bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Evasion byStaphylococcus aureus
Authors: de Jong Nienke W. M. , van Kessel Kok P. M. , van Strijp Jos A. G. 
Published: March 2019

ABSTRACTStaphylococcus aureushas become a serious threat to human health. In addition to having increased antibiotic resistance, the bacterium is a master at adapting to its host by evading almost every facet of the immune system, the so-called immune evasion proteins. Many of these immune evasion proteins target neutrophils, the most important immune cells in clearingS. aureusinfections. The neutrophil attacks pathogens via a plethora of strategies. Therefore, it is no surprise thatS. aureushas evolved numerous immune evasion strategies at almost every level imaginable. In this review we discuss step by step the aspects of neutrophil-mediated killing ofS. aureus, such as neutrophil activation, migration to the site of infection, bacterial opsonization, phagocytosis, and subsequent neutrophil-mediated killing. After each section we discuss howS. aureusevasion molecules are able to resist the neutrophil attack of these different steps. To date, around 40 immune evasion molecules ofS. aureusare known, but its repertoire is still expanding due to the discovery of new evasion proteins and the addition of new functions to already identified evasion proteins. Interestingly, because the different parts of neutrophil attack are redundant, the evasion molecules display redundant functions as well. Knowing how and with which proteinsS. aureusis evading the immune system is important in understanding the pathophysiology of this pathogen. This knowledge is crucial for the development of therapeutic approaches that aim to clear staphylococcal infections.
Use of clinical algorithms and rapid influenza testing to manage influenza-like illness: a cost-effectiveness analysis in Sri Lanka
Authors: Tillekeratne L Gayani , Bodinayake Champica , Nagahawatte Ajith , Kurukulasooriya Ruvini , Orlando Lori A , Simmons Ryan A , Park Lawrence P , Woods Christopher W , Reed Shelby D 
Published: March 2019

BackgroundAcute respiratory infections are a common reason for antibiotic overuse. We previously showed that providing Sri Lankan clinicians with positive rapid influenza test results was associated with a reduction in antibiotic prescriptions. The economic impact of influenza diagnostic strategies is unknown.MethodsWe estimated the incremental cost per antibiotic prescription avoided with three diagnostic strategies versus standard care when managing Sri Lankan outpatients with influenza-like illness (ILI): (1) influenza clinical prediction tool, (2) targeted rapid influenza testing and (3) universal rapid influenza testing. We compared findings with literature-based estimates of the cost of antimicrobial resistance attributable to each antibiotic prescription.ResultsStandard care was less expensive than other strategies across all parameter values in one-way sensitivity analyses. The incremental cost per antibiotic prescription avoided with clinical prediction versus standard care was US$3.0, which was lower than the base-case estimate of the cost of antimicrobial resistance per ILI antibiotic prescription (US$12.5). The incremental cost per antibiotic prescription avoided with targeted testing and universal testing versus standard care were both higher than the base-case cost of antimicrobial resistance per ILI antibiotic prescription: US$49.1 and US$138.3, respectively. To obtain a cost-effectiveness ratio lower than US$12.5 with targeted testing versus standard care, the test price must be <US$2.6. At a higher threshold of US$28.7, the test price must be <US$7.7.ConclusionClinical prediction tools and targeted rapid influenza testing may be cost-saving strategies in Sri Lanka when accounting for the societal cost of antimicrobial resistance.
Prescribing practice of pregabalin/gabapentin in pain therapy: an evaluation of German claim data
Authors: Viniol Annika , Ploner Tina , Hickstein Lennart , Haasenritter Jörg , Klein Karl Martin , Walker Jochen , Donner-Banzhoff Norbert , Becker Annette 
Published: March 2019

ObjectivesTo analyse the prevalence and incidence of pregabalin and gabapentin (P/G) prescriptions, typical therapeutic uses of P/G with special attention to pain-related diagnoses and discontinuation rates.DesignSecondary data analysis.SettingPrimary and secondary care in Germany.ParticipantsFour million patients in the years 2009–2015 (anonymous health insurance data).InterventionNone.Primary and secondary outcome measuresP/G prescribing rates, P/G prescribing rates associated with pain therapy, analysis of pain-related diagnoses leading to new P/G prescriptions and the discontinuation rate of P/G.ResultsIn 2015, 1.6% of insured persons received P/G prescriptions. Among the patients with pain first treated with P/G, as few as 25.7% were diagnosed with a typical neuropathic pain disorder. The remaining 74.3% had either not received a diagnosis of neuropathic pain or showed a neuropathic component that was pathophysiologically conceivable but did not support the prescription of P/G. High discontinuation rates were observed (85%). Among the patients who had discontinued the drug, 61.1% did not receive follow-up prescriptions within 2 years.ConclusionThe results show that P/G is widely prescribed in cases of chronic pain irrespective of neuropathic pain diagnoses. The high discontinuation rate indicates a lack of therapeutic benefits and/or the occurrence of adverse effects.
Music Interventions for Dementia and Depression in ELderly care (MIDDEL): protocol and statistical analysis plan for a multinational cluster-randomised trial
Authors: Gold Christian , Eickholt Jasmin , Assmus Jörg , Stige Brynjulf , Wake Jo Dugstad , Baker Felicity Anne , Tamplin Jeanette , Clark Imogen , Lee Young-Eun Claire , Jacobsen Stine Lindahl , Ridder Hanne Mette Ochsner , Kreutz Gunter , Muthesius Dorothea , Wosch Thomas , Ceccato Enrico , Raglio Alfredo , Ruggeri Mirella , Vink Annemiek , Zuidema Sytse , Odell-Miller Helen , Orrell Martin , Schneider Justine , Kubiak Christine , Romeo Renee , Geretsegger Monika 
Published: March 2019

IntroductionIn older adults, dementia and depression are associated with individual distress and high societal costs. Music interventions such as group music therapy (GMT) and recreational choir singing (RCS) have shown promising effects, but their comparative effectiveness across clinical subgroups is unknown. This trial aims to determine effectiveness of GMT, RCS and their combination for care home residents and to examine heterogeneity of treatment effects across subgroups.Methods and analysisThis large, pragmatic, multinational cluster-randomised controlled trial with a 2×2 factorial design will compare the effects of GMT, RCS, both or neither, for care home residents aged 65 years or older with dementia and depressive symptoms. We will randomise 100 care home units with ≥1000 residents in total across eight countries. Each intervention will be offered for 6 months (3 months 2 times/week followed by 3 months 1 time/week), with extension allowed if locally available. The primary outcome will be the change in the Montgomery-Åsberg Depression Rating Scale score at 6 months. Secondary outcomes will include depressive symptoms, cognitive functioning, neuropsychiatric symptoms, psychotropic drug use, caregiver burden, quality of life, mortality and costs over at least 12 months. The study has 90% power to detect main effects and is also powered to determine interaction effects with gender, severity and socioeconomic status.Ethics and disseminationEthical approval has been obtained for one country and will be obtained for all countries. Results will be presented at national and international conferences and published in scientific journals.Trial registration numbersNCT03496675; Pre-results, ACTRN12618000156280.
Does ethnic diversity explain intra-UK variation in mortality? A longitudinal cohort study
Authors: Schofield Lauren , Walsh David , Feng Zhiqiang , Buchanan Duncan , Dibben Chris , Fischbacher Colin , McCartney Gerry , Munoz-Arroyo Rosalia , Whyte Bruce 
Published: March 2019

ObjectivesIt has been proposed that part of the explanation for higher mortality in Scotland compared with England and Wales, and Glasgow compared with other UK cities, relates to greater ethnic diversity in England and Wales. We sought to assess the extent to which this excess was attenuated by adjusting for ethnicity. We additionally explored the role of country of birth in any observed differences.SettingScotland and England and Wales; Glasgow and Manchester.ParticipantsWe used the Scottish Longitudinal Study and the Office for National Statistics Longitudinal Study of England and Wales (2001–2010). Participants (362 491 in total) were aged 35–74 years at baseline.Primary outcome measuresRisk of all-cause mortality between 35 and 74 years old in Scotland and England and Wales, and in Glasgow and Manchester, adjusting for age, gender, socioeconomic position (SEP), ethnicity and country of birth.Results18% of the Manchester sample was non-White compared with 3% in Glasgow (England and Wales: 10.4%; Scotland: 1.2%). The mortality incidence rate ratio was 1.33 (95% CI 1.13 to 1.56) in Glasgow compared with Manchester. This reduced to 1.25 (1.07 to 1.47) adjusting for SEP, and to 1.20 (1.02 to 1.42) adjusting for ethnicity and country of birth. For Scotland versus England and Wales, the corresponding figures were 18% higher mortality, reducing to 10%, and then 7%. Non-Whites born outside the UK had lower mortality. In the Scottish samples only, non-Whites born in the UK had significantly higher mortality than Whites born in the UK.ConclusionsThe research supports the hypothesis that ethnic diversity and migration from outside UK play a role in explaining Scottish excess mortality. In Glasgow especially, however, a large excess remains: thus, previously articulated policy implications (addressing poverty, vulnerability and inequality) still apply.
Health informatics competencies in postgraduate medical education and training in the UK: a mixed methods study
Authors: Jidkov Lydia , Alexander Matthew , Bark Pippa , Williams John G , Kay Jonathan , Taylor Paul , Hemingway Harry , Banerjee Amitava 
Published: March 2019

ObjectiveTo assess health informatics (HI) training in UK postgraduate medical education, across all specialties, against international standards in the context of UK digital health initiatives (eg, Health Data Research UK, National Health Service Digital Academy and Global Digital Exemplars).DesignA mixed methods study of UK postgraduate clinician training curricula (71 specialties) against international HI standards: scoping review, curricular content analysis and expert consultation.Setting and participantsA scoping literature review (PubMed until March 2017) informed development of a contemporary framework of HI competency domains for doctors. National training curricula for 71 postgraduate medical specialties were obtained from the UK General Medical Council and were analysed. Seven UK HI experts were consulted regarding findings.OutcomesThe International Medical Informatics Association (IMIA) Recommendations for Biomedical and Health Informatics Education were used to develop a framework of competency domains. The number (maximum 50) of HI competency domains included in each of the 71 UK postgraduate medical specialties was investigated. After expert review, a universal HI competency framework was proposed.ResultsA framework of 50 HI competency domains was developed using 21 curricula from a scoping review, curricular content analysis and expert consultation. All 71 UK postgraduate medical curricula documents were mapped across 29 of 50 framework domains; that is, 21 domains were unrepresented. Curricula mapped between 0 (child and adolescent psychiatry and core surgical training) and 16 (chemical pathology and paediatric and perinatal pathology) of the 50 domains (median=7). Expert consultation found that HI competencies should be universal and integrated with existing competencies for UK clinicians and were under-represented in current curricula. Additional universal HI competencies were identified, including information governance and security and secondary use of data.ConclusionsPostgraduate medical education in the UK neglects HI competencies set out by international standards. Key HI competencies need to be urgently integrated into training curricula to prepare doctors for work in increasingly digitised healthcare environments.
Kids in Action: the protocol of a Youth Participatory Action Research project to promote physical activity and dietary behaviour
Authors: Anselma Manou , Altenburg Teatske , Chinapaw Mai 
Published: March 2019

IntroductionIn this study, researchers collaborate with children from a low socioeconomic neighbourhood in Amsterdam in developing, implementing and evaluating interventions targeting their health behaviours. This Youth Participatory Action Research project focuses on the promotion of physical activity and healthy dietary behaviour.Methods and analysisThis study is a controlled trial using participatory methods to develop interventions together with children aged 9–12 years. At four primary schools in a low socioeconomic neighbourhood in Amsterdam, an ‘Action Team’ is installed: a group of six to eight children who actively participate as co-researchers in developing, implementing and evaluating interventions. An academic researcher facilitates the participatory process. Four control schools, also located in low socioeconomic areas in and around Amsterdam, continue with their regular curriculum and do not participate in the participatory process. For the effect evaluation, physical activity and sedentary behaviour are assessed using accelerometers and self-reporting; dietary behaviour using self-reporting and motor fitness (strength, flexibility, coordination, speed and endurance) using the motor performance fitness test. Effectiveness of the interventions is evaluated by multilevel regression analysis. The process of co-creating interventions and the implemented interventions is continually evaluated during meetings of the Action Teams and with children participating in the interventions. Empowerment of children is evaluated during focus groups. Summaries and transcripts of meetings are coded and analysed to enrich children’s findings.Ethics and disseminationThe Medical Ethics Committee of the VU Medical Center approved the study protocol (2016.366).Trial registration numberTC=6604.
Risk of gastroschisis with maternal genitourinary infections: the US National birth defects prevention study 1997–2011
Authors: Feldkamp Marcia L , Arnold Kathryn E , Krikov Sergey , Reefhuis Jennita , Almli Lynn M , Moore Cynthia A , Botto Lorenzo D 
Published: March 2019

ObjectiveTo assess the association between occurrence and timing of maternal self-reported genitourinary tract infection (urinary tract infections [UTIs] and/or sexually transmitted infection [STI]) and risk for gastroschisis in the offspring.DesignPopulation-based case–control study.SettingNational Birth Defects Prevention Study, a multisite study in the USA.ParticipantsMothers of 1366 gastroschisis cases and 11 238 healthy controls.Main outcome measuresCrude and adjusted ORs (aORs) with 95% CIs.ResultsGenitourinary infections were frequent in case (19.3%) and control women (9.9%) during the periconceptional period (defined as 3 months prior to 3 months after conception). UTI and/or STI in the periconceptional period were associated with similarly increased risks for gastroschisis (aOR 1.5, 95% CI 1.3 to 1.8; aOR 1.6, 95% CI 1.2 to 2.3, respectively). The risk was increased with a UTI before (aOR 2.5; 95% CI 1.4 to 4.5) or after (aOR 1.7; 95% CI 1.1 to 2.6) conception only among women ≥25 years of age. The risk was highest among women <20 years of age with an STI before conception (aOR 3.6; 95% CI 1.5 to 8.4) and in women ≥25 years of age, the risk was similar for before (aOR 2.9; 95% CI 1.0 to 8.5) and after (aOR 2.8; 95% CI 1.3 to 6.1) conception. A specific STI pathogen was reported in 89.3% (50/56) of cases and 84.3% (162/191) of controls withChlamydia trachomatisthe most common (25/50 cases, 50%; 58/162 controls, 36%) and highest among women <20 years of age (16/25 cases, 64%; 22/33 controls, 67%).ConclusionsUTI and/or STI were associated with an increased risk for gastroschisis, with the strength of the association varying by maternal age and timing of infection.
The effect of luseogliflozin and alpha-glucosidase inhibitor on heart failure with preserved ejection fraction in diabetic patients: rationale and design of the MUSCAT-HF randomised controlled trial
Authors: Ejiri Kentaro , Miyoshi Toru , Nakamura Kazufumi , Sakuragi Satoru , Munemasa Mitsuru , Namba Seiji , Takaishi Atsushi , Ito Hiroshi 
Published: March 2019

IntroductionType 2 diabetes mellitus (T2DM) is a strong risk factor for coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction (HFpEF). The aim of the ongoing MUSCAT-HF (It stands for Prospective Comparison of Luseogliflozin and Alpha-glucosidase on the Management of Diabetic Patients with Chronic Heart Failure and Preserved Ejection Fraction) trial is to evaluate the efficacy of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, versus voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) as the index of therapeutic effect in T2DM patients with HFpEF.Methods and analysisA total of 190 patients with T2DM and HFpEF (ejection fraction >45%) who are drug-naïve or taking any anti-diabetic agents will be randomised (1:1) to receive luseogliflozin 2.5 mg one time per day or voglibose 0.2 mg three times per day. The patients will be stratified by age (<65 years, ≥65 years), baseline haemoglobin A1c (<8.0%, ≥8.0%), baseline BNP (<100 pg/mL, ≥100 pg/mL), baseline renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2, <60 mL/min/1.73 m2), use of thiazolidine or not and presence or absence of atrial fibrillation and flutter at screening. After randomisation, participants will receive the study drug for 12 weeks in addition to their background therapy. The primary endpoint is the proportional change in baseline BNP after 12 weeks of treatment. The key secondary endpoints are the change from baseline in the ratio of early mitral inflow velocity to mitral annular early diastolic velocity, body weight and glycaemic control after 12 weeks of treatment.Ethics and disseminationThe study has been approved by the ethics committee and the patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberUMIN000018395
Within-individual analysis of pain and sickness absence among employees from low and high occupational classes: a record linkage study
Authors: Hiilamo Aapo , Butterworth Peter , Shiri Rahman , Ropponen Annina , Pietiläinen Olli , Mänty Minna , Kouvonen Anne , Lahelma Eero , Rahkonen Ossi , Lallukka Tea 
Published: March 2019

ObjectivesPain is linked to an increased risk of sickness absence (SA); however, the extent to which unmeasured time-invariant differences explain this association is yet unknown. Therefore, we determined the within-individual associations between pain and short-term (in the survey year) and long-term (2 years following the survey years) SA risk in high and low occupational classes while controlling for the potential bias due to unobservable time-invariant characteristics.MethodsThe Helsinki Health Study data consisting of midlife public sector employees with mailed surveys from up to four time points, and SA record linkage were used (3983 persons). The within-individual estimates were calculated using hybrid negative binomial regression models.ResultsAcute/subacute pain was associated with a 13% increase in the rate of short-term SA days (incidence rate ratio 1.13 [95% CI 1.01 to 1.27]), while the association was somewhat stronger for chronic pain (1.32 [1.19–1.47]). For the employees in the low occupational class, these associations were robust (1.29 [1.10–1.50] for acute/subacute and 1.43 [1.23–1.66] for chronic pain), whereas only chronic pain was associated with SA among those in the high occupational class (1.25 [1.08–1.46]). Chronic pain was also associated with SA days in the long term without occupational class differences. Similar results were obtained for multisite pain (pain in several locations).ConclusionsThese results indicate that particularly chronic and multisite pain have a within-individual link to SA but ignoring unobservable differences between those reporting pain and those not might yield overstated effect sizes. Pain might have a different relation to SA in low and high occupational classes.
Trends in hepatitis C treatment initiation among HIV/hepatitis C virus-coinfected men engaged in primary care in a multisite community health centre in Maryland: a retrospective cohort study
Authors: Chen Yun-Chi , Thio Chloe L , Cox Andrea L , Ruhs Sebastian , Kamangar Farin , Wiberg Kjell J 
Published: March 2019

ObjectivesLittle is known about the cascade of hepatitis C care among HIV/hepatitis C virus (HCV)-coinfected patients in community-based clinics. Thus, we analysed our data from the interferon era to understand the barriers to HCV treatment, which may help improve getting patients into treatment in the direct-acting antivirals era.DesignRetrospective cohort study.SettingFour HIV clinics of a multisite community health centre in the USA.Participants1935 HIV-infected men with >1 medical visit to the clinic between 2011 and 2013. Of them, 371 had chronic HCV and were included in the analysis for HCV care continuum during 2003–2014.Outcome measuresHCV treatment initiation was designated as the primary outcome for analysis. Multivariate logistic regression was performed to identify factors associated with HCV treatment initiation.ResultsAmong the 371 coinfected men, 57 (15%) initiated HCV treatment. Entering care before 2008 (adjusted OR [aOR, 3.89; 95% CI, 1.95 to 7.78), higher educational attainment (aOR, 3.20; 95% CI, 1.59 to 6.44), HCV genotype 1 versus non-1 (aOR, 0.21; 95% CI, 0.07 to 0.65) and HIV suppression (aOR, 2.13; 95% CI, 1.12 to 4.06) independently predicted treatment initiation. Stratification by entering care before or after 2008 demonstrated that higher educational attainment was the only factor independently associated with treatment uptake in both periods (aOR, 2.79; 95% CI, 1.13 to 6.88 and aOR, 4.10; 95% CI, 1.34 to 12.50, pre- and post-2008, respectively). Additional associated factors in those entering before 2008 included HCV genotype 1 versus non-1 (aOR, 0.09; 95% CI, 0.01 to 0.54) and HIV suppression (aOR, 2.35; 95% CI, 1.04 to 5.33).ConclusionsSome traditional barriers predicted HCV treatment initiation in those in care before 2008; however, the patients’ level of educational attainment remained an important factor even towards the end of the interferon era. Further studies will need to determine whether educational attainment persists as an important determinant for initiating direct-acting antiviral therapies.