bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a patient decision aid for insulin initiation in patients with type 2 diabetes: a qualitative analysis of doctor–patient conversations in primary care consultations in Malaysia
Authors: Syed Ayeshah , Mohd Don Zuraidah , Ng Chirk Jenn , Lee Yew Kong , Khoo Ee Ming , Lee Ping Yein , Lim Abdullah Khatijah , Zainal Azlin 
Published: May 2017

ObjectiveTo investigate whether the use of apatient decision aid (PDA) for insulin initiation fulfils its purpose of facilitating patient-centred decision-making through identifying how doctors and patients interact when using the PDA during primary care consultations.DesignConversation analysis of seven single cases of audio-recorded/video-recorded consultations between doctors and patients with type 2 diabetes, using a PDA on starting insulin.SettingPrimary care in three healthcare settings: (1) one private clinic; (2) two public community clinics and (3) one primary care clinic in a public university hospital, in Negeri Sembilan and the Klang Valley in Malaysia.ParticipantsClinicians and seven patients with type 2 diabetes to whom insulin had been recommended. Purposive sampling was used to select a sample high in variance across healthcare settings, participant demographics and perspectives on insulin.Primary outcome measuresInteraction between doctors and patients in a clinical consultation involving the use of a PDA about starting insulin.ResultsDoctors brought the PDA into the conversation mainly by asking information-focused ‘yes/no’ questions, and used the PDA for information exchange only if patients said they had not read it. While their contributions were limited by doctors’ questions, some patients disclosed issues or concerns. Although doctors’ PDA-related questions acted as a presequence to deliberation on starting insulin, their interactional practices raised questions on whether patients were informed and their preferences prioritised.ConclusionsInteractional practices can hinder effective PDA implementation, with habits from ordinary conversation potentially influencing doctors’ practices and complicating their implementation of patient-centred decision-making. Effective interaction should therefore be emphasised in the design and delivery of PDAs and in training clinicians to use them.
Telehealthcare for patients suffering from chronic obstructive pulmonary disease: effects on health-related quality of life: results from the Danish ‘TeleCare North’ cluster-randomised trial
Authors: Lilholt Pernille Heyckendorff , Witt Udsen Flemming , Ehlers Lars , Hejlesen Ole K 
Published: May 2017

ObjectiveTo assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).DesignA cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).SettingTwenty-six municipal districts in the North Denmark Region of Denmark.ParticipantsPatients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.Main outcome measuresHealth-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2. Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.ResultsIn the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was −2.6 (SD 12.4) in the telehealthcare group and −2.8 (SD 11.9) in the usual practice group. The raw mean difference in MCS scores in the same period was −4.7 (SD 16.5) and −5.3 (SD 15.5) for telehealthcare and usual practice, respectively. The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI −1.4 to 1.7) and 0.4 (95% CI −1.7 to 2.4), respectively.ConclusionsThe overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.Trial registration numberNCT01984840; Results.
The effect of empagliflozin on oxidative nucleic acid modifications in patients with type 2 diabetes: protocol for a randomised, double-blinded, placebo-controlled trial
Authors: Larsen Emil List , Cejvanovic Vanja , Kjær Laura Kofoed , Vilsbøll Tina , Knop Filip Krag , Rungby Jørgen , Poulsen Henrik Enghusen 
Published: May 2017

IntroductionCardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D). Although glycaemic control reduces microvascular complications, the effect of intensive treatment strategies or individual drugs on macrovascular diseases is still debated. RNA oxidation is associated with increased mortality in patients with T2D. Inspired by animal studies showing effect of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor (empagliflozin) on oxidative stress and a recent trial evaluating empagliflozin that demonstrated improved cardiovascular outcomes in patients with T2D at high risk of cardiovascular events, we hypothesise that empagliflozin lowers oxidative stress.Methods and analysisIn this randomised, double-blinded and placebo-controlled study, 34 adult males with T2D will be randomised (1:1) to empagliflozin or placebo once daily for 14 days as add-on to ongoing therapy. The primary endpoints will be changes in 24-hour urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) determined before and after intervention (by ultra-performance liquid chromatography tandem mass-spectrometry). Additionally, fasting levels of malondialdehyde (MDA) will be determined in plasma before and after intervention (by high-performance liquid chromatography). Further, the plasma levels of iron, transferrin, transferrin-saturation, and ferritin are determined to correlate the iron metabolism to the markers of oxidative modifications.Ethics and disseminationThe study protocol has been approved by the Regional Committee on Biomedical Research Ethics (approval number H-16017433), the Danish Medicines Agency, and the Danish Data Protection Agency, and will be carried out under the surveillance and guidance of the GCP unit at Bispebjerg Frederiksberg Hospital, University of Copenhagen in compliance with the ICH-GCP guidelines and in accordance with the Declaration of Helsinki. The results of this study will be presented at national and international conferences, and submitted to a peer-reviewed international journal with authorship in accordance with Internation Committee of Medical Journal Editors (ICMJE) Recommendations state.Trial registrationStudy name: EMPOX; Pre-results: clinicaltrials.gov (NCT02890745). Protocol version 5.1 - August, 2016.
Nursing home team-care deprescribing study: a stepped-wedge randomised controlled trial protocol
Authors: Kua Chong-Han , Yeo Cindy Ying Ying , Char Cheryl Wai Teng , Tan Cheryl Wei Yan , Tan Poh Ching , Mak Vivienne SL , Lee Shaun Wen Huey , Leong Ian Yi-Onn 
Published: May 2017

IntroductionAn ageing population has become an urgent concern for Asia in recent times. In nursing homes, polypharmacy has also become a compounding issue. Deprescribing practice is an evidence-based strategy to provide a better outcome in this group of patients; however, its implementation in nursing homes is often challenging, and prospective outcome data on deprescribing practice in the elderly is lacking. Our study assesses the implementation of team-care deprescribing to understand the benefits of this practice in geriatric setting and to explore the factors affecting deprescribing practice.Methods and analysisThis multicentre prospective study consists of a prestudy interview questionnaire, and a preintervention and postintervention study to be conducted in the nursing home setting on residents at least 65 years old and on five or more medications. We will employ a cluster randomised stepped-wedge interventional design, based on a five-step (reviewing, checking, discussion, communication and documentation) team-care deprescribing practice coupled with the use of a deprescribing guide (consisting of Beers and STOPP criteria, as well as drug interaction checking), to assess the health and pharmacoeconomic outcome in nursing homes’ practice. Primary outcome measures of the intervention will consist of fall risks using a fall risk assessment tool. Other outcomes assessed include fall rates, pill burden including number of pills per day, number of doses per day and number of medications prescribed. Cost-related measures will include the use of cost–benefit analysis, which is calculated from the medication cost savings from deprescribing. For the prestudy interview questionnaire, findings will be analysed qualitatively using thematic analysis.Ethics and disseminationThis study is approved by the Domain Specific Review Board of National Healthcare Group, Singapore (2016/00422) and Monash University Human Research Ethics Committee (2016-1430-7791). The study findings shall be disseminated in international conferences and peer-reviewed publications. The study is registered with ClinicalTrials.gov (NCT02863341), Pre-results
Autism spectrum disorder: updated prevalence and comparison of two birth cohorts in a nationally representative Australian sample
Authors: May Tamara , Sciberras Emma , Brignell Amanda , Williams Katrina 
Published: May 2017

ObjectivesThis study aimed to (1) provide an update on the prevalence of parent-reported autism spectrum disorder (ASD) diagnosis and new information about teacher-reported ASD in two nationally representative Australian cohorts at ages 10–11 years, (2) examine differences in cohort demographic and clinical profiles and (3) compare the prevalence of teacher-reported ASD and any changes in categorisation over time across the cohorts.DesignSecondary analyses were undertaken using data from the Longitudinal Study of Australian Children (LSAC).ParticipantsChildren were recruited at kindergarten age (K cohort; birth year 1999/2000) and birth (B cohort; birth year 2003/2004), with follow-up of every 2  years for six waves.Primary outcome measuresParent-reported and teacher-reported ASD diagnosis was ascertained at three time points (waves 4–6).ResultsAt age 10–11 years, the adjusted prevalence of parent-reported ASD diagnosis was 3.9% (95% CI 3.2 to 4.5) and 2.4% (95% CI 1.6 to 2.9) in the B and K cohorts, respectively. Teacher-reported prevalence of ASD was 1.7% (95% CI 1.2 to 2.1) in the B cohort and 0.9% (95% CI 0.56 to 1.14) in the K cohort. Parents reported fewer conduct and peer problems and teachers more pro-social behaviour in B relative to K cohort ASD children. Children reported only by parents in the later-born B cohort had milder behaviour problems than parent-agreed and teacher-agreed cases. Although individual switching to ASD from other categories from 8–9 to 10–11 years was low (K cohort n=5, B cohort n=6), teachers reported more children with ASD in the B than K cohort at 10–11 years and fewer children with emotional/ behavioural problems.ConclusionsThe higher prevalence of parent-reported and teacher-reported ASD diagnosis in the later-born cohort may be partially explained by identifying children with milder behavioural problems as ASD and a change in the use of diagnostic categories in schools.
Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4 inhibitors in Japan: a study protocol for a prospective, multicentre, blinded-endpoint phase IV randomised controlled trial (PRIME-V study)
Authors: Koshizaka Masaya , Ishikawa Ko , Ishikawa Takahiro , Kobayashi Kazuki , Takemoto Minoru , Horikoshi Takuro , Shimofusa Ryota , Takahashi Sho , Nagashima Kengo , Sato Yasunori , Tatsuno Ichiro , Terano Takashi , Hashimoto Naotake , Kuribayashi Nobuichi , Uchida Daigaku , Yokote Koutaro 
Published: May 2017

IntroductionIn Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently used as the treatment of choice for patients with type 2 diabetes. In some cases, however, poor glycaemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and body weight in patients with type 2 diabetes. However, further investigation regarding the effects of SGLT-2 inhibitors on body composition, especially in the Asian population who tends to have relatively low-to-moderate body mass indices, is required. Therefore, we aim to determine the effects of treatment with SGLT-2 inhibitors or metformin for reducing visceral fat in 106 Asian patients with type 2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50 mg daily) for poor glycaemic control.Methods and analysisA prospective, multicentre, blinded-endpoint phase IV randomised controlled study will be conducted to evaluate the safety and efficacy of a 24-week treatment with either an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg daily) or metformin (1000 mg daily). The primary outcome is the rate of change in the total area of visceral fat for patients in both treatment groups, measured using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical information, will perform centralised analysis of the images in a unified measurement condition.Ethics and disseminationThe protocol was approved by the institutional review board of each hospital. This study is ongoing and due to finish in April 2017. The findings of this study will be disseminated via peer-reviewed publications and conference presentations, and will also be disseminated to participants.Trial registration numberUMIN000015170, R000016861 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000016861); Pre-results
Developing a decision rule to optimise clinical pharmacist resources for medication reconciliation in the emergency department
Authors: De Winter Sabrina , Vanbrabant Peter , Laeremans Pieter , Foulon Veerle , Willems Ludo , Verelst Sandra , Spriet Isabel 
Published: May 2017

BackgroundThe process of obtaining a complete medication history for patients admitted to the hospital from the ED at hospital admission, without discrepancies, is error prone and time consuming.ObjectivesThe goal of this study was the development of a clinical decision rule (CDR) with a high positive predictive value in detecting ED patients admitted to hospital at risk of at least one discrepancy during regular medication history acquisition, along with favourable feasibility considering time and budget constraints.MethodsData were based on a previous prospective study conducted at the ED in Belgium, describing discrepancies in 3592 medication histories. Data were split into a training and a validation set. A model predicting the number of discrepancies was derived from the training set with negative binomial regression and was validated on the validation set. The performance of the model was assessed. Several CDRs were constructed and evaluated on positive predictive value and alert rate.ResultsThe following variables were retained in the prediction model: (1) age, (2) gender, (3) medical discipline for which the patient was admitted, (4) degree of physician training, (5) season of admission, (6) type of care before admission, number of (7) drugs, (8) high-risk drugs, (9) drugs acting on alimentary tract and metabolism, (10) antithrombotics, antihaemorrhagics and antianaemic preparations, (11) cardiovascular drugs, (12) drugs acting on musculoskeletal system and (13) drugs acting on the nervous system; all recorded by the ED physician on admission. The final CDR resulted in an alert rate of 29% with a positive predictive value of 74%.ConclusionThe final CDR allows identification of the majority of patients with a potential discrepancy within a feasible workload for the pharmacy staff. Our CDR is a first step towards a rule that could be incorporated into electronic medical records or a scoring system.
What is the overlap between HIV and shigellosis epidemics in England: further evidence of MSM transmission?
Authors: Mohan Keerthi , Hibbert Matthew , Rooney Graeme , Canvin Malcolm , Childs Tristan , Jenkins Claire , Simms Ian , Kirwan Peter , Delpech Valerie , Yin Zheng , Hughes Gwenda , Field Nigel 
Published: May 2017

BackgroundEvidence suggests that sexual transmission between men has replaced foreign travel as the predominant mode ofShigellatransmission in England. However, sexuality and HIV status are not routinely recorded for laboratory-reportedShigella,and the role of HIV in theShigellaepidemic is not well understood.MethodsThe Modular Open Laboratory Information System containing allShigellacases reported to Public Health England (PHE) and the PHE HIV and AIDS Reporting System holding all adults living with diagnosed HIV in England were matched using a combination of Soundex code, date of birth and gender.ResultsFrom 2004 to 2015, 88 664 patients were living with HIV, and 10 269Shigellacases were reported in England; 9% (873/10 269) ofShigellacases were diagnosed with HIV, of which 93% (815/873) were in men.Shigellacases without reported travel history were more likely to be living with HIV than those who had travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the incidence ofShigellain men with HIV rose from 47/100 000 to 226/100 000 (p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the study period (0–24/100 000). AmongShigellacases without travel and with HIV, 91% (657/720) were men who have sex with men (MSM). HIV precededShigelladiagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50 copies/mL).DiscussionWe observed a sustained increase in the national rate of shigellosis in MSM with HIV, who may experience more serious clinical disease. Sexual history, HIV status and STI risk might require sensitive investigation in men presenting with gastroenteritis.
Augmenting Field Data for Testing Systems Subject to Incremental Requirements Changes
Authors: Di Nardo Daniel , Pastore Fabrizio , Briand Lionel 
Published: May 2017

When testing data processing systems, software engineers often use real-world data to perform system-level testing. However, in the presence of new data requirements, software engineers may no longer benefit from having real-world data with which to perform testing. Typically, new test inputs complying with the new requirements have to be manually written.
We propose an automated model-based approach that combines data modelling and constraint solving to modify existing field data to generate test inputs for testing new data requirements. The approach scales in the presence of complex and structured data, thanks to both the reuse of existing field data and the adoption of an innovative input generation algorithm based on slicing the model into parts.
We validated the scalability and effectiveness of the proposed approach using an industrial case study. The empirical study shows that the approach scales in the presence of large amounts of structured and complex data. The approach can produce, within a reasonable time, test input data that is over ten times larger in size than the data generated with constraint solving only. We also demonstrate that the generated test inputs achieve more code coverage than the test cases implemented by experienced software engineers.
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas
Authors: Grausam Katie B. , Dooyema Samuel D.R. , Bihannic Laure , Premathilake Hasitha , Morrissy A. Sorana , Forget Antoine , Schaefer Amanda M. , Gundelach Justin H. , Macura Slobodan , Maher Diane M. , Wang Xin , Heglin Alex H. , Ge Xijin , Zeng Erliang , Puget Stephanie , Chandrasekar Indra , Surendran Kameswaran , Bram Richard J. , Schüller Ulrich , Talyor Michael D. , Ayrault Olivier , Zhao Haotian 
Published: May 2017

Abstract
Medulloblastoma arising from the cerebellum is the most common pediatric brain malignancy, with leptomeningeal metastases often present at diagnosis and recurrence associated with poor clinical outcome. In this study, we used mouse medulloblastoma models to explore the relationship of tumor pathophysiology and dysregulated expression of the NOTCH pathway transcription factor ATOH1, which is present in aggressive medulloblastoma subtypes driven by aberrant Sonic Hedgehog/Patched (SHH/PTCH) signaling. In experiments with conditional ATOH1 mouse mutants crossed to Ptch1+/− mice, which develop SHH-driven medulloblastoma, animals with Atoh1 transgene expression developed highly penetrant medulloblastoma at a young age with extensive leptomeningeal disease and metastasis to the spinal cord and brain, resembling xenografts of human SHH medulloblastoma. Metastatic tumors retained abnormal SHH signaling like tumor xenografts. Conversely, ATOH1 expression was detected consistently in recurrent and metastatic SHH medulloblastoma. Chromatin immunoprecipitation sequencing and gene expression profiling identified candidate ATOH1 targets in tumor cells involved in development and tumorigenesis. Among these targets specific to metastatic tumors, there was an enrichment in those implicated in extracellular matrix remodeling activity, cytoskeletal network and interaction with microenvironment, indicating a shift in transcriptomic and epigenomic landscapes during metastasis. Treatment with bone morphogenetic protein or SHH pathway inhibitors decreased tumor cell proliferation and suppressed metastatic tumor growth, respectively. Our work reveals a dynamic ATOH1-driven molecular cascade underlying medulloblastoma metastasis that offers possible therapeutic opportunities. Cancer Res; 77(14); 3766–77. ©2017 AACR.