Safety of the Methotrexate-leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (Biobadabrasil)

2021 ◽  
pp. jrheum.201248
Author(s):  
Markus Bredemeier ◽  
Roberto Ranza ◽  
Adriana Maria Kakehasi ◽  
Aline Ranzolin ◽  
Inês Guimarães da Silveira ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Serious Adverse Events ◽  
Cox Proportional Hazards Models ◽  
Advanced Therapies ◽  
Serious Infections ◽  
Cox Analysis ◽  
Lower Hazard

Objective To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease modifying anti-rheumatic drugs (DMARDs) or JAK inhibitors (JAKi). Methods RA patients starting the first treatment course with a csDMARD (without previous use of biologic or JAKi) or first bDMARD/JAKi were followed-up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matched analysis (PSMA) were used for statistical comparisons. Results In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX plus LEF. The overall incidence of SAEs was 5.6/100 PY. The hazard of SAEs for MTX plus LEF was not higher than for MTX or LEF (adjusted hazard ratio: 1.00, 95% CI, 0.76 to 1.31, P=0.984). The MTX-LEF combo presented a lower hazard of SAEs (0.56, 0.36 to 0.88, P=0.011) and infectious SAEs (0.48, 0.25 to 0.94, P=0.031) than bDMARDs/JAKi with MTX or LEF. MTX plus LEF presented lower hazard of SAEs than MTX plus SSZ (0.33, 0.16 to 0.65, P=0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. Conclusion In our study, MTX plus LEF presented a relatively good overall safety profile in comparison to MTX plus SSZ and schemes involving advanced therapies in RA.

scholarly journals Depression as a risk factor for the development of rheumatoid arthritis: a population-based cohort study

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000670 ◽  
Author(s):  
Isabelle A Vallerand ◽  
Ryan T Lewinson ◽  
Alexandra D Frolkis ◽  
Mark W Lowerison ◽  
Gilaad G Kaplan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Future Research ◽  
Health Improvement ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Antidepressant Use

ObjectivesMajor depressive disorder (MDD) is associated with increased levels of systemic proinflammatory cytokines, including tumour necrosis factor alpha. As these cytokines are pathogenic in autoimmune diseases such as rheumatoid arthritis (RA), our aim was to explore on a population-level whether MDD increases the risk of developing RA.MethodsA retrospective cohort study was conducted using The Health Improvement Network (THIN) database (from 1986 to 2012). Observation time was recorded for both the MDD and referent cohorts until patients developed RA or were censored. Cox proportional hazards models were used to determine the risk of developing RA among patients with MDD, accounting for age, sex, medical comorbidities, smoking, body mass index and antidepressant use.ResultsA cohort of 403 932 patients with MDD and a referent cohort of 5 339 399 patients without MDD were identified in THIN. Cox proportional hazards models revealed a 31% increased risk of developing RA among those with MDD in an unadjusted model (HR=1.31, 95% CI 1.25 to 1.36, p<0.0001). When adjusting for all covariates, the risk remained significantly increased among those with MDD (HR=1.38, 95% CI 1.31 to 1.46, p<0.0001). Antidepressant use demonstrated a confounding effect that was protective on the association between MDD and RA.ConclusionMDD increased the risk of developing RA by 38%, and antidepressants may decrease this risk in these patients. Future research is necessary to confirm the underlying mechanism of MDD on the pathogenesis of RA.

scholarly journals Prevalence and Prognostic Value of Heart Failure Stages: An Elderly Inpatient Based Cohort Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Pei-Pei Zheng ◽  
Si-Min Yao ◽  
Di Guo ◽  
Ling-ling Cui ◽  
Guo-Bin Miao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Regression Tree ◽  
Cox Proportional Hazards ◽  
Hospitalized Patients ◽  
Classification And Regression Tree ◽  
Major Adverse Cardiovascular Events ◽  
Cox Proportional Hazards Models

Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear.Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan–Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE.Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ2 = 69.62, P &lt; 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174–6.098, P &lt; 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112–3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014–6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate.Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B.Trial Registration: ChiCTR1800017204; 07/18/2018.

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

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.

Association of pulse pressure with all-cause mortality in young adults

2019 ◽  
Vol 96 (1138) ◽  
pp. 461-466
Author(s):  
Jie LI ◽  
Jia-Yi Huang ◽  
Kenneth Lo ◽  
Bin Zhang ◽  
Yu-Qing Huang ◽  
...  
Keyword(s):  
Young Adults ◽  
Pulse Pressure ◽  
Subgroup Analysis ◽  
Proportional Hazards ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Cox Analysis

BackgroundPulse blood pressure was significantly associated with all-cause mortality in middle-aged and elderly populations, but less evidence was known in young adults.ObjectiveTo assess the association of pulse pressure (PP) with all-cause mortality in young adults.MethodsThis cohort from the 1999–2006 National Health and Nutrition Examination Survey included adults aged 18–40 years. All included participants were followed up until the date of death or 31 December 2015. PP was categorised into three groups: <50, 50~60, ≥60 mm Hg. Cox proportional hazards models and subgroup analysis were performed to estimate the adjusted HRs and 95% CIs for all-cause mortality.ResultsAfter applying the exclusion criteria, 8356 participants (median age 26.63±7.01 years, 4598 women (55.03%)) were included, of which 265 (3.17%) have died during a median follow-up duration of 152.96±30.45 months. When treating PP as a continuous variable, multivariate Cox analysis showed that PP was an independent risk factor for all-cause mortality (HR 1.94, 95% CI 1.02 to 3.69; p=0.0422). When using PP<50 mm Hg as referent, from the 50~60 mm Hg to the ≥60 mm Hg group, the risks of all-cause mortality for participants with PP ranging 50–60 mm Hg or ≥60 mm Hg were 0.93 (95% CI 0.42 to 2.04) and 1.15 (95% CI 0.32 to 4.07) (P for tend was 0.959). Subgroup analysis showed that PP (HR 2.00, 95% CI 1.05 to 3.82; p=0.0360) was associated with all-cause mortality among non-hypertensive participants.ConclusionAmong young adults, higher PP was significantly associated with an increased risk of all-cause mortality, particularly among those without hypertension.

scholarly journals Risk of depressive disorders after tobacco smoking cessation: a retrospective cohort study in Fukuoka, Japan

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025124 ◽  
Author(s):  
Takako Fujita ◽  
Akira Babazono ◽  
Yumi Harano ◽  
Peng Jiang
Keyword(s):  
Smoking Cessation ◽  
Cohort Study ◽  
Survival Analysis ◽  
Retrospective Cohort ◽  
Depressive Disorders ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Significant Difference

ObjectiveWe sought to examine the effect of smoking cessation on subsequent development of depressive disorders.DesignThis was a retrospective cohort study.MethodsWe used administrative claim and health check data from fiscal years 2010 to 2014, obtained from the largest health insurance association in Fukuoka, Japan. Study participants were between 30 and 69 years old. The end-point outcome was incidence of depressive disorders. Survival analysis and Cox proportional hazards models were conducted. The evaluated potential confounders were sex, age, standard monthly income and psychiatric medical history.ResultsThe final number of participants was 87 255, with 7841 in the smoking cessation group and 79 414 in the smoking group. The result of survival analysis showed no significant difference in depressive disorders between the two groups. The results of Cox proportional hazards models showed no significant difference by multivariate analysis between participants, including users of smoking cessation medication (HR 1.04, 95% Cl 0.89 to 1.22) and excluding medication use (HR 0.97, 95% Cl 0.82 to 1.15).ConclusionsThe present study showed that there were no significant differences with respect to having depressive disorders between smoking cessation and smoking groups. We also showed that smoking cessation was not related to incidence of depressive disorders among participants, including and excluding users of smoking cessation medication, after adjusting for potential confounders. Although the results have some limitations because of the nature of the study design, our findings will provide helpful information to smokers, health professionals and policy makers for improving smoking cessation.

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

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.

scholarly journals A cohort study of dietary fibre intake and menarche

2002 ◽  
Vol 5 (2) ◽  
pp. 353-360 ◽  
Author(s):  
Malcolm M Koo ◽  
Thomas E Rohan ◽  
Meera Jain ◽  
John R McLaughlin ◽  
Paul N Corey
Keyword(s):  
Cohort Study ◽  
Dietary Intake ◽  
Dietary Fibre ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Age At Menarche ◽  
Relative Hazard ◽  
Component Level ◽  
Cox Proportional Hazards Models

AbstractObjective:To evaluate the influence of dietary fibre on menarche in a cohort of pre-menarcheal girls.Design:Prospective cohort study.Setting:Ontario, Canada.Subjects:Free-living pre-menarcheal girls (n = 637), 6 to 14 years of age.Methodology:Information on dietary intake, physical activity and date of menarche was collected at baseline and was updated annually by self-administered questionnaires for three years. Cox proportional hazards models were used to evaluate the association between dietary fibre and menarche, adjusting for age at entry to the study and potential confounders.Results:A higher intake of energy-adjusted dietary fibre was associated with a lower risk of (i.e. a later age at) menarche (relative hazard 0.54, 95% confidence interval (CI) 0.31–0.94 for highest vs. lowest quartile, P for trend = 0.027). At the fibre component level, a higher intake of energy-adjusted cellulose was associated with a lower risk of menarche (relative hazard 0.45, 95% CI 0.26–0.76, P for trend = 0.009).Conclusions:The findings are consistent with the hypothesis that pre-menarcheal dietary intake can influence menarche.

U-Shaped Association of Serum Uric Acid With All-Cause and Cause-Specific Mortality in US Adults: A Cohort Study

2019 ◽  
Vol 105 (3) ◽  
pp. e597-e609 ◽  
Author(s):  
Lihua Hu ◽  
Guiping Hu ◽  
Benjamin Ping Xu ◽  
Lingjuan Zhu ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Uric Acid ◽  
Cohort Study ◽  
Serum Uric Acid ◽  
Inflection Point ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Specific Mortality ◽  
The Relationship

Abstract Background In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality. Methods This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality. Results During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females. Conclusion Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.

scholarly journals Predictors of 10-year hospital use in a community-dwelling population of Brazilian elderly: the Bambuí cohort study of aging

2011 ◽  
Vol 27 (suppl 3) ◽  
pp. s336-s344 ◽  
Author(s):  
James Macinko ◽  
Vitor Camargos ◽  
Josélia O. A. Firmo ◽  
Maria Fernanda Lima-Costa
Keyword(s):  
Cohort Study ◽  
Chronic Conditions ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Male Sex

We use data from a population-based cohort of elderly Brazilians to assess predictors of hospitalizations during ten years of follow-up. Participants were 1,448 persons aged 60 years and over at baseline (1997). The outcome was self-reported number of hospitalizations per year. Slightly more than a fifth (23%) experienced no hospitalizations during the 10 year follow-up. About 30% had 1-2 events, 31% had between 3 and 7 events, and about 18% had 8 or more events during this time. Results of multivariable hurdle and Cox proportional hazards models showed that the risk of hospitalization was positively associated with male sex, increased age, chronic conditions, and visits to the doctors in the previous 12 months. Underweight was a predictor of any hospitalization, while obesity was an inconsistent predictor of hospitalization.

scholarly journals Determinants of Mortality among Adult HIV-Infected Patients on Antiretroviral Therapy in a Rural Hospital in Southeastern Nigeria: A 5-Year Cohort Study

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Kelechi N. Eguzo ◽  
Adegboyega K. Lawal ◽  
Cynthia E. Eseigbe ◽  
Chisara C. Umezurike
Keyword(s):  
Cohort Study ◽  
Proportional Hazards ◽  
Tertiary Hospital ◽  
Cox Proportional Hazards ◽  
Cd4 Count ◽  
First Line ◽  
Southeastern Nigeria ◽  
Clinical Indicators ◽  
Predictors Of Mortality ◽  
Cox Proportional Hazards Models

Background. Study examined the determinants of mortality among adult HIV patients in a rural, tertiary hospital in southeastern Nigeria, comparing mortality among various ART regimens.Methods. Retrospective cohort study of 1069 patients on ART between August 2008 and October 2013. Baseline CD4 counts, age, gender, and ART regimen were considered in this study. Kaplan-Meier method was used to estimate survival and Cox proportional hazards models to identify multivariate predictors of mortality. Median follow-up period was 24 months (IQR 6–45).Results. 78 (7.3%) patients died with 15.6% lost to followup. Significant independent predictors of mortality include age (>45), sex (male > female), baseline CD4 stage (<200), and ART combination. Adjusted mortality hazard was 3 times higher among patients with CD4 count <200 cells/μL than those with counts >500 (95% CI 1.69–13.59). Patients on Truvada-based first-line regimens were 88% more likely to die than those on Combivir-based first line (95% CI 1.05–3.36), especially those with CD4 count <200 cells/μL.Conclusion. Study showed lower mortality than most studies in Nigeria and Africa, with mortality higher among males and patients with CD4 count <200. Further studies are recommended to further compare treatment outcomes between Combivir- and Truvada-based regimens in resource-limited settings using clinical indicators.

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