bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative efficacy of traditional non-selective NSAIDs and selective cyclo-oxygenase-2 inhibitors in patients with acute gout: a systematic review and meta-analysis
Authors: Li Mengtao , Yu Chen , Zeng Xiaofeng 
Published: September 2020

ObjectiveTo assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout.DesignSystematic review and meta-analysis.Data sourcesMedline, Web of Science, China National Knowledge Infrastructure and Wanfang Data published as of 4 April 2020.MethodsWe performed meta-analysis of randomised controlled trials (RCTs) of traditional non-selective NSAIDs versus cyclo-oxygenase-2 inhibitors and RCTs of various cyclo-oxygenase-2 inhibitors in patients with acute gout. The main outcome measures were mean change in pain Visual Analogue Scale (VAS) score and 5-point Likert scale score on days 2–8.ResultsTwenty-four trials involving five drugs were evaluated. For pain Likert scale, etoricoxib was comparable to indomethacin (standardised mean difference (SMD): −0.09, 95% CI: −0.27 to 0.08) but better than diclofenac 50 mg three times a day (SMD: −0.53, 95% CI: −0.98 to 0.09). Regarding pain VAS score, etoricoxib was comparable to diclofenac 75 mg two times per day (SMD: −1.63, 95% CI: −4.60 to 1.34) and diclofenac 75 mg four times a day (SMD: −1.82, 95% CI: −5.18 to 1.53), while celecoxib was comparable to diclofenac 100 mg four times a day (SMD: −2.41, 95% CI: −5.91 to 1.09). Etoricoxib showed similar patients’ global assessment of response (SMD: −0.10, 95% CI: −0.27 to 0.07) and swollen joint count (SMD: −0.25, 95% CI: −0.74 to 0.24), but better investigator’s global assessment of response (SMD: −0.29, 95% CI: −0.46 to 0.11) compared with indomethacin. Etoricoxib showed more favourable pain VAS score than celecoxib (SMD: −2.36, 95% CI: −3.36 to 1.37), but was comparable to meloxicam (SMD: −4.02, 95% CI: −10.28 to 2.24). Etoricoxib showed more favourable pain Likert scale than meloxicam (SMD: −0.56, 95% CI: −1.10 to 0.02). Etoricoxib 120 mg four times a day was more likely to achieve clinical improvement than celecoxib 200 mg two times per day (OR: 4.84, 95% CI: 2.19 to 10.72).ConclusionAlthough cyclo-oxygenase-2 inhibitors and traditional non-selective NSAIDs may be equally beneficial in terms of pain relief, cyclo-oxygenase-2 inhibitors (especially etoricoxib) may confer a greater benefit.
Associations between contextual and compositional characteristics of early childcare facilities with health, health behaviours and well-being among young children aged 06 years: protocol for a scoping review
Authors: Hilger-Kolb Jennifer , Schneider Sven , Herr Raphael , Osenbruegge Nina , Hoffmann Stephanie , Herke Max , Pischke Claudia , Sundmacher Leonie , Diehl Katharina 
Published: September 2020

IntroductionEarly childhood is an important life stage which is crucial for determining health and health inequalities in later life. At the meso-level (institutional-level), early childcare facilities (eg, kindergartens, preschools) are the most important agent of socialisation next to families in young children aged 06 years. In recent years, an increasing amount of studies has focused on contextual and compositional characteristics of early childcare facilities and their association with health (eg, self-rated health), health behaviour (eg, physical activity) and well-being (eg, emotional well-being) in this age group. However, as currently no overview of the available literature on this topic exists, we will conduct a scoping review including various study designs (eg, cross-sectional studies, prospective studies, qualitative studies).Methods and analysisWe will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. A systematic search of the following scientific databases will be conducted: PubMed/Medline, PsycInfo, Sociological Abstracts, Education Resources Information Center and The Cochrane Library. During the selection process, we will follow a two-step process. First, two reviewers will independently screen titles/abstracts of all potentially eligible articles by applying a set of previously defined inclusion and exclusion criteria. After the completion of the title/abstract screening, full texts of the remaining articles will be screened following the same procedure. To determine inter-rater agreement between reviewers, we will calculate Cohen’s Kappa after both steps. Key characteristics (eg, country of origin, sample size, study design) of included articles will be extracted. We will map the evidence available by providing a summary table on the key characteristics extracted and by presenting the associations using various types of illustrations.Ethics and disseminationSince no primary data will be collected for this review, ethical approval is not required. Our findings will be published in an international peer-reviewed journal and presented at national and international conferences.
Health-related quality of life in patients with non-communicable disease: study protocol of a cross-sectional survey
Authors: Van Wilder Lisa , Clays Els , Devleesschauwer Brecht , Pype Peter , Boeckxstaens Pauline , Schrans Diego , De Smedt Delphine 
Published: September 2020

IntroductionNon-communicable diseases (NCDs) are associated with lower health-related quality of life (HRQoL). However, knowledge about those diseases and predictors with a greater impact on patients’ HRQoL as well as knowledge on the complex relationship between HRQoL and comorbidities is lacking. The aim of this study is to assess the impact of NCDs on patients’ HRQoL, with a focus on multimorbidity and socioeconomic status.Methods and analysisA primary care-based cross-sectional study is conducted in Flanders (Belgium). Study participants (≥18 years) are medically diagnosed with at least one of the following diseases: cardiometabolic disorders, mental disorders and musculoskeletal disorders. A minimum of 50 general practitioners will participate to recruit participants (convenient sample) and a total of 531 patients will be enrolled (voluntary response sample). Each participant will complete a paper-based questionnaire to gather research outcomes. Statistical analyses will be performed using multiple linear regression models with HRQoL as main outcome parameter, adjusted for possible confounders. This study will generate new evidence on the key predictors of HRQoL in patients with NCDs, and particularly provide new insights in multimorbidity to improve the quality of care in primary care, to support patients’ self-management and to allocate resources more effectively.Ethics and disseminationThe study has been approved by the Ethical Committee of Ghent University Hospital, Ghent, Belgium (reference number: B670201939629) prior to the beginning of the recruitment. Study results will be disseminated through peer-reviewed publications and conference presentations.
What are the cost-savings and health benefits of improving detection and management for six high cardiovascular risk conditions in England? An economic evaluation
Authors: Thomas Chloe , Brennan Alan , Goka Edward , Squires Hazel Y , Brenner Gilly , Bagguley David , Buckley Woods Helen , Gillett Michael , Leaviss Joanna , Clowes Mark , Heathcote Laura , Cooper Katy , Breeze Penny 
Published: September 2020

ObjectivesTo estimate the cost savings and health benefits of improving detection of individuals at high risk of cardiovascular disease (CVD) in England, to determine to which patient subgroups these benefits arise, and to compare different strategies for subsequent management.DesignAn economic analysis using the School for Public Health Research CVD Prevention Model.SettingEngland 2018.ParticipantsAdults aged 16 and older with one or more high cardiovascular risk conditions, including hypertension, diabetes, non-diabetic hyperglycaemia, atrial fibrillation, chronic kidney disease and high cholesterol.InterventionsDetection of 100% of individuals with CVD high risk conditions compared with current levels of detection in England. Detected individuals are assumed to be managed either according to current levels of care or National Institute of Health and Care Excellence (NICE) guidelines.Main outcome measuresIncremental and cumulative costs, savings, quality adjusted life years (QALYs), CVD cases, and net monetary benefit, from a UK NHS and Personal Social Services perspective.Results£68 billion could be saved, 4.9 million QALYs gained and 3.4 million cases of CVD prevented over 25 years if all individuals in England with the six CVD high risk conditions were diagnosed and subsequently managed at current levels. Additionally, if all detected individuals were managed according to NICE guidelines, total savings would be £61 billion, 8.1 million QALYs would be gained and 5.2 million CVD cases prevented. Most benefits come from detection of high cholesterol in the short term and diabetes in the long term.ConclusionsSubstantial cost savings and health benefits would accrue if all individuals with conditions that increase CVD risk could be diagnosed, with detection of undiagnosed diabetes producing greatest benefits. Ensuring all conditions are managed according to NICE guidelines would further increase health benefits. Projected cost-savings could be invested in developing acceptable and cost-effective solutions for improving detection and management.
Occupational disparities in survival in Korean women with cancer: a nationwide registry linkage study
Authors: Lee Hye-Eun , KIM Eun-A , Zaitsu Masayoshi , Kawachi Ichiro 
Published: September 2020

ObjectivesWe sought to examine occupational disparities in survival among Korean women diagnosed with cancer.DesignPopulation-based, registry-linkage study.SettingSouth Korea.ParticipantsOur study population comprised female workers registered in the Korean national employment insurance programme during 1995–2000 and diagnosed with cancer between 1995 and 2008. A total of 61 110 women with cancer diagnoses was included in analysis. The occupation was categorised into four groups: (1) managers, professionals and technical workers, (2) clerks, (3) service/sales workers and (4) blue-collar workers.Primary and secondary outcome measureStudy population were linked to the national death registry until 2009. HRs for mortality adjusting for age and year of diagnosis were calculated in the study sample and subgroups with 10 specific cancer sites including thyroid, breast, stomach, cervix, colon or lung cancer using managers, professionals and technical workers as the reference.ResultsWomen in service/sales (HR 1.25, 95% CI 1.15 to 1.35) and blue-collar occupations (HR 1.34, 95% CI 1.25 to 1.44) had poorer survival for all cancer sites combined, while blue-collar workers showed poorer survival for lung (HR 1.41, 95% CI 1.14 to 1.77), breast (HR 1.28, 95% CI 1.06 to 1.54), cervical cancer (HR 1.42, 95% CI 1.02 to 2.06) and non-Hodgkin’s lymphoma (HR 1.69, 95% CI 1.09 to 2.77) compared with women in professional and managerial positions.ConclusionWe found substantial and significant inequalities in overall survival by the occupational group among Korean women with cancer, even in the context of universal access to cancer screening and treatment.
Cachexia is associated with depression, anxiety and quality of life in cancer patients
Authors: Sun Huihui , Sudip Thapa , Fu Xiaofen , Wen Su , Liu Huiquan , Yu Shiying 
Published: September 2020

ObjectivesThis study aimed to compare depression, anxiety and quality of life (QoL) between cachexia and non-cachexia patients, and explore the relationship between cachexia and depression, anxiety and QoL in patients with cancer.MethodsA total of 528 patients from cancer centres of four hospitals were enrolled in this cross-sectional study. All patients were divided into cachexia and non-cachexia according to international consensus definition of cachexia. Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Quality of Life Questionnaire-Cancer 30 (QLQ-C30) were used to evaluate depression, anxiety and QoL.Results285 patients (53.98%) were classified as cachexia. The prevalence of depression, anxiety, severe depression and severe anxiety in cachexia was 30.2%, 18.6%, 6.7% and 8.4%, respectively, which were significantly higher than in non-cachexia (all p<0.01). Patients with cachexia obviously acquired poorer physical function (PF), role function (RF), cognitive function (CF), emotional function (EF), social function (SF) and overall QoL than non-cachexia patients (all p<0.01). Cachexia was positively associated with depression (unstandardised coefficient (B)=2.123, p<0.001) and anxiety (B=1.123, p=0.024), and had a negative relationship with PF, CF, EF, SF and overall QoL (allB<0, all p<0.05).ConclusionsCachexia was associated with greater depression and anxiety and poorer QoL in patients with cancer, which emphasised the importance of timely identification and management of cachexia to improve the psychological problems and QoL among patients with cancer.
Constitutional de novo deletion CNV encompassing REST predisposes to diffuse hyperplastic perilobar nephroblastomatosis (HPLN)
Authors: Hyder Zerin , Fairclough Adele , Groom Mike , Getty Joan , Alexander Elizabeth , van Veen Elke M , Makin Guy , Sethuraman Chitra , Tang Vivian , Evans D Gareth , Maher Eamonn R , Woodward Emma R 
Published: September 2020

BackgroundNephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such as WT1, REST and TRIM28 have been described in apparently isolated (non-familial) WT.Despite constitutional CNVs being a well-studied cause of developmental disorders, their role in cancer predisposition is less well defined, so that the interpretation of cancer risks associated with specific CNVs can be complex.ObjectiveTo highlight the role of a constitutional deletion CNV (delCNV) encompassing the REST tumour suppressor gene in diffuse hyperplastic perilobar nephroblastomatosis (HPLN).Methods/resultsArray comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330–57,947,405)x1. The REST tumour suppressor gene is located at GRCh37 chr4:57,774,042–57,802,010.ConclusionThis delCNV encompassing REST is associated with nephroblastomatosis. Deletion studies should be included in the molecular work-up of inherited predisposition to WT/nephroblastomatosis. Detection of delCNVs involving known cancer predisposition genes can yield insights into the relationship between underlying genomic architecture and associated tumour risk.
Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways
Authors: Schierding William , Horsfield Julia A , O'Sullivan Justin M 
Published: September 2020

Background: The cohesin complex plays an essential role in genome organisation and cell division. A full complement of the cohesin complex and its regulators is important for normal development, since heterozygous mutations in genes encoding these components can be sufficient to produce a disease phenotype. The implication that genes encoding the cohesin subunits or cohesin regulators must be tightly controlled and resistant to variability in expression has not yet been formally tested.Methods: Here, we identify spatial-regulatory connections with potential to regulate expression of cohesin loci (Mitotic:SMC1A,SMC3,STAG1,STAG2,RAD21/RAD21-AS; Meiotic:SMC1B,STAG3,REC8,RAD21L1), cohesin-ring support genes (NIPBL,MAU2,WAPL,PDS5A,PDS5B) andCTCF, including linking their expression to that of other genes. We searched the genome-wide association studies (GWAS) catalogue for SNPs mapped or attributed to cohesin genes by GWAS (GWAS-attributed) and the GTEx catalogue for SNPs mapped to cohesin genes bycis-regulatory variants in one or more of 44 tissues across the human body (expression quantitative trail locus-attributed).Results: Connections that centre on the cohesin ring subunits provide evidence of coordinated regulation that has little tolerance for perturbation. We used the CoDeS3D SNP-gene attribution methodology to identify transcriptional changes across a set of genes coregulated with the cohesin loci that include biological pathways such as extracellular matrix production and proteasome-mediated protein degradation. Remarkably, many of the genes that are coregulated with cohesin loci are themselves intolerant to loss-of-function.Conclusions: The results highlight the importance of robust regulation of cohesin genes and implicate novel pathways that may be important in the human cohesinopathy disorders.
Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3
Authors: Maggi Lorenzo , Bello Luca , Bonanno Silvia , Govoni Alessandra , Caponnetto Claudia , Passamano Luigia , Grandis Marina , Trojsi Francesca , Cerri Federica , Ferraro Manfredi , Bozzoni Virginia , Caumo Luca , Piras Rachele , Tanel Raffaella , Saccani Elena , Meneri Megi , Vacchiano Veria , Ricci Giulia , Soraru' Gianni , D'Errico Eustachio , Tramacere Irene , Bortolani Sara , Pavesi Giovanni , Zanin Riccardo , Silvestrini Mauro , Politano Luisa , Schenone Angelo , Previtali Stefano Carlo , Berardinelli Angela , Turri Mara , Verriello Lorenzo , Coccia Michela , Mantegazza Renato , Liguori Rocco , Filosto Massimiliano , Marrosu Gianni , Siciliano Gabriele , Simone Isabella Laura , Mongini Tiziana , Comi Giacomo , Pegoraro Elena 
Published: September 2020

ObjectiveTo retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).MethodsInclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).ResultsWe included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18–72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14.ConclusionsOur data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear.
Preclinical to clinical translation of cenerimod, a novel S1P1receptor modulator, in systemic lupus erythematosus
Authors: Strasser Daniel S , Froidevaux Sylvie , Sippel Virginie , Gerossier Estelle , Grieder Ursula , Pierlot Gabin M , Kieninger-Graefitsch Andrea , Vezzali Enrico , Stalder Anna K , Renault Bérengère , Ryge Jesper , Hart Aaron , Mentzel Ulrich , Groenen Peter M A , Keller Marcel P , Trendelenburg Marten , Martinic Marianne M , Murphy Mark J 
Published: September 2020

Objectives:SLE is an autoimmune disease characterised by aberrant lymphocyte activation and autoantibody production. This study provides an in-depth preclinical and clinical characterisation of the treatment effect of cenerimod, a sphingosine-1-phosphate receptor type 1 (S1P1) modulator, in SLE.Methods:Cenerimod effect on lymphocyte numbers, organ pathology, inflammation, and survival was evaluated in the MRL/lpr lupus mouse model. Lymphocytes from healthy subjects and patients with SLE were assessed for cenerimod-induced S1P1receptor internalisation. Lymphocyte subsets and inflammatory biomarkers were characterised in a 12-week phase 2 clinical study (NCT-02472795), where patients with SLE were treated with multiple doses of cenerimod or placebo.Results:In MRL/lpr mice treated with cenerimod, blood lymphocytes were reduced, leading to reduced immune infiltrates into tissue, and decreased tissue pathology, proteinuria, and inflammation, resulting in increased survival. Cenerimod was potent and efficacious in inducing S1P1receptor internalisation in lymphocytes in both healthy subjects and patients with SLE. In patients with SLE, 12-week cenerimod treatment resulted in a dose-dependent reduction of blood lymphocytes, antibody-secreting cells (ASC), and plasma IFN-α.Conclusion:Cenerimod significantly ameliorated systemic and organ-specific pathology and inflammation in a mouse model of SLE. In lymphocytes from patients with SLE, the S1P1receptor remained functional despite concomitant background medication. The preclinical lymphocyte reduction translated to patients with SLE and resulted in the normalisation of ASC and the reduction of IFN-associated biomarkers. The efficacy and safety of cenerimod is being further investigated in a long-term clinical study in patients with SLE (CARE; NCT-03742037).
Association between number and type of different ACPA fine specificities with lung abnormalities in early, untreated rheumatoid arthritis
Authors: Joshua Vijay , Hensvold Aase Haj , Reynisdottir Gudrun , Hansson Monica , Cornillet Martin , Nogueira Leonor , Serre Guy , Nyren Sven , Karimi Reza , Eklund Anders , Sköld Magnus , Grunewald Johan , Chatzidionysiou Katerina , Catrina Anca 
Published: September 2020

BackgroundRheumatoid arthritis (RA)-associated anticitrullinated protein/peptide antibodies (ACPA) might originate at mucosal sites such as the lungs. We aimed to examine the relationship between the ACPA repertoire and lung abnormalities on high-resolution CT (HRCT) in patients with earlyuntreated RA.Methods106 patients with newly diagnosed untreated RA were examined with HRCT of the lungs. Blood samples were analysed for presence of rheumatoid factor (RF) and ACPA using either a CCP2 detection kit or an immunochip containing 10 different citrullinated peptides. Association between HRCT findings and the antibody repertoire was assessed by logistic regression analysis.ResultsThe number (%) of patients with HRCT abnormalities was 58 (54.7%) for parenchymal abnormalities and 68 (64.2%) for airway abnormalities. CCP2 IgG, RF IgA and antibodies against citrullinated fibrinogen were associated with the presence of parenchymal lung abnormalities. Interestingly, a high number of ACPA fine specificities gave a high risk of having parenchymal lung abnormalities at the time of RA diagnosis. No significant signals were identified between ACPA specificities and risk for airway abnormalities.ConclusionsThe presence of RF and ACPAs (especially against citrullinated fibrinogen peptides) as well as high number of ACPAs fine specificities are associated with parenchymal lung abnormalities in patients with early, untreated RA. This provides further support for an important pathogenic link between the lung and systemic autoimmunity, contributing to RA development.