bluuebunny/crossref_metadata_2025_split huggingface dataset:
In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial
Authors: Mokoka Matshediso C , Lombard Lorna , MacHale Elaine M , Walsh Joanne , Cushen Breda , Sulaiman Imran , Carthy Damien Mc , Boland Fiona , Doyle Frank , Hunt Eoin , Murphy Desmond M , Faul John , Butler Marcus , Hetherington Kathy , Mark FitzGerald J , Boven Job FM van , Heaney Liam G , Reilly Richard B , Costello Richard W 
Published: June 2017

IntroductionMany patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes.Methods and analysisThis prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated.Ethics and disseminationThe results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals.Trial registrationNCT02307669; Pre-results.
Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due toEnterobacteriaceae(SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial
Authors: López-Cortés Luis Eduardo , Rosso-Fernández Clara , Núñez-Núñez María , Lavín-Alconero Lucía , Bravo-Ferrer José , Barriga Ángel , Delgado Mercedes , Lupión Carmen , Retamar Pilar , Rodríguez-Baño Jesús 
Published: June 2017

IntroductionWithin the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable.Methods and analysisThe SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due toEnterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals.Ethics and disseminationEach participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals.DiscussionStrategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation.Trial registration numberThe European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov:NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry.
Screening for cancer in patients with unprovoked venous thromboembolism: protocol for a systematic review and individual patient data meta-analysis
Authors: van Es Nick , Gal Grégoire Le , Otten Hans-Martin , Robin Philippe , Piccioli Andrea , Lécumberri Ramon , Palomares Luis Jara , Religa Piotr , Rieu Viriginie , Rondina Matthew T. , Beckers Mariëlle M , Prandoni Paolo , Salaun Pierre-Yves , Nisio Marcello Di , Bossuyt Patrick M , Büller Harry R , Carrier Marc 
Published: June 2017

IntroductionOccult cancer is present in 4%–9% of patients with unprovoked venous thromboembolism (VTE). Screening for cancer may be considered in these patients, with the aim to diagnose cancers in an early, potentially curable stage. Information is needed about the risk of occult cancer, overall and in specific subgroups, additional risk factors and on the performance of different screening strategies.Methods and analysisMEDLINE, Embase and CENTRAL databases were searched from November 2007 to January 2016 for prospective studies that had evaluated protocol-mandated screening for cancer in patients with unprovoked VTE and with at least 12 months’ follow-up. Two reviewers independently assessed articles for eligibility. Ten eligible studies were identified and individual patient data were obtained from each of them. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool . Generalised linear mixed-effects models was used to calculate estimates in a one-stage meta-analytic approach, overall and in a number of subgroups, including patients undergoing limited screening only, elderly patients, patients with previous VTE, smokers and patients using oestrogens.Ethics and disseminationEthical approval is not required for this systematic review and individual patient data meta-analysis. Findings have been submitted for publication in peer-reviewed journals and presentations at national and international conferences to provide clinicians and other decision-makers with valid and precise risk estimates of occult cancer, overall and in specific clinical subgroups, with risk factors for occult cancer, with estimates of the diagnostic performance of limited screening and with an exploration of the benefit of extensive screening strategies.
Contextual and individual inequalities of multimorbidity in Brazilian adults: a cross-sectional national-based study
Authors: Nunes Bruno P , Chiavegatto Filho Alexandre D P , Pati Sanghamitra , Cruz Teixeira Doralice S , Flores Thaynã R , Camargo-Figuera Fabio A , Munhoz Tiago N , Thumé Elaine , Facchini Luiz A , Rodrigues Batista Sandro R 
Published: June 2017

ObjectivesThe study aims to evaluate the magnitude of multimorbidity in Brazilian adults, as well to measure their association with individual and contextual factors stratified by Brazilian states and regions.MethodsA national-based cross-sectional study was carried out in 2013 with Brazilian adults. Multimorbidity was evaluated by a list of 22 physical and mental morbidities (based on self-reported medical diagnosis and Patient Health Questionnaire-9 for depression). The outcome was analysed taking ≥2 and ≥3 diseases as cut-off points. Factor analysis (FA) was used to identify disease patterns and multilevel models were used to test association with individual and contextual variables.ResultsThe sample comprised 60 202 individuals. Multimorbidity frequency was 22.2% (95% CI 21.5 to 22.9) for ≥2 morbidities and 10.2% (95% CI 9.7 to 10.7) for ≥3 morbidities. In the multilevel adjusted models, females, older people, those living with a partner and having less schooling presented more multiple diseases. No linear association was found according to wealth index but greater outcome frequency was found in individuals with midrange wealth index. Living in states with higher levels of education and wealthier states was associated with greater multimorbidity. Two patterns of morbidities (cardiometabolic problems and respiratory/mental/muscle–skeletal disorders) explained 92% of total variance. The relationship of disease patterns with individual and contextual variables was similar to the overall multimorbidity, with differences among Brazilian regions.ConclusionsIn Brazil, at least 19 million adults had multimorbidity. Frequency is similar to that found in other Low and and Middle Income Countries. Contextual and individual social inequalities were observed.
What stage are low-income and middle-income countries (LMICs) at with patient safety curriculum implementation and what are the barriers to implementation? A two-stage cross-sectional study
Authors: Ginsburg Liane R , Dhingra-Kumar Neelam , Donaldson Liam J 
Published: June 2017

ObjectivesThe improvement of safety in healthcare worldwide depends in part on the knowledge, skills and attitudes of staff providing care. Greater patient safety content in health professional education and training programmes has been advocated internationally. While WHO Patient Safety Curriculum Guides (for Medical Schools and Multi-Professional Curricula) have been widely disseminated in low-income and middle-income countries (LMICs) over the last several years, little is known about patient safety curriculum implementation beyond high-income countries. The present study examines patient safety curriculum implementation in LMICs.MethodsTwo cross-sectional surveys were carried out. First, 88 technical officers in Ministries of Health and WHO country offices were surveyed to identify the pattern of patient safety curricula at country level. A second survey followed that gathered information from 71 people in a position to provide institution-level perspectives on patient safety curriculum implementation.ResultsThe majority, 69% (30/44), of the countries were either considering whether to implement a patient safety curriculum or actively planning, rather than actually implementing, or embedding one. Most organisations recognised the need for patient safety education and training and felt a safety curriculum was compatible with the values of their organisation; however, important faculty-level barriers to patient safety curriculum implementation were identified. Key structural markers, such as dedicated financial resources and relevant assessment tools to evaluate trainees’ patient safety knowledge and skills, were in place in fewer than half of organisations studied.ConclusionsGreater attention to patient safety curriculum implementation is needed. The barriers to patient safety curriculum implementation we identified in LMICs are not unique to these regions. We propose a framework to act as a global standard for patient safety curriculum implementation. Educating leaders through the system in order to embed patient safety culture in education and clinical settings is a critical first step.
Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey
Authors: Ma Christopher , Panaccione Remo , Fedorak Richard N , Parker Claire E , Khanna Reena , Levesque Barrett G , Sandborn William J , Feagan Brian G , Jairath Vipul 
Published: June 2017

IntroductionCrohn’s disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).Methods and analysisThe development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials.Ethics and disseminationGiven that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality.
Diabetic retinopathy screening and treatment in Myanmar: a pilot study
Authors: Patel Sarju , Klein Richard M , Patel Arun , Klein Ronnie Boriskin , Aung Mya , Hoe Wilbert 
Published: June 2017

Background/aimsThe goals of this pilot study were (a) to demonstrate the feasibility of identifying patients with vision-threatening diabetic retinopathy (DR) in a provincial area of Myanmar and treating them with portable lasers and (b) to gather data specific to Myanmar to help design larger cross-sectional studies of DR prevalence in Myanmar.Methods97 consecutive patients with diabetes mellitus (DM) were identified by local ophthalmologists over a period of 1 month in Pyinmana, Myanmar and were referred to the pilot screening programme. Patients’ demographics were recorded and their eyes were examined. Those with vision-threatening DR were treated with panretinal photocoagulation (PRP).ResultsOf the 97 patients with DM, 33 (34%) had evidence of DR, 23 (23.5%) had evidence of vision-threatening DR including 13 (13.5%) with proliferative DR and 33 eyes in 23 patients (23.5%) had PRP with portable green wavelength laser. Hypertension was a significant cofactor in the development of vision-threatening DR (p<0.01). The average time since diagnosis of DM was 6.0 years in patients with vision-threatening DR.ConclusionsThis study demonstrates the feasibility of identifying and treating patients with vision-threatening DR in a provincial area of Myanmar and provides initial data to plan a larger study to assess true prevalence, a prerequisite for establishing broader screening/treatment programs.
NADPH oxidase depletion in neutrophils from patients with cirrhosis and restoration via toll-like receptor 7/8 activation
Authors: Rolas Loïc , Boussif Abdelali , Weiss Emmanuel , Lettéron Philippe , Haddad Oualid , El-Benna Jamel , Rautou Pierre-Emmanuel , Moreau Richard , Périanin Axel 
Published: June 2017

ObjectiveCirrhosis downregulates phagocyte oxidant production via their antibacterial superoxide-generating system, NADPH oxidase (NOX2) and increases patients’ susceptibility to infection and mortality rate. To explore novel biochemical parameters that explain susceptibility to infections, we investigated the expression of NOX2 and partners in neutrophils of patients with severe alcoholic cirrhosis and have provided a novel approach to restore superoxide production capacity in patients’ neutrophils and blood.DesignNeutrophils were isolated from patients with decompensated alcoholic cirrhosis. NOX2 activity was assessed after stimulation of purified neutrophils or whole blood with the bacterial-derived peptide fMet-Leu-Phe. The expression of NOX2 and partners was studied by western blot analysis, flow cytometry and reverse transcription-PCR.ResultsThe impaired superoxide production by patients’ neutrophils was associated with a severe deficient expression of the NADPH oxidase catalytic core flavocytochrome-b558 (gp91phox/NOX2 and p22phox), its cytosolic partner p47phoxbut not p67phox. NOX2 expression decreased rapidly by protein degradation involving elastase released during degranulation of healthy neutrophils stimulated with fMet-Leu-Phe, or highly present in patients’ plasma. Interestingly, the deficient superoxide production was reversed by treatment of patients’ neutrophils and whole blood with toll-like receptor 7/8 (TLR7/8) agonists. This treatment stimulated a rapid NOX2 transcription and translation through a process involving mammalian target of rapamycin (mTOR) whose expression was also deficient in patients’ neutrophils. NOX2 expression was also increased by the TLR4 agonist lipopolysaccharide but with only a modest improvement of reactive oxygen species production.ConclusionImpairment of neutrophil oxidants production in alcoholic cirrhosis is associated with NOX2 degradation and deficient mTOR-dependent translational machinery. The NOX2 depletion can be reversed via TRL7/8 activation and might be used to restore antimicrobial responses of immunocompromised patients.
Incidence of irritable bowel syndrome and chronic fatigue following GI infection: a population-level study using routinely collected claims data
Authors: Donnachie Ewan , Schneider Antonius , Mehring Michael , Enck Paul 
Published: June 2017

ObjectivesTo investigate the occurrence of postinfectious IBS in routine outpatient care, comparing different types of GI infection and its interaction with psychosomatic comorbidity.DesignRetrospective cohort study using routinely collected claims data covering statutorily insured patients in Bavaria, Germany. Cases were defined as patients without prior record of functional intestinal disorder with a first-time diagnosis of GI infection between January 2005 and December 2013 and classed according to the type of infection. Each case was matched by age, sex and district of residence to a patient without history of GI infection. Prior psychological disorder (depression, anxiety or stress reaction disorder) was assessed in the 2 years prior to inclusion. Proportional hazards regression models were used to estimate the HRs for GI infection and psychological disorder. Chronic fatigue syndrome (CFS) was assessed as a comparator outcome.ResultsA total of 508 278 patients with first diagnosis of GI infection were identified, resulting in a matched cohort of 1 016 556 patients. All infection types were associated with an increased risk of IBS (HR: 2.19–4.25) and CFS (HR 1.35–1.82). Prior psychological disorder was a distinct risk factor for IBS (HR: 1.73) and CFS (HR: 2.08). Female sex was a further risk factor for both conditions.ConclusionPsychological disorder and GI infections are distinct risk factors for IBS. The high incidence of non-specific GI infection suggests that postinfectious IBS is a common clinical occurrence in primary care. Chronic fatigue is a further significant sequela of GI infection.
Smoking intensity and duration is associated with cardiac structure and function: the ECHOcardiographic Study of Hispanics/Latinos
Authors: Leigh J Adam , Kaplan Robert C , Swett Katrina , Balfour Pelbreton , Kansal Mayank M , Talavera Gregory A , Perreira Krista , Blaha Michael J , Benjamin Emelia J , Robertson Rosemarie , Bhartnagar Aruni , Rodriguez Carlos J 
Published: June 2017

ObjectiveCardiovascular disease is the leading cause of death in smokers and this relationship is complicated by the multiplicity of cardiovascular effects of smoking. However, the relationship between intensity and duration of cigarette smoking and echocardiographic measures of right and left ventricular structure and function has been poorly studied.MethodsWe examined ECHO-SOL (Echocardiographic Study of Hispanics/Latinos) participants, a subset of the Hispanic Community Health Study/Study of Latinos. Participants were administered a detailed tobacco exposure questionnaire and a comprehensive echocardiography exam. Multivariable linear regression models (adjusted for age, sex, obesity, hypertension and diabetes statuses) were performed using sampling weights. Statistical significance was defined at p<0.01.ResultsThere were 1818 ECHO-SOL participants (57.4% women, mean age 56.4 years). Among current smokers (n=304), increased duration of smoking, as measured by a younger age of smoking initiation, was significantly associated with higher mean left ventricular mass (LVM) and lower right ventricular (RV) function (lower right ventricular stroke volumes). More cigarettes smoked per day was significantly associated with higher mean LVM, worse diastolic function (higher E/e′ ratio), worse LV geometry (increased relative wall thickness) and worse RV function (decreasing right ventricular stroke volume). Among current smokers, higher mean lifetime pack-years (a combined measure of smoking intensity and duration) was associated with higher LVM, worse LV geometry, worse diastolic function, greater RV dilatation and worse RV function.ConclusionsThere is a dose–response relationship between intensity and duration of cigarette tobacco smoking with unfavourable changes of multiple measures of right-sided and left-sided cardiac structure and function.