bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data
Authors: Erviti Juan , Wright James , Bassett Ken , Ben-Eltriki Mohamed , Jauca Ciprian , Saiz Luis Carlos , Leache Leire , Gutiérrez-Valencia Marta , Perry Thomas L 
Published: December 2022

ObjectiveThe FOURIER trial showed a benefit of the PCSK9 inhibitor evolocumab over placebo with respect to cardiovascular outcomes in patients with cardiovascular disease. However, we observed some inconsistencies between the information in the Clinical Study Report (CSR) and that in the 2017 primary trial results publication. We aimed to restore the mortality data in the FOURIER trial based on the information contained in the death narratives in the CSR.MethodsMortality data in the primary results publication were compared with that in the CSR. In cases of discrepancy between the sources, an independent committee blindly readjudicated and restored the cause of death according to the information in the CSR narratives.ResultsFor 360/870 deaths (41.4%), the cause of death adjudicated by the FOURIER clinical events committee differed from that declared by the local clinical investigator. When comparing the CSR information with the 2017 primary results publication, we found 11 more deaths from myocardial infarction in the evolocumab group (36 vs 25) and 3 less deaths in the placebo group (27 vs 30, respectively). In the CSR, the number of deaths due to cardiac failure in the evolocumab group was almost double those in the placebo group (31 vs 16). While cardiac and vascular deaths were not assessed as separate outcomes in the original trial analysis, after readjudication, we noted that cardiac deaths were numerically, but non-significantly, higher in the evolocumab group (113) than in the placebo group (88; relative risk (RR) 1.28, 95% CI 0.97 to 1.69, p=0.078), whereas non-cardiac vascular deaths were similar between groups (37 in each; RR 1.00, 95% CI 0.63 to 1.58, p=0.999). The reported HR for cardiovascular mortality in the original trial analysis was 1.05 (95% CI 0.88 to 1.25); after readjudication, we found a greater (although still non-significant) relative increase in cardiovascular mortality in the evolocumab treatment group (RR 1.20, 95% CI 0.95 to 1.51, p=0.13).ConclusionAfter readjudication, deaths of cardiac origin were numerically higher in the evolocumab group than in the placebo group in the FOURIER trial, suggesting possible cardiac harm. At the time the trial was terminated early, a non-significantly higher risk of cardiovascular mortality was observed with evolocumab, which was numerically greater in our readjudication. A complete restoration of the FOURIER trial data is required. In the meantime, clinicians should be sceptical about prescribing evolocumab for patients with established atherosclerotic cardiovascular disease.Trial registration numbersNCT01764633.
Structural equation modelling analysis on relationships of job demands and resources with work engagement, burnout and work ability: an observational study among physicians in Dutch hospitals
Authors: Debets Maarten , Scheepers Renee , Silkens Milou , Lombarts Kiki 
Published: December 2022

ObjectiveTo investigate to what extent work engagement mediates the relationships of job resources with work ability, and to what extent burnout mediates the relationships of job demands and resources with work ability.DesignMulticentre observational study.SettingAcademic and non-academic hospitals in the Netherlands.ParticipantsPhysicians (n=385) participated in this study.Primary and secondary outcome measuresWe measured work ability with selected items from the validated Questionnaire of Experience and Evaluation of Work 2.0 (QEEW V.2.0), work engagement with the Utrecht Work Engagement Scale and burnout with the exhaustion subscale of the Oldenburg Burnout Inventory. The job demand ‘workload’ and job resources ‘development opportunities’, ‘participation in decision-making’, ‘inspirational leadership’ and ‘relationships with colleagues’ were measured using the QEEW V.2.0. The job demand ‘bureaucratic burden’ was measured with the Three Item Red Tape scale. A structural equation model was built to answer our research question.ResultsWork engagement mediated relationships of job resources with physicians’ work ability, and burnout mediated relationships of job resources and demands with work ability. Development opportunities (β=0.39, SE=0.12, p<0.001), participation in decision-making (β=0.18, SE=0.08, p=0.028) and relationships with colleagues (β=0.19, SE=0.19, p=0.002) were positively related to work engagement. Development opportunities (β=−0.20, SE=0.08, p=0.004) were negatively related and workload (β=0.51, SE=0.19, p<0.001) was positively related to burnout. Work engagement (β=0.22, SE=0.04, p<0.001) was positively related and burnout (β=−0.56, SE=0.06, p<0.001) was negatively related to work ability.ConclusionsPhysicians’ work engagement and burnout mediated the relationships of various job demands and resources with their work ability. More work-engaged and less burned-out physicians reported better work ability. Hospitals may attenuate excessive workloads and facilitate development opportunities, participation in decision-making and good collegial relationships to enhance physicians’ occupational well-being and performance.
Impact of COVID-19 pandemic on the mental health of healthcare workers during the first wave in Portugal: a cross-sectional and correlational study
Authors: Duarte Ivone , Pinho Rita , Teixeira Andreia , Martins Vera , Nunes Rui , Morgado Helder , Castro Luísa , Serrão Carla 
Published: December 2022

ObjectivesThe COVID-19 pandemic has had a negative impact on the mental health of healthcare workers (HCWs) worldwide. This study aims to identify the degree to which sociodemographic variables and indicators of subjective well-being and psychological resilience are associated, positively and negatively, with the outcomes of burnout, stress, depression and anxiety among Portuguese HCWs observed during the first wave. It also aims to evaluate the strength of association of these variables and indicators with each outcome.DesignCross-sectional quantitative study. The statistical methods used are simple logistic model, multiple logistic regression model and −2*log-likelihood statistic.SettingPortuguese HCWs living in Portugal and working in the Portuguese healthcare system.ParticipantsThe study included 1535 professionals, with a mean age of 38 years.Primary and secondary outcomes measuresPsychological variables were measured by Copenhagen Burnout Inventory, the Resilience Scale, the Depression, Anxiety and Stress Scales and the Satisfaction with Life Scale.ResultsHigh levels of personal (55%; n=844), work-related (55.1%; n=846) and client-related burnout (35.4%; n=543) were found. Additionally, participants expressed substantial levels of depression (28.7%; n=441), stress (36.4%; n=558) and anxiety (33.1%; n=508). About 1202 participants (78.3%) demonstrated moderate-to-high levels of resilience. Profession, work regime during the pandemic, having a health problem, resilience and satisfaction with life are independent variables significantly associated with the outcomes of burnout, stress, depression and anxiety. Satisfaction with life was the independent variable that had a major association with all outcomes.ConclusionsGovernments and hospital administrations should take action to promote resilience and satisfaction with life as these variables are protective relating to mental health problems. Interventions as educational sessions, psychological support at work, programmes promoting resilience and coping mechanisms and better work conditions may improve mental health. The implementation of measures to protect healthcare students from developing prejudicial outcomes seams very adequate and important.
Home-based and community-based activities that can improve mental wellness: a protocol for an umbrella review
Authors: Puyat Joseph H , Mohebbian Mana , Gupta Aanchel , Ellis Ursula , Ranote Harmanpreet , Almeida Alberto , Ridgway Lisa , Vila-Rodriguez Fidel , Kazanjian Arminee 
Published: December 2022

IntroductionMental disorders affect about 13% of the world’s population. While evidence-based mental health treatments are available, a significant number of persons with mental illnesses are untreated or do not receive adequate mental healthcare due to various reasons, including costs, stigma and the desire to self-manage symptoms. In the past few years, there has been an increase in the body of evidence regarding leisure activities and mental wellness. However, there is currently no published overview of the state of the evidence on these activities and their potential preventive and therapeutic effects on mental health.Methods and analysisUsing Joanna Briggs Institute (JBI) review guidelines, an umbrella review will be undertaken to synthesise findings from systematic reviews and meta-analyses on the mental health benefits of home-based and community-based activities. MEDLINE, PsycInfo, Embase, CINAHL, Web of Science, Epistemonikos, Cochrane Database of Systematic Reviews, JBI Database of Systematic Reviews and Implementation Reports will be searched for potentially relevant systematic reviews and meta-analyses published from January 1991 to present. Title/abstract screening, full-text review, data extraction and assessment of methodological quality will each be performed independently by two reviewers. A third review author will be available to resolve discrepancies in any of the review tasks. To assess the quality of potentially eligible reviews, the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses will be used. Findings will be presented in table form and will be summarised by study population, type of home-based or community-based activity or intervention, and type of mental health outcomes. Overall assessment of the strength of existing evidence from eligible systematic reviews will be provided following the grading of recommendation, assessment, development and evaluation approach.Ethics and disseminationNo ethical approval is required. Results of this umbrella review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42021266989.
Association between statin use during hospitalisation and mortality in patients with intracerebral haemorrhage: a propensity score-matched cohort study
Authors: Yuan Min , Zhou Xinhua , Lu Xiaoqing , Xiao Zhilong , Zhou Huangyan , Wang Xiaohua 
Published: December 2022

ObjectivesWe examined the relationship between statin use during hospitalisation and mortality in patients with intracerebral haemorrhage (ICH).DesignRetrospective propensity-matched cohort study.SettingPatients with ICH (≥18 years old) admitted to Beth Israel Deaconess Medical Center (Boston, Massachusetts, USA) from 2001 to 2012 registered in the Medical Information Mart for Intensive Care III database.Participants1043 patients with ICH (≥18 years) were evaluated for the relationship between statin use during hospitalisation and mortality.InterventionsStatin use.Primary and secondary outcome measuresThe primary outcome was 90-day mortality. We used multivariable Cox regression analyses to calculate the adjusted HR with 95% CI and used propensity score analysis and an inverse probability weighting (IPW) model to ensure the robustness of our findings.ResultsWe included 1043 patients with ICH (362 and 681 were statins and non-statin users, respectively) between 2001 and 2012. The overall 90-day mortality was 29.8% (311/1043); it was 33.3% (227/681) and 23.2% (84/362) for non-statin and statin users, respectively. After adjusted for potential confounders, we found that statin use was associated with 29% lower of 90-day mortality (HR=0.71, 95% CI 0.52 to 0.97, p<0.05). IPW also demonstrated a significantly lower 90-day mortality in statin users. The HR was 0.69 (95% CI 0.54 to 0.88, p<0.01). The results remain stable in subgroup analyses and propensity score matching.ConclusionStatin use during hospitalisation may be associated with reduced risk-adjusted mortality in patients with ICH. Further randomised controlled trials are needed to clarify this association.
Incidence and causes of stillbirth in the only tertiary referral hospital in the Solomon Islands: a hospital-based retrospective cohort study
Authors: De Silva Manarangi Sajini , Panisi Leeanne , Manubuasa Lenin , Honimae Catherine , Taragwanu Susan , Burggraaf Simon , Ogaoga Divinal , Lindquist Anthea Clare , Walker Susan P , Tong Stephen , Hastie Roxanne 
Published: December 2022

ObjectivesStillbirth is a major global health issue, which disproportionately affects families living in low-income and middle-income countries. The Solomon Islands is a Pacific nation with poor perinatal outcomes, however research investigating stillbirth is lacking. Thus, we aimed to investigate the incidence and cause of stillbirth occurring at the National Referral Hospital, Solomon Islands.DesignWe conducted a retrospective cohort study from January 2017 to December 2018.SettingAt the only tertiary referral hospital in the Solomon Islands, on the main island of Guadalcanal.ParticipantsAll births occurring in the hospital during the study period.Outcome measuresNumber of, causes and risk factors for stillbirths (fetal deaths before birth at ≥20 estimated gestational weeks, or ≥500 g in birth weight).ResultsOver 2 years 341 stillbirths and 11 056 total births were recorded, giving an institutional incidence of 31 stillbirths per 1000 births. Of the cases with a recorded cause of death, 72% were deemed preventable. Most stillbirths occurred antenatally and 62% at preterm gestations (<37 weeks). 59% had a birth weight below 2500 g and preventable maternal conditions were present in 42% of the cases. 46% of the cases were caused by an acute intrapartum event, and among these 92% did not receive intrapartum monitoring.ConclusionsStillbirth affects 31 in every 1000 births at the National Referral Hospital in the Solomon Islands and many cases are preventable. Our findings highlight the urgent need for increased focus on perinatal deaths in the Solomon Islands with universal classification and targeted training, improved quality of obstetrical care and community awareness.
Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT)
Authors: Maier Rebecca H , Plummer Chris , Kasim Adetayo S , Akhter Nasima , Ogundimu Emmanuel , Maddox Jamie , Graham Janine , Stewart Michael , Wardley Andrew , Haney Sophie , Vahabi Sharareh , Oxenham Helen , Humphreys Alison , Cresti Nicola , Verrill Mark , Graham Richard , Chang Lisa , Hancock Helen C , Austin David 
Published: December 2022

IntroductionAnthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin’s lymphoma (NHL) receiving anthracycline-based chemotherapy.Methods and analysisPROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects.Ethics and disseminationA favourable opinion was given following research ethics committee review by West Midlands—Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication.Trial registration numberNCT03265574.
Risk factors for severe disease and impact of severity on pregnant women with COVID-19: a case–control study based on data from a nationwide survey of maternity services in Japan
Authors: Arakaki Tatsuya , Hasegawa Junichi , Sekizawa Akihiko , Ikeda Tomoaki , Ishiwata Isamu , Kinoshita Katsuyuki 
Published: December 2022

ObjectiveTo identify independent risk factors for severe COVID-19 in pregnant women and to evaluate the impact of disease severity on preterm birth.DesignA case–control study based on data from a nationwide questionnaire-based survey of maternity services in Japan.SettingA questionnaire was mailed to all 2135 delivery institutions in Japan between July and August 2021. A total of 1288 institutions responded (60% of all delivery institutions in Japan). 566 facilities reported having cared for pregnant women with COVID-19, and 722 facilities reported having had no such patients.ParticipantsOne thousand and forty-three hospitalised and non-hospitalised pregnant women diagnosed with COVID-19 between July 2020 and 30 June 2021.Primary and secondary outcome measuresThe primary outcome was progression to severe COVID-19. The secondary outcome was preterm birth due to COVID-19 infection.Results56 cases (5.4%) were severe, and 987 (94.6%) were non-severe. Multivariable logistic regression analysis showed that gestational age≥24 weeks (adjusted OR (aOR) 6.68, 95% CI 2.8 to 16.0) and maternal age≥32 years (aOR 2.40, 95% CI 1.3 to 4.3) were independently associated with severe cases. Using the Kaplan-Meier method, the probability of continued pregnancy at 14 days after diagnosis for severe cases was 0.57 between 24 and 31 weeks’ gestation and 0.27 between 32 and 36 weeks’ gestation. The probability for non-severe cases was 1.0 between 24 and 31 weeks’ gestation and 0.8 between 32 and 36 weeks’ gestation. Among the patients with COVID-19 in the preterm period, preterm birth due to infection was significantly more common in severe than non-severe cases (48% vs 6%, p< 0.0001).ConclusionsSevere COVID-19 in pregnant women was associated with gestational age≥24 weeks and maternal age≥32. The rate of preterm delivery due to the infection was significantly higher in severe COVID-19 cases.
Mitigating Infectious morbidity and Growth deficits in HIV-exposed uninfected infanTs with human Milk Oligosaccharide (MIGH-T MO): a randomised trial protocol
Authors: Shivakoti Rupak , Slogrove Amy L , Laughton Barbara , Shafiq Mehr , Schoeman Elisma , Glashoff Richard H , Leu Cheng-Shiun , Wang Shuang , Bode Lars , Aldrovandi Grace , Kuhn Louise 
Published: December 2022

IntroductionChildren who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.Methods and analysisOne hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4–24 weeks and 4–48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.Ethics and disseminationEthical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.Trial registration numberClinicalTrials.gov Identifier:NCT05282485. SANCTR ID number: DOH-27-122021-6543.
Predicting the future development of diabetic retinopathy using a deep learning algorithm for the analysis of non-invasive retinal imaging
Authors: Rom Yovel , Aviv Rachelle , Ianchulev Tsontcho , Dvey-Aharon Zack 
Published: December 2022

AimsDiabetic retinopathy (DR) is the most common cause of vision loss in the working age. This research aimed to develop an artificial intelligence (AI) machine learning model which can predict the development of referable DR from fundus imagery of otherwise healthy eyes.MethodsOur researchers trained a machine learning algorithm on the EyePACS data set, consisting of 156 363 fundus images. Referrable DR was defined as any level above mild on the International Clinical Diabetic Retinopathy scale.ResultsThe algorithm achieved 0.81 area under receiver operating curve (AUC) when averaging scores from multiple images on the task of predicting development of referrable DR, and 0.76 AUC when using a single image.ConclusionOur results suggest that risk of DR may be predicted from fundus photography alone. Prediction of personalised risk of DR may become key in treatment and contribute to patient compliance across the board, particularly when supported by further prospective research.