bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quantitative analysis of the prevalence of clinical depression and anxiety in patients with prostate cancer undergoing active surveillance
Authors: Watts Sam , Leydon Geraldine , Eyles Caroline , Moore Caroline M , Richardson Alison , Birch Brian , Prescott Philip , Powell Catrin , Lewith George 
Published: May 2015

ObjectiveTo quantitatively determine the prevalence of anxiety and depression in men on active surveillance (AS).DesignCross-sectional questionnaire survey.SettingSecondary care prostate cancer (PCa) clinics across South, Central and Western England.Participants313 men from a total sample of 426 with a histological diagnosis of PCa currently managed with AS were identified from seven UK urology departments. The mean age of respondents was 70 (51–86) years with the majority (76%) being married or in civil partnerships. 94% of responders were of white British ethnicity.Primary outcome measuresThe prevalence of clinically meaningful depression and anxiety as assessed by the Hospital Anxiety and Depression Scale (HADS; score ≥8/21).Secondary outcome measuresPatient demographic data (age, employment, relationship, ethnic and educational status). Each demographic variable was cross-tabulated against patients identified as depressed or anxious to allow for the identification of variables that were significantly associated with depression and anxiety. In order to determine predictors for depression and anxiety among the demographic variables, logistic regression analyses were conducted, with p<0.05 considered as indicating statistical significance.ResultsThe prevalence of clinical anxiety and depression as determined via the HADS (HADS ≥8) was 23% (n=73) and 12.5% (n=39), respectively. Published data from men in the general population of similar age has shown prevalence rates of 8% and 6%, respectively, indicating a twofold increase in depression and a threefold increase in anxiety among AS patients. Our findings also suggest that AS patients experience substantially greater levels of anxiety than patients with PCa treated radically. The only demographic predictor for anxiety or depression was divorce.ConclusionsPatients with PCa managed with AS experienced substantially higher rates of anxiety and depression than that expected in the general population. Strategies to address this are needed to improve the management of this population and their quality of life.
Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study
Authors: Gallet Romain , Meyer Guy , Ternacle Julien , Biendel Caroline , Brunet Anne , Meneveau Nicolas , Rosario Roger , Couturaud Francis , Sebbane Mustapha , Lamblin Nicolas , Bouvaist Helene , Coste Pierre , Maitre Bernard , Bastuji-Garin Sylvie , Dubois-Rande Jean-Luc , Lim Pascal 
Published: May 2015

IntroductionIn acute pulmonary embolism (PE), poor outcome is usually related to right ventricular (RV) failure due to the increase in RV afterload. Treatment of PE with RV failure without shock is controversial and usually relies on fluid expansion to increase RV preload. However, several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilation and ischaemia, and increase left ventricular compression by RV dilation. By reducing RV enlargement, diuretic treatment may break this vicious circle and provide early improvement in normotensive patients referred for acute PE with RV failure.Methods and analysisTheDiuretic versus placebo inPulmonaryEmbolism withRight ventricular enlargement trial (DiPER) is a prospective, multicentre, randomised (1:1), double-blind, placebo controlled study assessing the superiority of furosemide as compared with placebo in normotensive patients with confirmed acute PE and RV dilation (diagnosed on echocardiography or CT of the chest) and positive brain natriuretic peptide result. The primary end point will be a combined clinical criterion derived from simplified Pulmonary Embolism Severity Index (PESI) score and evaluated at 24 h. It will include: (1) urine output >0.5 mL/kg/min for the past 24 h; (2) heart rate <110 bpm; (3) systolic blood pressure >100 mm Hg and (4) arterial oxyhaemoglobin level >90%. Thirty-day major cardiac events defined as death, cardiac arrest, mechanical ventilation, need for catecholamine and thrombolysis, will be evaluated as a secondary end point. Assuming an increase of 30% in the primary end point with furosemide and a β risk of 10%, 270 patients will be required.Ethics and disseminationEthical approval was received from the ethical committee of Ile de France (2014-001090-14). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations.Trial registration numberNCT02268903.
Teamwork, communication and safety climate: a systematic review of interventions to improve surgical culture
Authors: Sacks Greg D , Shannon Evan M , Dawes Aaron J , Rollo Johnathon C , Nguyen David K , Russell Marcia M , Ko Clifford Y , Maggard-Gibbons Melinda A 
Published: May 2015

ObjectivesTo define the target domains of culture-improvement interventions, to assess the impact of these interventions on surgical culture and to determine whether culture improvements lead to better patient outcomes and improved healthcare efficiency.BackgroundHealthcare systems are investing considerable resources in improving workplace culture. It remains unclear whether these interventions, when aimed at surgical care, are successful and whether they are associated with changes in patient outcomes.MethodsPubMed, Cochrane, Web of Science and Scopus databases were searched from January 1980 to January 2015. We included studies on interventions that aimed to improve surgical culture, defined as the interpersonal, social and organisational factors that affect the healthcare environment and patient care. The quality of studies was assessed using an adapted tool to focus the review on higher-quality studies. Due to study heterogeneity, findings were narratively reviewed.FindingsThe 47 studies meeting inclusion criteria (4 randomised trials and 10 moderate-quality observational studies) reported on interventions that targeted three domains of culture: teamwork (n=28), communication (n=26) and safety climate (n=19); several targeted more than one domain. All moderate-quality studies showed improvements in at least one of these domains. Two studies also demonstrated improvements in patient outcomes, such as reduced postoperative complications and even reduced postoperative mortality (absolute risk reduction 1.7%). Two studies reported improvements in healthcare efficiency, including fewer operating room delays. These findings were supported by similar results from low-quality studies.ConclusionsThe literature provides promising evidence for various strategies to improve surgical culture, although these approaches differ in terms of the interventions employed as well as the techniques used to measure culture. Nevertheless, culture improvement appears to be associated with other positive effects, including better patient outcomes and enhanced healthcare efficiency.Trial registration numberCRD42013005987.
Infection prevention and control in nursing homes: a qualitative study of decision-making regarding isolation-based practices
Authors: Cohen Catherine Crawford , Pogorzelska-Maziarz Monika , Herzig Carolyn T A , Carter Eileen J , Bjarnadottir Ragnhildur , Semeraro Patricia , Travers Jasmine L , Stone Patricia W 
Published: May 2015

BackgroundIsolation-based practices in nursing homes (NHs) differ from those in acute care. NHs must promote quality of life while preventing infection transmission. Practices used in NHs to reconcile these goals of care have not been characterised.PurposeTo explore decision-making in isolation-based infection prevention and control practices in NHs.MethodsA qualitative study was conducted with staff (eg, staff nurses, infection prevention directors and directors of nursing) employed in purposefully sampled US NHs. Semistructured, role-specific interview guides were developed and interviews were digitally recorded, transcribed verbatim and analysed using directed content analysis. The research team discussed emerging themes in weekly meetings to confirm consensus.ResultsWe inferred from 73 interviews in 10 NHs that there was variation between NHs in practices regarding who was isolated, when isolation-based practices took place, how they were implemented, and how they were tailored for each resident. Interviewees’ decision-making depended on staff perceptions of acceptable transmission risk and resident quality of life. NH resources also influenced decision-making, including availability of private rooms, extent to which staff can devote time to isolation-based practices and communication tools. A lack of understanding of key infection prevention and control concepts was also revealed.Conclusions and implicationsCurrent clinical guidelines are not specific enough to ensure consistent practice that meets care goals and resource constraints in NHs. However, new epidemiological research regarding effectiveness of varying isolation practices in this setting is needed to inform clinical practice. Further, additional infection prevention and control education for NH staff may be required.
Endoscopic biliary stenting in irretrievable common bile duct stones: stent exchange or expectant management—tertiary-centre experience and systematic review
Authors: Mohammed Noor , Pinder Matthew , Harris Keith , Everett Simon M 
Published: May 2015

IntroductionConventional endoscopic duct clearance may not be possible in up to 10%–15% of common bile duct stones (CBDS). Sphincterotomy and biliary drainage by endoprosthesis have for many years been the mainstay of management in irretrievable stones. Recent years have seen the advent of sphincteroplasty or cholangioscopically-guided electrohydraulic lithotripsy (EHL) permitting duct clearance in majority of cases. However, when bile duct clearance is not possible, options include long-term stenting followed by elective stent exchange (ESE) 6–12 monthly or permanent stent insertion (PSI) in selected cases, but it is not clear which management strategy among ESE and PSI is preferable.Methods and aimsA retrospective review of all patients in Leeds Teaching Hospitals NHS Trust who underwent plastic stent insertion for biliary access for difficult CBDS from January 2006 to December 2011 was undertaken. Adult patients with irretrievable CBDS who had plastic stent insertions throughout the follow-up period were included. Patients who underwent PSI and ESE annually were retrospectively reviewed to determine the long-term outcomes. A detailed systematic review was also performed, examining the outcomes of CBDS managed with stents.ResultsDuring the study period, 674 patients underwent 1769 biliary-stent-related procedures; of which, 246 patients met our inclusion criteria. 201 patients had subsequent duct clearance. 45 patients were, therefore, included in the final analysis, 28 of whom underwent annual ESEs and 17 PSIs. Patients in the PSI group had higher American Society of Anesthesiologists (ASA) scores compared with the ESE group. In the PSI group, 9/17 patients presented acutely with blocked stents, 5 of whom presented within 12 months. 2/9 patients were severely ill and died within a fortnight following the repeat endoscopic retrograde cholangiopancreatography (ERCP). In the ESE group, 4/28 patients had duct clearance in subsequent ERCPs, 1/28 patient presented with a blocked stent, and no biliary-related deaths were observed. The mean numbers of ERCPs performed were 0.52 and 1.95 in the PSI and ESE groups, respectively.ConclusionsOver 50% of patients treated with long-term stenting re-presented acutely with stent blockage, though many of these were before 12 months, meaning planned stent exchange would not have affected the outcome. Duct clearance using all possible modalities is the preferred option, but where not possible, management with biliary stenting either with elective exchange or permanent stenting remains a possibility for carefully selected patients, though maybe best suited to those with limited life expectancy.
A randomised controlled trial of low-dose aspirin for the prevention of fractures in healthy older people: protocol for the ASPREE-Fracture substudy
Authors: Barker Anna L , McNeil John J , Seeman Ego , Ward Stephanie A , Sanders Kerrie M , Khosla Sundeep , Cumming Robert G , Pasco Julie A , Bohensky Megan A , Ebeling Peter R , Woods Robyn L , Lockery Jessica E , Wolfe Rory , Talevski Jason 
Published: May 2015

BackgroundDisability, mortality and healthcare burden from fractures in older people is a growing problem worldwide. Observational studies suggest that aspirin may reduce fracture risk. While these studies provide room for optimism, randomised controlled trials are needed. This paper describes the rationale and design of the ASPirin in Reducing Events in the Elderly (ASPREE)-Fracture substudy, which aims to determine whether daily low-dose aspirin decreases fracture risk in healthy older people.MethodsASPREE is a double-blind, randomised, placebo-controlled primary prevention trial designed to assess whether daily active treatment using low-dose aspirin extends the duration of disability-free and dementia-free life in 19 000 healthy older people recruited from Australian and US community settings. This substudy extends the ASPREE trial data collection to determine the effect of daily low-dose aspirin on fracture and fall-related hospital presentation risk in the 16 500 ASPREE participants aged ≥70 years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100 mg) versus a matching placebo, randomised on a 1:1 basis. The primary outcome for this substudy is the occurrence of any fracture—vertebral, hip and non-vert-non-hip—occurring post randomisation. Fall-related hospital presentations are a secondary outcome.DiscussionThis substudy will determine whether a widely available, simple and inexpensive health intervention—aspirin—reduces the risk of fractures in older Australians. If it is demonstrated to safely reduce the risk of fractures and serious falls, it is possible that aspirin might provide a means of fracture prevention.Trial registration numberThe protocol for this substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).
Neighbourhood racial/ethnic composition and segregation and trajectories of cognitive decline among US older adults
Authors: Kovalchik Stephanie A , Slaughter Mary E , Miles Jeremy , Friedman Esther M , Shih Regina A 
Published: May 2015

BackgroundThe influence of the sociodemographic context of one's environment on cognitive ageing is not well understood.MethodsWe examined differences in cognitive trajectories according to the racial/ethnic characteristics of the residential environment. On the basis of 63 996 person-years of data from a nationally representative cohort of 6150 adults over the age of 50 years from the Health and Retirement Study, we used multivariate linear mixed models to determine the effect of neighbourhood racial/ethnic composition and county-level segregation on cognitive function and cognitive decline over a 10-year period.ResultsIn models adjusting for individual demographic and health characteristics, Hispanic composition had a significant positive association with cognitive function (standardised β=0.136, p<0.05) and moderate evidence of an association with greater cognitive decline (standardised β=−0.014, p=0.09). Greater Hispanic-white segregation was associated with statistically significant higher cognitive function at baseline (standardised β=0.099, p<0.001) and greater cognitive decline (standardised β=−0.011, p<0.01). For a 20 percentage-point increase in Hispanic composition and segregation, the observed associations implied 1 and 1.25 additional years of cognitive ageing over 10 years, respectively. These effects did not differ by individual race/ethnicity and were not explained by neighbourhood socioeconomic status or neighbourhood selection. Black composition and black-white segregation did not have a significant influence on cognitive ageing.DiscussionThis study demonstrates disparities in the progression of cognitive ageing according to racial/ethnic characteristics of the neighbourhood environment.
Groin complications in endovascular mechanical thrombectomy for acute ischemic stroke: a 10-year single center experience
Authors: Shah Veer A , Martin Coleman O , Hawkins Angela M , Holloway William E , Junna Shilpa , Akhtar Naveed 
Published: May 2015

BackgroundThe increasing utilization of balloon guide catheters (BGCs) in thrombectomy therapy for ischemic stroke has led to concerns about large-bore sheaths causing vascular groin complications.Objective To retrospectively assess the impact of large large-bore sheaths and vascular closure devices on groin complication rates at a comprehensive stroke center over a 10-year period.MethodsRadiological and clinical records of patients with acute ischemic stroke who underwent mechanical endovascular therapy with an 8Fr or larger sheaths were reviewed. A groin complication was defined as the formation of a groin hematoma, retroperitoneal hematoma, femoral artery pseudoaneurysm, or the need for surgical repair. Information collected included size of sheath, type of hemostatic device, and anticoagulation status of the patient. Blood bank records were also analyzed to identify patients who may have had an undocumented blood transfusion for a groin hematoma.ResultsA total of 472 patients with acute ischemic stroke who underwent mechanical thrombectomy with a sheath and BGC sized 8Fr or larger were identified. 260 patients (55.1%) had tissue Plasminogen Activator (tPA) administered as part of stroke treatment. Vascular closure devices were used in 97.9% of cases (n=462). Two patients were identified who had definite groin complications and a further two were included as having possible complications. There was a very low rate of clinically significant groin complications (0.4–0.8%) associated with the use of large-bore sheaths.ConclusionsThese findings suggest that concerns for groin complications should not preclude the use of BGCs and large-bore sheaths in mechanical thrombectomy for acute ischemic stroke.
Troponins and other biomarkers in the early diagnosis of acute myocardial infarction
Authors: Maznyczka Annette , Kaier Thomas , Marber Michael 
Published: May 2015

ABSTRACT
Chest pain is a common presenting symptom; however, the majority of emergency chest pain admissions are not due to acute myocardial infarction (AMI). AMI can be life threatening and early diagnosis or rule out of AMI might potentially improve morbidity and mortality, as well as reduce time to decision and therefore overall treatment costs. High-sensitivity troponin (hs-troponin) assays have been developed that enable precise quantification of extremely low troponin concentrations. Such hs-troponin assays are recommended in early rule-out protocols for AMI, when measured at presentation and again at 3–6 h. However, troponin is less than ideally suited for early diagnosis of acute myocardial injury because of its slow rise, late peak and low specificity for coronary plaque rupture. A new biomarker with a more rapid elevation to peak concentration than hs-troponin and lower background levels in patients with chronic cardiovascular conditions would be a preferred diagnostic test. This review discusses the development of hs-troponin assays and other biomarkers, evaluates their place in the early diagnosis of AMI, discusses troponin elevation without AMI and discusses current guideline recommendations.
Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies
Authors: Hanania Nicola A , Noonan Michael , Corren Jonathan , Korenblat Phillip , Zheng Yanan , Fischer Saloumeh K , Cheu Melissa , Putnam Wendy S , Murray Elaine , Scheerens Heleen , Holweg Cecile TJ , Maciuca Romeo , Gray Sarah , Doyle Ramona , McClintock Dana , Olsson Julie , Matthews John G , Yen Karl 
Published: May 2015

IntroductionIn a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity.MethodsLUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller. Patients received lebrikizumab 37.5, 125, 250 mg or placebo subcutaneously every four weeks. The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period. Analyses were performed on prespecified subgroups based on baseline serum periostin levels. Following the discovery of a host-cell impurity in the study drug material, protocols were amended to convert from phase III to phase IIb. Subsequently, dosing of study medication was discontinued early as a precautionary measure. The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies.ResultsThe median duration of treatment was approximately 24 weeks. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose–response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV1 in periostin-high patients (all doses: 9.1% placebo-adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement). Lebrikizumab was well tolerated and no clinically important safety signals were observed.ConclusionsThese data are consistent with, and extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment.Trial registration numbersThe LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov
TP53 Silencing Bypasses Growth Arrest of BRAFV600E-Induced Lung Tumor Cells in a Two-Switch Model of Lung Tumorigenesis
Authors: Shai Anny , Dankort David , Juan Joseph , Green Shon , McMahon Martin 
Published: May 2015

Abstract
Lung carcinogenesis is a multistep process in which normal lung epithelial cells are converted to cancer cells through the sequential acquisition of multiple genetic or epigenetic events. Despite the utility of current genetically engineered mouse (GEM) models of lung cancer, most do not allow temporal dissociation of the cardinal events involved in lung tumor initiation and cancer progression. Here we describe a novel two-switch GEM model for BRAFV600E-induced lung carcinogenesis allowing temporal dissociation of these processes. In mice carrying a Flp recombinase-activated allele of Braf (BrafFA) in conjunction with Cre-regulated alleles of Trp53, Cdkn2a, or c-MYC, we demonstrate that secondary genetic events can promote bypass of the senescence-like proliferative arrest displayed by BRAFV600E-induced lung adenomas, leading to malignant progression. Moreover, restoring or activating TP53 in cultured BRAFV600E/TP53Null or BRAFV600E/INK4A-ARFNull lung cancer cells triggered a G1 cell-cycle arrest regardless of p19ARF status. Perhaps surprisingly, neither senescence nor apoptosis was observed upon TP53 restoration. Our results establish a central function for the TP53 pathway in restricting lung cancer development, highlighting the mechanisms that limit malignant progression of BRAFV600E-initiated tumors. Cancer Res; 75(15); 3167–80. ©2015 AACR.