bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breath‐holding spells occur disproportionately more often in children with transient erythroblastopenia
Authors: Hellström Schmidt Sanna , Tedgård Ulf , Pronk Cornelis J.H. 
Published: April 2016

AbstractAimThis study aimed to evaluate the concomitant occurrence and possible association of breath‐holding spells (BHS) and transient erythroblastopenia of childhood (TEC).MethodsThis population‐based cohort study, carried out in Southern Sweden from 2004 to 2014, included patients with BHS and/or anaemia, including TEC. The subjects were evaluated for the presence of all three conditions and the diagnostic workups, disease characteristics and outcome were analysed.ResultsWe studied 443 470 children under the age of 10 years during 2004–2014. The total cohort included 321 patients (0.07%) with BHS and 366 patients with a selection of anaemia diagnoses, including 41 with TEC. We found that nine (2.5%) of the 366 patients with anaemia diagnoses also had BHS and that five (12.2%) of the 41 patients with TEC also had BHS. Treatment for anaemia resolved BHS in a number of patients.ConclusionOur population‐based analysis revealed an overrepresentation of BHS among children with TEC, and we identified five patients with concomitant TEC and BHS. We found that correcting anaemia was an effective means of ameliorating potentially debilitating BHS and that the presence of concomitant BHS and TEC was more common than previously assumed.
Utilisation of surgical fundoplication for patients with gastro‐oesophageal reflux disease in the USA has declined rapidly between 2009 and 2013
Authors: Khan F. , Maradey‐Romero C. , Ganocy S. , Frazier R. , Fass R. 
Published: April 2016

SummaryBackgroundSurgical fundoplication has been considered to be one of the leading therapeutic modalities for gastro‐oesophageal reflux disease (GERD) during the last several decades.AimTo determine the trend of surgical fundoplication utilisation in GERD patients during the last decade in the United States.MethodsPopulation‐based study using a large nationwide database, the Explorys database system, to identify patients diagnosed with GERD and those who underwent surgical fundoplication. Using a quadratic regression model, we determined and compared the trends of surgical fundoplication utilisation annually from 2004 to 2013.ResultsWe identified 4 059 060 patients with the diagnosis of GERD, of whom 2343 (0.05%) underwent surgical fundoplication between 2004 and 2013. There was a significant decline in the number of surgical fundoplications performed over the last 5 years from 0.062% in 2009 to 0.047% in 2013 (P < 0.05). Female patients accounted for the majority of those who underwent fundoplication (62.52%). Caucasian patients between the ages of 18 and 65 years were the most likely group to undergo surgical fundoplication (66.28%). The number of overweight patients undergoing surgical fundoplication has been significantly increasing over the last decade (P < 0.05). Importantly, 80% of surgical patients were treated with a proton pump inhibitor (PPI) post surgical fundoplication by 2013 (P < 0.001).ConclusionsUtilisation of surgical fundoplication in GERD patients has been steadily declining over the past 5 years. The vast majority of patients will resume PPI treatment after surgical fundoplication.
Predicting outcome in acute severe ulcerative colitis: comparison of the Travis and Ho scores using UK IBD audit data
Authors: Lynch R. W. , Churchhouse A. M. D. , Protheroe A. , Arnott I. D. R. ,   the UK IBD Audit Steering Group
Published: April 2016

SummaryBackgroundAcute severe ulcerative colitis is categorised using the Truelove & Witts criteria. The Travis and the Ho scores are calculated following 72 h of steroid treatment to identify patients at risk of failing steroid therapy who require colectomy or second‐line medical therapy.AimTo compare the Travis and the Ho scores in a large unselected cohort to determine which might be more clinically relevant.MethodsWe analysed 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit of which 984 had acute severe ulcerative colitis. 420 patients had sufficient data for analysis. Patients were allocated into either a Travis high‐ or low‐risk group and either a Ho high‐, intermediate‐ or low‐risk group. We assessed whether further medical or surgical intervention and outcomes varied between groups.ResultsHigh‐risk patients in Travis and the Ho groups, when compared to lower risk groups, were more likely to fail steroid therapy: 64.5% (131/203) vs. 38.7% (84/217) (P < 0.0001) for Travis and 66.2% (96/145) vs. 46.7% (85/182) vs. 36.6% (34/93) (P < 0.0001) for Ho. They were also more likely to undergo surgery 34.0% (69/203) vs. 9.7% (21/217) for Travis and 33.1% (48/145) vs. 17.0% (31/182) vs. 11.8% (11/93) (P < 0.0001) for Ho. Travis high patients were more likely to be refractory to second‐line medical therapy: 44.6% (37/83) vs. 20.0% (9/45) (P = 0.01).ConclusionsPatients identified as high risk using the Travis or the Ho scoring systems are more likely to be resistant to IV steroids and require surgery. Risk of surgery in both high‐risk populations is lower than previously reported.
Usage patterns of paracetamol in France
Authors: Duong Mai , Gulmez Sinem Ezgi , Salvo Francesco , Abouelfath Abdelilah , Lassalle Régis , Droz Cécile , Blin Patrick , Moore Nicholas 
Published: April 2016

AimsThe aim of the present study was to describe the real‐life usage patterns of paracetamol.MethodsThe Echantillon Généraliste de Bénéficiaires (EGB) database, the permanent 1/97 representative sample from the French national healthcare insurance system, was searched in 2011 to identify usage patterns, concomitant chronic diseases and use of cardiovascular medication in users prescribed single‐ingredient (SP) and combination (CP) paracetamol, representing 85% of all sales.ResultsOf 526 108 subjects aged ≥15 years in the EGB, 268 725 (51%) had paracetamol dispensed on ≥1 occasion; of these, 207 707 (77%) were dispensed only SP and 61 018 (23%) received CP with or without SP. SP users were younger (48.3 years vs. 50.5 years), and 57% of SP users vs. 58% of CP users were female. Chronic comorbidities were more common in CP than SP users. SP users had, on average, 3.4 dispensings per year vs. 5.0 for CP users, for 36 defined daily doses (DDD, 3 g) of SP vs. 53 DDD per year for CP; 49% SP users bought 14 DDD or fewer; 15% bought >60 DDD. Use of paracetamol increased with age from about 16 DDD per year in 15–30‐year‐olds to over 90 DDD per year in patients above the age of 75; 53% of patients ≤60 years bought fewer than 14 DDD per year, whereas 55% of those >60 bought more than 30 DDD per year. More than half the dispensings exceeded the legal per‐box limit of 8 g.ConclusionsOver 50% of the French adult population were dispensed paracetamol at least once over the course of a year, generally for short‐term use. Considering recent misgivings on the real efficacy and safety of paracetamol, such widespread use might have important public health consequences.
Quantifying rigidity of Parkinson's disease in relation to laxative treatment: a service evaluation
Authors: Augustin Aisha D. , Charlett André , Weller Clive , Dobbs Sylvia M. , Taylor David , Bjarnason Ingvar , Dobbs R. John 
Published: April 2016

AimTo estimate whether laxatives prescribed for constipation in Parkinson's disease (PD) could moderate rigidity. Constipation predates diagnosis of PD by decades. Deposition of misfolded protein may begin in the gut, driven by dysbiosis. Successive antimicrobial exposures are associated with cumulative increase in rigidity, and rigidity has biological gradients on circulating leukocyte‐subset counts.MethodsRetrospective service evaluation, in a gut/brain axis clinic, yielded an interrupted time series, relating maintenance laxative and other medication to rigidity, in consecutive outpatients identified by inclusion and exclusion criteria. Objective assessment of rigidity was used to bring greater sensitivity to change, validated against subjective gold standard (UPDRS).ResultsThere were 1493 measurements of torque required to extend (flexor rigidity) and flex (extensor rigidity) the forearm in 79 PD patients over 374 person‐years. Both were strongly associated with UPDRS (P < 0.001 and P = 0.008, respectively). Before exhibition of laxative, flexor rigidity increased by 6% (95% CI 1, 10) per year, plateauing at −2% (−4, 1) per year after, with no shift at initiation. Change in slope was significant (P = 0.002), and manifest in those naïve to antiparkinsonian medication. The change was replicated for individual laxative classes (bulk, osmotic, enterokinetic). There was no temporal change in extensor rigidity. Limited experience with a quanylate cyclase‐C receptor agonist (17 patients, 6 person‐years) indicated a large and significant step down in flexor and extensor rigidity, of 19% (1, 34) and 16% (6, 24) respectively (P = 0.04 and <0.001).ConclusionsMaintenance laxative usage was associated with apparent stemming of the temporal increase in rigidity in PD, adding to indicative evidence of a continuing role of gastrointestinal dysbiosis in pathogenesis.
Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi‐Modal Multi‐Tissue Human Experimental Model – An Explorative Study
Authors: Nielsen Lecia Møller , Olesen Anne Estrup , Sato Hiroe , Christrup Lona Louring , Drewes Asbjørn Mohr 
Published: April 2016

AbstractThe genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol‐O‐methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol‐O‐methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi‐modal and multi‐tissue experimental pain model in 40 healthy participants aged 20–65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non‐carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non‐carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity.
Confidence Sets for Optimal Factor Levels of a Response Surface
Authors: Wan Fang , Liu Wei , Bretz Frank , Han Yang 
Published: April 2016

SummaryConstruction of confidence sets for the optimal factor levels is an important topic in response surfaces methodology. In Wan et al. (2015), an exact confidence set has been provided for a maximum or minimum point (i.e., an optimal factor level) of a univariate polynomial function in a given interval. In this article, the method has been extended to construct an exact confidence set for the optimal factor levels of response surfaces. The construction method is readily applied to many parametric and semiparametric regression models involving a quadratic function. A conservative confidence set has been provided as an intermediate step in the construction of the exact confidence set. Two examples are given to illustrate the application of the confidence sets. The comparison between confidence sets indicates that our exact confidence set is better than the only other confidence set available in the statistical literature that guarantees the confidence level.
Approximate Median Regression for Complex Survey Data with Skewed Response
Authors: Fraser Raphael André , Lipsitz Stuart R. , Sinha Debajyoti , Fitzmaurice Garrett M. , Pan Yi 
Published: April 2016

SummaryThe ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling, and weighting. In this article, we accommodate these design features in the analysis of highly skewed response variables arising from large complex surveys. Specifically, we propose a double-transform-both-sides (DTBS)'based estimating equations approach to estimate the median regression parameters of the highly skewed response; the DTBS approach applies the same Box–Cox type transformation twice to both the outcome and regression function. The usual sandwich variance estimate can be used in our approach, whereas a resampling approach would be needed for a pseudo-likelihood based on minimizing absolute deviations (MAD). Furthermore, the approach is relatively robust to the true underlying distribution, and has much smaller mean square error than a MAD approach. The method is motivated by an analysis of laboratory data on urinary iodine (UI) concentration from the National Health and Nutrition Examination Survey.
Bayesian Hierarchical Modeling for Subject-Level Response Classification in Peptide Microarray Immunoassays
Authors: Imholte Gregory , Gottardo Raphael 
Published: April 2016

Summary
The peptide microarray immunoassay simultaneously screens sample serum against thousands of peptides, determining the presence of antibodies bound to array probes. Peptide microarrays tiling immunogenic regions of pathogens (e.g., envelope proteins of a virus) are an important high throughput tool for querying and mapping antibody binding. Because of the assay's many steps, from probe synthesis to incubation, peptide microarray data can be noisy with extreme outliers. In addition, subjects may produce different antibody profiles in response to an identical vaccine stimulus or infection, due to variability among subjects’ immune systems. We present a robust Bayesian hierarchical model for peptide microarray experiments, pepBayes, to estimate the probability of antibody response for each subject/peptide combination. Heavy-tailed error distributions accommodate outliers and extreme responses, and tailored random effect terms automatically incorporate technical effects prevalent in the assay. We apply our model to two vaccine trial data sets to demonstrate model performance. Our approach enjoys high sensitivity and specificity when detecting vaccine induced antibody responses. A simulation study shows an adaptive thresholding classification method has appropriate false discovery rate control with high sensitivity, and receiver operating characteristics generated on vaccine trial data suggest that pepBayes clearly separates responses from non-responses.
Variable Selection for Binary Spatial Regression: Penalized Quasi-Likelihood Approach
Authors: Feng Wenning , Sarkar Abdhi , Lim Chae Young , Maiti Tapabrata 
Published: April 2016

SummaryWe consider the problem of selecting covariates in a spatial regression model when the response is binary. Penalized likelihood-based approach is proved to be effective for both variable selection and estimation simultaneously. In the context of a spatially dependent binary variable, an uniquely interpretable likelihood is not available, rather a quasi-likelihood might be more suitable. We develop a penalized quasi-likelihood with spatial dependence for simultaneous variable selection and parameter estimation along with an efficient computational algorithm. The theoretical properties including asymptotic normality and consistency are studied under increasing domain asymptotics framework. An extensive simulation study is conducted to validate the methodology. Real data examples are provided for illustration and applicability. Although theoretical justification has not been made, we also investigate empirical performance of the proposed penalized quasi-likelihood approach for spatial count data to explore suitability of this method to a general exponential family of distributions.
Single-Index Varying Coefficient Model for Functional Responses
Authors: Luo Xinchao , Zhu Lixing , Zhu Hongtu 
Published: April 2016

SummaryRecently, massive functional data have been widely collected over space across a set of grid points in various imaging studies. It is interesting to correlate functional data with various clinical variables, such as age and gender, in order to address scientific questions of interest. The aim of this article is to develop a single-index varying coefficient (SIVC) model for establishing a varying association between functional responses (e.g., image) and a set of covariates. It enjoys several unique features of both varying-coefficient and single-index models. An estimation procedure is developed to estimate varying coefficient functions, the index function, and the covariance function of individual functions. The optimal integration of information across different grid points is systematically delineated and the asymptotic properties (e.g., consistency and convergence rate) of all estimators are examined. Simulation studies are conducted to assess the finite-sample performance of the proposed estimation procedure. Furthermore, our real data analysis of a white matter tract dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study confirms the advantage and accuracy of SIVC model over the popular varying coefficient model.
Internet‐based cognitive behaviour therapy and physical exercise – Effects studied by automated telephone assessments in mental ill‐health patients; a randomized controlled trial
Authors: Strid Catharina , Andersson Claes , Forsell Yvonne , Öjehagen Agneta , Lundh Lars‐Gunnar 
Published: April 2016

ObjectivesMental ill‐health has become a large health problem and it is important for caregivers to provide effective treatment alternatives. REGASSA is a randomized controlled study performed in primary care to study the effects of 12 weeks of Internet‐based cognitive behaviour therapy (ICBT) and physical exercise (PE) compared with treatment as usual (TAU) in patients with mild‐to‐moderate mental ill‐health. The present study aimed to examine the results of these treatment alternatives on psychological functioning, stress, and sleep disturbances.MethodsThe study comprised 879 patients with mental ill‐health taking part in the REGASSA study. Data were collected by Interactive Voice Response (IVR), a computerized, automated telephone technique. The treatments were compared at baseline, twice during treatment, at the end of treatment and at three follow‐ups after treatment. Measures used were the Outcome Questionnaire‐45, the short versions of the Perceived Stress Scale, and the Karolinska Sleep Questionnaire.ResultsLinear mixed models showed that the patients in ICBT and PE had better results than in TAU on psychological functioning and sleep disturbances, p < .001, with weak‐to‐moderate effect sizes. On stress there were no differences; all groups made improvements. Women had stronger effects than men. More patients recovered on psychological functioning (OQ‐45) in ICBT and PE than in TAU.ConclusionsInternet‐based cognitive behaviour therapy and PE proved to be effective treatment alternatives for patients with mild‐to‐moderate mental ill‐health in improving psychological functioning, stress, and sleep disturbances and could be useful alternatives in primary care.Practitioner points

Internet‐based cognitive behaviour therapy and physical exercise proved to be effective treatment alternatives for mental ill‐health patients in primary care.

Automated techniques (Interactive Voice Response) could be useful for following treatment course in large groups of patients in the health care.

It is important to use measures that capture different aspects of patients’ health problems.

The recruitment of participants was based on patients’ interest and inclusion criteria which may have affect the generalizability.
Impact of ELN recommendations in the management of first‐line treated chronic myeloid leukaemia patients: a French cross‐sectional study
Authors: Etienne Gabriel , Huguet Francoise , Guerci‐Bresler Agnès , Nicolini Franck E. , Maloisel Frédéric , Coiteux Valérie , Dauriac Charles , Carpentier Nathalie , Bourdeix Isabelle , Tulliez Michel , Cony‐Makhoul Pascale 
Published: April 2016

SummaryThe availability of tyrosine kinase inhibitors has extended therapeutic options for chronic myeloid leukaemia (CML) patients. Monitoring recommendations and clinical response goals have recently been updated. The objective of this study was to describe the profile of CML patients in chronic phase currently receiving first‐line therapy, including treatment, monitoring and response kinetics. A multicentre, cross‐sectional, epidemiological survey in unselected chronic phase CML patients in France attending consultations during a one‐month period was performed. 438 of 697 (62·8%) reported patients were currently receiving first‐line treatment and were analysed. Imatinib was the most frequently received treatment (72·4% of patients). Retrospective cytogenetic and molecular assessments at 3, 6, 12 or 18 months were available in 88·4% of patients. At the 12‐month assessment, 32·2% were not in major molecular response (MMR). At last assessment, among 355 patients with duration of treatment ≥ 12 months, 91·5% had achieved MMR and 66·5% were in deep molecular response. This study, performed in everyday practice population of CML patients, suggests that monitoring of molecular responses in real‐life practice is aligned with European LeukaemiaNet recommendations. The majority of patients still receiving first‐line treatment are in optimal response, with a few being classified as in the warning area or responding to failure.