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1.
Invest Ophthalmol Vis Sci ; 61(6): 3, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32492107

RESUMO

Purpose: Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. Methods: We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available after SNP microarray genotyping, imputation, and quality-control filtering. Results: We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 × 10-8, odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 × 10-7, OR = 1.22) and NOS2 (rs2274894, P = 8.22 × 10-7, OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rs10171979, P = 2.56 × 10-6, OR = 1.20), KIFAP3 (rs508063, P = 5.64 × 10-7, OR = 1.20), CLCN7 (rs67412457, P = 1.33 × 10-6, OR = 1.25), ACAA2 (rs9947182, P = 9.70 × 10-7, OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. Conclusions: We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.

2.
Aging Clin Exp Res ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504318

RESUMO

BACKGROUND: The LACE index scoring tool (Length of stay, Acuity of admission, Co-morbidities and Emergency department visits) has been designed to predict hospital readmissions. We evaluated the ability of the LACE index to predict age-specific frequent admissions and mortality. METHODS: Analysis of prospectively collected data of alive-discharge episodes between 01/04/2017 and 31/03/2019 in an NHS hospital. Data on 14,878 men and 17,392 women of mean age 64.0 years, SD = 20.5, range 18.0-106.7 years were analysed. The association of the LACE index with frequency of all-cause readmissions within 28 days of discharge and over a 2-year period, and with all-cause mortality within 30 days or within 6 months after discharge from hospital were evaluated. RESULTS: Within LACE index scores of 0-4, 5-9 or ≥ 10, the proportions of readmission ≥ 2 times within 28 days of discharge were 0.1, 1.3 and 9.2% (χ2 = 3070, p < 0.001) and over a 2-year period were 1.7, 4.8 and 19.1% (χ2 = 3364, p < 0.001). Compared with a LACE index score of 0-4, a score ≥ 10 increased the risk (adjusted for age, sex and frequency of admissions) of death within 6 months of discharge by 6.8-fold (5.1-9.0, p < 0.001) among all ages, and most strongly in youngest individuals (18.0-49.9 years): adjusted odds ratio = 16.1 (5.7-45.8, p < 0.001). For those aged 50-59.9, 60-69.9, 70-79.9 and ≥ 80 years, odds ratios reduced progressively to 9.6, 7.7, 5.1 and 2.3, respectively. Similar patterns were observed for the association of LACE index with mortality within 30 days of hospital discharge. CONCLUSIONS: The LACE index predicts short-term and long-term frequent admissions and short-term and medium-term mortality, most pronounced among younger individuals, after hospital discharge.

3.
Rheumatol Int ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32556474

RESUMO

Comorbid fibromyalgia, in axial spondyloarthritis (axSpA) has been shown to influence disease activity and function, and quality of life. Although several papers exist, there is no comprehensive and robust systematic review to determine the prevalence of fibromyalgia in this patient group. Thus, the aim of the current study was to provide a definitive estimate of prevalence of fibromyalgia in axSpA, and in axSpA sub-classifications. A systematic literature search was conducted in Ovid MEDLINE, EMBASE, Evidence Based Medicine (EBM), and Cochrane Library, updated to April 2020, combining keywords and relevant MeSH headings, to identify papers reporting the prevalence of fibromyalgia in axSpA, or data from which this could be computed. This was then combined in a meta-analysis with data from the Scotland Registry for Ankylosing Spondylitis (SIRAS), a national axSpA register in Scotland. Data was pooled using random or fixed effects models where heterogeneity was greater or lesser than 75%. From 3401 manuscripts initially identified, 15 papers were included in the final review, plus SIRAS, giving data from 16 separate sources. The prevalence of fibromyalgia, among a total of 5214 patients, was 16.4% (95% CI 12.3-20.5%). Prevalence varied with axSpA sub-classification: ankylosing spondylitis: 13.8% (9.1-18.6%); MRI positive non-radiographic axSpA 20.3% (6.5-34.1%); and 'clinical' disease: 11.1% (6.0-16.2%). Overall, around 1 in 6 patients with axSpA also meet criteria for fibromyalgia. While estimates from individual studies vary, comorbid fibromyalgia represents a considerable burden across all sub-classifications of axSpA. This emphasises that focusing management solely on inflammatory disease in this patient group is unlikely to yield optimal improvements in quality of life.

4.
Inflamm Bowel Dis ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32572468

RESUMO

BACKGROUND: Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. METHODS: All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. RESULTS: Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) responded to steroids. Admission C-reactive protein (CRP) (P = 0.009, odds ratio [OR] 1.006), albumin (P < 0.001, OR 0.894) and endoscopic severity (P < 0.001, OR 3.166) differed significantly between responders and nonresponders. A simple UC severity score (area under the curve [AUC] 0.754, P < 0.001) was derived from these variables; 78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician's global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value [PPV] 78.1%, negative predictive value [NPV] 87.1%). CONCLUSIONS: More than three quarters of patients scoring 3 (albumin ≤30 g/L, CRP ≥50 mg/L, and increased endoscopic severity) did not respond to IV steroids. This combination of parameters (ACE) identifies on admission a high-risk population who may benefit from earlier second-line medical treatment or surgical intervention.

5.
Intern Med J ; 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32388925

RESUMO

BACKGROUND: Clinical diagnosis of Alzheimer's disease (AD) is only 70% accurate. Reduced cerebral blood flow (CBF) and metabolism in parieto-temporal and posterior cingulate cortex may assist diagnosis. Whilst widely accepted that 18 F-FDG PET has superior accuracy to CBF SPECT for AD, there is very limited head-to-head data from clinically relevant populations and these studies relied on clinical diagnosis as the reference standard. AIM: To directly compare the accuracy of CBF-SPECT and 18 F-FDG PET in patients referred for diagnostic studies in detecting ß-amyloid PET confirmed AD. METHODS: 126 patients, 56% with mild cognitive impairment and 44% with dementia, completed both CBF-SPECT and 18 F-FDG PET as part of their diagnostic assessment, and subsequently underwent ß-amyloid PET for research purposes. Transaxial slices and Neurostat 3D-SSP analyses of 18 F-FDG PET and CBF-SPECT scans were independently reviewed by five nuclear medicine clinicians blinded to all other data. Operators selected the most likely diagnosis and their diagnostic confidence. Accuracy analysis used final diagnosis incorporating ß-amyloid PET as the reference standard. RESULTS: Clinicians reported high diagnostic confidence in 83% of 18 F-FDG PET compared to 67% for CBF-SPECT (p=0.001). All reviewers showed individually higher accuracy using 18 F-FDG PET. Based on majority read, the combined AUROC in diagnosing AD was 0.71 for 18 F-FDG PET and 0.61 for CBF-SPECT (p=0.02). The sensitivity of 18 F-FDG PET and CBF-SPECT was 76% vs 43% (p<0.001), whilst specificity was 74% vs 83% (p=0.45). CONCLUSION: 18 F-FDG PET is superior to CBF-SPECT in detecting Alzheimer's disease amongst patients referred for the assessment of cognitive impairment. This article is protected by copyright. All rights reserved.

6.
Environ Microbiol ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32372527

RESUMO

Members of the bacterial candidate phylum WPS-2 (or Eremiobacterota) are abundant in several dry, bare soil environments. In a bare soil deposited by an extinct iron-sulfur spring, we found that WPS-2 comprised up to 24% of the bacterial community and up to 108 cells per g of soil based on 16S rRNA gene sequencing and quantification. A single genus-level cluster (Ca. Rubrimentiphilum) predominated in bare soils but was less abundant in adjacent forest. Nearly complete genomes of Ca. Rubrimentiphilum were recovered as single amplified genomes (SAGs) and metagenome-assembled genomes (MAGs). Surprisingly, given the abundance of WPS-2 in bare soils, the genomes did not indicate any capacity for autotrophy, phototrophy, or trace gas metabolism. Instead, they suggest a predominantly aerobic organoheterotrophic lifestyle, perhaps based on scavenging amino acids, nucleotides, and complex oligopeptides, along with lithotrophic capacity on thiosulfate. Network analyses of the entire community showed that some species of Chloroflexi, Actinobacteria, and candidate phylum AD3 (or Dormibacterota) co-occurred with Ca. Rubrimentiphilum and may represent ecological or metabolic partners. We propose that Ca. Rubrimentiphilum act as efficient heterotrophic scavengers. Combined with previous studies, these data suggest that the phylum WPS-2 includes bacteria with diverse metabolic capabilities.

8.
Arthritis Rheumatol ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32307922

RESUMO

OBJECTIVES: Ectopic lymphoid structures (ELS) develop at sites of infection, autoimmunity and cancer. In patients with Sjogren's syndrome (SS), ELS support autoreactive B-cell activation and support lymphomagenesis. IL-27 is a key regulator of adaptive immunity and limits Th17 cell-driven pathology. Here, we elucidated the role of IL-27 in ELS formation and function in autoimmunity using a murine model of sialadenitis and in patients with SS. METHODS: ELS formation was induced in wild-type and IL27ra-/- mice via salivary gland (SG) cannulation of a replication-deficient adenovirus in the presence/absence of IL-17A neutralization. In SG biopsies IL-27-producing cells were identified by multicolour immune-fluorescence microscopy. Lesional and circulating IL-27 levels were determined by gene expression and ELISA. The in-vitro effect of IL-27 on T-cells was determined by FACS and cytokine release. RESULTS: In experimental sialadenitis, Il27ra-/- mice had larger and hyperactive ELS (focus score P<0.001), increased autoimmunity and an expanded Th17 response (P<0.001) compared to wild-type. IL-17 blockade in Il27ra-/- mice suppressed the aberrant ELS response (B and T cell reduction against control P<0.01). SS patients displayed increased circulating IL-27 (P<0.01) and in SG biopsies IL-27 was expressed by DC-LAMP+ dendritic cells in association with CD3+ T-cells. Remarkably, in SS T-cells but not in T-cells from patients with rheumatoid arthritis or healthy controls, IL-27-mediated suppression of IL-17 secretion was severely impaired and associated with an aberrant IFN-γ release upon IL-27 stimulation. CONCLUSIONS: Our data indicate that the physiological ability of IL-27 to limit the magnitude and function of ELS through control of Th17 cell expansion is severely impaired in SS patients highlighting a defective immunoregulatory checkpoint in this condition.

9.
Gut ; 69(6): 984-990, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32303607

RESUMO

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Doenças Inflamatórias Intestinais , Pandemias , Pneumonia Viral , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Medição de Risco , Reino Unido
10.
Artigo em Inglês | MEDLINE | ID: mdl-32337555

RESUMO

OBJECTIVES: Effective management of axial spondyloarthritis (axSpA)-related fatigue is a major unmet clinical need. Anti-TNF therapy may reduce fatigue levels, although any effect has yet to be definitively quantified and predictors of any such improvements are unknown. METHODS: The British Society of Rheumatology Register in Axial Spondyloarthritis (BSRBR-AS) prospectively recruited axSpA patients across the UK. Changes in fatigue levels (measured using the Chalder Fatigue Scale) >1 year were compared between those starting anti-TNF therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results were meta-analysed with the extant literature to calculate pooled estimates. Then, among those BSRBR-AS anti-TNF commencers with clinically relevant fatigue, baseline predictors of response were investigated. RESULTS: Of the 998 BSRBR-AS recruits with complete fatigue data, 310 were anti-TNF commencers. At 1-year follow-up, the former group reported a mean fatigue change of -2.6 (95% CI -4.1, -1.9) points while the latter reported a mean worsening of fatigue by 0.2 points. Following propensity score adjustment, those commencing anti-TNF therapy reduced fatigue by 3.0 points compared with those not. Of those with significant fatigue and commencing anti-TNF, poor sleep quality at baseline predicted fatigue improvement. In the meta-analysis, including 1109 subjects, treatment with anti-TNF therapy resulted in a significant improvement in fatigue [Standardized mean difference (SMD) = 0.36, 95% CI 0.15, 1.56]. CONCLUSION: Anti-TNF therapy results in a significant but modest reduction in fatigue amongst axSpA patients, with those reporting poor sleep quality most likely to report improvement. Effective management will likely require additional approaches.

11.
Exp Clin Transplant ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32281533

RESUMO

Wiskott-Aldrich syndrome is a rare primary immuno-deficiency disorder that is characterized by a triad of microthrombocytopenia, eczema, and recurrent infections. Progression to end-stage renal failure is common in survivors due to immunoglobulin A nephropathy. We describe the case of a 24-year-old male with Wiskott-Aldrich syndrome. The patient had previous hematopoietic stem cell transplant and was on hemodialysis due to end-stage renal failure. He subsequently underwent living-donor renal transplant from his mother as the donor. This is only the fifth case of renal transplant in a patient with Wiskott-Aldrich syndrome in the world. In all cases, the perioperative management of hemostatic function has been crucial. We used thromboelastography to guide our hemostatic decisions rather than platelet count, thus reducing exposure to unnecessary platelet transfusions and without increased bleeding risk. Our patient had an uneventful course after living-donor kidney transplant.

12.
Ann Rheum Dis ; 79(7): 914-919, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32327428

RESUMO

Management guidelines assume that results from clinical trials can be generalised, although seldom is data available to test this assumption. We aimed to determine the proportion of patients commencing tumour necrosis factor inhibition (TNFi) who would have been eligible for relevant clinical trials, and whether treatment response differs between these groups and the trials themselves. The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited a real-world cohort of TNFi-naïve spondyloarthritis patients with data collection from clinical records and patient questionnaires. Participant characteristics were extracted from trials identified from a recent Health Technology Assessment of TNFi for ankylosing spondylitis/non-radiographic axial spondyloarthritis. Descriptive statistics were used to determine the differences, including treatment response, between BSRBR-AS participants who would/would not have been eligible for the clinical trials and with trial participants. Among 2420 BSRBR-AS participants, those commencing TNFi (34%) had shorter symptom duration (15 vs 22 years) but more active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 6.4 vs 4.0; Bath Ankylosing Spondylitis Disease Functional Index (BASFI) 6.2 vs 3.8). Of those commencing TNFi, 41% met eligibility criteria for ≥1 of fourteen relevant trials; they reported higher disease activity (BASDAI 6.9 vs 6.1) and poorer function (BASFI 6.6 vs 6.0). 61.7% of trial participants reported a positive treatment response, vs 51.3% of BSRBR-AS patients (difference: 10.4%; 95% CI 4.4% to 16.5%). Potential eligibility for trials did not influence treatment response (difference 2.0%; -9.4% to 13.4%). Fewer patients in the real world respond to TNFi than is reported in the trial literature. This has important implications for the generalisability of trial results, and the cost-effectiveness of TNFi agents.

13.
Front Immunol ; 11: 183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117307

RESUMO

Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer, anti-helminth responses and colonic inflammation, the Mbd2-expressing cell types that control these responses are incompletely defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2 -/- mice displayed dramatically worse pathology than wild type controls during dextran sulfate sodium (DSS) induced colitis, with increased inflammatory (IL-1ß+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.

14.
PLoS One ; 15(2): e0228668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053663

RESUMO

Where humans and wildlife co-exist, mitigation is often needed to alleviate potential conflicts and impacts. Deterrence methods can be used to reduce impacts of human structures or activities on wildlife, or to resolve conservation conflicts in areas where animals may be regarded as a nuisance or pose a health hazard. Here we test two methods (acoustic and radar) that have shown potential for deterring bats away from areas where they forage and/or roost. Using both infrared video and acoustic methods for counting bat passes, we show that ultrasonic speakers were effective as bat deterrents at foraging sites, but radar was not. Ultrasonic deterrents decreased overall bat activity (filmed on infrared cameras) by ~80% when deployed alone and in combination with radar. However, radar alone had no effect on bat activity when video or acoustic data were analysed using generalised linear mixed effect models. Feeding buzzes of all species were reduced by 79% and 69% in the ultrasound only treatment when compared to the control and radar treatments, but only the ultrasound treatment was significant in post-hoc tests. Species responded differently to the ultrasound treatments and we recorded a deterrent effect on both Pipistrellus pipistrellus (~40-80% reduction in activity) and P. pygmaeus (~30-60% reduction), but not on Myotis species. However, only the ultrasound and radar treatment was significant (when compared to control and radar) in post-hoc tests for P. pipistrellus. Deterrent treatment was marginally non-significant for P. pygmaeus, but the ultrasound only treatment was significant when compared to radar in post-hoc tests. We therefore suggest that acoustic, but not radar methods are explored further as deterrents for bats. The use of acoustic deterrence should always be assessed on a case-by-case basis, with a focus on bat conservation.


Assuntos
Acústica , Quirópteros/fisiologia , Conservação dos Recursos Naturais , Radar , Som , Animais , Humanos , Raios Infravermelhos , Modelos Lineares , Especificidade da Espécie , Ultrassom , Gravação em Vídeo
15.
Artigo em Inglês | MEDLINE | ID: mdl-31990352

RESUMO

OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31960053

RESUMO

OBJECTIVES: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. METHODS: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. RESULTS: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. CONCLUSION: High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.

17.
Arthritis Care Res (Hoboken) ; 72(4): 591-599, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30762311

RESUMO

OBJECTIVE: Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout. RESULTS: For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (ß = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (ß = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers ß = -0.1, 95% CI -0.5, 0.3; current smokers ß = -0.01, 95% CI -0.4, 0.4) at 3 months. CONCLUSION: TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies.

18.
Arch Dis Child ; 105(5): 470-475, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31753832

RESUMO

OBJECTIVE: To determine the prevalence of work-related psychological distress in staff working in UK paediatric intensive care units (PICU). DESIGN: Online (Qualtrics) staff questionnaire, conducted April to May 2018. SETTING: Staff working in 29 PICUs and 10 PICU transport services were invited to participate. PARTICIPANTS: 1656 staff completed the survey: 1194 nurses, 270 physicians and 192 others. 234 (14%) respondents were male. Median age was 35 (IQR 28-44). MAIN OUTCOME MEASURES: The Moral Distress Scale-Revised (MDS-R) was used to look at moral distress, the abbreviated Maslach Burnout Inventory to examine the depersonalisation and emotional exhaustion domains of burnout, and the Trauma Screening Questionnaire (TSQ) to assess risk of post-traumatic stress disorder (PTSD). RESULTS: 435/1194 (36%) nurses, 48/270 (18%) physicians and 19/192 (10%) other staff scored above the study threshold for moral distress (≥90 on MDS-R) (χ2 test, p<0.00001). 594/1194 (50%) nurses, 99/270 (37%) physicians and 86/192 (45%) other staff had high burnout scores (χ2 test, p=0.0004). 366/1194 (31%) nurses, 42/270 (16%) physicians and 21/192 (11%) other staff scored at risk for PTSD (χ2 test, p<0.00001). Junior nurses were at highest risk of moral distress and PTSD, and junior doctors of burnout. Larger unit size was associated with higher MDS-R, burnout and TSQ scores. CONCLUSIONS: These results suggest that UK PICU staff are experiencing work-related distress. Further studies are needed to understand causation and to develop strategies for prevention and treatment.

20.
Phys Ther Sport ; 41: 29-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31715556

RESUMO

OBJECTIVES: To investigate the prevalence, nature and factors associated with injury among adult amateur rowers. DESIGN: Retrospective cross-sectional study. SETTING: UK-based amateur rowing clubs. PARTICIPANTS: 160 amateur rowers. MAIN OUTCOME MEASURES: Frequency, type, location, severity and rowing-related factors associated with injury. RESULTS: Injury rate was 5.7 per 1000 sessions, with no effect of sex (χ2 = 0.195, P = 0.659) or weight class (χ2 = 0.800, P = 0.371). The lower-back demonstrated an epidemiological incidence proportion (IP) of 0.39 (95%CI = 0.33 to 0.46). The IP for water- and land-based training was 0.39 (95%CI = 0.31 to 0.47) and 0.57 (95%CI = 0.49 to 0.65), respectively. IP was highest between January and March (0.13-0.15), whilst time loss was 0.49 (95%CI = 0.42-0.57). The IP for 'overuse' and 'traumatic' injuries was 0.71 (95%CI = 0.65 to 0.78) and 0.22 (95%CI = 0.16 to 0.27), respectively. Training volume was positively associated with injury rate (r = 0.418, P < 0.001). CONCLUSIONS: Injury rates appear higher among amateur rowers with the most common injury site being the lower-back. Our results suggest several contextual factors influence injury risk including seasonal phase, training type and training volume.

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