williams Anja , Schreiber Jutta , Hohmann Nicolas , Pruefer Ulrike , Krauss Jürgen , Jäger Dirk , Frömming Anna , Beyer Diana , Eulberg Dirk , Jungelius Jarf Ulf , Baumann Matthias , Mangasarian Aram , Halama Niels 
Published: October 2021

BackgroundImmunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models showed promising results on T cell activation and migration in combination with immune checkpoint inhibition.MethodsHere, we describe the successful application of anti-CXCL12 (NOX-A12) in patients with advanced stage pretreated metastatic colorectal and pancreatic cancer (OPERA trial). The treatment consisted of 2 weeks of anti-CXCL12 monotherapy with NOX-A12 followed by combination therapy with pembrolizumab (n=20 patients) until progression or intolerable toxicity had occurred.ResultsThe treatment was safe and well tolerated with 83.8% grade I/II, 15.5% grade III and 0.7% grade V adverse events. Of note, for a majority of patients, time on trial treatment was prolonged compared with their last standard treatment preceding trial participation. Systematic serial biopsies revealed distinct patterns of modulation. Tissue and clinical responses were associated with Th1-like tissue reactivity upon CXCL12 inhibition. A downregulation of a cytokine cassette of interleukin (IL)-2/IL-16/CXCL-10 was associated with tumor resistance and furthermore linked to a rare, CXCL12-associated CD14+CD15+promonocytic population. T cells showed aggregation and directed movement towards the tumor cells in responding tissues. Serum analyses detected homogeneous immunomodulatory patterns in all patients, regardless of tissue responses.ConclusionsWe demonstrate that the combination of CXCL12 inhibition and checkpoint inhibition is safe and grants further exploration of synergistic combinatorial strategies.
Optimizing orthopedic trauma care delivery during the COVID-19 pandemic. A closed-loop audit of implementing a virtual fracture clinic and fast-track pathway in a Dutch level 2 trauma center
Authors: Geerdink Thijs H , Salentijn Dorien A , de Vries Kristin A , Noordman Philou C W , van Dongen Johanna M , Haverlag Robert , Goslings J Carel , van Veen Ruben N 
Published: October 2021

BackgroundGuidelines concerning outpatient management of patients during the coronavirus pandemic required minimized face-to-face follow-up and increased remote care. In response, we established a virtual fracture clinic (VFC) review for emergency department (ED) patients with musculoskeletal injuries, meaning patients are reviewed ‘virtually’ the next workday by a multidisciplinary team, instead of routine referral for face-to-face fracture clinic review. Patients wait at home and are contacted afterwards to discuss treatment. Based on VFC review, patients with minor injuries are discharged, while for other patients an extensive treatment plan is documented using injury-specific care pathways. Additionally, we established an ED orthopedic trauma fast-track to reduce waiting time. This study aimed to evaluate the extent to which our workflow supported adherence to national coronavirus-related guidelines and effects on ED waiting time.MethodsA closed-loop audit was performed during two 4-week periods using predefined standards: (1) all eligible ED orthopedic trauma patients are referred for VFC review; (2) reached afterwards; and follow-up is (3) patient initiated, or (4) performed remotely, whenever possible. Total ED waiting time, time to review, time for review, and time after review were assessed during both audit periods and compared with previous measurements.ResultsDuring both audits, the majority of eligible ED patients were referred for VFC review (1st: n=162 (88.0%); 2nd: n=302 (98.4%)), and reached afterwards (1st: 98.1%; 2nd: 99.0%). Of all referred patients, 17.9% and 13.6% were discharged ‘virtually’ during first and second audits, respectively, while 45.0% and 41.1% of scheduled follow-up appointments were remote. Median total ED waiting time was reduced (1st: −36 minutes (p<0.001); 2nd: −33 minutes (p<0.001)). During the second audit, median ED time to review was reduced by −13 minutes (p<0.001), as well as time for review: −10 minutes (p=0.019).DiscussionIn line with national guidelines, our VFC review allowed time-effective review and triage of the majority of ED orthopedic trauma patients, supporting patient-initiated and remote follow-up, whenever possible. ED waiting time was reduced after implementing the VFC review and orthopedic trauma fast-track.Level of evidenceIV.
Model development for energy dissipation over gabion stepped weirs using GEP and GMDH techniques
Authors: Hussain Ajmal , Ansari Mujib Ahmad , Ahmed Md Nisar , Ahmad Faisal , Jahangeer Jahangeer 
Published: October 2021

A gabion stepped weir is a permeable weir that consists of a gabion box filled with stone aggregates. It is cost-effective structure used for the dissipation of water flow energy from upstream to downstream. Gabion weir also allows the movement of aquatic life and transportation of physical and chemical substances present in water. In this study, energy dissipation in terms of inverse relative energy dissipation (IRED) over gabion stepped weir has been studied. It was observed that the existing predictor does not give a reasonable estimate for IRED. Therefore, the data have been reanalysed to develop a generalized regression equation for IRED. Generalized models using Gene Expression Programming (GEP) and Group Method of Data Handling (GMDH) were also developed. The predictions based on GMDH model (R = 0.979, E = 0.96 and RMSE = 0.314) were found more satisfactory than those given by traditional regression equations (R = 0.929, E = 0.91 and RMSE = 0.557) as well as those given by the GEP model (R = 0.959, E = 0.94 and RMSE = 0.476). Sensitivity analysis shows that the Froude number before the jump is the most important parameter for the prediction of IRED.
Exploring the Mechanism of Resveratrol in Reducing the Soft Tissue Damage of Osteoarthritis Based on Network Pharmacology and Experimental Pharmacology
Authors: Long Zhiyong , Xiang Wang , Li Jun , Yang Tiejun , Yu Ganpeng 
Published: October 2021

Aim. To explore the mechanism of resveratrol in reducing the soft tissue damage of osteoarthritis (OA) based on network pharmacology. Methods. Pharmmapper was used to predict the target of resveratrol, OMIM and Genecards were used to collect OA-related disease genes, and David ver 6.8 was used for enrichment analysis. Then, animal experiments were carried out for verification. The rat OA model was established and the rats were randomly divided into 4 groups: model group, resveratrol low-dose group, resveratrol high-dose group, and blank control group for follow-up experiments. Hematoxylin-eosin (HE) staining was used to detect the degree of pathological damage of rat bones and joints. Enzyme-linked immunosorbent assay (ELISA) was used for the content of inflammatory factors. Western blot was used to detect the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), nuclear factor kappa B protein (NF-κB), cysteine protease-9 (CASP-9), Bcl-2 protein, and Bax protein. Results. Through network pharmacological analysis, this study found that resveratrol may regulate the TLR4 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Osteoclast differentiation, Rheumatoid arthritis, etc. Animal experiments showed that compared with the model group, the pathological damage of bone and joint in the resveratrol low-dose and high-dose groups was significantly improved. Compared with the model group, the serum levels of IL-1beta, IL-6, IL-17, TNF-α, and MCP-1 in the resveratrol low-dose and high-dose groups were significantly reduced (

P

< 0.05); protein levels of TLR-4, MyD88, and NF-κB p65 were significantly reduced (

P

< 0.05); caspase-9 and Bax protein levels were significantly reduced (

P

< 0.05), and Bcl-2 was significantly increased (

P

< 0.05). Conclusion. Resveratrol may inhibit the activation of the TLR4-mediated NF-κB signaling pathway and has a repairing effect on soft tissue damage in OA.
γδ T Cells Support Antigen-Specific αβ T cell–Mediated Antitumor Responses during BCG Treatment for Bladder Cancer
Authors: Ji Niannian , Mukherjee Neelam , Shu Zhen-Ju , Reyes Ryan M. , Meeks Joshua J. , McConkey David J. , Gelfond Jonathan A. , Curiel Tyler J. , Svatek Robert S. 
Published: October 2021

AbstractBacillus Calmette-Guérin (BCG) is the most effective intravesical agent at reducing recurrence for patients with high-grade, non–muscle-invasive bladder cancer. Nevertheless, response to BCG is variable and strategies to boost BCG efficacy have not materialized. Prior work demonstrated a requirement for either conventional αβ or nonconventional γδ T cells in mediating BCG treatment efficacy, yet the importance of T-cell antigen specificity for BCG's treatment effect is unclear. Here, we provide direct evidence to show that BCG increases the number of tumor antigen–specific αβ T cells in patients with bladder cancer and protects mice from subsequent same-tumor challenge, supporting BCG induction of tumor-specific memory and protection. Adoptive T-cell transfers of antigen-specific αβ T cells into immunodeficient mice challenged with syngeneic MB49 bladder tumors showed that both tumor and BCG antigen–specific αβ T cells contributed to BCG efficacy. BCG-specific antitumor immunity, however, also required nonconventional γδ T cells. Prior work shows that the mTOR inhibitor rapamycin induces the proliferation and effector function of γδ T cells. Here, rapamycin increased BCG efficacy against both mouse and human bladder cancer in vivo in a γδ T cell–dependent manner. Thus, γδ T cells augment antitumor adaptive immune effects of BCG and support rapamycin as a promising approach to boost BCG efficacy in the treatment of non–muscle-invasive bladder cancer.
The Use of Intraoperative Transit Time Flow Measurement for Coronary Artery Bypass Surgery: Systematic Review of the Evidence and Expert Opinion Statements
Authors: Gaudino Mario , Sandner Sigrid , Di Giammarco Gabriele , Di Franco Antonino , Arai Hirokuni , Asai Tohru , Bakaeen Faisal , Doenst Torsten , Fremes Stephen E. , Glineur David , Kieser Teresa M. , Lawton Jennifer S. , Lorusso Roberto , Patel Nirav , Puskas John D. , Tatoulis James , Taggart David P. , Vallely Michael , Ruel Marc 
Published: October 2021

Transit time flow measurement (TTFM) allows quality control in coronary artery bypass grafting but remains largely underused, probably because of limited information and the lack of standardization. We performed a systematic review of the evidence on TTFM and other methods for quality control in coronary artery bypass grafting following PRISMA standards and elaborated expert recommendations by using a structured process. A panel of 19 experts took part in the consensus process using a 3-step modified Delphi method that consisted of 2 rounds of electronic voting and a final face-to-face virtual meeting. Eighty percent agreement was required for acceptance of the statements. A 2-level scale (strong, moderate) was used to grade the statements based on the perceived likelihood of a clinical benefit.
The existing evidence supports an association between TTFM readings and graft patency and postoperative clinical outcomes, although there is high methodological heterogeneity among the published series. The evidence is more robust for arterial, rather than venous, grafts and for grafts to the left anterior descending artery. Although TTFM use increases the duration and the cost of surgery, there are no data to quantify this effect. Based on the systematic review, 10 expert statements for TTFM use in clinical practice were formulated. Six were approved at the first round of voting, 3 at the second round, and 1 at the virtual meeting.
In conclusion, although TTFM use may increase the costs and duration of the procedure and requires a learning curve, its cost/benefit ratio seems largely favorable, in view of the potential clinical consequences of graft dysfunction. These consensus statements will help to standardize the use of TTFM in clinical practice and provide guidance in clinical decision-making.