bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drugs for treating severe hypertension in pregnancy: a network meta‐analysis and trial sequential analysis of randomized clinical trials
Authors: Sridharan Kannan , Sequeira Reginald P. 
Published: July 2018

AimsSeveral antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta‐analysis comparing the efficacy and safety of these drugs.MethodsElectronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random‐effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates.ResultsFifty‐one studies were included in the systematic review and 46 in the meta‐analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [−15 (−20.6, −9.4)], nicardipine [−11.8 (−22.3, −1.2)], nifedipine/celastrol [−19.3 (−27.4, −11.1)], nifedipine/vitamin D [−17.1 (−25.7, −9.7)], nifedipine/resveratrol [−13.9 (−22.6, −5.2)] and glyceryl trinitrate [−33.8 (−36.7, −31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons.ConclusionThe present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs.
Co‐administration of proton pump inhibitors and/or of steroids may be a risk factor for low trough concentrations of posaconazole delayed‐released tablets in adult patients with haematological malignancies
Authors: Cojutti Pier Giorgio , Candoni Anna , Lazzarotto Davide , Rabassi Nicholas , Fanin Renato , Hope William , Pea Federico 
Published: July 2018

AimsThe aim of this study was to determine clinical variables associated with posaconazole exposure among adult patients with haematological malignancies who received posaconazole tablets for prophylaxis of invasive fungal infections (IFIs).MethodsThe study population included adult patients with haematological malignancies who received posaconazole delayed‐release tablets for prophylaxis of IFIs after induction chemotherapy for acute leukaemia or graft‐versus‐host‐disease (GVHD) complicating hematopoietic stem cell transplantation (HSCT) in the period January 2016–December 2017.ResultsSixty‐six consecutive patients with 176 posaconazole Cmin were included for evaluation in the study. Subtherapeutic posaconazole concentrations (< 0.7 mg l−1) were observed at least once in 33.3% of patients (22/66), and overall in 17.0% of therapeutic drug monitoring (TDM) episodes (30/176). At multilevel linear regression, use of PPIs (P = 0.008), use of intermediate or high dose steroids (>0.7 mg kg−1 daily) (P = 0.022) and male gender (P = 0.025) were significantly associated with decreased Cmin, whereas time from starting therapy (P = 0.032) was associated with increased Cmin in our patient population.ConclusionPosaconazole exposure during treatment with delayed‐released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.
Increased risk of all‐cause mortality associated with domperidone use in Parkinson's patients: a population‐based cohort study in the UK
Authors: Simeonova Marina , de Vries Frank , Pouwels Sander , Driessen Johanna H. M. , Leufkens Hubert G.M. , Cadarette Suzanne M. , Burden Andrea M. 
Published: July 2018

AbstractAimsDomperidone is used to treat gastrointestinal symptoms in patients with Parkinson's disease (PD) and is linked to an increased risk of mortality. We sought to examine the risk of all‐cause mortality associated with domperidone exposure in PD.MethodsWe conducted a cohort study using data from the Clinical Practice Research Datalink database (1987–2011). The first recorded PD diagnosis defined index date. Time‐dependent Cox proportional hazards models estimated hazard ratios (HRs) of all‐cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never used as the referent. Current domperidone users were stratified by daily dose, domperidone duration and other anti‐Parkinson's medications. A secondary analysis compared PD patients to matched (1:1) non‐PD patients.ResultsA total of 5114 PD patients were identified. Current use of domperidone among PD patients was associated with a two‐fold increase in all‐cause mortality (HRadj = 2.00, 95% confidence interval [CI]: 1.64–2.45), as compared to patients never exposed to domperidone. All‐cause mortality risk was highest in those starting domperidone in the previous month [HRadj = 2.97, 95% CI: 2.06–4.27]. When compared to matched non‐PD patients, PD was associated with a 43% increased risk of all‐cause mortality, yet this increased to a 2.4‐fold increased risk among PD patients currently using domperidone.ConclusionCurrent use of domperidone was associated with a two‐fold increased mortality risk in PD patients, as compared to PD patients that never used domperidone. The risk is highest in the first month of use and does not appear to be attributable to PD alone.
The ‘top 100’ drugs and classes in England: an updated ‘starter formulary’ for trainee prescribers
Authors: Audi Selma , Burrage Daniel R. , Lonsdale Dagan O. , Pontefract Sarah , Coleman Jamie J. , Hitchings Andrew W. , Baker Emma H. 
Published: July 2018

AimsPrescribing is a complex skill required of doctors and, increasingly, other healthcare professionals. Use of a personal formulary can help to develop this skill. In 2006–9, we developed a core list of the 100 most commonly prescribed drugs. Our aim in the present study was to update this ‘starter formulary’ to ensure its continued relevance for prescriber training.MethodsWe analysed large contemporary primary and secondary care datasets to identify the most frequently prescribed medicinal products. Items were classified into natural groups, broadly following their British National Formulary classification. The resulting drug groups were included in the core list if they comprised ≥0.1% prescriptions in both settings or ≥0.2–0.3% prescriptions in one setting. Drugs from emergency guidelines that did not qualify by prescribing frequency completed the list.ResultsOver 1 billion primary care items and approximately 1.8 million secondary care prescriptions were analysed. The updated list comprises 81 drug groups commonly prescribed in both settings; six from primary care; seven from secondary care; and six from emergency guidelines. Eighty‐eight per cent of the formulary was unchanged. Notable changes include entry of newer anti‐epileptics and dipeptidyl peptidase‐4 inhibitors and exit of phenytoin and thiazolidinediones.ConclusionsThe relative stability of the core drug list over 9 years and the current update ensure that learning based on this list remains relevant to practice. Trainee prescribers may be encouraged to use this ‘starter formulary’ to develop a sound basis of prescribing knowledge and skills that they can subsequently apply more widely.
A Partially Linear Proportional Hazards Model for Current Status Data
Authors: Lu Minggen , McMahan Christopher S. 
Published: July 2018

SummaryFor analyzing current status data, a flexible partially linear proportional hazards model is proposed. Modeling flexibility is attained through using monotone splines to approximate the baseline cumulative hazard function, as well as B-splines to accommodate nonlinear covariate effects. To facilitate model fitting, a computationally efficient and easy to implement expectation-maximization algorithm is developed through a two-stage data augmentation process involving carefully structured latent Poisson random variables. Asymptotic normality and the efficiency of the spline estimator of the regression coefficients are established, and the spline estimators of the nonparametric components are shown to possess the optimal rate of convergence under suitable regularity conditions. The finite-sample performance of the proposed approach is evaluated through Monte Carlo simulation and it is further illustrated using uterine fibroid data arising from a prospective cohort study on early pregnancy.
Cognitive impairment in hodgkin lymphoma survivors
Authors: Trachtenberg Estherina , Mashiach Tatiana , Ben Hayun Rachel , Tadmor Tamar , Fisher Tali , Aharon‐Peretz Judith , Dann Eldad J. 
Published: July 2018

SummaryCancer‐related cognitive impairment (CRCI) is commonly reported post‐chemotherapy in adults with solid tumours. Hodgkin lymphoma (HL) mostly affects young adults. Data regarding CRCI in HL survivors (HLS) are scarce. The current study aimed to objectively assess CRCI incidence and characteristics in HLS. HLS, who completed first‐line (chemotherapy ± radiation) therapy and remained in complete remission for 6 months to 5 years from therapy end, were evaluated. Age‐ and education‐matched healthy individuals served as controls (n = 14). Test results were compared to population norms and healthy controls. Study participants completed self‐reported questionnaires evaluating fatigue, depression, anxiety, quality of life and cognitive function. Subjects underwent neurocognitive evaluation, assessing processing speed, memory, attention, executive functions and intelligence domains. The present study included 51 HLS with a median age of 28 years, mean education of 14·5 ± 2·5 years. Complaints related to cognitive deterioration and fatigue were significantly more severe and frequent in HLS compared to healthy controls. Objective neurocognitive evaluation demonstrated that 30% of HLS were impaired in ≥2 cognitive domains. In conclusion, the present study demonstrates that fatigue and cognitive impairment, predominantly in executive functions and memory, constitute frequent and alarming findings in HLS. These adverse effects can persist and exert an impact on all aspects of life.
Prevalence and outcomes of uncommon BCR‐ABL1 fusion transcripts in patients with chronic myeloid leukaemia: data from a single centre
Authors: Qin Ya‐Zhen , Jiang Qian , Jiang Hao , Lai Yue‐Yun , Shi Hong‐Xia , Chen Wen‐Min , Yu Lu , Huang Xiao‐Jun 
Published: July 2018

SummaryTo explore the type, prevalence and outcomes in chronic myeloid leukaemia (CML) patients with uncommon BCR‐ABL1 transcripts in the era of tyrosine kinase inhibitors (TKIs), uncommon BCR‐ABL1 transcripts were screened in 4750 patients by multiplex polymerase chain reaction (PCR), and type‐specific real‐time quantitative PCR was regularly performed for molecular monitoring. A total of 19 uncommon transcripts, including e1a2, e1a3, e6a2, e8a2, e12a2, unusual e13a2, e13a3, unusual e14a2, e14a3 and e19a2 were identified in 83 (1·7%) patients. The three most frequent types were e19a2, e13a3/e14a3 and e1a2. Compared with the 571 newly diagnosed CML patients in chronic phase with common e13a2/e14a2 transcripts receiving frontline imatinib therapy, patients with the e19a2 (n = 16) and e1a2 (n = 11) transcripts had significantly reduced probabilities of 1‐year complete cytogenetic response (CCyR, P = 0·0004 and 0·016) and major molecular response (MMR, P = 0·0018 and 0·0035), and patients with the e13a3/e14a3 transcript (n = 10) had significantly increased probabilities of 1‐year CCyR (P = 0·0072) and MMR (P = 0·0073). Patients with the e19a2 transcript had low probabilities of 2‐year event‐free survival (EFS, P = 0·0004) and progression‐free survival (P = 0·0067), and patients with the e1a2 transcript had low probability of 2‐year EFS (P < 0·0001). Therefore, uncommon BCR‐ABL1 fusion transcripts are rare and diverse in patients with CML and may be relevant for TKI therapy outcomes.
Gene mutations and clonal architecture in myelodysplastic syndromes and changes upon progression to acute myeloid leukaemia and under treatment
Authors: Stosch Juliane M. , Heumüller Anezka , Niemöller Christoph , Bleul Sabine , Rothenberg‐Thurley Maja , Riba Julian , Renz Nathalie , Szarc vel Szic Katarzyna , Pfeifer Dietmar , Follo Marie , Pahl Heike L. , Zimmermann Stefan , Duyster Justus , Wehrle Julius , Lübbert Michael , Metzeler Klaus H. , Claus Rainer , Becker Heiko 
Published: July 2018

SummaryKnowledge of the molecular and clonal characteristics in the myelodysplastic syndromes (MDS) and during progression to acute myeloid leukaemia (AML) is essential to understand the disease dynamics and optimize treatment. Sequencing serial bone marrow samples of eight patients, we observed that MDS featured a median of 3 mutations. Mutations in genes involved in RNA‐splicing or epigenetic regulation were most frequent, and exclusively present in the major clone. Minor subclones were distinguishable in three patients. As the MDS progressed, a median of one mutation was gained, leading to clonal outgrowth. No AML developed genetically independent of a pre‐existing clone. The gained mutation mostly affected genes encoding signalling proteins. Additional acquisition of genomic aberrations frequently occurred. Upon treatment, emergence of new clones could be observed. As confirmed by single‐cell sequencing, multiple mutations in identical genes in different clones were present within individual patients. DNA‐methylation profiling in patients without identification of novel mutations in AML revealed methylation changes in individual genes. In conclusion, our data complement previous observations on the mutational and clonal characteristics in MDS and at progression. Moreover, DNA‐methylation changes may be associated with progression in single patients. Redundancy of mutated genes in different clones suggests fertile grounds promoting clonal selection or acquisition.
Small Is Beautiful? Emerging Organizational Strategies among Italian Professionals
Authors: Maestripieri Lara , Cucca Roberta 
Published: July 2018

AbstractThe traditional debate about professional groups has mainly focused on conflicts between professions and organizations, reinforcing dualisms and dichotomies. Few scholars have investigated the extent to which professionalism and organizations are intertwined while focusing on the case of professionals integrated into large organizations, and even less attention has been paid to emerging forms of organization among self‐employed professionals. Taking as an example organizational trends among architects (liberal professionals) and management consultants (emerging professionals) in Italy, this article investigates how small, flexible, and (often) interprofessional organizations promoted by self‐employed professionals are increasingly instrumental in overcoming market pressures and responding to emerging social needs in times of crisis and austerity.
The Corporate Elite and the Architecture of Climate Change Denial: A Network Analysis of Carbon Capital's Reach into Civil Society
Authors: Carroll William , Graham Nicolas , Lang Michael K. , Yunker Zoë , McCartney Kevin D. 
Published: July 2018

AbstractThis study employs social network analysis to map the Canadian network of carbon‐capital corporations whose boards interlock with key knowledge‐producing civil society organizations, including think tanks, industry associations, business advocacy organizations, universities, and research institutes. We find a pervasive pattern of carbon‐sector reach into these domains of civil society, forming a single, connected network that is centered in Alberta yet linked to the central‐Canadian corporate elite through hegemonic capitalist organizations, including major financial companies. This structure provides the architecture for a “soft” denial regime that acknowledges climate change while protecting the continued flow of profit to fossil fuel and related companies.
Towards complete identification of allergens in Jack Jumper (Myrmecia pilosula) ant venom and their clinical relevance: An immunoproteomic approach
Authors: Wanandy Troy , Wilson Richard , Gell David , Rose Hayley E. , Gueven Nuri , Davies Noel W. , Brown Simon G. A. , Wiese Michael D. 
Published: July 2018

SummaryBackgroundThe venomous stings of Jack Jumper ant (JJA; species of the Myrmecia pilosula taxonomic group) are a significant public health issue in parts of south‐eastern and south‐western Australia, causing anaphylaxis in approximately 3% of the population. Three allergenic peptides, Myr p 1, Myr p 2 and Myr p 3, and one histamine‐releasing peptide, pilosulin 5, have been fully described, but there are at least 5 additional high molecular weight IgE‐binding components that have not been identified.ObjectiveTo identify IgE‐binding components in JJA venom (JJAV) and to relate the IgE recognition of these components to relevant clinical parameters.MethodsIdentification of IgE‐binding components and determination of their sensitizing prevalence was performed using SDS‐PAGE immunoblot assay and sera from 90 patients with confirmed allergy to JJAV. Tandem mass spectrometry was used for identification of novel JJAV components fractionated by size exclusion chromatography (SEC) and SDS‐PAGE.ResultsUsing SDS‐PAGE immunoblot, 10 IgE‐binding bands were identified in JJAV, two of which were recognized by 81% and 47% of the population studied. Mass spectrometry identified 17 novel JJAV proteins, including 2 glycoproteins, and confirmed the presence of 4 known Myr p and pilosulin peptides in JJAV. Most of the newly identified IgE‐binding proteins were enzymes, including phospholipase A2, hyaluronidase, arginine kinase and dipeptidyl peptidase IV. Correlations were found between recognition of certain IgE‐binding bands with JJAV‐specific IgE titre by ImmunoCAP, intradermal test threshold and treatment‐related issues.Conclusions and Clinical RelevanceThis study has for the first time revealed the identity of various proteins with IgE‐binding capacity in the venom of JJA and demonstrated their clinical relevance in the diagnosis and treatment of JJAV allergy.
High ambient levels of grass, weed and other pollen are associated with asthma admissions in children and adolescents: A large 5‐year case‐crossover study
Authors: Shrestha Som K. , Katelaris Constance , Dharmage Shyamali C. , Burton Pamela , Vicendese Don , Tham Rachel , Abramson Michael J. , Erbas Bircan 
Published: July 2018

SummaryBackgroundPollen is an important aeroallergen that triggers asthma exacerbations in children, but we know little about the impact of different pollen types in cities with varying climatic conditions and pollen seasons.ObjectivesWe aimed to assess the role of ambient level of different types of pollen on a large time series of child and adolescent asthma hospitalizations in Sydney, Australia.MethodsChildhood asthma hospitalization and the daily ambient pollen concentrations of different species were collected in South‐West Sydney. With a bidirectional case‐crossover design, we fitted conditional logistic regression models to measure the associations between instantaneous and up to 3 days lagged effects of pollen concentrations on asthma hospitalizations after controlling for potential confounders and testing for interactions.ResultsA total of 2098 children, more boys (59.7%) and 2‐5 years old (62.6%), were hospitalized due to asthma. The geometric mean concentration of Cupressus, 7.88 [5.02] grains/m3, was the highest during the study period. The increase from 75th to 90th percentile of grass (OR = 1.037, 95% CI 1.005‐1.070), weed other than Plantago species (OR = 1.053, 95% CI 1.009‐1.098) and unclassified pollen (OR = 1.034, 95% CI 1.010‐1.058) were significantly associated with the odds of asthma hospitalizations. Boys were at greater risk of asthma exacerbations associated with grass (OR = 1.046, 95% CI 1.003‐1.090) and unclassified pollen (OR = 1.041, 95% CI 1.010‐1.073). There was evidence of effect modification by age groups for Cupressus, conifer, total tree and total pollen.ConclusionsAlthough boys are more vulnerable to grass pollen, weed, and other pollen are also important triggers of asthma exacerbations in all children and adolescents. These findings are important for urban green space planning and the development of pollen monitoring systems for families with children at risk of asthma exacerbations during peak pollen seasons.
Modeling temperature‐dependent development rate and phenology in insects: review of major developments, challenges, and future directions
Authors: Rebaudo François , Rabhi Victor‐Badre 
Published: July 2018

AbstractThe study of insect responses to temperature has a long tradition in science, starting from Réaumur's work on caterpillars in the 18th century. In 1932, Ernst Janisch wrote: ‘The problem is (and will be more and more in the future) one of the most important ones in entomology […]’. Almost 90 years after this paper, its prediction still holds true, with a sustained interest of the scientific community for the study of insect responses to temperature, especially in the context of climate change. We present a review of the major developments in the field of insect development responses to temperature and analyze the growing importance of modeling approaches in the literature using a bibliographic analysis. We discuss recent advances and future directions for phenology‐modeling based on temperature‐dependent development rate. Finally, we highlight the need for a change of paradigm toward a system‐based approach in order to overcome current challenges and to predict insect phenology more accurately, with direct implications in agriculture, conservation biology, and epidemiology.