Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study

ObjectivesTo identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD).MethodsPatients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous antibiotics or followed by death. SIs were categorised by aetiology and site. SI risk was assessed through Cox proportional hazards models. Best models were selected using machine learning Least Absolute Shrinkage and Selection Operator (LASSO) methodology.ResultsAmong 20 361 patients with RA and 6176 patients with NIRMD, 1600 and 276 first SIs were identified, respectively. Incidence of SIs was higher in RA compared with NIRMD (IRR = 1.5; 95% CI 1.2 to 1.5). The risk persisted after adjusting using the LASSO model (HR 1.7; 95% CI 1.5 to 1.8), but attenuated when additionally adjusted for glucocorticoid use (HR 1.3; 95% CI 1.2 to 1.5). SI risk was significantly higher in RA versus NIRMD for bacterial infections as well as for respiratory, skin, bone, joint, bloodstream infections and sepsis irrespective of glucocorticoid use. Compared with NIRMD, SI risk was significantly increased in patients with RA who were in moderate and high disease activity but was similar to those in low disease activity/remission (p trend < 0.001).ConclusionsThe risk of all SIs, particularly bacterial, respiratory, bloodstream, sepsis, skin, bone and joint infections are significantly increased in patients with RA compared with patients with NIRMD. This infection risk appears to be greatest in those with higher RA disease activity.

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Biomarker-related risk for myocardial infarction and serious infections in patients with rheumatoid arthritis: a population-based study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211727 ◽

2017 ◽

Vol 77 (3) ◽

pp. 386-392 ◽

Cited By ~ 12

Author(s):

Jeffrey R Curtis ◽

Fenglong Xie ◽

Lang Chen ◽

Kenneth G Saag ◽

Huifeng Yun ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Myocardial Infarction ◽

Disease Activity ◽

Large Scale ◽

Proportional Hazards ◽

Threshold Effect ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Few Data

BackgroundRheumatoid arthritis (RA) disease activity and associated systemic inflammation has been associated with serious infection (SIEs), myocardial infarction (MI) and coronary heart disease (CHD) events based on a few registry studies or clinical trials. There are few data from large-scale population-based studies given feasibility challenges in conducting such investigations.MethodsMultibiomarker disease activity (MBDA) test scores (n=77 641) were linked to Medicare for US patients with RA. Outcomes of interest were hospitalised pneumonia/sepsis (SIE), MI and a composite CHD outcome. The MBDA score ranges from 1 to 100 and was analysed as time-varying. Cox proportional hazards models evaluated the association between MBDA score and SIEs, MI and CHD events, controlling for potential confounders. A sensitivity analysis excluded C reactive protein (CRP) from the MBDA score.ResultsThere were 17 433 and 16 796 patients eligible for the SIE and MI/CHD analyses, respectively. Mean (SD) age was 69 (11) years, 79% were women, 81% were white and 38% were disabled. Over 16 424 person-years of follow-up, there were 452 SIE events, 132 MIs and 181 CHD events. Higher MBDA scores were associated with SIEs (HR=1.32, 95% CI 1.23 to 1.41 per 10 unit MBDA score change). For MI/CHD events, a threshold effect was present; higher disease activity by MBDA score was associated with increased MI (HR=1.52, 95% CI 0.92 to 2.49) and CHD rates (HR=1.54, 95% CI 1.01 to 2.34, comparing scores ≥30 vs <30). Analyses of the MBDA score without CRP yielded similar results.ConclusionHigher MBDA scores were associated with hospitalised infection, MI and CHD events in a large, predominantly older, US RA population.

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AB0655 RHEUMATOID ARTHRITIS ACTIVITY BEFORE AND AFTER COVID-19 LOCKDOWN PERIOD

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.576 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1360.1-1360

Author(s):

M. Jordhani ◽

D. Ruci ◽

F. Skana ◽

E. Memlika

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Musculoskeletal Diseases ◽

Statistical Tests ◽

Laboratory Data ◽

World Population ◽

Chronic Patients ◽

Das 28 ◽

Significant Difference ◽

Before And After

Background:The COVID-19 global pandemic has had a great impact on world population due to morbidity, mortality and restriction measures in order to stop the progression of COVID-19.Patients with rheumatic and musculoskeletic diseases, and especially rheumatoid arthritis (RA) patients, being one of the vulnerable classes of chronic patients, were recommended to follow the government’s rules1.Objectives:The aim of this study was to evaluate DAS-28-ESR in patients with rheumatoid arthritis before and after lockdown period.Methods:This is a multi-center observational study including 85 patients which were evaluated before and after lockdown for their disease activity score according to DAS-28-ESR score. They had been diagnosed with rheumatoid arthritis more than 5 years ago. A thorough physical examination was performed before and after the lockdown period. It included examination of tender and swollen joints and patient’s global health. They were completed with all required laboratory data, including erythrosedimentation rate. For a more accurate calculation, DAS-28-ESR was used in an electronic version. Patients with other inflammatory or infective diseases were excluded from the study. All data were statistically evaluated using statistical tests such as t-student test.Results:The first group (the one before lockdown) had an average DAS-28-ESR of 4.7 while after the lockdown period, the average DAS-28-ESR was 5.16.After statistically evaluating all data, it was found that there exists a significant difference between DAS-28-ESR score before and after COVID-19 lockdown (p=0.0011).Conclusion:Our study showed that lockdown period due to COVID-19 pandemic, has aggravated disease activity in patients with Rheumatoid Arthritis. This may be consequence of various causes such as physical inactivity and difficulty to follow-up or to take the medication properly.References:[1]Landewé RB, Machado PM, Kroon F, et al, EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2, Annals of the Rheumatic Diseases 2020;79:851-858.Disclosure of Interests:None declared.

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Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study

Rheumatology ◽

10.1093/rheumatology/keab101 ◽

2021 ◽

Author(s):

Carine Salliot ◽

Yann Nguyen ◽

Gaëlle Gusto ◽

Amandine Gelot ◽

Juliette Gambaretti ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Prospective Cohort ◽

Regression Models ◽

Proportional Hazards ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Smoking History ◽

Nulliparous Women ◽

Hormonal Exposures ◽

Incident Cases

Abstract Objective To assess the relationships between female hormonal exposures and risk of rheumatoid arthritis (RA), in a prospective cohort of French women. Methods E3N is an on-going French prospective cohort that included 98 995 women aged 40–65 years in 1990. Every 2–3 years, women completed mailed questionnaires on their lifestyles, reproductive factors, and health conditions. Cox proportional-hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Effect modification by smoking history was investigated. Results A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (<22 vs ≥27 years; HR = 1.34; 95%CI 1.0–1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95%CI 1.0–1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95%CI 1.0–2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95%CI 0.2–0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (>24 vs 0 months; multi-adjusted HR = 0.77; 95%CI 0.6–0.9). Conclusions These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.

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Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa503 ◽

2020 ◽

Author(s):

I Karaiskos ◽

G L Daikos ◽

A Gkoufa ◽

G Adamis ◽

A Stefos ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Active Agent ◽

Bloodstream Infections ◽

National Registry ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Fatal Disease

Abstract Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). Methods A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. Results One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. Conclusions Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

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Abdominal Obesity in Comparison with General Obesity and Risk of Developing Rheumatoid Arthritis in Women

The Journal of Rheumatology ◽

10.3899/jrheum.200056 ◽

2020 ◽

pp. jrheum.200056

Author(s):

Nathalie E. Marchand ◽

Jeffrey A. Sparks ◽

Sara K. Tedeschi ◽

Susan Malspeis ◽

Karen H. Costenbader ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Abdominal Obesity ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Health Study ◽

General Obesity ◽

Middle Aged ◽

Covariate Data ◽

Cox Proportional Hazards Models ◽

Younger Age

Objective Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at a younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity; thus, we investigated whether abdominal obesity, compared to general obesity, predicted RA risk in 2 prospective cohorts: the Nurses’ Health Study (NHS) and NHS II. Methods We followed 50,682 women (1986–2014) in NHS and 47,597 women (1993–2015) in NHS II, without RA at baseline. Waist circumference (WC), BMI, health outcomes, and covariate data were collected through biennial questionnaires. Incident RA cases and serologic status were identified by chart review. We examined the associations of WC and BMI with RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to age ≤ 55 years. Results During 28 years of follow-up, we identified 844 incident RA cases (527 NHS, 317 NHS II). Women with WC > 88 cm (35 in) had increased RA risk (HR 1.22, 95% CI 1.06–1.41). A similar association was observed for seropositive RA, which was stronger among young and middle-aged women. Further adjustment for BMI attenuated the association to null. In contrast, BMI was associated with RA (HRBMI ≥ 30 vs < 25 1.33, 95% CI 1.05–1.68) and seropositive RA, even after adjusting for WC, and, as in WC analyses, this association was stronger among young and middle-aged women. Conclusion Abdominal obesity was associated with increased RA risk, particularly for seropositive RA, among young and middle-aged women; however, it did not independently contribute to RA risk beyond general obesity.

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The prevalence and impact of comorbidities on patients with axial spondyloarthritis: results from a nationwide population-based study

Arthritis Research & Therapy ◽

10.1186/s13075-020-02301-0 ◽

2020 ◽

Vol 22 (1) ◽

Cited By ~ 1

Author(s):

Imke Redeker ◽

Johanna Callhoff ◽

Falk Hoffmann ◽

Ursula Marschall ◽

Hildrun Haibel ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Pulmonary Disease ◽

Functional Impairment ◽

Axial Spondyloarthritis ◽

Musculoskeletal Diseases ◽

Large Population ◽

Population Based ◽

Chronic Pulmonary Disease ◽

Collagen Vascular Diseases

Abstract Background In contrast to other chronic rheumatic musculoskeletal diseases such as rheumatoid arthritis, comorbidities in axial spondyloarthritis (axSpA) and their impact on disease outcomes are less well studied. The aim of this study was to investigate the prevalence of comorbidities and their association with disease activity and functional impairment in a large population-based cohort of patients with axSpA. Methods A random sample of patients with axSpA, stratified by age and sex, was drawn from health insurance data. Patients in the sample received a survey on demographic, socioeconomic, and disease-related parameters. Comorbidities were defined using the Elixhauser coding algorithms excluding rheumatoid arthritis/collagen vascular diseases and including osteoporosis and fibromyalgia, resulting in a set of 32 comorbidities. The prevalence of comorbidities in the axSpA patients and their pharmacological treatment were examined. Multivariable linear regression models were calculated to determine the association of comorbidities with disease activity and functional status. Results A total of 1776 axSpA patients were included in the analyses (response, 47%; mean age, 56 years; 46% female). The most prevalent comorbidities were hypertension, depression, and chronic pulmonary disorders. The number of comorbidities was significantly associated with both the BASDAI and BASFI: β (95% CI) = 0.17 (0.09–0.24) and 0.24 (0.15–0.32), respectively. When analysed separately, hypertension, depression, and chronic pulmonary disease were comorbidities with a significant and independent association with BASFI, while for BASDAI, such an association was found for depression and chronic pulmonary disease only. Conclusions Comorbidities are common in axSpA patients and are associated with higher disease activity and higher levels of functional impairment. Higher disease activity and higher levels of functional impairment might be indicators of severe disease resulting in the development of comorbidities.

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Risk of Recurrent Staphylococcus aureus Prosthetic Joint Infection in Rheumatoid Arthritis Patients—A Nationwide Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz451 ◽

2019 ◽

Vol 6 (11) ◽

Author(s):

Namrata Singh ◽

Rajeshwari Nair ◽

Michihiko Goto ◽

Martha L Carvour ◽

Ryan Carnahan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Staphylococcus Aureus ◽

Cohort Study ◽

Prosthetic Joint Infection ◽

Proportional Hazards ◽

Joint Infection ◽

International Classification Of Diseases ◽

Cox Proportional Hazards ◽

Prosthetic Joint ◽

Implant Retention

AbstractBackgroundTreatment of rheumatoid arthritis (RA) often involves immune-suppressive therapies. Concern for recurrent prosthetic joint infection (PJI) in RA patients might be high and could reduce use of joint implantation in these patients. We aimed to evaluate the risk of recurrence of PJI in RA patients compared with osteoarthritis (OA) patients by utilizing a large health care system.MethodsWe conducted a retrospective cohort study of all patients admitted for a Staphylococcus aureus PJI who underwent debridement, antibiotics, and implant retention (DAIR) or 2-stage exchange (2SE) between 2003 and 2010 at 86 Veterans Affairs Medical Centers. Both RA patients and the comparison group of osteoarthritis (OA) patients were identified using International Classification of Diseases, Ninth Revision, codes. All index PJI and recurrent positive cultures for S. aureus during 2 years of follow-up were validated by manual chart review. A Cox proportional hazards regression model was used to compare the time to recurrent PJI for RA vs OA.ResultsIn our final cohort of 374 veterans who had either DAIR or 2SE surgery for their index S. aureus PJI, 11.2% had RA (n = 42). The majority of the cohort was male (97.3%), and 223 (59.6%) had a methicillin-susceptible S. aureus PJI. RA patients had a similar risk of failure compared with OA patients, after adjusting for covariates (hazard ratio, 0.81; 95% confidence interval, 0.48–1.37).ConclusionsPrior diagnosis of RA does not increase the risk of recurrent S. aureus PJI. Further studies are needed to evaluate the effect of different RA therapies on outcomes of episodes of PJI.

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The association between lymphopenia and serious infection risk in rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/kez349 ◽

2019 ◽

Vol 59 (4) ◽

pp. 762-766

Author(s):

Sujith Subesinghe ◽

Alexander Kleymann ◽

Andrew Ian Rutherford ◽

Katie Bechman ◽

Sam Norton ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Mixed Effect ◽

Proportional Hazards Regression ◽

Effect Model ◽

Serious Infection ◽

Patients At Risk ◽

Using Data ◽

The Relationship

Abstract Objectives To investigate the relationship between occurrence of serious infection (SI) and lymphocyte counts in patients with RA using data from a single centre. Methods We used routinely captured data from a single tertiary rheumatology centre to explore the relationship between lymphopenia and SI risk. Adult RA patients were included over a 5-year follow-up period. Admissions due to confirmed SI were considered. SI rate with 95% confidence intervals was calculated. The association between SI with baseline lymphocyte counts, time-averaged lymphocyte counts throughout all follow-up, and a nadir lymphocyte count was assessed using Cox proportional hazards regression. The relationship between lymphopenia over time and SI was analysed using a mixed-effect model of lymphocyte counts prior to SI. Results This analysis included 1095 patients with 205 SIs during 2016 person-years of follow-up. The SI rate was 4.61/100 patient-years (95% CI: 3.76, 5.65). Compared with patients with nadir lymphocyte counts >1.5 × 109 cells/l, nadir lymphopenia <1 × 109 cells/l was significantly associated with higher SI risk (HR 3.28; 95% CI: 1.59, 6.76), increasing to HR 8.08 (95% CI: 3.74, 17.44) in patients with lymphopenia <0.5 × 109 cells/l. Lymphocyte counts were observed to be reduced in the 30-day period prior to SI. Conclusion Lymphocyte counts below <1.0 × 109 cells/l were associated with higher SI risk in RA patients; the strongest association between lymphopenia and SI was observed when lymphocyte counts were below <0.5 × 109 cells/l. Lymphopenia may be used as a measure to stratify patients at risk of SI.

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