bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits and risks of Iron interventions in children (BRISC): protocol for a three-arm parallel-group randomised controlled field trial in Bangladesh
Authors: Hasan Mohammed Imrul , Hossain Sheikh Jamal , Braat Sabine , Dibley Michael John , Fisher Jane , Grantham-McGregor Sally , Tofail Fahmida , Simpson Julie A , Arifeen Shams EI , Hamadani Jena , Biggs Beverley-Ann , Pasricha Sant-Rayn 
Published: November 2017

IntroductionAnaemia is a major global health problem affecting about 43% of preschool children globally and 60% of 6–24-month-old children in rural Bangladesh, half of which is attributed to iron deficiency (ID). Although WHO recommends universal supplementation with iron or home fortification with iron-containing multiple micronutrient powders (MMPs) to children under 2 years, evidence for benefits of these interventions on childhood development (a key rationale for these interventions) and harms (especially infection) remains limited. This study aims to evaluate the impact of iron or MMPs supplementation compared with placebo on (a) children’s development, (b) growth, (c) morbidity from infections and (d) haematological and iron indices.Methods and analysisThis study is a three-arm, blinded, double-dummy, parallel-group, placebo-controlled superiority trial using stratified individual block randomisation. The trial will randomise 3300 children aged 8–9 months equally to arm 1: iron syrup (12.5 mg elemental iron), placebo MMPs; arm 2: MMPs (including 12.5 mg elemental iron), placebo syrup; and arm 3: placebo syrup, placebo MNPs. Children will receive interventions for 3 months based on WHO recommendations and then be followed up for 9 months post intervention. The primary outcome is cognitive composite score measured by Bayley III. Secondary outcomes include motor and language composite score by Bayley III, behaviour rating using selected items from Wolke’s rating scales and BSID-II behaviour ratings, temperament, growth, haemoglobin, anaemia and iron status, and infectious morbidity. Outcomes will be measured at baseline, at the end of 3-month intervention and after 9 months postintervention follow-up.Ethics and disseminationThe trial has been approved by the Ethical Review Committee of icddr,b (Dhaka, Bangladesh) and the Melbourne Health Human Research Ethics Committee (Melbourne, Australia). Results of the study will be disseminated through scientific publications, presentations at international meetings and policy briefs to key stakeholders.Trial registration numberACTRN12617000660381;Pre-results.WHO Universal Trial NumberU1111-1196-1125.
Dynamic treatment selection and modification for personalised blood pressure therapy using a Markov decision process model: a cost-effectiveness analysis
Authors: Choi Sung Eun , Brandeau Margaret L , Basu Sanjay 
Published: November 2017

ObjectivePersonalised medicine seeks to select and modify treatments based on individual patient characteristics and preferences. We sought to develop an automated strategy to select and modify blood pressure treatments, incorporating the likelihood that patients with different characteristics would benefit from different types of medications and dosages and the potential severity and impact of different side effects among patients with different characteristics.Design, setting and participantsWe developed a Markov decision process (MDP) model to incorporate meta-analytic data and estimate the optimal treatment for maximising discounted lifetime quality-adjusted life-years (QALYs) based on individual patient characteristics, incorporating medication adjustment choices when a patient incurs side effects. We compared the MDP to current US blood pressure treatment guidelines (the Eighth Joint National Committee, JNC8) and a variant of current guidelines that incorporates results of a major recent trial of intensive treatment (Intensive JNC8). We used a microsimulation model of patient demographics, cardiovascular disease risk factors and side effect probabilities, sampling from the National Health and Nutrition Examination Survey (2003–2014), to compare the expected population outcomes from adopting the MDP versus guideline-based strategies.Main outcome measuresCosts and QALYs for the MDP-based treatment (MDPT), JNC8 and Intensive JNC8 strategies.ResultsCompared with the JNC8 guideline, the MDPT strategy would be cost-saving from a societal perspective with discounted savings of US$1187 per capita (95% CI 1178 to 1209) and an estimated discounted gain of 0.06 QALYs per capita (95% CI 0.04 to 0.08) among the US adult population. QALY gains would largely accrue from reductions in severe side effects associated with higher treatment doses later in life. The Intensive JNC8 strategy was dominated by the MDPT strategy.ConclusionsAn MDP-based approach can aid decision-making by incorporating meta-analytic evidence to personalise blood pressure treatment and improve overall population health compared with current blood pressure treatment guidelines.
Diagnostic and laboratory test ordering in Northern Portuguese Primary Health Care: a cross-sectional study
Authors: Sá Luísa , Teixeira Andreia Sofia Costa , Tavares Fernando , Costa-Santos Cristina , Couto Luciana , Costa-Pereira Altamiro , Hespanhol Alberto Pinto , Santos Paulo , Martins Carlos 
Published: November 2017

ObjectivesTo characterise the test ordering pattern in Northern Portugal and to investigate the influence of context-related factors, analysing the test ordered at the level of geographical groups of family physicians and at the level of different healthcare organisations.DesignCross-sectional study.SettingNorthern Primary Health Care, Portugal.ParticipantsRecords about diagnostic and laboratory tests ordered from 2035 family physicians working at the Northern Regional Health Administration, who served approximately 3.5 million Portuguese patients, in 2014.OutcomesTo determine the 20 most ordered diagnostic and laboratory tests in the Northern Regional Health Administration; to identify the presence and extent of variations in the 20 most ordered diagnostic and laboratory tests between the Groups of Primary Care Centres and between health units; and to study factors that may explain these variations.ResultsThe 20 most ordered diagnostic and laboratory tests almost entirely comprise laboratory tests and account for 70.9% of the total tests requested. We can trace a major pattern of test ordering for haemogram, glucose, lipid profile, creatinine and urinalysis. There was a significant difference (P<0.001) in test orders for all tests between Groups of Primary Care Centres and for all tests, except glycated haemoglobin (P=0.06), between health units. Generally, the Personalised Healthcare Units ordered more than Family Health Units.ConclusionsThe results from this study show that the most commonly ordered tests in Portugal are laboratory tests, that there is a tendency for overtesting and that there is a large variability in diagnostic and laboratory test ordering in different geographical and organisational Portuguese primary care practices, suggesting that there may be considerable potential for the rationalisation of test ordering. The existence of Family Health Units seems to be a strong determinant in decreasing test ordering by Portuguese family physicians. Approaches to ensuring more rational testing are needed.
Views of commissioners, managers and healthcare professionals on the NHS Health Check programme: a systematic review
Authors: Mills Katie , Harte Emma , Martin Adam , MacLure Calum , Griffin Simon J , Mant Jonathan , Meads Catherine , Saunders Catherine L , Walter Fiona M , Usher-Smith Juliet A 
Published: November 2017

ObjectiveTo synthesise data concerning the views of commissioners, managers and healthcare professionals towards the National Health Service (NHS) Health Check programme in general and the challenges faced when implementing it in practice.DesignA systematic review of surveys and interview studies with a descriptive analysis of quantitative data and thematic synthesis of qualitative data.Data sourcesAn electronic literature search of MEDLINE, Embase, Health Management Information Consortium, Cumulative Index of Nursing and Allied Health Literature, Global Health, PsycInfo, Web of Science, OpenGrey, the Cochrane Library, NHS Evidence, Google Scholar, Google, ClinicalTrials.gov and the International Standard Randomised Controlled Trial Number registry from 1 January 1996 to 9 November 2016 with no language restriction and manual screening of reference lists of all included papers.Inclusion criteriaPrimary research reporting views of commissioners, managers or healthcare professionals on the NHS Health Check programme and its implementation in practice.ResultsOf 18 524 citations, 15 articles met the inclusion criteria. There was evidence from both quantitative and qualitative studies that some commissioners and general practice (GP) healthcare professionals were enthusiastic about the programme, whereas others raised concerns around inequality of uptake, the evidence base and cost-effectiveness. In contrast, those working in pharmacies were all positive about programme benefits, citing opportunities for their business and staff. The main challenges to implementation were: difficulties with information technology and computer software, resistance to the programme from some GPs, the impact on workload and staffing, funding and training needs. Inadequate privacy was also a challenge in pharmacy and community settings, along with difficulty recruiting people eligible for Health Checks and poor public access to some venues.ConclusionsThe success of the NHS Health Check Programme relies on engagement by those responsible for its commissioning, management and delivery. Recognising and addressing the challenges identified in this review, in particular the concerns of GPs, are important for the future of the programme.
Smoking and quit attempts during pregnancy and postpartum: a longitudinal UK cohort
Authors: Cooper Sue , Orton Sophie , Leonardi-Bee Jo , Brotherton Emma , Vanderbloemen Laura , Bowker Katharine , Naughton Felix , Ussher Michael , Pickett Kate E , Sutton Stephen , Coleman Tim 
Published: November 2017

ObjectivesPregnancy motivates women to try stopping smoking, but little is known about timing of their quit attempts and how quitting intentions change during pregnancy and postpartum. Using longitudinal data, this study aimed to document women’s smoking and quitting behaviour throughout pregnancy and after delivery.DesignLongitudinal cohort survey with questionnaires at baseline (8–26 weeks’ gestation), late pregnancy (34–36 weeks) and 3 months after delivery.SettingTwo maternity hospitals in one National Health Service hospital trust, Nottingham, England.Participants850 pregnant women, aged 16 years or over, who were current smokers or had smoked in the 3 months before pregnancy, were recruited between August 2011 and August 2012.Outcome measuresSelf-reported smoking behaviour, quit attempts and quitting intentions.ResultsSmoking rates, adjusting for non-response at follow-up, were 57.4% (95% CI 54.1 to 60.7) at baseline, 59.1% (95% CI 54.9 to 63.4) in late pregnancy and 67.1% (95% CI 62.7 to 71.5) 3 months postpartum. At baseline, 272 of 488 current smokers had tried to quit since becoming pregnant (55.7%, 95% CI 51.3 to 60.1); 51.3% (95% CI 44.7 to 58.0) tried quitting between baseline and late pregnancy and 27.4% (95% CI 21.7 to 33.2) after childbirth. The percentage who intended to quit within the next month fell as pregnancy progressed, from 40.4% (95% CI 36.1 to 44.8) at baseline to 29.7% (95% CI 23.8 to 35.6) in late pregnancy and 14.2% (95% CI 10.0 to 18.3) postpartum. Postpartum relapse was lower among women who quit in the 3 months before pregnancy (17.8%, 95% CI 6.1 to 29.4) than those who stopped between baseline and late pregnancy (42.9%, 95% CI 24.6 to 61.3).ConclusionsMany pregnant smokers make quit attempts throughout pregnancy and postpartum, but intention to quit decreases over time; there is no evidence that smoking rates fall during gestation.
Method for sterility testing of corneal storage and transport media after removal of interfering antimicrobials: prospective validation study in compliance with the European Pharmacopoeia
Authors: Mistò Raffaela , Giurgola Laura , Pateri Francesca , Frigerio Elisabetta , Limongelli Anna , D’Amato Tóthová Jana 
Published: November 2017

ObjectiveThis study aimed at validating the method for sterility testing of the corneal culture medium, TISSUE-C, and the transport/deswelling medium, CARRY-C, according to the method suitability test, as defined by the European Pharmacopoeia (EP), using RESEP, which is a new medical device for removal of antimicrobial agents and an automated culture system.Methods and analysisThe six EP reference strains were inoculated in TISSUE-C and CARRY-C. Half of the samples were treated with RESEP (RESEP+ group) prior to the sterility testing, whereas the remaining samples were untreated (RESEP− group). Growth controls were obtained by direct inoculation of the micro-organisms in the culture broths. Microbial growth was read by an automated light scattering culture system within 48 hours.ResultsThe use of RESEP allowed detection of microbial growth in 100% of the tested samples, with a mean time to detection (TTD) comparable with that of the growth control group. Significantly lower sensitivity (38.83%±20.03% for both media, P<0.05) and TTD variability, depending on the tested micro-organism, were observed in the RESEP− group. The method specificity was 100% for both groups.ConclusionThe use of RESEP increased the sensitivity of the sterility testing method to 100% and, for the first time, allowed validation of the method for sterility testing of corneal storage media according to the EP method suitability test. This further increases the safety of the corneas intended for transplantation.
Single-session versus staged procedures for elective multivessel percutaneous coronary intervention
Authors: Toyota Toshiaki , Morimoto Takeshi , Shiomi Hiroki , Yamaji Kyohei , Ando Kenji , Ono Koh , Shizuta Satoshi , Saito Naritatsu , Kato Takao , Kaji Shuichiro , Furukawa Yutaka , Nakagawa Yoshihisa , Kadota Kazushige , Horie Minoru , Kimura Takeshi 
Published: November 2017

ObjectivesTo clarify the effect of single-session multivessel percutaneous coronary intervention (PCI) strategy relative to the staged multivessel strategy on clinical outcomes in patients with stable coronary artery disease (CAD) or non-ST-elevation acute coronary syndrome.MethodsIn the Coronary REvascularisation Demonstrating Outcome Study in Kyoto PCI/coronary artery bypass grafting registry cohort-2, there were 2018 patients who underwent elective multivessel PCI. Primary outcome measure was composite of all-cause death, myocardial infarction and stroke at 5-year follow-up.ResultsSingle-session multivessel PCI and staged multivessel PCI were performed in 707 patients (35.0%) and 1311 patients (65.0%), respectively. The cumulative 5-year incidence of and adjusted risk for the primary outcome measure were not significantly different between the single-session and staged groups (26.7% vs 23.0%, p=0.45; HR 0.91, 95% CI 0.72 to 1.16, p=0.47). The 30-day incidence of all-cause death was significantly higher in the single-session group than in the staged group (1.1% vs 0.2%, p=0.009). However, the causes of death in 11 patients who died within 30 days were generally not related to the procedural complications, but related to the serious clinical status before PCI. For the subgroup analyses including age, gender, extent of CAD, severe chronic kidney disease and heart failure, there was no significant interaction between the subgroup factors and the effect of the single-session strategy relative to the staged strategy for the primary outcome measure.ConclusionsThe single-session multivessel PCI strategy was associated with at least comparable 5-year clinical outcomes compared with the staged multivessel PCI, although the prevalence of the single-session strategy was low in the present study.
Mammary phyllodes tumour: a 15-year multicentre clinical review
Authors: Co Michael , Chen Clement , Tsang Julia Y , Tse Gary , Kwong Ava 
Published: November 2017

AimsPhyllodes tumour (PT) is an uncommon fibroepithelial tumour of the breast. It has a spectrum of aggressiveness in biological behaviour with chance of local recurrence and, occasionally, metastasis.MethodsA 15-year retrospective review from a multicentre database in Hong Kong was performed.ResultsClinical and pathological records of 465 patients with 469 PTs between 1998 and 2014 were reviewed. Median age of occurrence was 44 years (range 12–86 years). 281 (59.9%) PTs were benign, 124 (26.4%) were borderline and 64 (13.6%) were malignant. About half of all PTs (239, 51.5%) were between 2 and 5 cm while another 186 (40.1%) were >5 cm in size. Most PT (84.6%) were radiologically benign. Breast-conserving surgery (BCS) was feasible in 384 (82%) patients, whereas 84 (18%) patients had mastectomy. Multivariate analysis found that positive surgical margin (P<0.001) and BCS (P<0.001) were the only significant risk factors for local recurrence, while large tumour size (P=0.008) and malignant PT histotype (P<0.001) were the only significant risk factors for metastasis. Long-term prognosis of benign and borderline PT was excellent. After median follow-up interval of 85 months (range 12–180 months), the disease-specific survival of benign, borderline and malignant PT were 99.6%, 100% and 90.6%, respectively.ConclusionsLocal recurrence of PTs occurs irrespective of the tumour grade. Surgical margin is the only amendable factor to reduce the chance of recurrence.
Impact of increasing tobacco taxes on working-age adults: short-term health gain, health equity and cost savings
Authors: Cleghorn Christine L , Blakely Tony , Kvizhinadze Giorgi , van der Deen Frederieke S , Nghiem Nhung , Cobiac Linda J , Wilson Nick 
Published: November 2017

ObjectiveThe health gains and cost savings from tobacco tax increase peak many decades into the future. Policy-makers may take a shorter-term perspective and be particularly interested in the health of working-age adults (given their role in economic productivity). Therefore, we estimated the impact of tobacco taxes in this population within a 10-year horizon.MethodsAs per previous modelling work, we used a multistate life table model with 16 tobacco-related diseases in parallel, parameterised with rich national data by sex, age and ethnicity. The intervention modelled was 10% annual increases in tobacco tax from 2011 to 2020 in the New Zealand population (n=4.4 million in 2011). The perspective was that of the health system, and the discount rate used was 3%.ResultsFor this 10-year time horizon, the total health gain from the tobacco tax in discounted quality-adjusted life years (QALYs) in the 20–65 year age group (age at QALY accrual) was 180 QALYs or 1.6% of the lifetime QALYs gained in this age group (11 300 QALYs). Nevertheless, for this short time horizon: (1) cost savings in this group amounted to NZ$10.6 million (equivalent to US$7.1 million; 95% uncertainty interval: NZ$6.0 million to NZ$17.7 million); and (2) around two-thirds of the QALY gains for all ages occurred in the 20–65 year age group. Focusing on just the preretirement and postretirement ages, the QALY gains in each of the 60–64 and 65–69 year olds were 11.5% and 10.6%, respectively, of the 268 total QALYs gained for all age groups in 2011–2020.ConclusionsThe majority of the health benefit over a 10-year horizon from increasing tobacco taxes is accrued in the working-age population (20–65 years). There remains a need for more work on the associated productivity benefits of such health gains.
Effects of dietary lysine level on the content and fatty acid composition of intramuscular fat in late-stage finishing pigs
Authors: Wang Taiji , Crenshaw Mark A. , Regmi Naresh , Rude Brian J. , Shamimul Hasan M. , Sukumaran Anuraj T. , Dinh Thu , Liao Shengfa F. 
Published: November 2017

This study was conducted to investigate how dietary lysine level affects the intramuscular fat (IMF) content and fatty acid (FA) composition in late-stage finishing pigs. Nine crossbred barrows [94.4 ± 6.7 kg body weight (BW)] were randomly allotted to three treatment groups (n = 3). Three corn- and soybean-meal-based diets were formulated to meet the National Research Council (2012) requirements for various nutrients except for lysine, whose concentrations were 0.43%, 0.71%, and 0.98% (as-fed basis) for Diets 1 (lysine-deficient), 2 (lysine-adequate), and 3 (lysine-excess), respectively. After 5 wk of ad libitum access to diets, pigs were harvested and longissimus dorsi samples were collected. The IMF content and FA composition of the samples were analyzed by gas chromatography. Results showed that the IMF content of the muscle was increased linearly (P < 0.05) with decreasing dietary lysine level from 0.98% to 0.43%. Dietary lysine level altered the composition of FA, especially the unsaturated FA, in the muscle. Particularly, the percentages of C18:1 n-9 and total monounsaturated FA were higher, whereas the percentages of C18:2 n-6 and total polyunsaturated FA were lower, in the muscle of the pigs fed Diet 1. Collectively, dietary lysine deficiency increased the proportion of monounsaturated FA and decreased the proportion of polyunsaturated FA, which may benefit pork palatability.
Characterization of SGN-CD123A, A Potent CD123-Directed Antibody–Drug Conjugate for Acute Myeloid Leukemia
Authors: Li Fu , Sutherland May Kung , Yu Changpu , Walter Roland B. , Westendorf Lori , Valliere-Douglass John , Pan Lucy , Cronkite Ashley , Sussman Django , Klussman Kerry , Ulrich Michelle , Anderson Martha E. , Stone Ivan J. , Zeng Weiping , Jonas Mechthild , Lewis Timothy S. , Goswami Maitrayee , Wang Sa A. , Senter Peter D. , Law Che-Leung , Feldman Eric J. , Benjamin Dennis R. 
Published: November 2017

Abstract
Treatment choices for acute myelogenous leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. IL3 receptor alpha (IL3Rα, or CD123) is expressed on the majority of AML blasts, and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here, we report the generation and preclinical characterization of SGN-CD123A, an antibody–drug conjugate using the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation. Mechanistically, SGN-CD123A induces activation of DNA damage response pathways, cell-cycle changes, and apoptosis in AML cells. In vitro, SGN-CD123A–mediated potent cytotoxicity of 11/12 CD123+ AML cell lines and 20/23 primary samples from AML patients, including those with unfavorable cytogenetic profiles or FLT3 mutations. In vivo, SGN-CD123A treatment led to AML eradication in a disseminated disease model, remission in a subcutaneous xenograft model, and significant growth delay in a multidrug resistance xenograft model. Moreover, SGN-CD123A also resulted in durable complete remission of a patient-derived xenograft AML model. When combined with a FLT3 inhibitor quizartinib, SGN-CD123A enhanced the activity of quizartinib against two FLT3-mutated xenograft models. Overall, these data demonstrate that SGN-CD123A is a potent antileukemic agent, supporting an ongoing trial to evaluate its safety and efficacy in AML patients (NCT02848248). Mol Cancer Ther; 17(2); 554–64. ©2017 AACR.