bluuebunny/crossref_metadata_2025_split huggingface dataset:
Click chemistry enables preclinical evaluation of targeted epigenetic therapies
Authors: Tyler Dean S. , Vappiani Johanna , Cañeque Tatiana , Lam Enid Y. N. , Ward Aoife , Gilan Omer , Chan Yih-Chih , Hienzsch Antje , Rutkowska Anna , Werner Thilo , Wagner Anne J. , Lugo Dave , Gregory Richard , Ramirez Molina Cesar , Garton Neil , Wellaway Christopher R. , Jackson Susan , MacPherson Laura , Figueiredo Margarida , Stolzenburg Sabine , Bell Charles C. , House Colin , Dawson Sarah-Jane , Hawkins Edwin D. , Drewes Gerard , Prinjha Rab K. , Rodriguez Raphaël , Grandi Paola , Dawson Mark A. 
Published: July 2017

Are better drugs just a click away?Drugs that show promise in preclinical models often fail in the clinic, in part because of limited information on drug localization within cells and across tissues. In a proof-of-concept study, Tyleret al.applied click chemistry methods to study the localization of bromodomain inhibitors. These are cancer drugs that alter chromatin structure and gene expression. Clickable derivatives of the drugs localized within chromatin and showed that the drugs exhibit distinct modes of binding at responsive and unresponsive genes. In a mouse leukemia model, the click-probes revealed that the drugs accumulate to different extents in the spleen and bone marrow, which are two tissue sources of leukemic cells.Science, this issue p.1397
Association of perceived tinnitus with duration of hormone replacement therapy in Korean postmenopausal women: a cross-sectional study
Authors: Lee Seong-Su , Han Kyung-do , Joo Young-Hoon 
Published: July 2017

ObjectiveThe purpose of this study was to determine the relationship between hormone replacement therapy (HRT) and tinnitus in South Korea using data from the Korea National Health and Nutrition Examination Surveys (KNHANES) (2010–2012).Study designCross-sectional analysis of a nationwide health survey.MethodsKNHANES is a nationally representative cross-sectional survey of South Korea population. Only postmenopausal women aged 19–65 years were included in the study (n=2736). Auditory function was evaluated using pure-tone audiometric testing according to established KNHANES protocols. Subjects were questioned about their experience with tinnitus. Exogenous hormone-related factors included the starting age and duration of HRT.ResultsThe overall prevalence of tinnitus was 22.2% among postmenopausal women. (1) Tinnitus severity was significantly higher in women using HRT (p=0.0024) and (2) significantly lower in women who breast fed their children (p=0.0386). (3) According to logistic regression models, the longer duration of HRT was significantly associated with increasing tinnitus (OR=1.323, 95% CI 1.007 to 1.737, p=0.0441).ConclusionA longer duration of HRT was associated with developing tinnitus in Korean postmenopausal women. Further experimental and epidemiological researches are needed to elucidate the causal relationship between HRT and tinnitus.
Translation, adaptation and measurement properties of an electronic version of the Danish Western Ontario Shoulder Instability Index (WOSI)
Authors: Eshoj Henrik , Bak Klaus , Blønd Lars , Juul-Kristensen Birgit 
Published: July 2017

ObjectivesTo translate and adapt the Western Ontario Shoulder Instability (WOSI) questionnaire into Danish and, to evaluate measurement properties of an electronic Danish WOSI version.MethodsThe Swedish WOSI version was used for translation and adaptation into Danish followed by examination of test-retest reproducibility (14-day interval) besides concurrent and construct validity. Concurrent validity was examined by comparing WOSI in paper version with an electronic version, whereas construct validity was examined by comparing WOSI with Numeric Pain Rating Scale (NPRS) and the Oxford Shoulder Score (OSS). Reproducibility was evaluated with Intraclass correlations (ICC), Standard Error of Measurement (SEM), minimal detectable change (MDC) and limits of agreement (LOA). Validity was evaluated with Pearson’s (r)and Concordance Correlation Coefficients (CCC).Results41 subjects (median age 34, range 18–57) were included in the analysis of reproducibility. An ICC of 0.97 (95% CI 0.95 to 0.99) for the total WOSI score was found. SEM was 100.1, resulting in an MDC of 277.5 and LOAs within the range of -246.4 and 308.6. 25 subjects (median age 34, range 18–72) were included in the analysis of concurrent validity obtaining a CCC of 0.96 (95% CI 0.91 to 0.98). Construct validity was investigated in 62 subjects (median age 31, range 18–72) obtaining correlations of 0.83 (95% CI 0.68 to 0.97) (NPRS) and 0.79 (95% CI 0.62 to 0.94) (OSS).ConclusionsAn electronic Danish version of WOSI presented excellent test-retest reproducibility and acceptable measurement errors. Also, concurrent validity between paper and electronic version was highly satisfactory as was the construct validity. Surprisingly, though, the NPRS correlated more with WOSI than OSS.
Description of the rates, trends and surgical burden associated with revision for prosthetic joint infection following primary and revision knee replacements in England and Wales: an analysis of the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man
Authors: Lenguerrand Erik , Whitehouse Michael R , Beswick Andrew D , Toms Andrew D , Porter Martyn L , Blom Ashley W 
Published: July 2017

ObjectivesTo describe the prevalence rates of revision surgery for the treatment of prosthetic joint infection (PJI) for patients undergoing knee replacement, their time trends, the cumulative incidence function of revision for PJI and estimate the burden of PJI at health service level.DesignWe analysed revision knee replacements performed due to a diagnosis of PJI and the linked index procedures recorded in the National Joint Registry from 2003 to 2014 for England and Wales. The cohort analysed consisted of 679 010 index primary knee replacements, 33 920 index revision knee replacements and 8247 revision total knee replacements performed due to a diagnosis of PJI. The prevalence rates, their time trends investigated by time from index surgery to revision for PJI, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression.ResultsThe incidence of revision total knee replacement due to PJI at 2 years was 3.2/1000 following primary and 14.4/1000 following revision knee replacement, respectively. The prevalence of revision due to PJI in the 3 months following primary knee replacement has risen by 2.5-fold (95% CI 1.2 to 5.3) from 2005 to 2013 and 7.5-fold (95% CI 1.0 to 56.1) following revision knee replacement. Over 1000 procedures per year are performed as a consequence of knee PJI, an increase of 2.8 from 2005 to 2013. Overall, 75% of revisions were two-stage with an increase in use of single-stage from 7.9% in 2005 to 18.8% in 2014.ConclusionsAlthough the risk of revision due to PJI following knee replacement is low, it is rising, and coupled with the established and further predicted increased incidence of both primary and revision knee replacements, this represents an increasing and substantial treatment burden for orthopaedic service delivery in England and Wales. This has implications for future service design and the funding of individual and specialist centres.
Words do matter: a systematic review on how different terminology for the same condition influences management preferences
Authors: Nickel Brooke , Barratt Alexandra , Copp Tessa , Moynihan Ray , McCaffery Kirsten 
Published: July 2017

ObjectivesChanging terminology for low-risk, screen-detected conditions has now been recommended by several expert groups in order to prevent overdiagnosis and reduce the associated harms of overtreatment. However, the effect of terminology on patients’ preferences for management is not well understood. This review aims to synthesise existing studies on terminology and its impact on management decision making.DesignSystematic review.MethodsStudies were included that compared two or more terminologies to describe the same condition and measured the effect on treatment or management preferences and/or choices. Studies were identified via database searches from inception to April 2017, and from reference lists. Two authors evaluated the eligibility of studies with verification from the study team, extracted and crosschecked data, and assessed the risk of bias of included studies.ResultsOf the 1399 titles identified, seven studies, all of which included hypothetical scenarios, met the inclusion criteria. Six studies were quantitative and one was qualitative. Six of the studies were of high quality. Studies covered a diverse range of conditions: ductal carcinoma in situ (3), gastro-oesophageal reflux disease (1), conjunctivitis (1), polycystic ovary syndrome (1) and a bony fracture (1). The terminologies compared in each study varied based on the condition assessed. Based on a narrative synthesis of the data, when a more medicalised or precise term was used to describe the condition, it generally resulted in a shift in preference towards more invasive managements, and/or higher ratings of anxiety and perceived severity of the condition.ConclusionsDifferent terminology given for the same condition influenced management preferences and psychological outcomes in a consistent pattern in these studies. Changing the terminology may be one strategy to reduce patient preferences for aggressive management responses to low-risk conditions.Trial registration numberPROSPERO: CRD42016035643.
Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study
Authors: Morawiec Beata , Fournier Stephane , Tapponnier Maxime , Prior John O , Monney Pierre , Dunet Vincent , Lauriers Nathalie , Recordon Frederique , Trana Catalina , Iglesias Juan-Fernando , Kawecki Damian , Boulat Olivier , Bardy Daniel , Lamsidri Sabine , Eeckhout Eric , Hugli Olivier , Muller Olivier 
Published: July 2017

BackgroundHighly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay’s performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented.PurposeTo assess hs-TnT assay’s performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain.MethodsPatients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography.ResultsForty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively.ConclusionsOur findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value.Trial registration numberClinicalTrials.gov Identifier:NCT01374607.
Development in the number of clinical trial applications in Western Europe from 2007 to 2015: retrospective study of data from national competent authorities
Authors: Dombernowsky Tilde , Hædersdal Merete , Lassen Ulrik , Thomsen Simon Francis 
Published: July 2017

ObjectiveTo investigate the development in the number of applications for authorisation of clinical trials of medicines (CTAs) submitted annually to national competent authorities in 10 Western European member states of the European Union from 2007 to 2015.DesignRegistry study.SettingData from national competent authorities.ParticipantsGermany, Italy, Spain, France, the UK, Belgium, the Netherlands, Austria, Denmark and Sweden. Inclusion criteria were Western European member states of the European Union, receiving more than 200 CTAs per year.Outcome measuresSummarised number of CTAs and distribution of CTAs by type of sponsor (commercial or non-commercial) and trial phase (I–IV). Average annual growth rates (AAGRs) based on linear regressions. Data were evaluated 2007–2011 and 2012–2015 to compare findings with the European Commission’s statement of a 25% decrease in CTAs in the EU from 2007 to 2011.ResultsFrom 2007 to 2011, the summarised number of CTAs decreased significantly (AAGR −3.9% (p=0.02)), primarily due to a decrease in commercially sponsored CTAs. From 2012 to 2015, the change was insignificant (AAGR 2.6% (p=0.27)), however with a 10% increase from 2014 to 2015 after stagnation from 2012 to 2014. Overall, the number of CTAs and distribution by type of sponsor varied considerably between countries. No distinct trends were observed when evaluating CTAs by type of trial phase.ConclusionsThis study found a significant decrease in the number of CTAs in Western Europe from 2007 to 2011 (AAGR −3.9%). This development is possibly attributable to several factors such as the European Clinical Trials Directive, national and local political decisions, and a potential global shift in clinical trial activity. From 2014 to 2015, the number of CTAs increased markedly (10%). However, it is yet too soon to determine if this constitutes a transient fluctuation or a new trend.
Ethnic differences in current smoking and former smoking in the Netherlands and the contribution of socioeconomic factors: a cross-sectional analysis of the HELIUS study
Authors: Brathwaite Rachel , Smeeth Liam , Addo Juliet , Kunst Anton E , Peters Ron J G , Snijder Marieke B , Derks Eske M , Agyemang Charles 
Published: July 2017

ObjectivesData exploring how much of the ethnic differences in smoking prevalence and former smoking are explained by socioeconomic status (SES) are lacking. We therefore assessed ethnic differences in smoking prevalence and former smoking and the contribution of both educational level and occupational-related SES to the observed ethnic differences in smoking behaviour.MethodsData of 22 929 participants (aged 18–70 years) from the multiethnic cross-sectional Healthy Life in an Urban Setting study in the Netherlands were analysed. Poisson regression models with a robust variance were used to estimate prevalence ratios.ResultsCompared with the Dutch, after adjustment for age and marital status, smoking prevalence was higher in men of Turkish (prevalence ratio 1.69, 95% CI 1.54 to 1.86), African Surinamese (1.55, 95% CI 1.41 to 1.69) and South-Asian Surinamese origin (1.53, 95% CI 1.40 to 1.68), whereas among women, smoking prevalence was higher in Turkish, similar in African Surinamese but lower in all other ethnic origin groups. All ethnic minority groups, except Ghanaians, had a significantly lower smoking cessation prevalence than the Dutch. Socioeconomic gradients in smoking (higher prevalence among those lower educated and with lower level employment) were observed in all groups except Ghanaian women (a higher prevalence was observed in the higher educated). Ethnic differences in smoking prevalence and former smoking are largely, but not completely, explained by socioeconomic factors.ConclusionsOur findings imply that antismoking policies designed to target smoking within the lower socioeconomic groups of ethnic minority populations may substantially reduce ethnic inequalities in smoking particularly among men and that certain groups may benefit from targeted smoking cessation interventions.
Leisure-time physical activity and circulating 25-hydroxyvitamin D levels in cancer survivors: a cross-sectional analysis using data from the US National Health and Nutrition Examination Survey
Authors: Yang Lin , Toriola Adetunji T 
Published: July 2017

ObjectivesCirculating 25-hydroxyvitamin D (25-OHD) is associated with improved cancer prognosis in some studies, yet it may be a surrogate marker for physical activity. We investigated the associations of leisure-time physical activity (LTPA) with circulating 25-OHD levels in cancer survivors, and determined whether associations differ by indoor and outdoor activity.DesignCross-sectional study.SettingThe US National Health and Nutrition Examination Survey (NHANES).ParticipantsCancer survivors with available data on demographic information, measures of adiposity, smoking history, self-reported LTPA and circulating 25-OHD levels in five waves of NHANES (2001–2010).Main outcomes measuresCirculating 25-OHD levels.ResultsMultivariable linear regression and logistic regression models were used to evaluate the associations of self-reported LTPA with 25-OHD, adjusting for potential confounders. Due to the differences in LTPA measure, the analyses were conducted separately for 2001–2006 and 2007–2010 data. We further estimated associations by indoor and outdoor activity in the 2001–2006 data. There were 1530 cancer survivors (mean age=60.5 years, mean body mass index=28.6 kg/m2). The prevalent cancer sites were breast (19.3%), prostate (18.8%), cervix (10.4%) and colon (8.6%). Compared with inactive cancer survivors, being physically active was associated with higher circulating 25-OHD levels (8.07 nmol/L, 95% CI 4.63 to 11.52) for 2001–2006 data. In the mutually adjusted model, higher outdoor activity (5.83 nmol/L, 95% CI 1.64 to 10.01), but not indoor activity (2.93 nmol/L, 95% CI −1.80 to 7.66), was associated with statistically significantly higher 25-OHD levels. The interaction between indoor and outdoor activities was, however, not significant (p=0.29). The only statistically significant association seen in the 2007–2010 data was among obese cancer survivors.ConclusionPhysical activity, particularly outdoor activity, is associated with higher 25-OHD levels in cancer survivors. In view of the possible beneficial effects of vitamin D on cancer prognosis, engaging in outdoor physical activity could provide clinically meaningful increases in 25-OHD levels among cancer survivors.
Prevalence and antibiotic resistance ofMycoplasma genitaliumamong STI clinic attendees in Western Canada: a cross-sectional analysis
Authors: Gratrix Jennifer , Plitt Sabrina , Turnbull LeeAnn , Smyczek Petra , Brandley Judith , Scarrott Ron , Naidu Prenilla , Parker Penny , Blore Brenda , Bull Amy , Shokoples Sandy , Bertholet Lindsay , Martin Irene , Chernesky Max , Read Ron , Singh Ameeta 
Published: July 2017

ObjectivesTo determine the prevalence and correlates ofMycoplasmagenitalium(MG) infection among men and women, determine the prevalence of gene mutations conferring resistance and compare test performance of female specimen types.MethodsA cross-sectional study was conducted on specimens collected for gonorrhoea (NG,Neisseria gonorrhoeae) and chlamydia (CT,Chlamydia trachomatis) among male and female Alberta STI clinic attendees using theM. genitaliumtranscription-mediated amplification-research use only test. Positive specimens were sequenced for 23SrRNA,parCandgyrAgenes. Gender-stratified analysis compared test results using χ2or Fisher’s exact test, Mann-Whitney U test and logistic regression. Female endocervical and urine specimens were compared.ResultsA total of 2254 individuals were tested; 53.8% (n=1212) were male. Male prevalence of MG was 5.3%; CT was 5.9% and NG was 1.8%. Correlates of male infection were a non-gonococcal urethritis diagnosis and NG coinfection. MG prevalence for women was 7.2%; CT was 5.8% and NG was 1.8%. Correlates of female infection were younger age, Indigenous/Other ethnicity and CT/NG coinfection. Nearly two-thirds of eligible specimens had mutations associated with macrolide resistance and 12.2% of specimens had aparCmutation signifying possible moxifloxacin resistance. There was high concordance (98.1%) of results between urine and endocervical swabs.ConclusionsThe high prevalence of MG relative to CT and NG supports the incorporation of MG testing into routine sexually transmissible infection screening. The high rate of resistance to macrolides and moxifloxacin raises concerns about treatment options. The good concordance of results between urine and endocervical swabs supports the use of female urine specimens for testing.
The involvement of physician assistants in inpatient care in hospitals in the Netherlands: a cost-effectiveness analysis
Authors: Timmermans Marijke J C , van den Brink Geert T , van Vught Anneke J A H , Adang Eddy , van Berlo Charles L H , Boxtel Kim van , Braunius Weibel W , Janssen Loes , Venema Alyssa , van den Wildenberg Frits J , Wensing Michel , Laurant Miranda G H 
Published: July 2017

ObjectiveTo investigate the cost-effectiveness of substitution of inpatient care from medical doctors (MDs) to physician assistants (PAs).DesignCost-effectiveness analysis embedded within a multicentre, matched-controlled study. The traditional model in which only MDs are employed for inpatient care (MD model) was compared with a mixed model in which, besides MDs, PAs are also employed (PA/MD model).Setting34 hospital wards across the Netherlands.Participants2292 patients were followed from admission until 1 month after discharge. Patients receiving daycare, terminally ill patients and children were excluded.Primary and secondary outcome measuresAll direct healthcare costs from day of admission until 1 month after discharge. Health outcome concerned quality-adjusted life years (QALYs), which was measured with the EuroQol five dimensions questionnaire (EQ-5D).ResultsWe found no significant difference for QALY gain (+0.02, 95% CI −0.01 to 0.05) when comparing the PA/MD model with the MD model. Total costs per patient did not significantly differ between the groups (+€568, 95% CI −€254 to €1391, p=0.175). Regarding the costs per item, a difference of €309 per patient (95% CI €29 to €588, p=0.030) was found in favour of the MD model regarding length of stay. Personnel costs per patient for the provider who is primarily responsible for medical care on the ward were lower on the wards in the PA/MD model (−€11, 95% CI −€16 to −€6, p<0.01).ConclusionsThis study suggests that the cost-effectiveness on wards managed by PAs, in collaboration with MDs, is similar to the care on wards with traditional house staffing. The involvement of PAs may reduce personnel costs, but not overall healthcare costs.Trial registration numberNCT01835444.