bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social determinants of health associated with the development of sepsis in adults: a scoping review protocol
Authors: Machon Christina , Sheikh Fatima , Fox-Robichaud Alison 
Published: October 2020

IntroductionSepsis, the life-threatening immune response to infection, affects millions of people annually. Understanding of the factors associated with the development of sepsis is crucial for improving population health and public health efforts; in particular, literature exploring the relationship between sepsis and social determinants of health is lacking. This review seeks to establish and amalgamate existing evidence of the relationships between sepsis and the following social determinants: frailty, registration with a family physician, mental illness, alcohol abuse, social support levels, smoking status, illicit drug use disorders, socioeconomic status, gender and race/ethnicity.Methods and analysisThis study will analyse qualitative and quantitative studies using standard processes. The selected social determinants of health and their potential link to adult sepsis will be analysed separately under distinct headings. Findings will be consolidated in a final discussion. PubMed and Medline will be searched for articles published between 1970 and 2020 using search strings combining ‘sepsis’ and other variations, such as ‘septicaemia’ with each social determinant of interest. ‘Sepsis’ and at least one social determinant of interest must be present in a study’s title for inclusion in the review; the results of the initial search will be filtered based on predetermined inclusion and exclusion criteria. Evidence from this scoping review will provide information on the impact of social determinants of health on the risk of developing adult sepsis, which can inform clinicians of the various risk factors to consider when admitting patients.Ethics and disseminationApproval from a research ethics board is not needed for this amalgamation of information from studies for which the primary investigators have obtained their own, respective ethics board approval. Once completed, the review will be submitted for publication in a peer-reviewed journal, and findings will be presented in local and national forums.
Effects of oil-soluble versus water-soluble contrast media at hysterosalpingography on pregnancy outcomes in women with a low risk of tubal disease: study protocol for a randomised controlled trial
Authors: Liang Guiling , Zhu Qian , He Xiaoqing , Wang Xiaofeng , Jiang Ling , Zhu Chenfeng , Xie Li , Qian Zhaoxia , Zhang Jian 
Published: October 2020

IntroductionIn recent years, due to various factors, the rate of infertility in China has increased and now affects over 10% of women of reproductive age. Hysterosalpingography (HSG) is a common diagnostic procedure during fertility examinations. However, there is no consensus on the choice of contrast agents and their effects. As the largest multicentre, randomised controlled trial (H2Oil trial from the Netherlands) has shown that oil-soluble contrast at HSG can enhance fertility compared with water-soluble contrast, we propose this study to examine whether the use of oil-soluble contrast media results in increased rates of pregnancy in Chinese women undergoing HSG.Methods and analysisThis study is a single-centre, randomised, controlled, parallel-group, superiority trial. Patients with low risk of tubal disease will be randomised to undergo HSG using iodinated oil injection (OSCM group, oil-soluble contrast media) or ioversol injection (WSCM group, water-soluble contrast media). To evaluate the potential superiority of the OSCM group, with 1:1 allocation ratio, 90% statistical power and a two-sided significance level of 5%, we have calculated a sample of 520 women per group to be enrolled, for a total of 1040 including 10% loss to follow-up or protocol variation. The primary outcome is the rate of ongoing pregnancy during 6 months after randomisation. The secondary outcomes will consist of thyroid function of patients and newborns, pain scores during HSG, rate of live birth, clinical pregnancies, miscarriages, ectopic pregnancy, time to ongoing pregnancy, time to live birth, cost calculations of the OSCM group/WSCM group, and assisted reproductive technology treatments between the two groups.Ethics and disseminationThis protocol received authorisation from the Medical Research Ethics Committee of International Peace Maternity and Child Health Hospital on 18 January 2020 (approval no GKLW2020-02). The findings will be reported in peer-reviewed publications and presentations at international scientific meetings.Trial registration numberChiCTR2000031612.
Should we care: a qualitative exploration of the factors that influence the decision of early marriage among young men in urban slums of Bangladesh
Authors: Biswas Subas Chandra , Karim Shuchi , Rashid Sabina Faiz 
Published: October 2020

ObjectivesTo explore how adolescent and young men negotiate the complex realities of lives to explain their pathways into and reasons for early marriage in urban slums of Bangladesh.DesignThe qualitative data used here came from a larger 3-year study that used both quantitative and qualitative research methods.SettingInterviews were conducted in two of the largest slums in Dhaka and Chittagong city of Bangladesh between December 2015 and March 2018.ParticipantsThis paper uses qualitative data from 22 in-depth interviews (IDIs) and three focus group discussions (FGDs) with adolescent and young men aged 15–24 years; 13 IDIs and 4 FGDs with parents and 11 key-informant interviews with community leaders. The purposively selected respondents were interviewed in their respective settings.ResultsIn the context of urban slums, this study revealed multiple factors influence early marriage decision-making processes among young men. These factors include socially perceived phenomenon of adulthood and readiness of marriage, poverty leading to drop out from schools and early initiation to earning livelihood, manifestations of increasing individual aspiration and agency, fulfilment of romance and erotic desires and dreams of forming one’s own family. In addition, parental and immediate societal interference to preserve norms around gender and society can act as catalysts for this decision.ConclusionsStudy findings imply that complex structural factors, social and gender norms that are contributing to the early marriage for both adolescent boys and young men in Bangladesh’s urban slums. These are locations where conservatism, poverty and urbanisation intersect resulting in early and often unprepared entry to adulthood for young men impacting on their development and well-being. It is, therefore, critical that young men should be included in the national and global conversations around child marriage and child marriage prevention programme.
Quality of life and experiences of sarcoma trajectories (the QUEST study): protocol for an international observational cohort study on diagnostic pathways of sarcoma patients
Authors: Soomers Vicky , Desar Ingrid ME , van de Poll-Franse Lonneke V , Husson Olga , van der Graaf Winette TA 
Published: October 2020

IntroductionSarcomas are rare tumours with considerable heterogeneity. Early and accurate diagnosis is important to optimise patient outcomes in terms of local disease control, overall survival (OS) and health-related quality of life (HRQoL). Time to diagnosis is variable in bone as well as soft tissue sarcoma. Possible factors for a long time from first symptom to diagnosis (the total interval) include patient, tumour and healthcare characteristics, but until now the most relevant risk factors and its association with outcomes remain unknown. Our study aims to (1) quantify total interval, the time interval from first symptom until (histological) diagnosis; (2) identify factors associated with interval length and (3) determine the association between total interval and HRQoL, stage and tumour size at diagnosis, progression-free survival (PFS) and OS.Methods and analysisWe will conduct a longitudinal, prospective, international, multicentre cohort study among patients aged ≥18 years with newly diagnosed bone or soft tissue sarcoma at eight centres (three in UK, five in The Netherlands). Patients will be asked to complete questionnaires at five points in time; one at diagnosis and at follow-up points of 3, 6, 12 and 24 months. Questionnaire data is collected within the Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry: an international data management system for collection of patient-reported outcomes. Clinical data will be extracted from patient records. The primary endpoint is HRQoL at diagnosis, measured with the EORTC QLQ-C30. Secondary endpoints are stage and tumour size at diagnosis, PFS, OS, additional patient-reported outcomes, such as quality-adjusted life years and psychological distress.Ethics and disseminationEthical approval was given by the Health Research Authority and Research Ethics Committee for the United Kingdom (18/WA/0096) and medical ethical committee of Radboudumc for The Netherlands (2017-3881). Results will be presented in peer-reviewed journals and presented at meetings.Trial registration numberNCT03441906.
Prevalence and severity of burnout in Hong Kong doctors up to 20 years post-graduation: a cross-sectional study
Authors: Ng Amy Pui Pui , Chin Weng Yee , Wan Eric Yuk Fai , Chen Julie , Lau Chak Sing 
Published: October 2020

ObjectiveTo estimate the prevalence and severity of burnout and explore the factors associated with burnout among Hong Kong medical graduates up to 20 years post-graduation.DesignCross-sectional survey.SettingHong Kong.ParticipantsDoctors who graduated from the University of Hong Kong between 1995 and 2014.Primary and secondary outcome measuresBurnout as measured by the Copenhagen Burnout Inventory (CBI), alcohol consumption as measured by the Alcohol Use Disorders Identification Test Version C, lifestyle behaviours (hours of sleep and work, exercise, smoking, substance use), career satisfaction and sociodemographic characteristics were obtained using paper or online questionnaires.ResultsResponse rate was 30.9% (496/1607). Prevalence of CBI burnout was 63.1% (personal), 55.9% (work-related) and 35.4% (patient-related). The mean CBI subscale scores were 57.4±21.4 (personal), 48.9±7.4 (work-related) and 41.5±21.8 (client-related). Factors associated with personal and patient-related burnout included age (coeff −0.437, 95% CI −0.779 to −0.095 and coeff −0.596, 95% CI −0.965 to −0.228, respectively), practice setting (coeff −5.759, 95% CI −10.665 to −0.853 and coeff −5.317, 95% CI −10.602 to −0.032, respectively) and regular exercise (coeff −6.855, 95% CI −11.102 to −2.608 and coeff −6.769, 95% CI −11.333 to −2.205, respectively). Gender (coeff 5.1, 95% CI 1.382 to 8.818), average hours of sleep per night (coeff −5.200, 95% CI −7.139 to −3.262) and work hours per week (coeff 0.226, 95% CI 0.099 to 0.353) were associated with personal burnout only. No factors were significantly associated with work-related burnout.ConclusionBurnout is highly prevalent among Hong Kong medical graduates. Younger doctors, women and those working in the public sector appear to be at higher risk for burnout and may benefit from targeted interventions. Policymakers and healthcare authorities should consider measures to help reduce burnout by enabling adequate sleep, reducing work hours and encouraging exercise.
Mortality and morbidity in patients with congenital heart disease hospitalised for viral pneumonia
Authors: Diller Gerhard-Paul , Enders Dominic , Lammers Astrid E , Orwat Stefan , Schmidt Renate , Radke Robert M , Gerss Joachim , De Torres Alba Fernando , Kaleschke Gerrit , Bauer Ulrike M , Marschall Ursula , Baumgartner Helmut 
Published: October 2020

ObjectivesData on the clinical outcome of patients with congenital heart disease (CHD) affected by severe viral pneumonia are limited. We analysed morbidity and mortality of viral pneumonia and evaluated the association between medical conditions, medication, vaccination and outcome specifically in patients with CHD requiring hospitalisation for viral pneumonia.MethodsBased on data from one of Germany’s largest health insurers, all cases of viral pneumonia requiring hospital admission (2005–2018) were studied. Mortality, and composites of death, transplantation, mechanical circulatory support, ventilation or extracorporeal lung support served as endpoints.ResultsOverall, 26 262 viral pneumonia cases occurred in 24 980 patients. Of these, 1180 cases occurred in patients with CHD. Compared with patients without CHD, mortality rate was elevated in patients with CHD. As a group, patients with CHD aged 20–59 years even exceeded mortality rates in patients without CHD aged >60 years. No mortality was observed in patients with CHD with simple defects <60 years of age without associated cardiovascular risk factors. On multivariable logistic regression analysis, age, CHD complexity, chromosomal anomalies, cardiac medication, use of immunosuppressants and absence of vaccination for influenza emerged as risk factors of adverse outcome.ConclusionsWe present timely data on morbidity and mortality of severe viral pneumonia requiring hospital admission in patients with CHD. Need for mechanical ventilation and risk of death in CHD increase early in life, reaching a level equivalent to non-CHD individuals >60 years of age. Our data suggest that except for patients with isolated simple defects, patients with CHD should be considered higher-risk individuals when faced with severe viral pneumonia.
Endogenous HLA-DQ8αβ programs superantigens (SEG/SEI) to silence toxicity and unleash a tumoricidal network with long-term melanoma survival
Authors: Knopick Peter , Terman David , Riha Nathan , Alvine Travis , Larson Riley , Badiou Cedric , Lina Gerard , Ballantyne John , Bradley David 
Published: October 2020

BackgroundAs the most powerful T cell agonists known, superantigens (SAgs) have enormous potential for cancer immunotherapy. Their development has languished due to high incidence (60%–80%) of seroreactive neutralizing antibodies in humans and tumor necrosis factor-α (TNFα)-mediated cardiopulmonary toxicity. Such toxicity has narrowed their therapeutic index while neutralizing antibodies have nullified their therapeutic effects.MethodsFemale HLA-DQ8 (DQA*0301/DQB*0302) tg mice expressing the human major histocompatibility complex II (MHCII) HLA-DQ8 allele on a high proportion of PBL, spleen and lymph node cells were used. In the established tumor model, staphylococcal enterotoxin G and staphylococcal enterotoxin I (SEG/ SEI) (50 µg each) were injected on days 6 and 9 following tumor inoculation. Lymphoid, myeloid cells and tumor cell digests from tumor tissue were assayed using flow cytometry or quantitated using a cytometric bead array. Tumor density, necrotic and viable areas were quantitated using the ImageJ software.ResultsIn a discovery-driven effort to address these problems we introduce a heretofore unrecognized binary complex comprizing SEG/SEI SAgs linked to the endogenous human MHCII HLA-DQ8 allele in humanized mice. By contrast to staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) deployed previously in clinical trials, SEG and SEI does not exhibit neutralizing antibodies in humans or TNFα-mediated toxicity in humanized HLA-DQ8 mice. In the latter model wherein SAg behavior is known to be ‘human-like’, SEG/SEI induced a powerful tumoricidal response and long-term survival against established melanoma in 82% of mice. Other SAgs deployed in the same model displayed toxic shock. Initially, HLA-DQ8 mediated melanoma antigen priming, after which SEG/SEI unleashed a broad CD4+ and CD8+ antitumor network marked by expansion of melanoma reactive T cells and interferon-γ (IFNy) in the tumor microenvironment (TME). SEG/SEI further initiated chemotactic recruitment of tumor reactive T cells to the TME converting the tumor from ‘cold’ to a ‘hot’. Long-term survivors displayed remarkable resistance to parental tumor rechallenge along with the appearance of tumor specific memory and tumor reactive T memory cells.ConclusionsCollectively, these findings show for the first time that the SEG/SEI-(HLA-DQ8) empowers priming, expansion and recruitment of a population of tumor reactive T cells culminating in tumor specific memory and long-term survival devoid of toxicity. These properties distinguish SEG/SEI from other SAgs used previously in human tumor immunotherapy. Consolidation of these principles within the SEG/SEI-(HLA-DQ8) complex constitutes a conceptually new therapeutic weapon with compelling translational potential.
Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19
Authors: Al-Chalabi Ammar , Chiò Adriano , Merrill Charlotte , Oster Gerry , Bornheimer Rebecca , Agnese Wendy , Apple Stephen 
Published: October 2020

ObjectiveThis was a post hoc analysis of the Edaravone Phase III Study MCI186-19 (‘Study 19’) to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS).MethodsAmyotrophic Lateral Sclerosis Functional Rating Scale—Revised item scores from Study 19 were retrospectively mapped to King’s stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King’s and MiToS stages during Study 19. We also assessed disease progression in subgroups of patients according to baseline King’s stage.ResultsDuring double-blind treatment, the percentage of patients who experienced a progression in King’s stage was lower for edaravone (42.0%, 95% CI 30.4% to 53.6%) than placebo (55.9%, 95% CI 44.1% to 67.6%). The most pronounced effect was noted among patients who were in stage 1 and was maintained throughout open-label treatment. An analysis of a ≥2-stage progression in MiToS stage showed no difference between treatment arms during double-blind treatment, but during the open-label period, more rapid progression was noted among patients in the placebo–edaravone arm than among those in the edaravone–edaravone arm (log-rank test, p<0.001).ConclusionsThe King’s and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales.
High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up
Authors: Rydberg Mattias , Dahlin Lars B , Gottsäter Anders , Nilsson Peter M , Melander Olle , Zimmerman Malin 
Published: October 2020

IntroductionOsteoarthritis (OA) of the first carpometacarpal (CMC-1) joint is a common hand disorder with symptoms including pain and weakness of the thumb. Previous studies have associated high BMI with OA of weight-bearing joints, whereas studies regarding non-weight-bearing joints have shown conflicting results. Thus, the aim of this study was to investigate the influence of overweight and obesity on incident OA of the CMC-1 joint.MethodDuring 1974 to 1992, 33 346 participants aged 26–61 years were included in the population-based cohort Malmö Preventive Project. Endpoint data were retrieved from Swedish national registers until end of 2018. Sex-stratified Cox regression models adjusted for potential confounders were calculated using BMI as a continuous variable and stratified for normal weight, overweight and obesity.ResultsMedian follow-up was 36 years for men and 32 years for women. A one-unit increment of BMI was independently associated with incident OA of the CMC-1 joint in men (HR 1.12; 95% CI 1.09 to 1.15, p<0.001) and women (HR 1.05; 95% CI 1.03 to 1.08, p<0.001). Stratifying for BMI groups, obesity was independently associated with OA of the CMC-1 joint in men (HR 3.57; 95% CI 2.68 to 4.77, p<0.001) and women (HR 1.98; 95% CI 1.44 to 2.73, p<0.001).ConclusionHigh BMI and obesity are major risk factors for OA of the CMC-1 joint. The association was stronger among men but could be demonstrated also among women. Future studies are warranted to clarify underlying pathophysiological mechanisms for this association, enabling identification of potential therapeutic targets related to obesity in order to prevent the development of OA of the CMC-1 joint.
Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts
Authors: Çolak Yunus , Nordestgaard Børge G , Afzal Shoaib 
Published: October 2020

Background
Vitamin D may regulate the innate immune system, and randomised controlled trials suggest a beneficial effect of vitamin D supplementation against acute respiratory tract infections. By using a Mendelian randomisation approach, we tested the hypothesis that low 25-hydroxyvitamin D is associated with increased risk of bacterial pneumonia in observational and genetic analyses.

Methods

We genotyped 116 335 randomly chosen white Danes aged 20 to 100 from the Copenhagen City Heart Study and Copenhagen General Population Study for plasma 25-hydroxyvitamin D decreasing genetic variants around
CYP2R1
(rs117913124, rs12794714 and rs10741657),
DHCR7
(rs7944926 and rs11234027),
GEMIN2
(rs2277458) and
HAL
(rs3819817). Information on plasma 25-hydroxyvitamin D was available on 35 833 individuals. Individuals were followed from 1981 through 2018 for hospital diagnoses of bacterial pneumonias.

Results

During up to 38 years follow-up, we observed 6342 bacterial pneumonias in observational analyses and 13 916 in genetic analyses. In observational analyses, multivariable adjusted HR for bacterial pneumonias was 1.27 (95% CI: 1.16 to 1.40) for individuals with 25-hydroxyvitamin D<25 nmol/L compared with those with ≥25 nmol/L. In genetic analyses, the OR for bacterial pneumonia per 10 nmol/L lower plasma 25-hydroxyvitamin D was 1.12 (95% CI: 1.02 to 1.23) in Wald’s ratio, 1.12 (95% CI: 1.04 to 1.20) in inverse-variance weighted, 1.63 (95% CI: 0.96 to 2.78) in MR-Egger and 1.15 (95% CI: 1.05 to 1.26) in weighted median instrumental variable analysis. This association was strongest for genetic variants around
CYP2R1
. There was no observational or genetic evidence to support that 25-hydroxyvitamin D is associated with risk of urinary tract infections, skin infections, sepsis or gastroenteritis, which were used as negative control outcomes.

Conclusions
Low vitamin D is associated observationally and genetically with increased risk of bacterial pneumonias.