bluuebunny/crossref_metadata_2025 huggingface dataset:
Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study
Authors: Williams Thomas C , MacRae Clare , Swann Olivia V , Haseeb Haris , Cunningham Steve , Davies Philip , Gibson Neil , Lamb Christopher , Levin Richard , McDougall Catherine M , McFadzean Jillian , Piper Ian , Turner Alastair , Turner Stephen W , Van Dijke Margrethe , Urquhart Donald S , Guthrie Bruce , Langley Ross J
Published: January 2021

Objectives

To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020.

Design

National retrospective cohort study.

Setting

Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records.

Participants

273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years.

Main outcome measures

Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019.

Results

The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019.

Conclusions

National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.
Paraneoplastic acral vascular syndrome: case presentation and literature review
Authors: AlRasbi Sara , Al-Badi Amira H , Al Alawi Abdullah M
Published: January 2021

A 65-year-old man, a smoker, presented to the emergency department with progressive digital ischaemia, fever and weight loss. The clinical examination revealed generalised lymphadenopathy and ischaemic changes of the right distal phalanges of the second, third and fourth fingers. He had an ultrasound-guided biopsy of the cervical lymph node, which showed histopathological findings of classic Hodgkin’s lymphoma. Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon and seen more in solid malignancies. There are very few reported cases of PAVS in haematological malignancies, including Hodgkin’s lymphoma. This case highlights the idea that the presence of acral vascular syndrome—especially in older patients—should alert physicians to search for an underlying malignancy as part of the medical evaluation. Also, it shows that medical treatment may slow the progress of the digital ischaemia until the culprit tumour has been identified and treated.
OCT-angiography detects longitudinal microvascular changes in glaucoma: a systematic review
Authors: Miguel Ana , Silva André , Barbosa-Breda Joao , Azevedo Luis , Abdulrahman Abdulkarim , Hereth Esther , Abegão Pinto Luis , Lachkar Yves , Stalmans Ingeborg
Published: January 2021

Background/aims

Optical coherence tomography angiography (OCTA) allows the study of vessel density (VD). We intended to perform a systematic review of studies focusing on longitudinal changes in peripapillary and macular VD measurements in glaucoma.

Methods

A search was performed across MEDLINE, Scopus, ISI Web of Science and Google Scholar, using the following query from inception until 20 September 2019: ((“optical coherence tomography angiography”[tiab]) OR (optical coherence tomography angiography[MeSH]) OR (“OCTA”[tiab]) OR (“OCT-A”[tiab]) OR (“angio-OCT”[tiab]) OR (“OCT- angiography”[tiab]) OR (“OCT-angio”[tiab]) OR (“OCT-angiographie”[tiab])) AND (glaucom*[tiab] OR glaucoma[MeSH]). Prospective studies that quantitatively assessed the longitudinal changes in VD in glaucoma with at least 3 months of follow-up were included.

Results

Ten out of 4516 studies were included. The rate of VD change in glaucoma varied from 0.036/year to 1.08/year and 1.3% to 3.2% per year, with significantly different rates between glaucoma and healthy controls. Five studies assessed VD change after glaucoma surgery, obtaining variable results, ranging from a temporary VD decrease to increase after 3 months. Meta-analysis was not possible due to a wide variation in methods, measurements and region of VD.

Conclusion

OCTA is a non-invasive technology, which shows promise in glaucoma. Measures should be taken to increase the quality and standardise the methodology of VD measures in OCTA longitudinal studies, for future meta-analyses.
Effect of the vancomycin minimum inhibitory concentration on clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus bacteraemia: a systematic review and meta-analysis
Authors: Shi Changcheng , Ye Jian , Xu Renjie , Jin Weizhong , Xu Shuang , Teng Fei , Lin Nengming
Published: January 2021

Objective

The use of the vancomycin minimum inhibitory concentration (MIC) as a prognostic predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) has been debated in the last decade. We performed a systematic review and meta-analysis to investigate whether an elevated vancomycin MIC is associated with a worse prognosis for patients with MSSA bacteraemia.

Design

Systematic review and meta-analysis.

Data sources

PubMed, Embase and the Cochrane Library were searched from inception to December 2019.

Eligibility criteria

Randomised controlled trials or observational studies were considered eligible if they provided clinical outcomes of patients with MSSA bacteraemia, stratified by vancomycin MIC.

Data synthesis

Primary outcome was mortality. Secondary outcomes included septic thrombophlebitis, persistent bacteraemia and complicated bacteraemia. Pooled ORs and 95% CIs were calculated. Subgroup analyses included the susceptibility testing method.

Results

Fifteen observational studies were included. Bacteraemia due to MSSA isolates with high vancomycin MICs was associated with higher mortality than isolates with low MICs (OR 1.44; 95% CI 1.12 to 1.84; I2=40.3%). Additionally, significantly greater septic thrombophlebitis (OR 3.16; 95% CI 1.11 to 9.00; I2=58.6%) and a trend towards more persistent bacteraemia (OR 1.79; 95% CI 0.97 to 3.31; I2=0%) were observed in patients with high vancomycin MICs than in patients with low MICs. Differences in complicated bacteraemia were not significant. Similar findings were obtained in subgroup analyses using Etest. However, significant differences in outcomes were not observed between the high and low vancomycin MICs detected using broth microdilution.

Conclusion

The available data suggest an association between elevated vancomycin MICs detected using Etest and adverse clinical outcomes for patients with MSSA bacteraemia. Future studies should validate these findings and explore the potential mechanisms.

PROSPERO registration number

CRD42018090547.
A patient–clinician James Lind Alliance partnership to identify research priorities for hyperemesis gravidarum
Authors: Dean Caitlin R , Bierma Hyke , Clarke Ria , Cleary Brian , Ellis Patricia , Gadsby Roger , Gauw Norah , Lodge Karen , MacGibbon Kimber , McBride Marian , Munro Deirdre , Nelson-Piercy Catherine , O'Hara Margaret , Penny Helen , Shorter Katherine , Spijker René , Trovik Jone , Watford Emma , Painter Rebecca C
Published: January 2021

Objective

There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians.

Methods

Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop.

Results

1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings.

Conclusions

By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries.
Prospective cohort study of children with suspected SARS-CoV-2 infection presenting to paediatric emergency departments: a Paediatric Emergency Research Networks (PERN) Study Protocol
Authors: Funk Anna L. , Florin Todd A. , Dalziel Stuart R. , Mintegi Santiago , Salvadori Marina I. , Tancredi Daniel Joseph , Neuman Mark I. , Payne Daniel C. , Plint Amy C. , Klassen Terry P. , Malley Richard , Ambroggio Lilliam , Kim Kelly , Kuppermann Nathan , Freedman Stephen B.
Published: January 2021

Introduction

Relatively limited data are available regarding paediatric COVID-19. Although most children appear to have mild or asymptomatic infections, infants and those with comorbidities are at increased risk of experiencing more severe illness and requiring hospitalisation due to COVID-19. The recent but uncommon association of SARS-CoV-2 infection with development of a multisystem inflammatory syndrome has heightened the importance of understanding paediatric SARS-CoV-2 infection.

Methods and analysis

The Paediatric Emergency Research Network-COVID-19 cohort study is a rapid, global, prospective cohort study enrolling 12 500 children who are tested for acute SARS-CoV-2 infection. 47 emergency departments across 12 countries on four continents will participate. At enrolment, regardless of SARS-CoV-2 test results, all children will have the same information collected, including clinical, epidemiological, laboratory, imaging and outcome data. Interventions and outcome data will be collected for hospitalised children. For all children, follow-up at 14 and 90 days will collect information on further medical care received, and long-term sequelae, respectively. Statistical models will be designed to identify risk factors for infection and severe outcomes.

Ethics and dissemination

Sites will seek ethical approval locally, and informed consent will be obtained. There is no direct risk or benefit of study participation. Weekly interim analysis will allow for real-time data sharing with regional, national, and international policy makers. Harmonisation and sharing of investigation materials with WHO, will contribute to synergising global efforts for the clinical characterisation of paediatric COVID-19. Our findings will enable the implementation of countermeasures to reduce viral transmission and severe COVID-19 outcomes in children.

Trial registration number

NCT04330261
Uveitis as a potential predictor of acute myocardial infarction in patients with Behcet’s disease: a population-based cohort study
Authors: Chen Yu-Yen , Lai Yun-Ju , Yen Yung-Feng , Chen Hsin-Hua , Chou Pesus
Published: January 2021

Objectives

To investigate whether uveitis is a predictor of acute myocardial infarction (AMI) among patients with Behcet’s disease (BD).

Design

Retrospective cohort study.

Setting

Patients with BD were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013.

Participants

Among the 6508 patients with BD, 2517 (38.7%) were in the uveitis group and 3991 were in the non-uveitis group.

Primary and secondary outcome measures

Kaplan-Meier curves were generated to compare the cumulative hazard of AMI in the uveitis and non-uveitis groups. Multivariate Cox regression analysis was used to estimate the adjusted HRs and 95% CI of AMI, and was adjusted for age, gender, systemic comorbidities (eg, hypertension, diabetes, hyperlipidaemia, smoking) and clinical manifestation of BD (eg, oral ulcers, genital ulcers, skin lesions, arthritis and gastrointestinal involvement).

Results

The mean age of the BD cohort was 38.1±15.1 years. Compared with non-uveitis patients, uveitis patients were significantly younger and male predominant. There was no significant difference between the two groups for most proportions of systemic comorbidities and clinical manifestations. The Kaplan-Meier method with the log-rank test showed that the uveitis group had a significantly higher cumulative hazard for patients with AMI compared with the non-uveitis group (p<0.0001). In the multivariable Cox regression after adjustment for confounding factors, patients with uveitis had a significantly higher risk of AMI (adjusted HR 1.87; 95% CI 1.52 to 2.29). Other significant risk factors for AMI were age, hypertension, smoking, and skin lesions.

Conclusions

Statistical analyses from the nationwide database demonstrated that uveitis is a potential predictor of AMI in patients with BD.
Description and prediction of outcome of drowning patients in New South Wales, Australia: protocol for a data linkage study
Authors: Peden Amy E , Sarrami Pooria , Dinh Michael , Lassen Christine , Hall Benjamin , Alkhouri Hatem , Daniel Lovana , Burns Brian
Published: January 2021

Introduction

Despite being a preventable cause of death, drowning is a global public health threat. Australia records an average of 288 unintentional drowning deaths per year; an estimated annual economic burden of $1.24 billion AUD ($2017). On average, a further 712 hospitalisations occur due to non-fatal drowning annually. The Australian state of New South Wales (NSW) is the most populous and accounts for 34% of the average fatal drowning burden. This study aims to explore the demographics and outcome of patients who are admitted to hospitals for drowning in NSW and also investigates prediction of patients’ outcome based on accessible data.

Methods and analysis

This protocol describes a retrospective, cross-sectional data linkage study across secondary data sources for any person (adult or paediatric) who was transferred by NSW Ambulance services and/or admitted to a NSW hospital for fatal or non-fatal drowning between 1/1/2010 and 31/12/2019. The NSW Admitted Patient Data Collection will provide data on admitted patients’ characteristics and provided care in NSW hospitals. In order to map patients’ pathways of care, data will be linked with NSW Ambulance Data Collection and the NSW Emergency Department Data Collection. Finally patient’s mortality will be assessed via linkage with NSW Mortality data, which is made up of the NSW Register of Births, Deaths and Marriages and a Cause of Death Unit Record File. Regression analyses will be used to identify predicting values of independent variables with study outcomes.

Ethics and dissemination

This study has been approved by the NSW Population & Health Services Research Ethics Committee. Results will be disseminated through peer-reviewed publications, mass media releases and at academic conferences. The study will provide outcome data for drowning patients across NSW and study results will provide data to deliver evidence-informed recommendations for improving patient care, including updating relevant guidelines.
‘Care for Outcomes’: systematic development of a set of outcome indicators to improve patient-relevant outcomes for patients with lung cancer
Authors: Cramer-van der Welle Christine M , van Loenhout Lotte , van den Borne Ben EEM , Schramel Franz MNH , Dijksman Lea M
Published: January 2021

Objectives

Measuring quality of care is important, however many of the quality indicators used do not focus on outcome of treatment and aspects which are valuable for patients and physicians. The project ‘Care for Outcomes’ aims to establish a relevant set of outcome indicators for lung cancer.

Setting

Network of seven large, non-university teaching hospitals in the Netherlands (Santeon).

Methods

By reviewing the literature, a list of potential outcome indicators for patients with lung cancer was composed and subsequently prioritised by expert’s opinion. Three external parties, with expertise on lung cancer, clinical management and public health, evaluated and reduced the list of indicators to a working set. Finally, the resulting selection of outcome indicators was tested for feasibility and discrimination in patient data, by collecting retrospective data and performing regression and survival analyses.

Participants

Development of the indicator set in six Santeon hospitals. Retrospective cohort study in 5922 patients diagnosed with lung cancer (all types and stages).

Results

Selected outcome indicators were divided into three levels of outcome (tiers). The first tier about survival and the process of recovery include mortality, survival, positive resection margins, rethoracotomy after resection and quality of life at baseline and after 3, 6 and 12 months. Tier 2 concerning the sustainability of the recovery include complications after resection and toxicity after chemotherapy and/or radiation. Tier 3 about sustainability of health revealed no measurable outcomes. The retrospective data collection showed differences between hospitals and variation in case mix.

Conclusion

A relevant set of outcome indicators for lung cancer was systematically developed. This set has the potential to compare quality of care between hospitals and inform patients with lung cancer about outcomes. The project is ongoing in the current Santeon Value-Based Health Care programme through quality and improvement cycles.
Subcutaneous furosemide in advanced heart failure: service improvement project
Authors: Birch Francesca , Boam Emily , Parsons Sharon , Ghosh Justin , Johnson Miriam J
Published: January 2021

Objectives

In severe heart disease, parenteral administration of loop diuretic is often needed. We present clinical outcomes from episodes of care using subcutaneous continuous subcutaneous infusion of furosemide (CSCI-furosemide).

Methods

Retrospective review of service improvement data. The heart failure nurse specialist, supported by the heart failure-palliative care multidisciplinary team, works with the community or hospice staff who administer the CSCI-furosemide. Data collected for consecutive patients receiving CSCI-furosemide included: age, sex, New York Heart Association (NYHA) class, preferred place of care, goal of treatment, infusion-site reactions, and signs and symptoms of fluid retention (including weight and self-reported breathlessness).

Results

116 people (men 86 (66%); mean age 79 years, 49–97; NYHA class 3 (36/116, 31%) or 4 heart failure (80/116, 69%)) received 130 episodes of CSCI-furosemide (average duration 10 days, 1–49), over half in the patient’s own home/care home (80/129,; 61%) aiming to prevent hospital admission. 40/129 (31%) were managed in the hospice, and 9 (7.0%) in a community hospital. Average daily furosemide dose was 125 mg (40–300 mg). The goal of treatment was achieved in (119/130, 91.5%) episodes.

The median reduction in weight was 4 kg (IQR −7 to −2 kgs, −22 to 9 kgs). Self-reported breathlessness reduced from 8.2 (±1.9) to 5.2 (±1.8). Adverse events occurred in 31/130 (24%) episodes; all but 4/130 (3%, localised skin infection) were mild.

Conclusions

These preliminary data indicate that CSCI-furosemide is safe and effective for people with severe heart failure. An adequately powered randomised controlled trial is indicated.
Pneumatic dilation for persistent dysphagia after antireflux surgery, a multicentre single-blind randomised sham-controlled clinical trial
Authors: Schuitenmaker Jeroen M , van Hoeij Froukje B , Schijven Marlies P , Tack Jan , Conchillo José M , Hazebroek Eric J , Smout André J P M , Bredenoord Albert J
Published: January 2021

Objective

There is no evidence-based treatment for persistent dysphagia after laparoscopic fundoplication. The aim of this study was to evaluate the effect of pneumatic dilation on persistent dysphagia after laparoscopic fundoplication.

Design

We performed a multicentre, single-blind, randomised sham-controlled trial of patients with persistent dysphagia (>3 months) after laparoscopic fundoplication. Patients with an Eckardt symptom score ≥4 were randomly assigned to pneumatic dilation (PD) using a 35 mm balloon or sham dilation. Primary outcome was treatment success, defined as an Eckardt score <4 and a minimal reduction of 2 points in the Eckardt score after 30 days. Secondary outcomes included change in stasis on timed barium oesophagogram, change in high-resolution manometry parameters and questionnaires on quality of life, reflux and dysphagia symptoms.

Results

Forty-two patients were randomised. In the intention-to-treat analysis, the success rates of PD (7/21 patients (33%)) and sham dilation (8/21 patients (38%)) were similar after 30 days (risk difference −4.7% (95% CI (−33.7% to 24.2%) p=0.747). There was no significant difference in change of stasis on the timed barium oesophagogram after 2 min (PD vs sham: median 0.0 cm, p25–p75 range 0.0–4.3 cm vs median 0.0 cm, p25–p75 range 0.0–0.0; p=0.122) or change in lower oesophageal sphincter relaxation pressure (PD vs sham: 10.54±6.25 vs 14.60±6.17 mm Hg; p=0.052). Quality of life, reflux and dysphagia symptoms were not significantly different between the two groups.

Conclusion

Pneumatic dilation with a 35 mm balloon is not superior to sham dilation for the treatment of persistent dysphagia after fundoplication.
Risk of out-of-hospital cardiac arrest in patients with bipolar disorder or schizophrenia
Authors: Barcella Carlo Alberto , Mohr Grimur , Kragholm Kristian , Christensen Daniel , Gerds Thomas A , Polcwiartek Christoffer , Wissenberg Mads , Bang Casper , Folke Fredrik , Torp-Pedersen Christian , Kessing Lars Vedel , Gislason Gunnar Hilmar , Bach Søndergaard Kathrine
Published: January 2021

Objective

Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated.

Methods

We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001–2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs.

Results

We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics—but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)—increased OHCA hazard compared with no use in both disorders.

Conclusions

Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms.
CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer
Authors: Yang Moran , Lu Jiaqi , Zhang Guodong , Wang Yiying , He Mengdi , Xu Qing , Xu Congjian , Liu Haiou
Published: January 2021

Background

Most patients with high-grade serous ovarian cancer (HGSC) lack an effective response to immune checkpoint blockade, highlighting the need for more knowledge about what is required for successful treatment. As follicular cytotoxic CXCR5+CD8+T cells are maintained by reinvigoration by immune checkpoint blockade in tumors, we attempted to reveal the relationship between CXCR5+CD8+T cells and the tumor microenvironment to predict immunotherapy responses in HGSC.

Methods

264 patients with HGSC from two cohorts and 340 HGSC cases from The Cancer Genome Atlas cohort were enrolled. Ex vivo and in vivo studies were conducted with human HGSC tumors and murine tumor models. The spatial correlation between CXC-chemokine ligand 13 (CXCL13), CXCR5, CD8, and CD20 was evaluated by immunohistochemistry and immunofluorescence. Survival was compared between different subsets of patients using Kaplan-Meier analysis. The therapeutic effect of CXCL13 and programmed cell death-1 (PD-1) blockade was validated using human HGSC tumors and murine models.

Results

High CXCL13 expression was associated with prolonged survival. Tumors with high CXCL13 expression exhibited increased infiltration of activated and CXCR5-expressing CD8+T cells. Incubation with CXCL13 facilitated expansion and activation of CXCR5+CD8+T cells ex vivo. CXCR5+CD8+T cells appeared in closer proximity to CXCL13 in tumors and chemotaxis towards CXCL13 in vitro. The combination of CXCL13, CXCR5, and CD8+T cells was an independent predictor for survival. In addition, CXCL13 was associated with clusters of CD20+B cells. CD20+B cells predicted better patient survival in the presence of CXCL13. Histological evaluation highlighted colocalization of CXCL13 with tertiary lymphoid structures (TLSs). TLSs carried prognostic benefit only in the presence of CXCL13. CXCL13 in combination with anti-PD-1 therapy retarded tumor growth in a CD8+T-cell-dependent manner, resulting in increased infiltration of cytotoxic CD8+T cells and CXCR5+CD8+T cells.

Conclusions

These data define a critical role of CXCL13 in shaping antitumor microenvironment by facilitating the maintenance of CXCR5+CD8+T cells in TLSs and support a clinical investigation for a combination of CXCL13 and PD-1 blockade therapy in HGSC.
Occupational use of high-level disinfectants and asthma incidence in early- to mid-career female nurses: a prospective cohort study
Authors: Dumas Orianne , Gaskins Audrey J , Boggs Krislyn M , Henn Scott A , Le Moual Nicole , Varraso Raphäelle , Chavarro Jorge E , Camargo Jr Carlos A
Published: January 2021

Objectives

Occupational use of disinfectants among healthcare workers has been associated with asthma. However, most studies are cross-sectional, and longitudinal studies are not entirely consistent. To limit the healthy worker effect, it is important to conduct studies among early- to mid-career workers. We investigated the prospective association between use of disinfectants and asthma incidence in a large cohort of early- to mid-career female nurses.

Methods

The Nurses’ Health Study 3 is an ongoing, prospective, internet-based cohort of female nurses in the USA and Canada (2010–present). Analyses included 17 280 participants without a history of asthma at study entry (mean age: 34 years) and who had completed ≥1 follow-up questionnaire (sent every 6 months). Occupational use of high-level disinfectants (HLDs) was evaluated by questionnaire. We examined the association between HLD use and asthma development, adjusted for age, race, ethnicity, smoking status and body mass index.

Results

During 67 392 person-years of follow-up, 391 nurses reported incident clinician-diagnosed asthma. Compared with nurses who reported ≤5 years of HLD use (89%), those with >5 years of HLD use (11%) had increased risk of incident asthma (adjusted HR (95% CI), 1.39 (1.04 to 1.86)). The risk of incident asthma was elevated but not statistically significant in those reporting >5 years of HLD use and current use of ≥2 products (1.72 (0.88 to 3.34)); asthma risk was significantly elevated in women with >5 years of HLD use but no current use (1.46 (1.00 to 2.12)).

Conclusions

Occupational use of HLDs was prospectively associated with increased asthma incidence in early- to mid-career nurses.
Slip-resistant footwear reduces slips among National Health Service workers in England: a randomised controlled trial
Authors: Cockayne Sarah , Fairhurst Caroline , Frost Gillian , Liddle Mark , Cunningham-Burley Rachel , Zand Michael , Hewitt Catherine , Iles-Smith Heather M , Green Lorraine , Torgerson David J
Published: January 2021

Objectives

Assess the effectiveness of 5* GRIP-rated slip-resistant footwear in preventing slips in the workplace compared to usual footwear (control group).

Methods

A multicentre, randomised controlled trial; 4553 National Health Service (NHS) staff were randomised 1:1 to the intervention group (provided with 5* GRIP-rated slip-resistant footwear) or the control group. The primary outcome of incidence rate of self-reported slips in the workplace over 14 weeks was analysed using a mixed-effects negative binomial model. Secondary outcome measures included incidence rate of falls from a slip, falls not from a slip, proportion of participants reporting a slip, fall or fracture and time to first slip and fall.

Results

6743 slips were reported: 2633 in the intervention group (mean 1.16 per participant, range 0 to 36) and 4110 in the control group (mean 1.80 per participant, range 0 to 83). There was a statistically significant reduction in slip rate in the intervention group relative to the control group (incidence rate ratio (IRR) 0.63, 95% CI 0.57 to 0.70, p<0.001). Statistically significant differences, in favour of the intervention group, were observed in falls from a slip (IRR 0.51, 95% CI 0.28 to 0.92, p=0.03), the proportion of participants who reported a slip (OR 0.58, 95% CI 0.50 to 0.66, p<0.001) or fall (OR 0.73, 95% CI 0.54 to 0.99, p=0.04) and time to first slip (HR 0.73, 95% CI 0.67 to 0.80, p<0.001).

Conclusions

The offer and provision of 5* GRIP-rated footwear reduced slips in NHS staff in the workplace.

Trial registration number

ISRCTN33051393.
Changes in UK medical trainees' perceptions of workplace-based assessments across 10 years: results from two cross-sectional studies
Authors: Cheston Hannah , Graham David , Johnson Gavin , Woodland Philip
Published: January 2021

Objectives

Workplace-based assessments (WPBAs) have become embedded in the training and assessment of UK medical trainees since the onset of the 21st century. When first introduced WPBA required a significant adjustment in both trainees' and educators' training behaviour, and was met with scepticism in some quarters. In this study, we aimed to evaluate how trainees' perceptions of WPBAs have evolved over a 10-year period, as experience with them has increased.

Design

Two online questionnaires were constructed and distributed to UK trainees. The first was distributed in 2008, the second in 2018. Questions related to trainees' perception of WPBAs as a learning process and as a reflection of their competence.

Setting and participants

All UK medical trainees were eligible to respond. In 2008, 482 trainees from 96 hospitals completed the questionnaire. In 2018, 356 trainees from 103 hospitals completed the questionnaire.

Main outcome measures

Data were analysed both quantitatively and qualitatively. A comparison between the numbers of each WPBA modality completed in 2008 and 2018 was assessed using chi-squared test. Comparisons of Likert scale values between 2008 and 2018 were assessed using unpaired t-test. Thematic analysis was carried out on free-text answers.

Results

The number of forms completed per participant increased significantly from 2008 to 2018. In 2008, forms were most commonly completed immediately after a learning observation (34%). In 2018, forms were most commonly completed between 1 week and 1 month after observation (58%). In 2018, significantly fewer WPBAs were followed by an educational/beneficial discussion in comparison to 2008 data. The most common free-text theme in the 2008 data set was ‘supervisor issues’ whereas in 2018 the most commonly noted theme was ‘limited educational benefit’.

Conclusions

Our study suggests trainees' perspectives of WPBAs have not changed in the 10 years since implementation. Trainees do not perceive WPBA as an accurate reflection of their competency but instead as a ‘tick-box’ bureaucratic exercise to enable career progression. Development of educator training and trainer and trainee job-planning is required to ensure that WPBAs are genuinely educational activities that offer an accurate reflection of trainees' medical competence.
Efficacy and safety of caudal dexmedetomidine in pediatric infra-umbilical surgery: a meta-analysis and trial-sequential analysis of randomized controlled trials
Authors: Shah Ushma Jitendra , Nguyen Derek , Karuppiaah Niveditha , Martin Janet , Sehmbi Herman
Published: January 2021

Background

Dexmedetomidine is used as a local-anesthetics adjuvant in caudal block to prolong analgesia in pediatric infra-umbilical surgery.

Objective

We evaluated the analgesic efficacy and safety of the addition of caudal dexmedetomidine to local anesthetics (vs local anesthetics alone) in pediatric infra-umbilical surgery.

Evidence review

We searched 10 databases for randomized controlled trials (RCTs) of pediatric patients undergoing infra-umbilical surgery, comparing caudal block with and without dexmedetomidine as local anesthetic adjuvant. We performed a frequentist random-effects meta-analysis (R statistical package). We analyzed continuous outcomes as a ratio of means (ROM) and dichotomous data as relative risk (RR), along with 95% CI. We included 19 RCTs (n=1190 pediatric patients) in the meta-analysis. The primary outcome was duration of analgesia (defined as ‘the time from caudal injection to the time at which the study-specific pain score was greater than a cut-off threshold’).

Findings

Data from 19 included RCTs (n=1190) suggested that compared with control (mean duration 346 min), the addition of caudal dexmedetomidine significantly prolonged the duration of analgesia (ratio of means 2.14, 95% CI 1.83 to 2.49, p<0.001; ‘moderate’ evidence). Trial-sequential analysis showed adequate ‘information size’ for the primary outcome. Caudal dexmedetomidine also reduced the number of analgesic administrations (‘low’ evidence), total acetaminophen dose (‘moderate’ evidence) and the risk of emergence delirium (‘moderate’ evidence). There were no significant differences in adverse effects such as hypotension, bradycardia, post-operative nausea and vomiting, urinary retention and respiratory depression.

Conclusions

Our results suggest that the addition of dexmedetomidine to local anesthetic in caudal block significantly improves the duration of analgesia and reduces the analgesic requirements, while maintaining a similar risk-profile compared with local anesthetic alone. Further data on neurological safety are needed.
Chemsex and diagnoses of syphilis, gonorrhoea and chlamydia among men who have sex with men in the UK: a multivariable prediction model using causal inference methodology
Authors: MacGregor Louis , Kohli Manik , Looker Katharine J , Hickson Ford , Weatherburn Peter , Schmidt Axel J , Turner Katy ME
Published: January 2021

Introduction

In the last decade diagnoses of most STIs have risen among men who have sex with men (MSM). Although a significant proportion of this is likely due to increased STI screening, understanding the role of behavioural drivers remains critical. We measure the associations between stimulant use to enhance and prolong sexual experiences (chemsex) and bacterial STI diagnoses in UK MSM, individually considering HIV-diagnosed MSM, pre-exposure prophylaxis (PrEP) users and other MSM.

Methods

We used the UK 2017–2018 European MSM Internet Survey data (n=9375). We constructed causal inference models using multivariable logistic regression, calculating adjusted OR (aOR) and 95% CI of the associations between participation in recent (≤12 months) exclusively dyadic or multipartner chemsex versus no chemsex and recent self-reported diagnoses of syphilis, gonorrhoea and chlamydia.

Results

Among MSM with an HIV diagnosis, 25% of users indicated recent multipartner chemsex, vs 28% of PrEP users and 5% of other MSM. Adjusting for age, ethnicity, UK birth, cis-trans status, sexual identity, education, settlement size and relationship status, participation in recent multipartner chemsex versus no chemsex was associated with greater odds of recent syphilis, gonorrhoea and chlamydia diagnosis. aORs for recent syphilis, gonorrhoea and chlamydia diagnoses were 2.6 (95% CI 1.7 to 4.1), 3.9 (95% CI 2.6 to 5.8) and 2.9 (95% CI 1.9 to 4.3), respectively, in HIV-diagnosed MSM; 1.9 (95% CI 1.1 to 3.3), 2.9 (95% CI 2.0 to 4.2) and 1.9 (95% CI 1.3 to 2.8), respectively, in PrEP users; and 4.0 (95% CI 2.3 to 6.9), 2.7 (95% CI 1.9 to 3.8) and 2.3 (95% CI 1.6 to 3.4), respectively, in other MSM. Conversely, exclusively dyadic chemsex had no significant associations with bacterial STI diagnoses among HIV-diagnosed MSM, only gonorrhoea (aOR 2.4, 95% CI 1.2 to 4.7) among PrEP users and syphilis (aOR 2.8, 95% CI 1.4 to 5.6) among other MSM.

Discussion

Multipartner chemsex may drive the association between chemsex and bacterial STI diagnoses and thus should be the focus of future tailored chemsex interventions. Additionally, PrEP acceptability among MSM and particularly chemsex participants has generated an emergent group suitable for such interventions.
Multiple tobacco product use among cigarette smokers: a longitudinal examination of menthol and non-menthol smokers during young adulthood
Authors: Mantey Dale , Harrell Melissa , Chen Baojiang , Kelder Steven H , Perry Cheryl , Loukas Alexandra
Published: January 2021

Background

Multiple tobacco product (MTP) use is common among young adults. Most MTP users are combustible cigarette smokers that use one or more other tobacco products. This study aims to explore menthol as a risk factor for MTP use among a cohort of young adult cigarette smokers.

Methods

Participants were 18–29 years cigarette smokers at 24 Texas colleges in a 6-wave study. Participants (n=4700 observations) were classified as: single product users (ie, exclusive cigarette smoking); dual product users and poly product users. A multilevel, ordered logistic regression model was used to examine the association between menthol cigarette smoking and MTP use. Two longitudinal, multilevel, multinomial logistic regressions were used to examine the relationship between menthol cigarette smoking and number of tobacco products used.

Results

Overall, 40.7% of the sample were single product users, 33.7% were dual product users and 25.6% were poly product users. Menthol was associated with 1.28 greater odds of MTP use. Further, menthol was associated with 1.19 greater risk of dual and 1.40 greater risk of poly product use, relative to single product use. Lastly, menthol cigarette smoking was associated with 1.18 greater risk of poly product use, relative to dual product use.

Conclusions

There was a gradient relationship between menthol cigarette smoking and number of tobacco products used among young adult cigarette smokers. Findings provide for greater regulatory and programmatic efforts to reduce the use of menthol cigarettes.
Autumn lipid reserves, overwinter lipid depletion, and high winter mortality of rainbow trout in experimental lakes
Authors: Biro Peter A. , Post John R. , Beckmann Christa
Published: January 2021

Accumulation of lipid reserves is considered important for the overwinter survival of many animals. Fish are thought to deplete lipids until they reach a critical minimum below which starvation mortality occurs, meaning that lipid-dependent selective overwinter mortality may be a strong selective pressure leading to life-history evolution favouring lipid accumulation and storage. Much of our current knowledge comes from either laboratory studies or field studies that are not well controlled, but rarely is overwinter survival directly estimated to evaluate selective mortality. Here, we studied patterns of lipid storage, overwinter lipid depletion, and subsequent survival of a single strain of rainbow trout (Oncorhynchus mykiss) stocked into experimental lakes that differed in productivity but experienced the same local winter conditions. Productive lakes produced trout with higher lipid content and steeper allometric slopes in contrast with trout in low food lakes; however, these field-based values were all substantially lower than those determined in the lab. Surviving trout from low productivity lakes emerged from winter in poor condition, close to the expected critical minimum needed for survival, in comparison with survivors from higher-productivity lakes. As expected, overwinter mortality was lipid-dependent, with fish in low food lakes nearing 90% mortality and about 60% mortality in high food lakes. Importantly, these estimates are higher than from laboratory (∼70%) and modelling studies (0% to 14%) for this species. These results, though from stocked populations, suggest winter mortality is an even stronger selective pressure than previously thought, creating a tight population bottleneck in young fish cohorts and likely promoting life-history strategies that favour energy storage at the expense of somatic growth.
Flatfish may be underestimated in the diet of gray seals (Halichoerus grypus)
Authors: Dufault Michelle N. , Olson Zachary H. , Mellone Dominique M. , Flanders Kelly R. , Ono Kathryn A.
Published: January 2021

The United States east coast population of the gray seal (Halichoerus grypus (Fabricius, 1791)) was once hunted to near extirpation, but the population has since rebounded due to protection by the Marine Mammal Protection Act of 1972. Although this population growth is seen as a success by conservationists, others are concerned about the economic and ecological impact of gray seals on New England fisheries. The study objective was to quantify flatfish presence in the diet of gray seals using an analysis of prey DNA in seal scat (molecular scatology). This may reduce a potential bias in other diet analysis methods since flatfish may not be swallowed whole, and therefore, their identifying otoliths may not be present. Scats were collected from Muskeget and Monomoy islands off Cape Cod, Massachusetts, USA, in 2016, 2017, and 2018 and analyzed for flatfish presence using species-specific polymerase chain reaction (PCR) assays and a hard parts analysis using otoliths. Frequency of occurrence for flatfish species from DNA was higher than estimated in previous literature on gray seal diet and a concurrent otolith analysis of the same samples, suggesting that previous analyses may have potentially underestimated the importance of flatfish in the diet.
Finding new physics without learning about it: anomaly detection as a tool for searches at colliders
Authors: Crispim Romão M. , Castro N. F. , Pedro R.
Published: January 2021

In this paper we propose a new strategy, based on anomaly detection methods, to search for new physics phenomena at colliders independently of the details of such new events. For this purpose, machine learning techniques are trained using Standard Model events, with the corresponding outputs being sensitive to physics beyond it. We explore three novel AD methods in HEP: Isolation Forest, Histogram-Based Outlier Detection, and Deep Support Vector Data Description; alongside the most customary Autoencoder. In order to evaluate the sensitivity of the proposed approach, predictions from specific new physics models are considered and compared to those achieved when using fully supervised deep neural networks. A comparison between shallow and deep anomaly detection techniques is also presented. Our results demonstrate the potential of semi-supervised anomaly detection techniques to extensively explore the present and future hadron colliders’ data.
Van der Meer scan luminosity measurement and beam–beam correction
Authors: Balagura Vladislav
Published: January 2021

The main method for calibrating the luminosity at Large Hadron Collider (LHC) is van der Meer scan where the beams are swept transversely across each other. This beautiful method was invented in 1968. Despite the honourable age, it remains the preferable tool at hadron colliders. It delivers the lowest calibration systematics, which still often dominates the overall luminosity uncertainty at LHC experiments. Various details of the method are discussed in the paper. One of the main factors limiting proton–proton van der Meer scan accuracy is the beam–beam electromagnetic interaction. It modifies the shapes of the colliding bunches and biases the measured luminosity. In the first years of operation, four main LHC experiments did not attempt to correct the bias because of its complexity. In 2012 a correction method was proposed and then subsequently used by all experiments. It was based, however, on a simplified linear approximation of the beam–beam force and, therefore, had limited accuracy. In this paper, a new simulation is presented, which takes into account the exact non-linear force. Depending on the beam parameters, the results of the new and old methods differ by $$\sim 1\%$$

∼
1
%

. This needs to be propagated to all LHC cross-section measurements after 2012. The new simulation is going to be used at LHC in future luminosity calibrations.
Fast decay of 23S1 positronium atoms in an MgO lined cavity
Authors: Gurung Lokesh , Babij Tamara J. , Cassidy David B.
Published: January 2021

We report experiments in which radiatively metastable $2\,^{3}\mathrm {S}_{1}$
2

3

S

1

positronium (Ps) atoms entered a waveguide whose internal surfaces were lined with smoked magnesium oxide (MgO) powder. The waveguide was built such that time-delayed microwave radiation pulses, tuned to drive $2\,^{3}\mathrm {S}_{1}\rightarrow 2\,^{3}\mathrm {P}_{2}$
2

3

S

1

→
2

3

P

2

transitions, could be applied to the Ps ensemble. The lifetime of $2\,^{3}\mathrm {S}_{1}$
2

3

S

1

atoms was measured using time-delayed microwave induced decay, yielding ≈200 ns. This is considerably shorter than the Zeeman shifted lifetime of 1070 ns, indicating that Ps atoms in the $2\,^{3}\mathrm {S}_{1}$
2

3

S

1

state do not survive multiple collisions with MgO nanocrystals.