bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial
Authors: MacDonald Thomas M , Williams Bryan , Caulfield Mark , Cruickshank J Kennedy , McInnes Gordon , Sever Peter , Webb David J , Mackenzie Isla S , Salsbury Jackie , Morant Steve , Ford Ian , Brown Morris J 
Published: August 2015

IntroductionPrevious studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension.Methods and analysisThe study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg.Ethics and disseminationPATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the results.Trial registration numberUKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.
Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension
Authors: Brown Morris J , Williams Bryan , MacDonald Thomas M , Caulfield Mark , Cruickshank J Kennedy , McInnes Gordon , Sever Peter , Webb David J , Salsbury Jackie , Morant Steve , Ford Ian 
Published: August 2015

IntroductionThiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide.Methods and analysisThis is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. ThePrimary end pointis the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24.Secondary outcomesinclude the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators.Ethics and disseminationPATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal.Trial registration numbersEudract number 2009-010068-41 and clinical trials registration number:NCT02351973.
What are the most effective behaviour change techniques to promote physical activity and/or reduce sedentary behaviour in inactive adults? A systematic review protocol
Authors: Howlett Neil , Trivedi Daksha , Troop Nicholas A , Marie Chater Angel 
Published: August 2015

IntroductionLarge proportions of the population are not meeting recommended levels of physical activity and have increasingly sedentary lifestyles. Low levels of physical activity are predictive of poor health outcomes and time spent sedentary is related to a host of risk factors independently of physical activity levels. Building an evidence base of the best approaches to intervene in the lifestyles of inactive individuals is crucial in preventing long-term disease, disability and higher mortality rates.Methods and analysisSystematic searches will be conducted on all relevant databases (eg, PubMed, Scopus, CINAHL, PsycINFO). Studies will be included if they assess interventions aimed at changing physical activity or sedentary behaviour levels in adults (over 18) who are inactive and do not suffer from chronic conditions. Studies must also be randomised controlled trials (RCTs), have a primary outcome of physical activity or sedentary behaviour, and measure outcomes at least 6 months after intervention completion. Studies will be coded using the Behaviour Change Technique (BCT) taxonomy v1 and Template for Intervention Description and Replication (TIDieR) guidelines. 2 reviewers will independently screen full-text articles and extract data on study characteristics, participants, BCTs, intervention features and outcome measures. Study quality will also be assessed independently by 2 reviewers using the Cochrane risk of bias tool. A meta-analysis will be considered if there is sufficient homogeneity across outcomes. GRADE criteria will be used to assess quality of evidence.DisseminationThis will be the first review to systematically appraise interventions aimed at changing the physical activity or sedentary behaviour of inactive individuals using RCT designs with a 6-month follow-up post-intervention. This review will better inform intervention designers targeting inactive populations and inform the design of a future complex intervention.Review registration numberThis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 17 October 2014 (registration number: CRD42014014321).
Prevention And Treatment of Hypertension With Algorithm-based therapy (PATHWAY) number 2: protocol for a randomised crossover trial to determine optimal treatment for drug-resistant hypertension
Authors: Williams Bryan , MacDonald Thomas M , Caulfield Mark , Cruickshank J Kennedy , McInnes Gordon , Sever Peter , Webb David J , Salsbury Jackie , Morant Steve , Ford Ian , Brown Morris J 
Published: August 2015

IntroductionResistant hypertension is inadequately controlled blood pressure (BP) despite treatment with at least three BP-lowering drugs. A popular hypothesis is that resistant hypertension is due to excessive Na+-retention, and that ‘further diuretic therapy’ will be superior to alternative add-on drugs.Methods and analysisPlacebo-controlled, random crossover study of fourth-line treatment when added to standard (A+C+D) triple drug therapy: ACE inhibitor or Angiotensin receptor blocker (A) +Calcium channel blocker (C)+Diuretic (D). Patients (aged 18–79 years) with clinical systolic BP≥140 mm Hg (135 mm Hg in diabetics) and Home BP Monitoring (HBPM) systolic BP average ≥130 mm Hg on treatment for at least 3 months with maximum tolerated doses of A+C+D are randomised to four consecutive randomly allocated 12-week treatment cycles with an α-blocker, β-blocker, spironolactone and placebo. The hierarchical coprimary end point is the difference in HBPM average systolic BP between (in order) spironolactone and placebo, spironolactone and the average of the other two active drugs, spironolactone and each of the other two drugs. A key secondary outcome is to determine whether plasma renin predicts the BP response to the different drugs. A sample size of 346 (allowing 15% dropouts) will confer 90% power to detect a 3 mm Hg HBPM average systolic BP difference between any two drugs. The study can also detect a 6 mm Hg difference in HBPM average systolic BP between each patient's best and second-best drug predicted by tertile of plasma renin.Ethics and disseminationThe study was initiated in May 2009 and results are expected in 2015. These will provide RCT evidence to support future guideline recommendations for optimal drug treatment of resistant hypertension.Trial registration numberClinicaltrials.govNCT02369081, EUDract number: 2008-007149-30.
A longitudinal population-based analysis of relationship status and mortality in KwaZulu-Natal, South Africa 2001–2011
Authors: Channon Melanie , Hosegood Victoria , McGrath Nuala 
Published: August 2015

BackgroundMortality risk is lower in married than in unmarried men and women. However, little is known about the association between mortality and relationship status in South Africa where marriage rates are low, migration is common, many couples are not co-resident and HIV prevalence is high.MethodUsing demographic surveillance data collected from 2001 to 2011, relationship status was categorised as conjugal (partners belong to the same household), non-conjugal (partners do not belong to the same household) or not partnered. Rates of relationship formation and dissolution were calculated by age and sex. Controlling for antiretroviral treatment (ART) introduction in 2005 as well as education, sex-specific and age-specific Cox proportional hazards models were used to investigate the association between relationship status and (1) all-cause mortality and (2) non-AIDS mortality.ResultsBefore 2005, individuals in conjugal relationships had a lower hazard of all-cause mortality in all age groups than not partnered men and women. Non-conjugal relationships lowered the risk of dying compared with not partnered men and women in fewer age groups. After ART introduction, the protective association of conjugal relationships was weaker but remained generally significant for men and women but not in non-conjugal relationships. In the later period, the association is reversed in young men (20–29 years) with mortality higher in conjugal and non-conjugal relationships compared with men not partnered. The analysis of non-AIDS deaths provided similar results.ConclusionsThe higher degree of social connections within a shared household environment that characterises conjugal relationships affords men and women greater protection against mortality.
Student loans and racial disparities in self-reported sleep duration: evidence from a nationally representative sample of US young adults
Authors: Walsemann Katrina M , Ailshire Jennifer A , Gee Gilbert C 
Published: August 2015

BackgroundStudent loans are the second largest source of personal debt in the USA and may represent an important source of financial strain for many young adults. Little attention has been paid to whether debt is associated with sleep duration, an important health-promoting behaviour. We determine if student loans are associated with sleep duration. Since black young adults are more likely to have student debt and sleep less, we also consider whether this association varies by race.MethodsData come from the US National Longitudinal Survey of Youth 1997. The main analytic sample includes 4714 respondents who were ever enrolled in college and who reported on sleep duration in 2010. Most respondents had completed their college education by 2010, when respondents were 25 to 31 years old. Multivariable linear regression models assessed the cross-sectional association between student loans accumulated over the course of college and sleep duration in 2010, as well as between student debt at age 25 and sleep duration in 2010.ResultsBlack young adults with greater amounts of student loans or more student debt reported shorter sleep duration, controlling for occupation, hours worked, household income, parental net worth, marital status, number of children in the household and other sociodemographic and health indicators. There was no association between student loans or debt with sleep for white or latino adults and other racial/ethnic groups.ConclusionsStudent loans may contribute to racial inequities in sleep duration. Our findings also suggest that the student debt crisis may have important implications for individuals’ sleep, specifically and public health, more broadly.
Clinical, morphological, and hemodynamic independent characteristic factors for rupture of posterior communicating artery aneurysms
Authors: Zhang Ying , Jing Linkai , Liu Jian , Li Chuanhui , Fan Jixing , Wang Shengzhang , Li Haiyun , Yang Xinjian 
Published: August 2015

ObjectiveTo identify clinical, morphological, and hemodynamic independent characteristic factors that discriminate posterior communicating artery (PCoA) aneurysm rupture status.Methods173 patients with single PCoA aneurysms (108 ruptured, 65 unruptured) between January 2012 and June 2014 were retrospectively collected. Patient-specific models based on their three-dimensional digital subtraction angiography images were constructed and analyzed by a computational fluid dynamic method. All variables were analyzed by univariate analysis and multivariate logistic regression analysis.ResultsTwo clinical factors (younger age and atherosclerosis), three morphological factors (higher aspect ratio, bifurcation type, and irregular shape), and six hemodynamic factors (lower mean and minimum wall shear stress, higher oscillatory shear index, a greater portion of area under low wall shear stress, unstable and complex flow pattern) were significantly associated with PCoA aneurysm rupture. Independent factors characterizing the rupture status were identified as age (OR 0.956, p=0.015), irregular shape (OR 6.709, p<0.001), and minimum wall shear stress (OR 0.001, p=0.038).ConclusionsWe combined clinical, morphological, and hemodynamic characteristics analysis and found the three strongest independent factors for PCoA aneurysm rupture were younger age, irregular shape, and low minimum wall shear stress. This may be useful for guiding risk assessments and subsequent treatment decisions for PCoA aneurysms.
Exocrine pancreatic insufficiency, MRI of the pancreas and serum nutritional markers in patients with coeliac disease
Authors: Vujasinovic Miroslav , Tepes Bojan , Volfand Jasna , Rudolf Sasa 
Published: August 2015

ABSTRACT

Objectives
To determine whether exocrine pancreatic function is impaired in patients with coeliac disease (CD) in our population and to evaluate its clinical importance.

Methods
Pancreatic exocrine function was determined by measuring faecal elastase-1 (FE) concentration. CD was diagnosed by serological testing using IgA anti-tissue transglutaminase antibody (IgAtTg) and small bowel biopsy using the Marsh classification. MRI of the pancreas was performed to evaluate any morphological changes. The study took place from January 2012 to December 2013.

Results
90 patients (73 women and 17 men) of mean age 43.8±17.7 years (range 20–80) were included in the study. Mean time from CD confirmation was 5.8±0.7 years (range 1–25). Exocrine pancreatic insufficiency (EPI) was diagnosed in four (4.4%) patients (one with mild EPI and three with severe EPI). MRI showed no morphological changes in any of the four patients. In all patients with EPI at least one serological nutritional marker was below the lower limit of normal.

Conclusions
EPI is present in a small number of patients with CD. EPI should be excluded in all patients with CD in the presence of overt malnutrition or in cases of persistent gastrointestinal symptoms despite a gluten-free diet. Measurement of a serum nutritional panel, regardless of the presence of clinical symptoms of EPI, can be of clinical importance. MRI should be performed to exclude any morphological change in the pancreas.
Examination of the musculoskeletal system: junior doctors’ perceptions of the usefulness of the Gait, Arms, Legs and Spine (GALS) technique
Authors: Patel Veena , Patel Prashanth , Jeffery Rachel , Taylor James , Thomas Hywel 
Published: August 2015

ABSTRACT

Background
Musculoskeletal (MSK) conditions affect millions of people around the world. Gait, Arms, Legs and Spine (GALS) is a simple and useful screening tool for routine MSK examination in hospitals and general practice and has been integrated into the undergraduate medical curriculum. Despite this, there is evidence that doctors lack competency in MSK examination and that GALS are underperformed routinely.

Objectives
The study explored the views of junior doctors (JDs) on how they were taught MSK examination as undergraduates; the usefulness of GALS as a technique for excluding significant MSK problems; why MSK examination was often poorly carried out and how this could be improved.

Methods
A qualitative study was performed with data gathered through focus group interviews from 32 JDs working in two acute NHS hospitals. Six interviews were conducted over a 6-week period from mid-June to the end of July in consecutive years 2013 and 2014.

Results
Ninety JDs were invited to participate in the focus group interviews; 32 (36%) agreed to participate, 28 (88%) of whom had graduated in the UK. The perception of JDs was that undergraduate training for GALS and regional MSK examination was adequate, but reasons for lack of MSK competency in the workplace are multifactorial and complex.

Conclusions
Proposing more practical and interactive sessions to reinforce MSK skills during postgraduate training may not resolve issues of MSK competency among JDs. Recognition of the complexity of workplace learning and the influence of tacit learning is required if MSK competency is to be enhanced.
3D characterization of fracture systems using Terrestrial Laser Scanning: an example from the Lewisian basement of NW Scotland
Authors: Pless J. C. , McCaffrey K. J. W. , Jones R. R. , Holdsworth R. E. , Conway A. , Krabbendam M. 
Published: August 2015

Abstract
Fractured gneiss lithologies form a basement-cored high, the Rona Ridge in the Faroe–Shetland Basin. Basement structures are known to play an important role in the petroleum system for the overlying giant Clair Field. An onshore analogue exposure in the Lewisian Gneiss Complex at Kinlochbervie in NW Scotland provides an example of a hanging-wall damage zone of a large basement-hosted normal fault. In this study, we used remote sensing (2D), outcrop line sample methods (1D) and a virtual outcrop created by terrestrial laser scanning methods (3D) to characterize spatial variations of the fracture systems. Spacing distributions from 1D line samples collected from exposures and pseudo-wells constructed through the virtual outcrop show power-law distributions. The virtual outcrop data enable us to extend the scale-invariant description from 1 to 3 orders of magnitude. We developed a novel box-counting workflow to provide an assessment of 2- and 3D variations in the fracture properties. Fracture density and fractal dimension are elevated whereas the number of intersections is decreased within a 220 m-wide volume adjacent to the fault. We discuss how the methods and results from this study can aid the development of analogue for basement reservoirs in the offshore UK continental shelf.
Randomized Phase II Study of Adjuvant Chemotherapy with Long-term S-1 versus Cisplatin+S-1 in Completely Resected Stage II–IIIA Non–Small Cell Lung Cancer
Authors: Iwamoto Yasuo , Mitsudomi Tetsuya , Sakai Kazuko , Yamanaka Takeharu , Yoshioka Hiroshige , Takahama Makoto , Yoshimura Masahiro , Yoshino Ichiro , Takeda Masayuki , Sugawara Shunichi , Kawaguchi Tomoya , Takahashi Toshiaki , Ohta Mitsunori , Ichinose Yukito , Atagi Shinji , Okada Morihito , Saka Hideo , Nakagawa Kazuhiko , Nakanishi Yoichi , Nishio Kazuto 
Published: August 2015

Abstract
Purpose: The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non–small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome.
Experimental Design: A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m2 twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m2) on day 1 plus oral S-1 (40 mg/m2 twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity.
Results: The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3–74.0%) in the S group and 58.1% (95% CI, 47.7–67.2%) in the CS group. The only gene with interaction of P &lt; 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine.
Conclusions: Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy. Clin Cancer Res; 21(23); 5245–52. ©2015 AACR.
CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer
Authors: Leclerc Bruno G. , Charlebois Roxanne , Chouinard Guillaume , Allard Bertrand , Pommey Sandra , Saad Fred , Stagg John 
Published: August 2015

Abstract
Purpose: CD73 is an adenosine-generating ecto-enzyme that suppresses antitumor immunity in mouse models of cancer, including prostate cancer. Although high levels of CD73 are associated with poor prognosis in various types of cancer, the clinical impact of CD73 in prostate cancer remains unclear.
Experimental Design: We evaluated the prognostic value of CD73 protein expression and CD8+ cell density in 285 cases of prostate cancer on tissue microarray (TMA). Normal adjacent and tumor tissues were evaluated in duplicates.
Results: Univariate and multivariate analyses revealed that high levels of CD73 in normal adjacent prostate epithelium were significantly associated with shorter biochemical recurrence (BCR)-free survival. Notably, CD73 expression in normal epithelium conferred a negative prognostic value to prostate-infiltrating CD8+ cells. Surprisingly, high levels of CD73 in the tumor stroma were associated with longer BCR-free survival in univariate analysis. In vitro studies revealed that adenosine signaling inhibited NF-κB activity in human prostate cancer cells via A2B adenosine receptors. Consistent with these results, CD73 expression in the prostate tumor stroma negatively correlated with p65 expression in the nuclei of prostate tumor cells.
Conclusions: Our study revealed that CD73 is an independent prognostic factor in prostate cancer. Our data support a model in which CD73 expression in the prostate epithelium suppresses immunosurveillance by CD8+ T cells, whereas CD73 expression in the tumor stroma reduces NF-κB signaling in tumor cells via A2B adenosine receptor signaling. CD73 expression, including in normal adjacent prostate epithelium, can thus effectively discriminate between aggressive and indolent forms of prostate cancer. Clin Cancer Res; 22(1); 158–66. ©2015 AACR.