bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study
Authors: Huybrechts Krista F , Bateman Brian T , Pawar Ajinkya , Bessette Lily G , Mogun Helen , Levin Raisa , Li Hu , Motsko Stephen , Scantamburlo Fernandes Maria Fernanda , Upadhyaya Himanshu P , Hernandez-Diaz Sonia 
Published: February 2020

Abstract

Objective
To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine.

Design
Cohort study nested in the Medicaid Analytic eXtract for 2004-13.

Setting
Publicly insured pregnancies in the United States.

Participants
Pregnant women 18 to 55 years of age and their liveborn infants.

Interventions
Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy.

Main outcome measures
Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage.

Results
Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses.

Conclusions
On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient.

Trial registration
EUPAS 15946.
Comparison of emergency department trauma triage performance of clinicians and clinical prediction models: a cohort study in India
Authors: Wärnberg Gerdin Ludvig , Khajanchi Monty , Kumar Vineet , Roy Nobhojit , Saha Makhan Lal , Soni Kapil Dev , Mishra Anurag , Kamble Jyoti , Borle Nitin , Verma Chandrika Prasad , Gerdin Wärnberg Martin 
Published: February 2020

ObjectiveThe aim of this study was to evaluate and compare the abilities of clinicians and clinical prediction models to accurately triage emergency department (ED) trauma patients. We compared the decisions made by clinicians with the Revised Trauma Score (RTS), the Glasgow Coma Scale, Age and Systolic Blood Pressure (GAP) score, the Kampala Trauma Score (KTS) and the Gerdin et al model.DesignProspective cohort study.SettingThree hospitals in urban India.ParticipantsIn total, 7697 adult patients who presented to participating hospitals with a history of trauma were approached for enrolment. The final study sample included 5155 patients. The majority (4023, 78.0%) were male.Main outcome measureThe patient outcome was mortality within 30 days of arrival at the participating hospital. A grid search was used to identify model cut-off values. Clinicians and categorised models were evaluated and compared using the area under the receiver operating characteristics curve (AUROCC) and net reclassification improvement in non-survivors (NRI+) and survivors (NRI−) separately.ResultsThe differences in AUROCC between each categorised model and the clinicians were 0.016 (95% CI −0.014 to 0.045) for RTS, 0.019 (95% CI −0.007 to 0.058) for GAP, 0.054 (95% CI 0.033 to 0.077) for KTS and −0.007 (95% CI −0.035 to 0.03) for Gerdin et al. The NRI+ for each model were −0.235 (−0.37 to −0.116), 0.17 (−0.042 to 0.405), 0.55 (0.47 to 0.65) and 0.22 (0.11 to 0.717), respectively. The NRI− were 0.385 (0.348 to 0.4), −0.059 (−0.476 to −0.005), −0.162 (−0.18 to −0.146) and 0.039 (−0.229 to 0.06), respectively.ConclusionThe findings of this study suggest that there are no substantial differences in discrimination and net reclassification improvement between clinicians and all four clinical prediction models when using 30-day mortality as the outcome of ED trauma triage in adult patients.Trial registration numberClinicalTrials.gov Registry (NCT02838459).
Economic evaluation of the OSAC randomised controlled trial: oral corticosteroids for non-asthmatic adults with acute lower respiratory tract infection in primary care
Authors: Moure-Fernandez Aida , Hollinghurst Sandra , Carroll Fran E , Downing Harriet , Young Grace , Brookes Sara , May Margaret , El-Gohary Magdy , Harnden Anthony , Kendrick Denise , Lafond Natasher , Little Paul , Moore Michael , Orton Elizabeth , Thompson Matthew , Timmins David , Wang Kay , Hay Alastair D 
Published: February 2020

ObjectiveTo estimate the costs and outcomes associated with treating non-asthmatic adults (nor suffering from other lung-disease) presenting to primary care with acute lower respiratory tract infection (ALRTI) with oral corticosteroids compared with placebo.DesignCost-consequence analysis alongside a randomised controlled trial. Perspectives included the healthcare provider, patients and productivity losses associated with time off work.SettingFifty-four National Health Service (NHS) general practices in England.Participants398 adults attending NHS primary practices with ALRTI but no asthma or other chronic lung disease, followed up for 28 days.Interventions2× 20 mg oral prednisolone per day for 5 days versus matching placebo tablets.Outcome measuresQuality-adjusted life years using the 5-level EuroQol-5D version measured weekly; duration and severity of symptom. Direct and indirect resources related to the disease and its treatment were also collected. Outcomes were measured for the 28-day follow-up.Results198 (50%) patients received the intervention (prednisolone) and 200 (50%) received placebo. NHS costs were dominated by primary care contacts, higher with placebo than with prednisolone (£13.11 vs £10.38) but without evidence of a difference (95% CI £3.05 to £8.52). The trial medication cost of £1.96 per patient would have been recouped in prescription charges of £4.30 per patient overall (55% participants would have paid £7.85), giving an overall mean ‘profit’ to the NHS of £7.00 (95% CI £0.50 to £17.08) per patient. There was a quality adjusted life years gain of 0.03 (95% CI 0.01 to 0.05) equating to half a day of perfect health favouring the prednisolone patients; there was no difference in duration of cough or severity of symptoms.ConclusionsThe use of prednisolone for non-asthmatic adults with ALRTI, provided small gains in quality of life and cost savings driven by prescription charges. Considering the results of the economic evaluation and possible side effects of corticosteroids, the short-term benefits may not outweigh the long-term harms.Trial registration numbersEudraCT 2012-000851-15 and ISRCTN57309858; Pre-results.
Postoperative surveillance and long-term outcome after endovascular aortic aneurysm repair in the Netherlands: study protocol for the retrospective ODYSSEUS study
Authors: Geraedts Anna Catharina Maria , de Mik Sylvana , Ubbink Dirk , Koelemay Mark , Balm Ron 
Published: February 2020

IntroductionStrict imaging surveillance protocols to detect complications following endovascular aneurysm repair (EVAR) are common practice. However, controversy exists as to whether all EVAR patients need intense surveillance. The 2019 European Society for Vascular Surgery guidelines for management of abdominal aortic aneurysm (AAA) suggest that patients may be considered for limited follow-up with imaging if classified as ‘low risk’ for complications based on their initial postoperative imaging. The current study aims to investigate the intervention-free survival and overall survival stratified for patients with and without yearly imaging surveillance.Methods and analysisThe Observing a Decade of Yearly Standardised Surveillance in EVAR patients with Ultrasound or CT Scan study comprises a national multicentre retrospective cohort study in 17 medical centres. Consecutive patients with an asymptomatic or symptomatic infrarenal AAA who underwent EVAR between January 2007 and January 2012 will be included in this study with follow-up until December 2018. Clinical variables and all follow-up information will be retrieved in extensive data collection from the patient’s medical records. In addition, an e-survey was sent to vascular surgeons at the 17 participating centres to gauge their opinions regarding the possibility of safely reducing the frequency of imaging surveillance. Primary endpoints are intervention after EVAR and aneurysm-related mortality. The initial estimated sample size is 1997 patients.Ethics and disseminationThe study has been approved by the Medical Ethics Review Committee of the Amsterdam UMC, location Academic Medical Centre, Amsterdam, the Netherlands. Study findings will be disseminated via presentations at conferences and publications in peer-reviewed journal.Trial registration numberThe Netherlands Trial Registry, NL6953 (old: NTR28773).
Effectiveness of a blended care programme for the discontinuation of benzodiazepine use for sleeping problems in primary care: study protocol of a cluster randomised trial, the Big Bird trial
Authors: Coteur Kristien , Van Nuland Marc , Vanmeerbeek Marc , Henrard Gilles , Anthierens Sibyl , Van den Broeck Kris , De Sutter An , Creupelandt Hanne , Devroey Dirk , Van Overmeire Roel , Offermans Anne-Marie , Kacenelenbogen Nadine , Laenen Annouschka , Mathei Catharina 
Published: February 2020

IntroductionProblematic benzodiazepine use is a global health issue. Although the adverse side effects of long-term use of benzodiazepines are well known, it remains difficult to implement interventions for discontinuation in primary care. Considering the success of blended care for the treatment of sleeping disorders and the support of substance use disorders, evidence suggests that a blended care approach, combining face-to-face consultations with the general practitioner with web-based self-learning by the patient, is beneficial for the discontinuation of chronic benzodiazepine use for primary insomnia in general practice. Therefore, the aim of this study is to evaluate the effectiveness of such an approach for the discontinuation of benzodiazepine and zolpidem, zopiclone and zaleplon drugs ((z-)BZD) use in the long term and evaluate the implementation process.Methods and analysisThis study is a multicentre, pragmatic, cluster randomised controlled trial with 1200 patients, included by 120 general practitioners. Allocation to usual or blended care happens at the level of the general practice in a 1:1 ratio using a block randomisation system stratified per language. The study population consists of adult primary care patients who have been using (z-)BZD for primary insomnia on a daily basis for at least 6 months. Primary outcome measure is the proportion of patients that discontinued (z-)BZD at 12 months assessed by toxicological screening for (z-)BZD in urine. Secondary outcomes include discontinuation of (z-)BZD at 6 months, quality of life and the number of defined daily doses of (z-)BZD prescribed. Data will be collected using a study-specific online platform and analysed using the intention-to-treat approach. The process of implementing blended care will be evaluated in a nested study.Ethics and disseminationThis trial was approved by the Ethics Committee for Research of UZ/KU Leuven (ref. S61194). Study results will be disseminated via open-access, peer-reviewed publications and conference presentations.Trial registration numberNCT03937180.
Trajectories of self-rated health in an older general population and their determinants: the Lifelines Cohort Study
Authors: Feenstra Marlies , van Munster Barbara C , MacNeil Vroomen Janet L , de Rooij Sophia E , Smidt Nynke 
Published: February 2020

ObjectivesPoor self-rated health (SRH) is a strong predictor of premature mortality in older adults. Trajectories of poor SRH are associated with multimorbidity and unhealthy behaviours. Whether trajectories of SRH are associated with deviating physiological markers is unclear. This study identified trajectories of SRH and investigated the associations of trajectory membership with chronic diseases, health risk behaviours and physiological markers in community-dwelling older adults.Study design and settingProspective general population cohort.ParticipantsTrajectories of SRH over 5 years were identified using data of 11 600 participants aged 65 years and older of the Lifelines Cohort Study.Outcome measuresTrajectories of SRH were the main outcome. Covariates included demographics (age, gender, education), chronic diseases, health-risk behaviour (physical activity, smoking, drinking) and physiological markers (body mass index, cardiovascular function, lung function, glucose metabolism, haematological condition, endocrine function, renal function, liver function and cognitive function).ResultsFour stable trajectories were identified, including excellent (n=607, 6%), good (n=2111, 19%), moderate (n=7677, 65%) and poor SRH (n=1205, 10%). Being women (OR: 1.4; 95% CI: 1.0 to 1.9), low education (OR: 2.1; 95% CI: 1.5 to 3.0), one (OR: 10.4; 95% CI: 7.4 to 14.7) or multiple chronic diseases (OR: 37.8; 95% CI: 22.4 to 71.8), smoking (OR: 1.8; 95% CI: 1.0 to 3.2), physical inactivity (OR: 3.1; 95% CI: 1.8 to 5.2), alcohol abstinence (OR: 2.2; 95% CI: 1.4 to 3.2) and deviating physiological markers (OR: 1.5; 95% CI: 1.1 to 2.0) increase the odds for a higher probability of poor SRH trajectory membership compared with excellent SRH trajectory membership.ConclusionSRH of community-dwelling older adults is stable over time with the majority (65%) having moderate SRH. Older adults with higher probabilities of poor SRH often have unfavourable health status.
Efficacy and safety of a supplement combination for hand osteoarthritis pain: protocol for an internet-based randomised placebo-controlled trial (The RADIANT study)
Authors: Liu Xiaoqian , Robbins Sarah , Eyles Jillian , Fedorova Tatyana , Virk Sonika , Deveza Leticia A , McLachlan Andrew , Hunter David 
Published: February 2020

IntroductionHand osteoarthritis (HOA) is a highly prevalent disabling joint disease. The current management regimens are limited. Potentially as a consequence, many people turn to complementary and alternative medicines for symptomatic relief. A combination of two or more supplements is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to investigate the efficacy of a supplement combination for treating symptomatic HOA in comparison to placebo.Methods and analysisThe RADIANT study is an internet-based, parallel, superiority, double-blind, placebo-controlled, randomised, two-arm clinical trial. A participatory design is used to facilitate the study procedures. One hundred and six participants aged over 40 years with painful HOA and structural change on X-ray (Kellgren and Lawrence grade (KLG) ≥2) will be recruited from the community and randomly allocated to receive either a supplement combination composed of: (1) combined supplement containingBoswellia serrataextract, pine bark extract and methylsulfonylmethane and (2) curcumin or placebo for 12 weeks. The primary outcome will be 12-week change in hand pain on a visual analogue scale (VAS). Main secondary outcomes include adverse events, change in hand function, patient global assessment of disease activity and quality of life. A range of additional measures will be recorded, and an individual patient placebo response will be performed. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored weekly throughout the study.Ethics and disseminationThis protocol has been approved by the University of Sydney Human Research Ethics Committee (HREC No. 2018/766). Dissemination will occur through conferences, social media, scientific publications and PhD thesis.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000835145); Pre-results
What do we really assess with organisational culture tools in healthcare? An interpretive systematic umbrella review of tools in healthcare
Authors: Malik Romana Fattimah , Buljac-Samardžić Martina , Akdemir Nesibe , Hilders Carina , Scheele Fedde 
Published: February 2020

IntroductionA toxic organisational culture (OC) is a major contributing factor to serious failings in healthcare delivery. Poor OC with its consequences of unprofessional behaviour, unsafe attitudes of professionals and its impact on patient care still need to be addressed. Although various tools have been developed to determine OC and improve patient safety, it remains a challenge to decide on the suitability of tools for uncovering the underlying factors which truly impact OC, such as behavioural norms, or the unwritten rules. A better understanding of the underlying dimensions that these tools do and do not unravel is required.ObjectivesThe aim of this study is to provide an overview of existing tools to assess OC and the tangible and intangible OC dimensions these tools address.MethodsAn interpretive umbrella review was conducted. Literature reviews were considered for inclusion if they described multiple tools and their dimensional characteristics in the context of OC, organisational climate, patient safety culture or climate. OC tools and the underlying dimensions were extracted from the reviews. A qualitative data analysis software program (MAX.QDA 2007) was used for coding the dimensions, which resulted in tangible and intangible themes.ResultsFifteen reviews met our inclusion criteria. A total of 127 tools were identified, which were mainly quantitative questionnaires covering tangible key dimensions. Qualitative analyses distinguished nine intangible themes (commitment, trust, psychological safety, power, support, communication openness, blame and shame, morals and valuing ethics, and cohesion) and seven tangible themes (leadership, communication system, teamwork, training and development, organisational structures and processes, employee and job attributes, and patient orientation).ConclusionThis umbrella review identifies the essential tangible and intangible themes of OC tools. OC tools in healthcare do not seem to be designed to determine deeper underlying dimensions of culture. We suggest approaching complex underlying OC problems by focusing on the intangible dimensions, rather than putting the tangible dimensions up front.
Glucose as an additional parameter to National Early Warning Score (NEWS) in prehospital setting enhances identification of patients at risk of death: an observational cohort study
Authors: Vihonen Hanna , Lääperi Mitja , Kuisma Markku , Pirneskoski Jussi , Nurmi Jouni 
Published: February 2020

BackgroundTo determine if prehospital blood glucose could be added to National Early Warning Score (NEWS) for improved identification of risk of short-term mortality.MethodsRetrospective observational study (2008–2015) of adult patients seen by emergency medical services in Helsinki metropolitan area for whom all variables for calculation of NEWS and a blood glucose value were available. Survival of 24 hours and 30 days were determined. The NEWS parameters and glucose were tested by multivariate logistic regression model. Based on ORs we formed NEWSgluc model with hypoglycaemia (≤3.0 mmol/L) 3, normoglycaemia 0 and hyperglycaemia (≥11.1 mmol/L) 1 points. The scores from NEWS and NEWSgluc were compared using discrimination (area under the curve), calibration (Hosmer-Lemeshow test), likelihood ratio tests and reclassification (continuous net reclassification index (cNRI)).ResultsData of 27 141 patients were included in the study. Multivariable regression model for NEWSgluc parameters revealed a strong association with glucose disturbances and 24-hour and 30-day mortality. Likelihood ratios (LRs) for mortality at 24 hours using a cut-off point of 15 were for NEWSgluc: LR+ 17.78 and LR− 0.96 and for NEWS: LR+ 13.50 and LR− 0.92. Results were similar at 30 days. Risks per score point estimation and calibration model showed glucose added benefit to NEWS at 24 hours and at 30 days. Although areas under the curve were similar, reclassification test (cNRI) showed overall improvement of classification of survivors and non-survivors at 24 days and 30 days with NEWSgluc.ConclusionsIncluding glucose in NEWS in the prehospital setting seems to improve identification of patients at risk of death.
Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake
Authors: Meslier Victoria , Laiola Manolo , Roager Henrik Munch , De Filippis Francesca , Roume Hugo , Quinquis Benoit , Giacco Rosalba , Mennella Ilario , Ferracane Rosalia , Pons Nicolas , Pasolli Edoardo , Rivellese Angela , Dragsted Lars Ove , Vitaglione Paola , Ehrlich Stanislav Dusko , Ercolini Danilo 
Published: February 2020

ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.DesignEighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.ResultsIncreased MD adherence in the MedD group successfully reprogrammed subjects’ intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degradingFaecalibacterium prausnitziiand of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.ConclusionSwitching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.