bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Italian preparticipation evaluation programme: diagnostic yield, rate of disqualification and cost analysis
Authors: Vessella Teresina , Zorzi Alessandro , Merlo Laura , Pegoraro Cinzia , Giorgiano Flaviano , Trevisanato Michele , Viel Mirella , Formentini Pietro , Corrado Domenico , Sarto Patrizio 
Published: July 2019

Introduction
Italian law mandates that every competitive athlete must undergo annual preparticipation evaluation (PPE) to identify cardiovascular (CV) diseases that pose a risk of sudden death (SD) during sport and other conditions that may threaten the athlete’s health. We investigated the diagnostic yield, rate of disqualification and costs of our PPE.

Methods
We included 5910 consecutive apparently healthy athletes (61% males, mean age 15±4 years) who underwent annual PPE performed by a sports medicine specialist. The PPE included history, physical examination, weight, height and blood pressure measurement, test of visual acuity, spirometry, urine chemistry, resting 12-lead ECG and exercise testing with ECG monitoring. In cases of abnormal findings, we carried out second-line investigations.

Results
During a 12-month study period, 5.326 (90.2%) athletes were cleared for competition after a normal first-line evaluation and 584 (9.8%) underwent one or more further examinations. Of those, 88 (1.5%) were diagnosed to have a CV disease (including 18 (0.3%) at-risk of SD) and 31 (0.5%) had a non-CV diagnosis. A total of 32 (0.5%) athletes were temporarily (n=15) or permanently (n=17) disqualified from competitive sports. The average cost per athlete was €79, which consisted of €64 (80%) for first-line evaluations and €15 (20%) for additional investigations.

Conclusion
PPE according to the Italian model identified a range of diseases in 2.0% of apparently healthy athletes at an average cost of €79.
Spending on World Health Organization essential medicines in Medicare Part D, 2011-15: retrospective cost analysis
Authors: Li David G , Najafzadeh Mehdi , Kesselheim Aaron S , Mostaghimi Arash 
Published: July 2019

AbstractObjectivesTo characterize the trends, drivers, and potential modifiers of increased spending by US Medicare beneficiaries on medicines deemed essential by the World Health Organization.DesignRetrospective cost analysis of Medicare Part D Prescriber Public Use File, detailing annual generic and brand name drug prescribing and spending from 2011 through 2015 by Medicare Part D participants who filled prescriptions for WHO essential medicines.SettingUS Medicare System.Main outcome measuresTotal and per beneficiary Medicare spending, total and per beneficiary out-of-pocket patient spending, cumulative beneficiary count, claim count, and per unit drug cost. All spending measures were adjusted for inflation and reported in 2015 US dollars.ResultsMedicare Part D expenditures on 265 WHO essential medicines between 2011 and 2015 was $87.2bn (£68.4bn; €76.5bn), with annual spending increasing from $11.9bn in 2011 to $25.8bn in 2015 (116%). Patients’ out-of-pocket spending for essential medicines over the same period was $12.1bn. Total annual out-of-pocket spending increased from $2.0bn to $2.9bn (47%), and annual per beneficiary out-of-pocket spending on these drugs increased from $20.42 to $21.17 (4%). Total prescription count increased from 376.1m to 498.9m (33%), and cumulative beneficiary count grew from 95.9m to 135.8m (42%). Of the essential medicines included in the study, the per unit cost of 133 (50%) agents increased faster than the average inflation rate during this period. Overall, approximately 58% of the increase in total spending during this period can be attributed to the introduction of novel agents.ConclusionsSpending associated with essential medicines grew substantially from 2011 to 2015, driven largely by the increased use of two expensive novel drugs used in treating hepatitis C. Approximately 22% of increased total spending during this period can be attributed to increases in per unit cost of existing drugs. These trends may limit patients’ access to essential drugs while also increasing healthcare system costs.
Descriptive analysis of real-world medication use pattern of statins and antiplatelet agents among patients with acute coronary syndrome in Hong Kong and the USA
Authors: Wang Yun , Nichol Michael B , Yan Bryan PY , Wu Joanne , Tomlinson Brian , Lee Vivian WY 
Published: July 2019

ObjectivesThe objective was to explore the differences in medication use pattern of lipid-lowering drug (LLD) and antiplatelet agents among post-percutaneous coronary intervention patients with acute coronary syndrome aged <65 in Hong Kong (HK) and the USA.DesignRetrospective study.SettingThis study used deidentified claims data from Clinformatics Data Mart database (OptumInsight, Eden Prairie, Minnesota, USA) and electronic health records from HK Hospital Authority Clinical Data Analysis and Reporting System database.ParticipantsWe used 1 year prescription records of LLDs and antiplatelet agents among 1013 USA patients and 270 HK Chinese patients in 2011–2013.Primary and secondary outcome measuresContinuity was investigated on the assumption that one defined daily dose represented 1 day treatment. Medication possession ratio method was used to evaluate the adherence. Multivariate-adjusted logistic regressions were constructed to compare the good continuity and adherence levels in the merged database with the cutoffs set at 80%, and Cox proportional hazard models were built using the time to discontinuation as the dependent variable, to assess the persistence level.ResultsHK Chinese patients were less adherent (67.41% vs 84.60%, adjusted odds ratio (AOR) for Americans over Chinese=2.23 (95% CI=1.60 to 3.12), p<0.001) to antiplatelet agents compared with American patients but better adherent to statins (90.00% vs 78.18%, AOR=0.37 (0.23 to 0.58), p<0.001). The discontinuation with statins was more common in American patients (13.33% vs 34.25%, adjusted hazard ratio (AHR)=2.95 (2.05 to 4.24), p<0.001). Low-to-moderate potency statins and clopidogrel were favoured by our HK local physicians, while American patients received higher doses of statins and prasugrel.ConclusionsWe seemed to find HK physicians tended to prescribe cheaper and lower doses of statins and antiplatelet agents when compared with the privately insured patients in the USA, though the adherence and persistence levels of HK patients with statins were relatively good.
National medical expenditures by smoking status in American adults: an application of Manning’s two-stage model to nationally representative data
Authors: Swedler David I , Miller Ted R , Ali Bina , Waeher Geetha , Bernstein Steven L 
Published: July 2019

ObjectivesTo assess the medical expenditures of American adults by their smoking status—Current, Former or Never smokers. We update these expenditures through 2015 controlling for personal characteristics and medical history and assess the impact of years-since-quitting and decade of life.Setting and participantsWeighted sample of American adults, 2011–2015. The linked National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS) are annual weighted representations of approximately 250 million adults. Sampling of NHIS is multistage with data collected throughout the year.Primary outcome measuresUsing data from NHIS and MEPS, we collected demographic data, self-reported medical history and current smoking status. Smoking status was designated as Never, Current and Former, along with years-since-quitting. Total medical expenditures were collected from MEPS for 2011–2015. We used Manning’s two-part model to estimate average expenditures per individual and marginal costs for individuals at all levels of smoking status.ResultsAmerican adults averaged US$4830 in average medical expenditures. Never smokers (US$4360, 95% CI 4154.3 to 4566.3), had lower expenditures than Current (US$5244, 95% CI 4707.9 to 5580.3) and Former (US$5590, 95% CI 5267.4 to 5913.5) smokers. CI for Current and Former smokers overlapped. Results were similarly significant when controlling for disease history. Years-since-quitting did not affect expenditures. In each decade of adult life, Former smokers had the highest annual medical expenditures, followed by Current and then Never smokers.ConclusionsWe updated annual medical expenditures during the Affordable Care Act era by smoking status using the current best practice model. While we identify Former smokers as having higher medical expenditures than Current smokers, we do not examine how care-seeking behaviour varies between levels of each risk factor.
Methodology for developing and evaluating food-based dietary guidelines and a Healthy Eating Index for Ethiopia: a study protocol
Authors: Bekele Tesfaye Hailu , de Vries Jeanne JHM , Trijsburg Laura , Feskens Edith , Covic Namukolo , Kennedy Gina , Brouwer Inge D 
Published: July 2019

IntroductionFood-based dietary guidelines (FBDGs) are used to promote and maintain healthy eating in a population, by providing country-specific guidance. However, many African countries like Ethiopia do not have FBDGs. This paper describes the methodology for the development of Ethiopian FBDGs and for creating and evaluating a Healthy Eating Index and a scoring tool that can be used to monitor the adherence of the population to FBDGs.Methods and analysisA multidisciplinary technical working group will be tasked to develop FBDGs for the general population above 2 years of age based on identification of priority diet-related public health problems and risk factors, and a systematic review of dietary patterns in relation to the identified priority health outcomes, following a multistep process. FBDGs will be translated into daily food choices for specific subpopulations by applying linear programming using data from the National Food Consumption Survey (NFCS) of 2011. FBDGs will be evaluated for cultural appropriateness, acceptability, consumer understanding and practicality. A dietary gap assessment will be conducted by comparing the national food supply with the country’s food demand. In addition an Ethiopian Healthy Eating Index (EHEI) will be developed based on the FBDGs using the NFCS data. The EHEI will be evaluated by comparing the EHEI Score based on 24 hours diet recall with that of the EHEI Score based on a Food Frequency Questionnaire, by analysing the association of the EHEI Score with population characteristics and micronutrient intake with or without additional adjustment for energy intake. Finally, a brief Food Quality Screening tool scoring for the important EHEI components will be developed to enable evaluation for counselling.Ethics and disseminationEthical approval is received from the Scientific and Ethical Review Office of the Ethiopian Public Health Institute. The findings will be disseminated through peer-reviewed publications.A dissemination workshop will be organised with key implementing sectors of the food system for a healthier diet (http://a4nh.cgiar.org/our-research/research-flagships/) and with key public and private partners. The findings from this study will be translated into FBDGs and shared through conferences, reports and the mass media (TV and radio).Trial registration numberNCT03394963; Pre-results.
Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine
Authors: Herd Clare P , Tomlinson Claire L , Rick Caroline , Scotton William J , Edwards Julie , Ives Natalie J , Clarke Carl E , Sinclair AJ 
Published: July 2019

ObjectivesTo assess the effects of botulinum toxin for prevention of migraine in adults.DesignSystematic review and meta-analysis.Data sourcesCENTRAL, MEDLINE, Embase and trial registries.Eligibility criteriaWe included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache.Data extraction and synthesisCochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed.ResultsTwenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of −2.0 migraine days/month (95% CI −2.8 to −1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of −2.70 cm (95% CI −3.31 to −2.09, n=75) and −4.9 cm (95% CI −6.56 to −3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes.ConclusionsIn chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.
Lowering blood pressure after acute intracerebral haemorrhage: protocol for a systematic review and meta-analysis using individual patient data from randomised controlled trials participating in the Blood Pressure in Acute Stroke Collaboration (BASC)
Authors: Moullaali Tom J , Wang Xia , Woodhouse Lisa J , Law Zhe Kang , Delcourt Candice , Sprigg Nikola , Krishnan Kailash , Robinson Thompson G , Wardlaw Joanna M , Al-Shahi Salman Rustam , Berge Eivind , Sandset Else C , Anderson Craig S , Bath Philip M 
Published: July 2019

IntroductionConflicting results from multiple randomised trials indicate that the methods and effects of blood pressure (BP) reduction after acute intracerebral haemorrhage (ICH) are complex. The Blood pressure in Acute Stroke Collaboration is an international collaboration, which aims to determine the optimal management of BP after acute stroke including ICH.Methods and analysisA systematic review will be undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (IPD) guideline. A search of Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception will be conducted to identify randomised controlled trials of BP management in adults with acute spontaneous (non-traumatic) ICH enrolled within the first 7 days of symptom onset. Authors of studies that meet the inclusion criteria will be invited to share their IPD. The primary outcome will be functional outcome according to the modified Rankin Scale. Safety outcomes will be early neurological deterioration, symptomatic hypotension and serious adverse events. Secondary outcomes will include death and neuroradiological and haemodynamic variables. Meta-analyses of pooled IPD using the intention-to-treat dataset of included trials, including subgroup analyses to assess modification of the effects of BP lowering by time to treatment, treatment strategy and patient’s demographic, clinical and prestroke neuroradiological characteristics.Ethics and disseminationNo new patient data will be collected nor is there any deviation from the original purposes of each study where ethical approvals were granted; therefore, further ethical approval is not required. Results will be reported in international peer-reviewed journals.PROSPERO registration numberCRD42019141136.
Expression of the type 3 InsP3receptor is a final common event in the development of hepatocellular carcinoma
Authors: Guerra Mateus T , Florentino Rodrigo M , Franca Andressa , Lima Filho Antonio C , dos Santos Marcone L , Fonseca Roberta C , Lemos Fernanda O , Fonseca Matheus C , Kruglov Emma , Mennone Albert , Njei Basile , Gibson Joanna , Guan Fulan , Cheng Yung-Chi , Ananthanarayanam Meenakshisundaram , Gu Jianlei , Jiang Jianping , Zhao Hongyu , Lima Cristiano X , Vidigal Paula T , Oliveira Andre G , Nathanson Michael H , Leite Maria Fatima 
Published: July 2019

Background & objectivesHepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Several types of chronic liver disease predispose to HCC, and several different signalling pathways have been implicated in its pathogenesis, but no common molecular event has been identified. Ca2+signalling regulates the proliferation of both normal hepatocytes and liver cancer cells, so we investigated the role of intracellular Ca2+release channels in HCC.DesignExpression analyses of the type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR3) in human liver samples, liver cancer cells and mouse liver were combined with an evaluation of DNA methylation profiles of ITPR3 promoter in HCC and characterisation of the effects of ITPR3 expression on cellular proliferation and apoptosis. The effects ofde novoITPR3 expression on hepatocyte calcium signalling and liver growth were evaluated in mice.ResultsITPR3 was absent or expressed in low amounts in hepatocytes from normal liver, but was expressed in HCC specimens from three independent patient cohorts, regardless of the underlying cause of chronic liver disease, and its increased expression level was associated with poorer survival. TheITPR3gene was heavily methylated in control liver specimens but was demethylated at multiple sites in specimens of patient with HCC. Administration of a demethylating agent in a mouse model resulted in ITPR3 expression in discrete areas of the liver, and Ca2+signalling was enhanced in these regions. In addition, cell proliferation and liver regeneration were enhanced in the mouse model, and deletion ofITPR3from human HCC cells enhanced apoptosis.ConclusionsThese results provide evidence thatde novoexpression of ITPR3 typically occurs in HCC and may play a role in its pathogenesis.
Interaction of ischaemic postconditioning and thrombectomy in patients with ST-elevation myocardial infarction
Authors: Nepper-Christensen Lars , Høfsten Dan Eik , Helqvist Steffen , Lassen Jens Flensted , Tilsted Hans-Henrik , Holmvang Lene , Pedersen Frants , Joshi Francis , Sørensen Rikke , Bang Lia , Bøtker Hans Erik , Terkelsen Christian Juhl , Maeng Michael , Jensen Lisette Okkels , Aarøe Jens , Kelbæk Henning , Køber Lars , Engstrøm Thomas , Lønborg Jacob 
Published: July 2019

ObjectiveThe Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction – Ischaemic Postconditioning (DANAMI-3-iPOST) did not show improved clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with ischaemic postconditioning. However, the use of thrombectomy was frequent and thrombectomy may in itself diminish the effect of ischaemic postconditioning. We evaluated the effect of ischaemic postconditioning in patients included in DANAMI-3-iPOST stratified by the use of thrombectomy.MethodsPatients with STEMI were randomised to conventional primary percutaneous coronary intervention (PCI) or ischaemic postconditioning plus primary PCI. The primary endpoint was a combination of all-cause mortality and hospitalisation for heart failure.ResultsFrom March 2011 until February 2014, 1234 patients were included with a median follow-up period of 35 (interquartile range 28 to 42) months. There was a significant interaction between ischaemic postconditioning and thrombectomy on the primary endpoint (p=0.004). In patients not treated with thrombectomy (n=520), the primary endpoint occurred in 33 patients (10%) who underwent ischaemic postconditioning (n=326) and in 35 patients (18%) who underwent conventional treatment (n=194) (adjusted hazard ratio (HR) 0.55 (95%confidence interval (CI) 0.34 to 0.89), p=0.016). In patients treated with thrombectomy (n=714), there was no significant difference between patients treated with ischaemic postconditioning (n=291) and conventional PCI (n=423) on the primary endpoint (adjusted HR 1.18 (95% CI 0.62 to 2.28), p=0.62).ConclusionsIn this post-hoc study of DANAMI-3-iPOST, ischaemic postconditioning, in addition to primary PCI, was associated with reduced risk of all-cause mortality and hospitalisation for heart failure in patients with STEMI not treated with thrombectomy.Trial registration numberNCT01435408.
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial
Authors: Heber Stefan , Fischer Beatrix , Sallaberger-Lehner Marina , Hausharter Maria , Ocenasek Helmuth , Gleiss Andreas , Fischer Michael J M , Pokan Rochus , Assinger Alice , Volf Ivo 
Published: July 2019

ObjectiveTo compare effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on platelet function in patients undergoing cardiac rehabilitation, as hyper-reactive platelets are involved in atherogenesis and atherothrombosis.MethodsIn this single-centre parallel group randomised controlled trial, male patients after an acute coronary syndrome under dual antiplatelet therapy performed MICT or HIIT+MICT for 12 weeks. Main outcome was platelet reactivity measured by the half-maximal concentration (EC50) of platelet agonist thrombin receptor-activating peptide-6 (TRAP-6) in terms of P-selectin expression. EC50was determined at baseline, after 6 and 12 weeks, each time at physical rest and on exertion.Results82 patients were randomised to MICT or HIIT+MICT. Mean (95% CI) baseline EC50values at physical rest were 6.7 µM (6.3 µM to 7.0 µM) TRAP-6. After 6/12 weeks, 36/33 MICT and 34/28 HIIT+MICT patients were examined. HIIT+MICT patients had 0.9 µM (0.4 µM to 1.4 µM)/0.5 µM (−0.1 µM to 1.0 µM) higher EC50values than MICT ones, and the propensity of their platelets to form aggregates with monocytes was significantly lower after 12 weeks. Short-term strenuous physical exertion was generally associated with platelet activation and an EC50reduction of 0.7 µM (0.6 µM to 0.8 µM). HIIT+MICT patients tended to be fitter after 12 weeks. No serious harms were observed.ConclusionsIncluding HIIT in cardiac rehabilitation seems to confer additional benefits compared with MICT alone, which should be confirmed in clinical trials with hard endpoints. Exertion-induced platelet activation and hyper-reactivity occur despite dual antiplatelet therapy.Trial registration numberNCT02930330; Results.