bluuebunny/crossref_metadata_2025_split huggingface dataset:
A validation study of a new classification algorithm to identify rheumatoid arthritis using administrative health databases: case–control and cohort diagnostic accuracy studies. Results from the RECord linkage On Rheumatic Diseases study of the Italian Society for Rheumatology
Authors: Carrara Greta , Scirè Carlo A , Zambon Antonella , Cimmino Marco A , Cerra Carlo , Caprioli Marta , Cagnotto Giovanni , Nicotra Federica , Arfè Andrea , Migliazza Simona , Corrao Giovanni , Minisola Giovanni , Montecucco Carlomaurizio 
Published: January 2015

ObjectivesTo develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region.DesignCase–control and cohort diagnostic accuracy study.MethodsIn a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region.ResultsThe algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%).ConclusionsAHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.
Hazardous alcohol consumption among university students in Ireland: a cross-sectional study
Authors: Davoren Martin P , Shiely Frances , Byrne Michael , Perry Ivan J 
Published: January 2015

ObjectiveThere is considerable evidence of a cultural shift towards heavier alcohol consumption among university students, especially women. The aim of this study is to investigate the prevalence and correlates of hazardous alcohol consumption (HAC) among university students with particular reference to gender and to compare different modes of data collection in this population.SettingA large Irish university.DesignA cross-sectional study using a classroom distributed paper questionnaire.ParticipantsA total of 2275 undergraduates completed the classroom survey, 84% of those in class and 51% of those registered for the relevant module.Main outcome measuresPrevalence of HAC measured using the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) and the proportion of university students reporting 1 or more of 13 adverse consequences linked to HAC. HAC was defined as an AUDIT-C score of 6 or more among males and 5 or more among females.ResultsIn the classroom sample, 66.4% (95% CI 64.4 to 68.3) reported HAC (65.2% men and 67.3% women). In women, 57.4% met HAC thresholds for men. Similar patterns of adverse consequences were observed among men and women. Students with a hazardous consumption pattern were more likely to report smoking, illicit drug use and being sexually active.ConclusionsThe findings highlight the high prevalence of HAC among university students relative to the general population. Public policy measures require review to tackle the short-term and long-term risks to physical, mental and social health and well-being.
Understanding the motivation and performance of community health volunteers involved in the delivery of health programmes in Kampala, Uganda: a realist evaluation protocol
Authors: Vareilles Gaëlle , Pommier Jeanine , Kane Sumit , Pictet Gabriel , Marchal Bruno 
Published: January 2015

IntroductionThe recruitment of community health volunteers to support the delivery of health programmes is a well-established approach in many countries, particularly where health services are not readily available. However, studies on management of volunteers are scarce and current research on human resource management of volunteers faces methodological challenges. This paper presents the protocol of a realist evaluation that aims at identifying the factors influencing the performance of community health volunteers involved in the delivery of a Red Cross immunisation programme in Kampala (Uganda) with a specific focus on motivation.Methods and analysisThe realist evaluation cycle structures the protocol. To develop the theoretical basis for the evaluation, the authors conducted interviews and reviewed the literature on community health volunteers’ performance, management and organisational behaviour. This led to the formulation of the initial programme theory, which links the intervention inputs (capacity-building strategies) to the expected outcomes (positive work behaviour) with mechanisms that point in the direction of drivers of motivation. The contextual elements include components such as organisational culture, resource availability, etc. A case study design will be adopted. We define a case as a Red Cross branch, run by a programme manager, and will select two cases at the district level in Kampala. Mixed methods will be used in data collection, including individual interviews of volunteers, participant observation and document review. The thematic analysis will be based on the initial programme theory and will seek for context-mechanism-outcome configurations. Findings from the two cases will be compared.DiscussionWe discuss the scope for applying realist evaluation and the methodological challenges we encountered in developing this protocol.Ethics and disseminationThe study was approved by the Ethical Committee at Rennes University Hospital, France. Results will be published in scientific journals, and communicated to respondents and relevant institutions.
The POPPY Research Programme protocol: investigating opioid utilisation, costs and patterns of extramedical use in Australia
Authors: Degenhardt Louisa , Blanch Bianca , Gisev Natasa , Larance Briony , Pearson Sallie 
Published: January 2015

IntroductionOpioid prescribing is increasing in many countries. In Australia, there is limited research on patterns of prescribing and access, or the outcomes associated with this use. The aim of this research programme is to use national dispensing data to estimate opioid use and costs, including problematic or extramedical use in the Australian population.Methods and analysisIn a cohort of persons dispensed at least one opioid in 2013, we will estimate monthly utilisation and costs of prescribed opioids, overall and according to individual opioid formulations and strengths. In a cohort of new opioid users, commencing therapy between 1 July 2009 and 31 December 2013, we will examine patterns of opioid use including initiation of therapy, duration of treatment and concomitant use of opioids and other prescribed medicines. We will also examine patterns of extramedical opioid use based on indicators including excess dosing, use of more than one opioid concomitantly, doctor/pharmacy shopping and accelerated time to prescription refill.Ethics and disseminationThis protocol was approved by the NSW Population and Health Services Ethics Committee (March 2014) and data access approved by the Department of Human Services External Review Evaluation Committee (June 2014). This will be one of the first comprehensive Australian studies with the capability to investigate individual patterns of use and track extramedical use. In the first instance our analysis will be based on 5 years of dispensing data but will be expanded with ongoing annual data updates. This research has the capability to contribute significantly to pharmaceutical policy within Australia and globally. In particular, the trajectory of extramedical prescription-opioid use has been the subject of limited research to date. The results of this research will be published widely in general medical, pharmacoepidemiology, addiction and psychiatry journals.
Protocol of a longitudinal cohort study on physical activity behaviour in physically disabled patients participating in a rehabilitation counselling programme: ReSpAct
Authors: Alingh Rolinde A , Hoekstra Femke , van der Schans Cees P , Hettinga Florentina J , Dekker Rienk , van der Woude Lucas H V 
Published: January 2015

IntroductionStimulating physical activity behaviour in persons with a physical disability is important, especially after discharge from rehabilitation. A tailored counselling programme covering both the period of the rehabilitation treatment and the first months at home seems on the average effective. However, a considerable variation in response is observed in the sense that some patients show a relevant beneficial response while others show no or only a small response on physical activity behaviour. The Rehabilitation, Sports and Active lifestyle (ReSpAct) study aims to estimate the associations of patient and programme characteristics with patients’ physical activity behaviour after their participation in a tailored counselling programme.Methods and analysisA questionnaire-based nationwide longitudinal prospective cohort study is conducted. Participants are recruited from 18 rehabilitation centres and hospitals in The Netherlands. 2000 participants with a physical disability or chronic disease will be followed during and after their participation in a tailored counselling programme. Programme outcomes on physical activity behaviour and patient as well as programme characteristics that may be associated with differences in physical activity behaviour after programme completion are being assessed. Data collection takes place at baseline and 14, 33 and 52 weeks after discharge from rehabilitation.Ethics and disseminationThe study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Groningen and at individual participating institutions. All participants give written informed consent. The study results will provide new insights into factors that may help explain the differences in physical activity behaviour of patients with a physical disability after they have participated in the same physical activity and sports stimulation programme. Thereby, it will support healthcare professionals to tailor their guidance and care to individual patients in order to stimulate physical activity after discharge in a more efficient and effective way.Trial registration numberNTR3961.
Predictors of infection from dog bite wounds: which patients may benefit from prophylactic antibiotics?
Authors: Tabaka Meg E , Quinn James V , Kohn Michael A , Polevoi Steven K 
Published: January 2015

ObjectivesTo determine a current infection rate of dog bite wounds and predictors of wounds at risk for infection that may benefit from prophylactic antibiotics.MethodsA prospective multicentre observational study was conducted over 4.5 years. At the time of treatment Emergency Physicians completed a structured data form evaluating patient, wound and treatment characteristics of patients with dog bite wounds. Patients were followed up at 30 days to assess for infection. Predictor variables were analysed with univariate analysis, using either χ2, parametric or nonparametric methods where appropriate. Significant variables and those with important interactions on univariate analysis were considered in a logistic regression (LR) analysis.Results495 patients with dog bites were enrolled and 345 had complete follow-up. Eighteen patients (5.2%, 95% CI 3.1% to 8.1%) had bites that became infected. On univariate analysis, only puncture wounds were found to be significantly associated with infection RR 2.8 (95% CI 1.2 to 6.9). However, location and wound closure met criteria for entry into the model having important interactions; facial wounds had a higher risk of infection than anticipated but were also more likely to be closed (p < 0.0001). A LR model considering puncture wounds, wound closure and wound location found that puncture wounds (OR 4.1 [95% CI 1.4 to 11.7]) and wound closure (OR 3.1 [95% CI 1.03 to 9.0]) were independent predictors of infection. The incidence of infection in wounds that were not punctured or closed during treatment was only 2.6% (95% CI 0.7% to 6.5%).ConclusionsPuncture wounds or wounds closed during treatment are dog bite wounds at a high risk of infection and should be considered for treatment with prophylactic antibiotics.
Systematic analysis of missed colorectal cancer cases and common pitfalls in diagnosis
Authors: Vaughan-Shaw P G , Aung M , Knight H , Williams T , Borley N R , Wheeler J M D 
Published: January 2015

BackgroundMissed colorectal cancer on endoscopic or radiological investigations may delay diagnosis and impact outcome. This study audits incidence of previous investigations in patients with colorectal cancer, considers outcome in ‘missed’ cancer cases and examines the diagnostic pathway in the derived case series to identify common pitfalls in diagnosis.MethodsPatients diagnosed with colorectal cancer in 2011 at a single National Health Service (NHS) Trust were reviewed. Incidence of endoscopic and radiological investigations in the 3 years preceding diagnosis and outcome data were collected. Cases of prior investigation not leading to diagnosis were considered ‘missed’ cancers and survival compared with ‘detected’ cases. The diagnostic pathway in each ‘missed’ case was reviewed.Results395 colorectal cancer cases were studied. Eighteen (4.6%) patients underwent previous investigation including colonoscopy (n=4), flexible sigmoidoscopy (n=5), barium enema (n=5) and diagnostic abdominal CT scan (n=12), median 708 days prior to diagnosis. Previous investigation predicted reduced overall and disease-free survival (HR 2.07, p=0.04 and HR 2.66, p<0.0001), after age and gender adjustment. Ten different categories termed ‘pitfalls’ were derived from analysis of the diagnostic pathway. These included CT scanning for abdominal pain without further investigation (n=7), rectosigmoid cancer following a previous diagnosis of diverticular disease (n=4) and incomplete diagnostic investigations without adequate follow-up (n=3).ConclusionsA proportion of patients diagnosed with colorectal cancer have previously been investigated for gastrointestinal symptoms and survival appears reduced in these patients. Regular audit and analysis of previous investigations can identify common pitfalls in diagnosis, which should be used to inform training and improve practice.
Constitutive Activation of Myosin-Dependent Contractility Sensitizes Glioma Tumor-Initiating Cells to Mechanical Inputs and Reduces Tissue Invasion
Authors: Wong Sophie Y. , Ulrich Theresa A. , Deleyrolle Loic P. , MacKay Joanna L. , Lin Jung-Ming G. , Martuscello Regina T. , Jundi Musa A. , Reynolds Brent A. , Kumar Sanjay 
Published: January 2015

Abstract
Tumor-initiating cells (TIC) perpetuate tumor growth, enable therapeutic resistance, and drive initiation of successive tumors. Virtually nothing is known about the role of mechanotransductive signaling in controlling TIC tumorigenesis, despite the recognized importance of altered mechanics in tissue dysplasia and the common observation that extracellular matrix (ECM) stiffness strongly regulates cell behavior. To address this open question, we cultured primary human glioblastoma (GBM) TICs on laminin-functionalized ECMs spanning a range of stiffnesses. Surprisingly, we found that these cells were largely insensitive to ECM stiffness cues, evading the inhibition of spreading, migration, and proliferation typically imposed by compliant ECMs. We hypothesized that this insensitivity may result from insufficient generation of myosin-dependent contractile force. Indeed, we found that both pharmacologic and genetic activation of cell contractility through RhoA GTPase, Rho-associated kinase, or myosin light chain kinase restored stiffness-dependent spreading and motility, with TICs adopting the expected rounded and nonmotile phenotype on soft ECMs. Moreover, constitutive activation of RhoA restricted three-dimensional invasion in both spheroid implantation and Transwell paradigms. Orthotopic xenotransplantation studies revealed that control TICs formed tumors with classical GBM histopathology including diffuse infiltration and secondary foci, whereas TICs expressing a constitutively active mutant of RhoA produced circumscribed masses and yielded a 30% enhancement in mean survival time. This is the first direct evidence that manipulation of mechanotransductive signaling can alter the tumor-initiating capacity of GBM TICs, supporting further exploration of these signals as potential therapeutic targets and predictors of tumor-initiating capacity within heterogeneous tumor cell populations. Cancer Res; 75(6); 1113–22. ©2015 AACR.
Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease
Authors: Taipaleenmäki Hanna , Browne Gillian , Akech Jacqueline , Zustin Jozef , van Wijnen Andre J. , Stein Janet L. , Hesse Eric , Stein Gary S. , Lian Jane B. 
Published: January 2015

Abstract
Progression of breast cancer to metastatic bone disease is linked to deregulated expression of the transcription factor Runx2. Therefore, our goal was to evaluate the potential for clinical use of Runx2-targeting miRNAs to reduce tumor growth and bone metastatic burden. Expression analysis of a panel of miRNAs regulating Runx2 revealed a reciprocal relationship between the abundance of Runx2 protein and two miRNAs, miR-135 and miR-203. These miRNAs are highly expressed in normal breast epithelial cells where Runx2 is not detected, and absent in metastatic breast cancer cells and tissue biopsies that express Runx2. Reconstituting metastatic MDA-MB-231-luc cells with miR-135 and miR-203 reduced the abundance of Runx2 and expression of the metastasis-promoting Runx2 target genes IL11, MMP-13, and PTHrP. In addition, tumor cell viability was decreased and migration suppressed in vitro. Orthotopic implantation of MDA-MB-231-luc cells delivered with miR-135 or miR-203, followed by an intratumoral administration of the synthetic miRNAs, reduced the tumor growth and spontaneous metastasis to bone. Furthermore, intratibial injection of these miRNA-delivered cells impaired tumor growth in the bone environment and inhibited bone resorption. Importantly, reconstitution of Runx2 in MDA-MB-231-luc cells delivered with miR-135 and miR-203 reversed the inhibitory effect of the miRNAs on tumor growth and metastasis. Thus, we have identified that aberrant expression of Runx2 in aggressive tumor cells is related to the loss of specific Runx2-targeting miRNAs and that a clinically relevant replacement strategy by delivery of synthetic miRNAs is a candidate for a therapeutic approach to prevent metastatic bone disease by this route. Cancer Res; 75(7); 1433–44. ©2015 AACR.
Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas
Authors: Chong Elise A. , Ahmadi Tahamtan , Aqui Nicole A. , Svoboda Jakub , Nasta Sunita D. , Mato Anthony R. , Walsh Kristy M. , Schuster Stephen J. 
Published: January 2015

AbstractPurpose: Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cell-mediated cytotoxicity, has the potential to synergize with rituximab, an anti-CD20 mAb. We hypothesized that the addition of lenalidomide to rituximab would improve clinical outcomes in patients with B-cell lymphomas who were previously rituximab resistant, defined as no response to or progression of lymphoma within 6 months of rituximab-based therapy.Experimental Design: We conducted a single-center, phase II trial in patients with indolent B-cell or mantle cell lymphomas who were previously rituximab resistant. Patients received 10 mg lenalidomide daily for 8 weeks, and then received four weekly doses of 375 mg/m2 rituximab; lenalidomide continued during and after rituximab. Response to therapy was assessed after 8 weeks of lenalidomide and 12 weeks after first dose of rituximab. The primary endpoint was overall response rate (ORR) after lenalidomide and rituximab.Results: Fifty patients were enrolled and 43 patients completed both response assessments. ORR after 8 weeks of lenalidomide was 30.2%; 12 weeks after the addition of rituximab to lenalidomide, ORR increased to 62.8% (N = 43). For all patients (N = 50), median progression-free survival (PFS) is 22.2 months (median follow-up, 39.2 months). PFS after lenalidomide–rituximab was significantly longer than the PFS for the antecedent regimen used to define rituximab resistance (22.2 vs. 9.13 months, P = 0.0004).Conclusions: This trial is the first to show that the combination of lenalidomide and rituximab overcomes prior rituximab resistance in patients with indolent B-cell and mantle cell lymphomas. Clin Cancer Res; 21(8); 1835–42. ©2015 AACR.
Cholesteryl Ester Transfer Protein Inhibition Enhances Endothelial Repair and Improves Endothelial Function in the Rabbit
Authors: Wu Ben J. , Shrestha Sudichhya , Ong Kwok L. , Johns Douglas , Hou Liming , Barter Philip J. , Rye Kerry-Anne 
Published: January 2015

Objective—
High-density lipoproteins (HDLs) can potentially protect against atherosclerosis by multiple mechanisms, including enhancement of endothelial repair and improvement of endothelial function. This study asks if increasing HDL levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, enhances endothelial repair and improves endothelial function in New Zealand White rabbits with balloon injury of the abdominal aorta.

Approach and Results—
New Zealand White rabbits received chow or chow supplemented with 0.07% or 0.14% (wt/wt) des-fluoro-anacetrapib for 8 weeks. Endothelial denudation of the abdominal aorta was carried out after 2 weeks. The animals were euthanized 6 weeks postinjury. Treatment with 0.07% and 0.14% des-fluoro-anacetrapib reduced cholesteryl ester transfer protein activity by 81±4.9% and 92±12%, increased plasma apolipoprotein A–I levels by 1.4±0.1-fold and 1.5±0.1-fold, increased plasma HDL-cholesterol levels by 1.8±0.2-fold and 1.9±0.1-fold, reduced intimal hyperplasia by 37±11% and 51±10%, and inhibited vascular cell proliferation by 25±6.1% and 35±6.7%, respectively. Re-endothelialization of the injured aorta increased from 43±6.7% (control) to 69±6.6% and 76±7.7% in the 0.07% and 0.14% des-fluoro-anacetrapib-treated animals, respectively. Aortic ring relaxation and guanosine 3′,5′-cyclic monophosphate production in response to acetylcholine were also improved. Incubation of HDLs from the des-fluoro-anacetrapib-treated animals with human coronary artery endothelial cells increased cell proliferation and migration relative to control. These effects were abolished by knockdown of scavenger receptor-B1 and PDZ domain-containing protein 1 and by pharmacological inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt.

Conclusions—
Increasing HDL levels by inhibiting cholesteryl ester transfer protein reduces intimal thickening and regenerates functional endothelium in damaged New Zealand White rabbit aortas in an scavenger receptor-B1-dependent and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt-dependent manner.