bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate Stochastic Volatility with Large and Moderate Shocks
Authors: Izzeldin Marwan , Tsionas Mike G. , Michaelides Panayotis G. 
Published: March 2019

SummaryThe paper proposes a multivariate stochastic volatility model where shifts in volatility are endogenously driven by large return shocks. The model proposed generalizes the univariate stochastic volatility model of Dendramis and colleagues to a multivariate context. Allowing for multivariate dependence permits the volatility of common return factors to affect individual stock returns volatility jointly. The model is further extended to allow for endogenous thresholds that depend on covariates. Model selection priors are introduced and the new techniques are applied by using data from the FTSE100-index.
Autoimmune heparin‐induced thrombocytopenia and venous limb gangrene after aortic dissection repair: in vitro and in vivo effects of intravenous immunoglobulin
Authors: Arcinas Liane A. , Manji Rizwan A. , Hrymak Carmen , Dao Vi , Sheppard Jo‐Ann I. , Warkentin Theodore E. 
Published: March 2019

BACKGROUNDHeparin‐induced thrombocytopenia (HIT) is a prothrombotic disorder characterized by heparin‐dependent antibodies that activate platelets (PLTs) via PLT FcγIIa receptors. “Autoimmune” HIT (aHIT) indicates a HIT subset where thrombocytopenia progresses or persists despite stopping heparin; aHIT sera activate PLTs strongly even in the absence of heparin (heparin‐independent PLT‐activating properties). Affected patients are at risk of severe complications, including dual macro‐ and microvascular thrombosis leading to venous limb gangrene. High‐dose intravenous immunoglobulin (IVIG) offers an approach to interrupt heparin‐independent PLT‐activating effects of aHIT antibodies.CASE REPORTA 78‐year‐old male who underwent cardiopulmonary bypass for aortic dissection developed aHIT, disseminated intravascular coagulation, and deep vein thrombosis; progression to venous limb gangrene occurred during partial thromboplastin time (PTT)‐adjusted bivalirudin infusion (underdosing from “PTT confounding”). Thrombocytopenia recovered with high‐dose IVIG, although the PLT count increase began only after the third dose of a 5‐day IVIG regimen (0.4 g/kg/day × 5 days). We reviewed case reports and case series of IVIG for treating HIT, focusing on various IVIG dosing regimens used.RESULTSPatient serum–induced PLT activation was inhibited in vitro by IVIG in a dose‐dependent fashion; inhibition of PLT activation by IVIG was much more marked in the absence of heparin versus the presence of heparin (0.2 U/mL). Our literature review indicated 1 g/kg × 2 IVIG dosing as most common for treating HIT, usually associated with rapid PLT count recovery.CONCLUSIONOur clinical and laboratory observations support dose‐dependent efficacy of IVIG for decreasing PLT activation and thus correcting thrombocytopenia in aHIT. Our case experience and literature review suggests dosing of 1 g/kg IVIG × 2 for patients with severe aHIT.
Evaluation of the NCCN guidelines using the RIGHT Statement and AGREE-II instrument: a cross-sectional review
Authors: Wayant Cole , Cooper Craig , Turner D’Arcy , Vassar Matt 
Published: March 2019

Introduction
Robust, clearly reported clinical practice guidelines (CPGs) are essential for evidence-based clinical practice. The Reporting Items for practice Guidelines in HealThcare (RIGHT) Statement and Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument were published to improve the methodological and reporting quality in healthcare CPGs.

Methods
We applied the RIGHT Statement checklist and AGREE-II instrument to 48 National Comprehensive Cancer Network (NCCN) guidelines. Our primary objective was to assess the adherence to RIGHT and AGREE-II items. Since neither RIGHT nor AGREE-II can judge the clinical usefulness of a guideline, our study is designed to only focus on the methodological and reporting quality of each guideline.

Results
The NCCN guidelines demonstrated notable strengths and weaknesses. For example, RIGHT Statement items 19 (conflicts of interest), 7b (description of subgroups) and 13a (clear, precise recommendations) were fully reported in all guidelines. However, the guidelines inconsistently incorporated patient values and preferences and cost. Regarding the AGREE-II instrument, the NCCN guidelines scored highly on the domains 4 (clear, precise recommendations) and 6 (handling of conflicts of interest), but lowest on domain 2 (inclusion of all relevant stakeholders).

Conclusions
In this investigation, we found that NCCN CPGs demonstrate key strengths and weaknesses with respect to the reporting of key items essential to CPGs. We recommend the continued use of NCCN guidelines and improvements to weaknesses in reporting and methods. Doing so serves to improve the evidence delivered to healthcare providers, thus potentially improving patient care.
Pancreatic cancer ‘mismatch’ in Lynch syndrome
Authors: Hendifar Andrew E , Larson Brent K , Rojansky Rebecca , Guan Michelle , Gong Jun , Placencio Veronica , Tuli Richard , Hitchins Megan 
Published: March 2019

ObjectiveImmune therapy with the PD1 inhibitor pembrolizumab has been approved to treat unresectable/metastatic solid tumours exhibiting mismatch repair (MMR) deficiency. Lynch syndrome (LS), caused by autosomal dominant germline mutations of a MMR gene, predisposes to the development of MMR-deficient cancers. We report a case ofMSH2-LS with an MMR-intact pancreatic ductal adenocarcinoma (PDAC) ineligible for treatment with pembrolizumab.DesignImmunohistochemistry of MMR proteins was performed in each malignancy developed in aMSH2-LS patient to determine MMR status.ResultsThe patient carried a pathogenicMSH2germline mutation and had a history of LS-type cancers, including endometrial carcinoma, colorectal adenocarcinoma, urothelial carcinoma of the bladder and PDAC. Three malignancies (endometrial, colorectal, urothelial) lacked MSH2 and MSH6 expression, consistent withMSH2-associated tumorigenesis. However, MSH2 and MSH6 expression were intact in the PDAC, suggesting the sporadic occurrence of the pancreatic tumour unrelated to the germlineMSH2mutation. These inconsistent MMR statuses among the tumours rendered the patient ineligible for the immunotherapy pembrolizumab.ConclusionTesting for MMR protein expression is recommended for each tumour in patients with LS, especially pancreatic, as discordant results may have profound effects on treatment opportunities. To our knowledge, this is the first documented case of MMR-intact PDAC in a patient withMSH2-LS.
Ontario Brain Injury Association Peer Support Program: a mixed methods protocol for a pilot randomised controlled trial
Authors: Munce Sarah E P , Jaglal Susan , Kastner Monika , Nelson Michelle L A , Salbach Nancy M , Shepherd John , Sweet Shane N , Wilcock Ruth , Thoms Carla , Bayley Mark T 
Published: March 2019

IntroductionThe objective of this study is to conduct a pilot randomised controlled trial (RCT) of the Ontario Brain Injury Association (OBIA) Peer Support Program. The RCT is designed to evaluate the effectiveness and dose–response of the Peer Support Program in improving participation and mood for people with moderate-to-severe traumatic brain injury compared with a wait-list control group.Methods and analysisThe proposed research is a three-phase, mixed methods pilot RCT. Consistent with an integrated knowledge translation approach, the study design has been informed in consultation with the knowledge user (ie, OBIA). It will include an initial qualitative examination of barriers and enablers to the trial implementation (phase 1), a pilot RCT (phase 2) and conclude with a qualitative component (phase 3). A qualitative descriptive approach will be adopted for both qualitative phases of the study (n=20–25) and thematic analysis will be used. The 6 months phase-2 trial will be conducted with 60 participants. These participants will be randomised to one of three groups: a twice a week programme (n=20), a once a week programme (n=20) or the wait-list control group (n=20). The feasibility of participant recruitment and retention, data collection, as well as participant adherence to the OBIA Peer Support Program will be evaluated. The primary outcome measure will be participation, as measured by the Participation Assessment with Recombined Tools–Objective. Other proposed outcomes of interest will include mood, health-related quality of life and self-efficacy.Ethics and disseminationEthics approval will be obtained from the principal author’s institution (University Health Network Research Ethics Board). The results of this study will inform the development of a larger scale RCT and will inform future iterations of the OBIA Peer Support Program including a revised programme curriculum.Trial registration numberNCT03450460; Pre-results.
Patient trade-offs between continuity and access in primary care interprofessional teaching clinics in Canada: a cross-sectional survey using discrete choice experiment
Authors: Oliver Doug , Deal Ken , Howard Michelle , Qian Helen , Agarwal Gina , Guenter Dale 
Published: March 2019

ObjectiveTimely access to care and continuity with a specific provider are important determinants of patient satisfaction when booking appointments in primary care settings. Advanced access booking systems restrict the majority of providers’ appointment spots for same-day appointments and keep the number of prebooked appointments to a minimum. In the teaching clinic environment, continuity with the same provider can be a challenge. This study examines trade-offs that patients may consider during appointment bookings for six different clinical scenarios across a number of key access and continuity attributes using a discrete choice experiment (DCE) method.DesignCross-sectional survey.SettingTwo urban family medicine teaching clinics in Canada.ParticipantsConvenience sample of 430 patients of family medicine clinics aged 18 and older.InterventionDiscrete choice conjoint experiment survey.Primary outcome measuresPatient preferences on six attributes: appointment booking method, appointment wait time, time spent in the waiting room, appointment time convenience, familiarity with healthcare provider and position of healthcare provider. Data were analysed by hierarchical Bayes analysis to determine estimates of part-worth utilities for each respondent.ResultsPatients rated appointment wait time as the most highly valued attribute, followed by position of provider, then familiarity with the provider. Patients showed a significant preference (p<0.02) for their own physician for booking of routine annual check-ups and other logical preferences across attributes overall and by clinical scenario.ConclusionsPatients preferred timely access to their primary care team over other attributes in the majority of health state scenarios tested, especially urgent issues, however they were willing to wait for a check-up. These results support the notion that advanced access booking systems which leave the majority of appointment spots for same day access and still leave a few for continuity (check-up) bookings, align well with trends in patient preferences.
Is knowledge retained by healthcare providers after training? A pragmatic evaluation of drug-resistant tuberculosis management in China
Authors: Wu Shishi , Li Renzhong , Su Wei , Ruan Yunzhou , Chen Mingting , Khan Mishal S 
Published: March 2019

ObjectivesConsidering the urgent need of training to improve standardised management of drug-resistant infectious disease and the lack of evidence on the impact of training, this study evaluates whether training participants’ knowledge on multidrug-resistant tuberculosis (MDR-TB) is improved immediately and a year after training.Setting and participantsThe study involved 91 MDR-TB healthcare providers (HCPs), including clinical doctors, nurses and CDC staff, who attended a new MDR-TB HCP training programme in Liaoning and Jiangxi provinces, China.Main outcome measuresA phone-based assessment of participants’ long-term retention of knowledge about MDR-TB management was conducted in July 2017, approximately 1 year after training. The proportion of correct responses in the long-term knowledge assessment was compared with a pretraining test and an immediate post-training test using a χ2test. Factors influencing participants’ performance in the long-term knowledge assessment were analysed using linear regression.ResultsAcross both provinces, knowledge of definitions of drug-resistant TB, standardised MDR-TB case detection protocols and laboratory diagnosis was improved 1 year after the training by 14.5% (p=0.037), 32.4% (p<0.001) and 31% (p<0.001) relative to pretraining. However, compared with immediately after training, the knowledge of the three topics declined by 26.5% (p=0.003), 19.8% (p=0.018) and 52.7% (p<0.001) respectively in Jiangxi, while no significant decline was observed in Liaoning. Additionally, we found that obtaining a higher score in the long-term knowledge assessment was associated with longer years of clinical experience (coefficient=0.51; 95 CI% 0.02 to 0.99; p=0.041) and attending training in Liaoning (coefficient=0.50; 95% CI 0.14 to 0.85; p=0.007).ConclusionOur study, the first to assess knowledge retention of MDR-TB HCPs 1 year after training, showed an overall positive long-term impact of lecture-style group training on participants’ knowledge. Knowledge decline 1 year after training was observed in one province, Jiangxi, and this may be partly addressed by targeted support to HCPs with fewer years of clinical experience.
Comparison of medical comorbidity between patients with primary angle-closure glaucoma and a control cohort: a population-based study from Taiwan
Authors: Chen Hsin-Yi , Lin Cheng-Li 
Published: March 2019

ObjectiveTo determine the prevalence and risk of systemic comorbidities in primary angle-closure glaucoma in Taiwan population.MethodsWe included 3322 primary angle-closure glaucoma (PACG) subjects and randomly selected patients without PACG from the Taiwan National Health Insurance Research Database and frequency matched four of them (n=13 288) to each PACG patient, based on age and sex. The univariable and multivariable unconditional logistic regression models were used to estimate the effect of comorbidities on the risk of PACG as indicated by the OR with 95% CI.ResultsThe mean age of the PACG group was 65.2±12.7 years, and 61.1% of the patients were female. The risk of PACG was greater for patients with the comorbidities of hyperlipidaemia (ORs: 1.11), headaches (ORs: 1.13), liver diseases (ORs: 1.14), peptic ulcers (ORs: 1.10) and cataract (ORs: 3.80). For the male group, diabetes (ORs: 1.19), liver diseases (ORs: 1.29) and cataract (ORs: 4.30) were significantly associated with increasing PACG risk. For the female group, hyperlipidaemia (ORs: 1.13), headaches (ORs: 1.15), peptic ulcers (ORs: 1.14) and cataract (ORs: 3.54) were significantly associated with increasing PACG risk. For the age group of 64 years and younger, patients with comorbidity of hyperlipidaemia (ORs: 1.20), peptic ulcers (ORs: 1.21) and cataract (ORs: 5.91) were significantly associated with increasing PACG risk. For the age group of 65 years and older, patients with cataract were significantly associated with increasing PACG risk (ORs: 5.07).ConclusionsClinicians should be aware of slightly increased PACG risk in the subjects with the medical comorbidities of hyperlipidaemia, headaches, liver diseases and peptic ulcers. However, cataract is the strongest risk factor of PACG.
Prophylactic epinephrine for the prevention of transbronchial lung biopsy-related bleeding in lung transplant recipients (PROPHET) study: a protocol for a multicentre randomised, double-blind, placebo-controlled trial
Authors: Kalchiem-Dekel Or , Iacono Aldo , Pickering Edward M , Sachdeva Ashutosh , Shah Nirav G , Sperry Mark , Tran Bich-Chieu , Reed Robert M 
Published: March 2019

IntroductionTransbronchial lung biopsy (TBLB) is frequently performed in single-lung and double-lung transplant recipients for evaluation of clinical and radiological findings as well as routine surveillance for acute cellular rejection. While rates of clinically significant TBLB-related haemorrhage are <1% for all comers, the incidence in lung transplant recipients is reported to be higher, presumably due to persistent allograft inflammation and alterations in allograft blood flow. While routinely performed by some bronchoscopists, the efficacy and safety profile of prophylactic administration of topical intrabronchial diluted epinephrine for the prevention of TBLB-related haemorrhage has not been explored in a prospective manner.Methods and analysisIn this randomised, double-blind, placebo-controlled multicentre trial (PROPHET Study), single-lung and double-lung transplant adult recipients from participating institutions who are scheduled for bronchoscopy with TBLB for clinical indications will be identified. Potential participants who meet inclusion and exclusion criteria and sign an informed consent will be randomised to receive either diluted epinephrine or placebo prior to performance of TBLB. The degree of TBLB-related haemorrhage will be graded by the performing bronchoscopist as well as independent observers. The primary analysis will compare the rates of severe and very severe bleeding in participants treated with epinephrine or placebo. The study will also evaluate the safety profile of prophylactic topical epinephrine including the occurrence of serious cardiovascular and haemodynamic adverse events. Additional secondary outcomes to be explored include rates of non-severe TBLB-related haemorrhage, overall yield of the bronchoscopic procedure and non-serious cardiovascular and haemodynamic adverse effects.Ethics and disseminationThe study procedures were reviewed and approved by institutional review boards in participating institutions. This study is being externally monitored, and a data and safety monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences.Trial registration numberNCT03126968; Pre-results.
Assessing societal and offender perspectives on the value of offender healthcare: a stated preference research protocol
Authors: Settumba Stella Nalukwago , Shanahan Marian , Chambers Georgina, M , Schofield Peter , Butler Tony 
Published: March 2019

IntroductionThe increasing burden that offenders place on justice and health budgets necessitates better methods to determine the benefits of and value society places on offender programmes to guide policy regarding resource allocation. The aim of this paper is to demonstrate how economic methods will be used to determine the strength of preferences and value of violent offender treatment programmes from the perspectives of offenders, their families and the general population.Methods and analysisTwo stated preference economic methods, discrete choice experiment (DCE) and contingent valuation (CV), will be used to assess society’s and offenders' value of treatment programmes. The mixed methods process involves a literature review and qualitative methods to derive attributes and levels for the DCE and payment card values for the CV. Consensus building approaches of voting, ranking and the Delphi method will be used to further refine the findings from the qualitative phase. Attributes and their levels will be used in a D-efficient Bayesian experimental design to derive choice scenarios for the development of a questionnaire that will also include CV questions. Finally, quantitative surveys to assess societal preferences and value in terms of willingness to pay will be conducted.Ethics and disseminationEthics approval for this study was obtained from the University of New South Wales (UNSW) Human Research Ethics Committee, Corrective Services New South Wales Ethics Committee and the Aboriginal Health and Medical Research Council ethics committee. The findings will be made available on the Kirby Institute UNSW website, published in peer-reviewed journals and presented at national and international conferences.
Progress and setbacks in socioeconomic inequalities in adolescent health-related behaviours in Brazil: results from three cross-sectional surveys 2009–2015
Authors: Azeredo Catarina Machado , de Rezende Leandro F M , Mallinson Poppy Alice Carson , Ricardo Camila Zancheta , Kinra Sanjay , Levy Renata B , Barros Aluisio J D 
Published: March 2019

ObjectivesDespite some progress, Brazil is still one of the most unequal countries, and the extent of socioeconomic inequalities in adolescent health is unclear. We assessed trends in socioeconomic inequalities in adolescent’s health-related behaviours in Brazil between 2009 and 2015.DesignWe used cross-sectional data from the Brazilian National Survey of School Health carried out in 2009, 2012 and 2015.SettingBrazilian state capitals.ParticipantsStudents attending ninth grade from public and private schools in Brazilian state capitals in 2009 (60 973 students), 2012 (61 145 students) and 2015 (51 192 students).Main outcome measureWe assessed 12 health-related behaviours (irregular fruit, vegetables and bean consumption; regular soft drink consumption; irregular physical activity; alcohol, drug and tobacco use; unsafe sex; involvement in gun fights; bullying victimisation and domestic violence victimisation), under the broad domains of lifestyle risk behaviours, engagement in risky activities and exposure to violence. Socioeconomic status was assessed through an asset-based wealth index derived from principal component analysis. Absolute and relative inequalities in these health behaviours and inequalities trends were investigated.ResultsFrom 2009 to 2015, prevalence of certain harmful health-related behaviours increased, such as unsafe sex (21.5% to 33.9%), domestic violence (9.5% to 16.2%), bullying victimisation (14.2% to 21.7%) and irregular consumption of beans (37.5% to 43.7%). Other indicators decreased: alcohol use (27.1% to 23.2%), irregular physical activity (83.0% to 75.6%) and consumption of soft drinks (37.2% to 28.8%). Over the period, we found consistent evidence of decreasing health inequalities for lifestyle behaviours (fruit, bean and soft drink consumption) and alcohol use, set against increasing inequalities in violence (domestic violence, fights using guns and bullying victimisation).ConclusionSocioeconomic inequality increased in the violence domain and decreased for lifestyle behaviours among Brazilian adolescents. Widening gaps in violence domain urge immediately policy measures in Brazil.