bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence-based, disease-specific estimate of the social cost of smoking in Singapore
Authors: Cher Boon Piang , Chen Cynthia , Yoong Joanne 
Published: April 2017

ObjectiveTo estimate the cost of smoking in Singapore in 2014 from the societal perspective.MethodsA prevalence-based, disease-specific approach was undertaken to estimate the smoking-attributable costs. These include direct and indirect costs of inpatient treatment, premature mortality, loss of productivity due to medical leaves and smoking breaks.ResultsIn 2014, the social cost of smoking in Singapore was conservatively estimated to be at least US$479.8 million, ∼0.2% of the 2014 gross domestic product. Most of this cost was attributable to productivity losses (US$464.9 million) and largely concentrated in the male population (US$434.9 million). Direct healthcare costs amounted to US$14.9 million where ischaemic heart disease and lung cancer had the highest cost burden.ConclusionsThe social cost of smoking is smaller in Singapore than in other Asian countries. However, there is still cause for concern. A recently observed increase in smoking prevalence, particularly among adolescent men, is likely to result in rising total cost. Most significantly, our results suggest that a large share of the overall cost burden lies outside the healthcare system or may not be highly salient to the relevant decision makers. This is partly because of the nature of such costs (indirect or intangible costs such as productivity losses are often not salient) or data limitations (a potentially significant fraction of direct healthcare expenditure may be in private primary care where costs are not systematically captured and reported). The case of Singapore thus illustrates that even in countries perceived as success stories, strong multisectoral anti-tobacco strategies and a supporting research agenda continue to be needed.
External validation and extension of a diagnostic model for obstructive coronary artery disease: a cross-sectional predictive evaluation in 4888 patients of the Austrian Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort
Authors: Edlinger Michael , Wanitschek Maria , Dörler Jakob , Ulmer Hanno , Alber Hannes F , Steyerberg Ewout W 
Published: April 2017

ObjectiveTo externally validate and extend a recently proposed prediction model to diagnose obstructive coronary artery disease (CAD), with the ultimate aim to better select patients for coronary angiography.DesignAnalysis of individual baseline data of a prospective cardiology cohort.SettingSingle-centre secondary and tertiary cardiology clinic.Participants4888 patients with suspected CAD, without known previous CAD or other heart diseases, who underwent an elective coronary angiography between 2004 and 2008 as part of the prospective Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort. Relevant data were recorded as in routine clinical practice.Main outcome measuresThe probability of obstructive CAD, defined as a stenosis of minimally 50% diameter in at least one of the main coronary arteries, estimated with the predictors age, sex, type of chest pain, diabetes status, hypertension, dyslipidaemia, smoking status and laboratory data. Missing predictor data were multiply imputed. Performance of the suggested models was evaluated according to discrimination (area under the receiver operating characteristic curve, depicted by the c statistic) and calibration. Logistic regression modelling was applied for model updating.ResultsAmong the 4888 participants (38% women and 62% men), 2127 (44%) had an obstructive CAD. The previously proposed model had a c statistic of 0.69 (95% CI 0.67 to 0.70), which was lower than the expected c statistic while correcting for case mix (c=0.80). Regarding calibration, there was overprediction of risk for high-risk patients. All logistic regression coefficients were smaller than expected, especially for the predictor ‘chest pain’. Extension of the model with high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and C reactive protein led to better discrimination (c=0.72, 95% CI 0.71 to 0.74, p<0.001 for improvement).ConclusionsThe proposed prediction model has a moderate performance to diagnose obstructive CAD in an unselected patient group with suspected CAD referred for elective CA. A small, but significant improvement was attained by including easily available and measurable cardiovascular risk factors.
Employment status and psychological distress in a population-based cross-sectional study in Sweden: the impact of migration
Authors: Sidorchuk Anna , Engström Karin , Johnson Charisse M , Kayser Leeoza Naima , Möller Jette 
Published: April 2017

ObjectivesUnemployment and temporary employment are known to impact psychological health. However, the extent to which the effect is altered by migration-related and sociodemographic determinants is less clear. The purpose of this study was to investigate whether the association between employment status and psychological distress differs between immigrants and Swedish-born and to what extent, the association is modified by gender and reason for immigration.DesignCross-sectional survey study.Participants and settingData from public health surveys undertaken in 2002, 2006 and 2010 from random samples of Stockholm County residents, Sweden, were used to analyse a weighted sample of 51 118 individuals aged 18–64 (43 444 Swedish-born, 4055 non-refugees, 3619 refugees). According to their activity in the labour market, the participants were categorised into permanently/self-employed, temporarily employed and unemployed.Outcomes measuresAssociations between self-reported employment and psychological distress measured by a 12-item version of the General Health Questionnaire were explored across individuals with different migration status and reasons for immigration using logistic regression and pairwise comparisons. The analyses were stratified by gender and adjusted for age, socioeconomic characteristics and survey year.ResultsUnemployment was associated with elevated likelihood of psychological distress across the study population, regardless of migration status and gender. Fully adjusted models revealed nearly a 3-fold higher odds of distress in unemployed Swedish-born (OR 3.05, 95% CI 2.66 to 3.51), non-refugees (OR 3.51, 95% CI 2.44 to 5.05) and refugees (OR 2.91, 95% CI 2.20 to 3.85) when compared with permanently/self-employed. Temporary employment also increased the likelihood of distress, particularly among refugees and Swedish-born.ConclusionsThe effect of unemployment on increased likelihood of poor psychological well-being overcomes gender-specific and migration-specific differences and is equally pronounced for Swedish-born, non-refugees and refugees. Exclusion from the labour market appears to be a major determinant of psychological health inequalities in contemporary Sweden.
Are Jordanian primary healthcare practitioners fulfilling their potential in cancer prevention and community health? Findings from a cross-sectional survey
Authors: Obeidat N A , Habashneh M A , Shihab R A , Hawari F I 
Published: April 2017

IntroductionPrimary healthcare practitioners (PHCPs) can contribute to the control of cancer by promoting healthy lifestyles to patients. Given the scarcity of data in the Middle East on this subject, we sought to determine, through a cross-sectional survey, the status of healthy lifestyle promotion by PHCPs (physicians, nurses, midwives, nurse aids) in Jordan.MethodsBuilding on published studies, an Arabic questionnaire was developed to measure knowledge, perceptions and practices of Jordanian PHCPs with regard to healthy lifestyle counselling. A purposive sample of 20 clinics covering the main regions of Jordan was selected and all PHCPs were asked to complete the questionnaire.Results322 practitioners (32.3% physicians) responded (a 75.1% response rate). 24.4% of PHCPs were current cigarette smokers (physicians 44.2%). Roughly 58% of physicians and 50% of non-physicians reported advising the majority of patients to quit tobacco, but proportions were lower for providing other services (eg, asking about frequency of tobacco use, inquiring about diet and exercise, providing evidence-based guidance on quitting tobacco or improving diet and activity). Only 8% of the sample reported collectively asking the majority of patients about smoking status, exercise and diet; and providing evidence-based tips to improve these. Among physicians and non-physicians, 14.2% and 40.4% were able to identify the lifestyle-related risk factors associated with breast, colorectal and lung cancer. In multivariable analyses, confidence was the only significant variable associated with provision of counselling on healthy lifestyles.ConclusionsAmong Jordanian PHCPs, primary prevention services are underprovided, and data suggest ample room to improve PHCPs' skills and practices.
The interaction of socioeconomic position and type 2 diabetes mellitus family history: a cross-sectional analysis of the Lifelines Cohort and Biobank Study
Authors: van Zon Sander K.R. , Snieder Harold , Bültmann Ute , Reijneveld Sijmen A. 
Published: April 2017

BackgroundLow socioeconomic position (SEP) and family history of type 2 diabetes mellitus (T2DM) contribute to increased T2DM risk, but it is unclear whether they exacerbate each other’s effect. This study examined whether SEP reinforces the association of T2DM family history with T2DM, and whether behavioural and clinical risk factors can explain this reinforcement.MethodsWe used cross-sectional data on 51 725 participants from Lifelines. SEP was measured as educational level and was self-reported, just as family history of T2DM. T2DM was diagnosed based on measured fasting plasma glucose and glycated haemoglobin, combined with self-reported disease and recorded medication use. We assessed interaction on the additive scale by calculating the relative excess risk due to interaction (RERI).ResultsORs of T2DM were highest for males (4.37; 95% CI 3.47 to 5.51) and females (7.77; 5.71 to 10.56) with the combination of low SEP and a family history of T2DM. The RERIs of low SEP and a family history of T2DM were 0.64 (−0.33 to 1.62) for males and 3.07 (1.53 to 4.60) for females. Adjustment for behavioural and clinical risk factors attenuated associations and interactions, but risks remained increased.ConclusionLow SEP and family history of T2DM are associated with T2DM, but they also exacerbate each other’s impact in females but not in males. Behavioural and clinical risk factors partly explain these gender differences, as well as the associations underlying the interaction in females. The exacerbation by low SEP of T2DM risks in T2DM families deserves attention in prevention and community care.
The impact of rifaximin-α on the hospital resource use associated with the management of patients with hepatic encephalopathy: a retrospective observational study (IMPRESS)
Authors: Hudson Mark , Radwan Amr , Di Maggio Paola , Cipelli Riccardo , Ryder Stephen D , Dillon John F , Cash William Jonathan , Przemioslo Robert T , Wright Mark , Shawcross Debbie L , Jalan Rajiv , Saksena Sushma , Allison Michael , Richardson Paul , Farrington Elizabeth , Aspinall Richard J 
Published: April 2017

ObjectiveTo compare all-cause and liver-related hospital resource use in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation in UK patients with hepatic encephalopathy (HE).DesignA UK multicentre, retrospective, observational study. Patients' medical records were reviewed for demographics, clinical outcomes and adverse events (AEs) to rifaximin-α. Details of hospital admissions/attendances in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation were extracted from hospital electronic databases.Setting13 National Health Service centres.Patients207 patients with HE who initiated rifaximin-α between July 2008 and May 2014. Hospital resource use data were available for 145/207 patients.Main outcome measureChange in mean number of liver-related hospital bed days/patient (total and critical care) between the 6 months pre-rifaximin-α and post-rifaximin-α initiation.ResultsComparing the 6 months pre-rifaximin-α and post-rifaximin-α initiation in alive patients at the end of the observation period (N=114): there were significant reductions in the mean number of hospitalisations/patient (liver-related 1.3 to 0.5, p<0.001; all-cause 1.9 to 0.9, p<0.001), hospital bed days/patient (liver-related 17.8 to 6.8, p<0.001; all-cause 25.4 to 10.6, p<0.001), 30-day hospital readmissions/patient (liver-related 0.5 to 0.2, p=0.039; all-cause 0.8 to 0.4, p=0.024) and emergency department (ED) attendances/patient (all-cause, 1.0 to 0.5, p<0.001). The mean critical care bed days/patient reduced significantly for all-cause admissions (1.3 to 0.3, p=0.049); non-significant reduction for liver-related admissions. 4% of patients (9/207) developed AEs.ConclusionsIn UK clinical practice, treatment with rifaximin-α for HE is well-tolerated and associated with significant reductions in hospitalisations, bed days (including critical care), ED attendances and 30-day readmissions.
CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells
Authors: Manic Gwenola , Signore Michele , Sistigu Antonella , Russo Giorgio , Corradi Francesca , Siteni Silvia , Musella Martina , Vitale Sara , De Angelis Maria Laura , Pallocca Matteo , Amoreo Carla Azzurra , Sperati Francesca , Di Franco Simone , Barresi Sabina , Policicchio Eleonora , De Luca Gabriele , De Nicola Francesca , Mottolese Marcella , Zeuner Ann , Fanciulli Maurizio , Stassi Giorgio , Maugeri-Saccà Marcello , Baiocchi Marta , Tartaglia Marco , Vitale Ilio , De Maria Ruggero 
Published: April 2017

ObjectiveCancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.DesignTo discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein microarray (RPPA) and cytogenetic analyses, and validated by immunostainings. DNA replication stress (RS) was increased by employing DNA replication-perturbing or polyploidising agents.ResultsThe drug-library screening led to the identification of LY2606368 as a potent anti-CSC agent acting in vitro and in vivo in tumour cells from a considerable number of patients (∼36%). By inhibiting checkpoint kinase (CHK)1, LY2606368 affected DNA replication in most CRC-SCs, including RAS-mutated ones, forcing them into premature, lethal mitoses. Parallel genomic, RPPA and cytogenetic analyses indicated that CRC-SCs sensitive to LY2606368 displayed signs of ongoing RS response, including the phosphorylation of RPA32 and ataxia telangiectasia mutated serine/threonine kinase (ATM). This was associated with mutation(s) in TP53 and hyperdiploidy, and made these CRC-SCs exquisitely dependent on CHK1 function. Accordingly, experimental increase of RS sensitised resistant CRC-SCs to LY2606368.ConclusionsLY2606368 selectively eliminates replication-stressed, p53-deficient and hyperdiploid CRC-SCs independently of RAS mutational status. These results provide a strong rationale for biomarker-driven clinical trials with LY2606368 in patients with CRC.
Diagnostic accuracy of endometrial biopsy in relation to the amount of tissue
Authors: Reijnen Casper , Visser Nicole C M , Bulten Johan , Massuger Leon F A G , van der Putten Louis J M , Pijnenborg Johanna M A 
Published: April 2017

AimsFor the diagnostic workup of postmenopausal bleeding, histological examination of the endometrium is frequently performed. Failure of endometrial sampling due to insufficient material is often reported but objective criteria for quality assessment of endometrial biopsies are lacking. The aim of the present study is to evaluate the association between the amount of tissue obtained by endometrial sampling and the diagnostic accuracy, and to establish a cut-off level for a minimal amount of tissue required for a conclusive diagnosis.MethodsFor this retrospective cohort study, clinicopathological data and Pipelle endometrial sampling slides of 139 patients who were treated with hysterectomy were collected. The surface of evaluable endometrial tissue was measured by means of structured digital assessment. The correlation between the predictive values in relation to the endometrial tissue surface was calculated for different cut-off values.ResultsThe median endometrial tissue surface was 4.7 mm2(range 0.4–156.4) for benign endometrium, 27.8 mm2(range 0.0–208.4) for premalignant endometrium and 43.8 mm2(range 0.0–223.6) for malignant endometrium. There was a significant association between the endometrial tissue surface and the correctness of diagnosis. A minimal endometrial tissue surface of 35 mm2could be defined, for positive and negative predictive values of 92.6% and 85.7%, respectively.ConclusionsThe diagnostic accuracy of Pipelle endometrial sampling is associated with the amount of endometrial tissue surface, with a minimal cut-off value of 35 mm2required to classify an endometrial sample as conclusive. Quantification of endometrial tissue can contribute to standardisation of quality assessment of endometrial samplings.
Paediatric hypoglycaemia; are we investigating appropriately and adequately?
Authors: Ramsden Louise , Wright Katherine , Natarajan Anuja 
Published: April 2017

ABSTRACTIntroductionPaediatric hypoglycaemia is a relatively common medical emergency. To allow identification of the underlying cause, investigations need to be performed urgently prior to treatment being given. Careful consideration is needed to ensure correct patient selection, as inadequate investigations have further cost and patient safety implications.Methods49 cases of proven or suspected hypoglycaemia (glucose ≤2.6 mmol/L) were identified via the laboratory. Clinical notes, laboratory investigations and results were reviewed.ResultsOnly 41% of patients (15 neonates, 5 children) required investigation with a ‘Hyposcreen’. Of these 20 patients, 3 had no investigations performed. In the remaining patients the cause for hypoglycaemia was identifiable, but 6 had investigations regardless. In total 23 patients had ‘Hyposcreen’ but only 2 were complete. Intermediary metabolites (96%), lactate (100%), cortisol (100%), insulin (83%) and growth hormone (87%) were taken most commonly with urine samples (52%) and ammonia (30%) taken least often. 40% cortisol, 29% insulin and 56% intermediary metabolite results were abnormal affecting 10 patients, but only 5 had follow-up. A total of £6977 was spent on investigations, of which £1630 has subsequently been found to be unnecessary. If investigations in the 23 children had been complete, this would have totalled £2700 of unnecessary expenditure.ConclusionsInvestigations for hypoglycaemia are generally incomplete (91%) or inappropriate (21%). This has major cost implications for both the National Health Service and the individual who is investigated inadequately or incorrectly. We need national evidence-based guidance for investigation thresholds and normal ranges to help avoid inappropriate investigations and delay in diagnosis.
Evaluation of multiple referral strategies for axial spondyloarthritis in the SPondyloArthritis Caught Early (SPACE) cohort
Authors: Abawi Ozair , van den Berg Rosaline , van der Heijde Désirée , van Gaalen Floris A 
Published: April 2017

BackgroundSeveral models have been proposed to refer patients with possible axial spondyloarthritis (axSpA) to a rheumatologist. Our aim was to evaluate performance of these models in a single cohort.Methods13 referral models found in the literature were evaluated in the Leiden SPondyloArthritis Caught Early (SPACE) cohort, which includes patients with back pain (≥3 months, ≤2 years, onset <45 years; n=261) referred to a rheumatology outpatient clinic. Imaging was not considered as a referral parameter. Performance of the strategies was evaluated (sensitivity, specificity, positive likelihood ratio (LR+)) using diagnosis by a rheumatologist as an external standard. For secondary analyses, fulfilment of the Assessment in SpondyloArthritis international Society (ASAS) axSpA criteria was used as an external standard.ResultsIn total, 107/261 patients were diagnosed with axSpA. Most models performed well regarding sensitivity and specificity. The MASTER strategy showed a balanced sensitivity/specificity with the highest LR+. The ASAS and Brandt I strategies are the most sensitive strategies. Using classification by ASAS axSpA criteria as the external standard gave comparable results. Most patients missed by the strategies fulfilled the imaging arm of the ASAS axSpA criteria.ConclusionsMost referral models performed well, although patients in SPACE have already been referred, which may have led to overestimation of performance. If no patient is to be missed, the ASAS strategy would be most preferable. If the number of referrals needs to be limited, the MASTER strategy seems to perform best. The ‘ideal’ referral strategy may be different from country to country, due to differences in healthcare structure and prevalence of referral parameters such as human leucocyte antigen-B27.
Geology and seepage in the NE Atlantic region
Authors: Vis Geert-Jan 
Published: April 2017

Abstract
Exploration for hydrocarbons in the NE Atlantic mainly focuses on the central eastern margin. The western margin has remained virtually unexplored, with no exploration wells drilled so far. A cost-efficient way to infer the presence of natural hydrocarbons in the poorly explored regions of the NE Atlantic is the application of synthetic aperture radar (SAR). This study presents four areas, the Western Barents Sea Margin, the Irish Atlantic Margin, East Greenland and Jan Mayen, where clustered oil-slick data indicate possible active oil seepage. The eastern margin of the NE Atlantic contains numerous oil-slick observations, but along the western margin the number of observations is limited, partly due to a persistent sea-ice coverage. Based on the tectonostratigraphic setting, it is suggested that Triassic and Jurassic source rocks are the most likely candidates for the generation of seeps in the areas studied. Near Jan Mayen and East Greenland, Cenozoic source rocks could also be present. SAR data are a useful tool in an early stage of exploration, but further work is needed to improve the understanding of the subsurface below the observed oil slicks in the NE Atlantic to determine the origin of the seepage.