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1.
Arthritis Rheumatol ; 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073264

RESUMO

OBJECTIVE: We aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA-interstitial lung disease (ILD). METHODS: We performed a retrospective, matched cohort study of RA and RA-ILD within the Veterans Health Administration (VA) between 2000 and 2019. Patients with RA and RA-ILD were identified with validated administrative-based algorithms, then matched (up to 1:10) on age, gender, and VA enrollment year to individuals without RA. Lung cancers were identified from a VA oncology database and the National Death Index. Conditional Cox regression models assessed lung cancer risk adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden among matched individuals. Several sensitivity analyses were performed. RESULTS: We matched 72,795 patients with RA with 633,937 patients without RA (mean age 63 years; 88% male). Over 4,481,323 patient-years, 17,099 incident lung cancers occurred. RA was independently associated with an increased lung cancer risk (adjusted hazard ratio [aHR] 1.58 [95% confidence interval (CI) 1.52-1.64]), which persisted in never smokers (aHR 1.65 [95% CI 1.22-2.24]) and in those with incident RA (aHR 1.54 [95% CI 1.44-1.65]). Compared to non-RA controls, prevalent RA-ILD (n = 757) was more strongly associated with lung cancer risk (aHR 3.25 [95% CI 2.13-4.95]) than RA without ILD (aHR 1.57 [95% CI 1.51-1.64]). Analyses of both prevalent and incident RA-ILD produced similar results (RA-ILD vs non-RA aHR 2.88 [95% CI 2.45-3.40]). CONCLUSION: RA was associated with a >50% increased risk of lung cancer, and those with RA-ILD represented a particularly high-risk group with an approximate three-fold increased risk. Increased lung cancer surveillance in RA, and especially RA-ILD, may be a useful strategy for reducing the burden posed by the leading cause of cancer death.

2.
Arthritis Care Res (Hoboken) ; 76(9): 1287-1293, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38682605

RESUMO

OBJECTIVE: The study was to determine the prevalence of baseline risk factors for cardiovascular outcomes and cancer among commercially-insured patients with rheumatoid arthritis (RA) during their first dispensed treatment for either tumor necrosis factor inhibitors (TNFi) or JAK inhibitors (JAKi). METHODS: Patients with RA from August 16, 2019 to March 31, 2022 were identified in the Merative MarketScan Commercial and Medicare databases. The first date that a TNFi or JAKi was dispensed was the index date, and baseline risk factors were assessed among patients continuously eligible for 12 months before the index date. Patients who had the following were stratified into an elevated risk category: age ≥65 years, smoking, or a history of a major adverse cardiovascular event, venous thromboembolism, or cancer. The prevalence of modifiable risk factors was also reported: hypertension, hyperlipidemia, obesity, and diabetes. The crude prevalence and prevalence difference (PD) were reported. RESULTS: A total of 12,673 patients (TNFi [n = 7,748; 61%] and JAKi [n = 4,925; 39%]) met inclusion criteria. The prevalence of elevated risk was the same for all patients using TNFi (n = 2,051; 26%) and JAKi (n = 1,262; 26%). Compared with patients having low risk, patients with an elevated risk also had a higher prevalence of at least one primary modifiable risk factor for both patients using JAKi (79% vs 58%; PD 21%, 95% confidence interval [CI] 18%-24%) and TNFi (81% vs 60%; PD 21%, 95% CI 19%-23%). CONCLUSION: In recent years, JAKi and TNFi were used in similar proportions to treat RA among commercially-insured patients at elevated cardiovascular and cancer risk. Because uncontrolled disease, modifiable comorbidities, and treatment with JAKi are associated with these adverse events, future studies evaluating how practice patterns may be affected by the emergence of safety data will be of value.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Inibidores de Janus Quinases , Neoplasias , Inibidores do Fator de Necrose Tumoral , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Neoplasias/epidemiologia , Idoso , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Prevalência , Doenças Cardiovasculares/epidemiologia , Fatores de Risco de Doenças Cardíacas , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto , Medição de Risco , Bases de Dados Factuais , Estudos Retrospectivos
3.
Rheumatol Ther ; 11(2): 363-380, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38345715

RESUMO

INTRODUCTION: Data assessing longer-term real-world effectiveness and treatment patterns with upadacitinib (UPA), a Janus kinase inhibitor, in rheumatoid arthritis (RA) are lacking. We assessed improvement in clinical and patient-reported outcomes and treatment patterns for up to 12 months among adult patients with RA initiating UPA. METHODS: Data were collected from the CorEvitas® RA Registry (08/2019-04/2022). Eligible patients had moderate to severe RA (Clinical Disease Activity Index [CDAI] > 10) and follow-up visits at 6 or 12 months after UPA initiation. Outcomes were mean change from baseline, percentage achieving minimal clinically important differences (MCID) in clinical and patient-reported outcomes, and disease activity at follow-up. We evaluated clinical outcomes and therapy changes among patients with tumor necrosis factor inhibitor (TNFi) experience and among those receiving UPA as first-line therapy, as well as those receiving UPA as monotherapy versus as part of combination therapy. We further evaluated whether outcomes were similar among those that remained on therapy. RESULTS: Patients treated with UPA (6-month cohort, N = 469; 12-month cohort, N = 263) had statistically significant improvements (p < 0.001) in mean CDAI, tender/swollen joint counts, pain, and fatigue at follow-up. At 12 months, 46.0% achieved MCID in CDAI and 40.0% achieved low disease activity/remission. Overall, 43.0% discontinued UPA at 12 months; of those receiving combination treatment (N = 90) with conventional therapies and UPA, 42.2% (N = 38) discontinued conventional therapy. Findings were similar in the 6-month cohort and among subgroups. Changes from baseline and proportions of patients achieving MCID or clinical outcomes tended to be numerically lower among patients with TNFi experience and numerically higher among those receiving UPA as first-line therapy. CONCLUSIONS: UPA initiation was associated with improvements in clinical and patient-reported outcomes, with meaningful clinical improvements regardless of prior TNFi experience, line of therapy, or concomitant use of conventional therapies. Further research is needed to better understand sustained response of UPA over longer treatment periods.

4.
Ann Rheum Dis ; 83(4): 429-436, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38171598

RESUMO

PURPOSE: To determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate response. METHODS: This is a secondary analysis of the Rheumatoid Arthritis Comparison of Active Treatments (RACAT) trial and the (TEAR) trial. Both studies compared treatment strategies starting with conventional disease-modifying anti-rheumatic drugs (DMARDs) (triple therapy) versus etanercept plus methotrexate. We compared response rates between TNFi and triple therapy among patients with different BMI. Adipokines were measured at enrolment and associations with treatment response were examined using regression, adjusting for age, sex, BMI and baseline disease activity. RESULTS: In RACAT (n=306), participants who were normal/underweight were more likely to benefit from TNFi versus triple therapy, with greater change in Disease Activity Score in 28 and greater ACR20 response (ACR 20: 64% vs 23%, p=0.001). In contrast, overweight/obese participants had similar response to TNFi versus triple therapy (p-for-interaction=0.001). Similarly, but modest patterns were observed in TEAR (n=601; ACR20: 67% vs 52%, p=0.05). In RACAT, adipokine scores consistent with lower adiposity also predicted greater response to TNFi (ACR20: 58% vs 37%, p=0.01) with better model fit compared with BMI alone. CONCLUSIONS: Lower BMI and evidence of lower adiposity based on adipokine profiles were associated with a superior response to TNFi compared with triple therapy. There was no difference between treatments among overweight/obese participants. The results support TNFi being a particularly important therapeutic among normal/underweight patients, with implications for clinical decisions and trial design.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Adipocinas , Adiposidade , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Metotrexato/uso terapêutico , Obesidade , Sobrepeso/induzido quimicamente , Sobrepeso/tratamento farmacológico , Magreza/induzido quimicamente , Magreza/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
J Clin Endocrinol Metab ; 109(10): e1839-e1846, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-38189426

RESUMO

PURPOSE: We evaluated associations between adiponectin and the risk of diabetes among patients with rheumatoid arthritis (RA), a systemic inflammatory disease associated with metabolic disturbance. METHODS: This prospective cohort study included adults with RA from the Veterans Affairs Rheumatoid Arthritis Registry. Adiponectin and inflammatory cytokines/chemokines were measured at enrollment on stored serum samples. Adiponectin levels were categorized, and clinical variables were described across categories (<10 µg/mL; 10-40 µg/mL; >40 µg/mL). Multivariable Cox proportional hazard models evaluated associations between adiponectin and incident diabetes adjusting for age, sex, race, smoking status, body mass index (BMI), disease-modifying therapy use, calendar year, and comorbidity. Testing for modification of effect in the context of elevated cytokines/chemokines was performed. RESULTS: Among 2595 patients included in the analysis, those with adiponectin levels >40 µg/mL (N = 379; 15%) were older and had lower BMI. There were 125 new cases of diabetes among 1689 patients without prevalent disease at enrollment. There was an inverse association between adiponectin and incident diabetes; however, the association was positive among patients with adiponectin levels >40 µg/mL. Patients with levels >40 µg/mL were at higher risk compared to those with levels 10-40 µg/mL (HR: 1.70 [1.34, 2.16] P < .001). Those with adiponectin levels >40 µg/mL had significantly higher levels of inflammatory cytokines with evidence of a modified effect of adiponectin on diabetes risk in the setting of inflammation. CONCLUSION: The relationship between adiponectin and incident diabetes risk is U-shaped in RA. Patients with very high adiponectin levels have greater systemic inflammation and an altered relationship between adiponectin and diabetes risk.


Assuntos
Adiponectina , Artrite Reumatoide , Humanos , Artrite Reumatoide/sangue , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/complicações , Adiponectina/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/sangue , Incidência , Sistema de Registros , Fatores de Risco , Biomarcadores/sangue
6.
Musculoskelet Sci Pract ; 69: 102886, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38096594

RESUMO

BACKGROUND: Chronic low back pain often progresses to widespread pain. Although many factors are associated with progression, their roles in contributing to chronic widespread pain (CWP) are often unclear. OBJECTIVE: To determine if pain catastrophizing is an independent risk factor for CWP. DESIGN: Retrospective cohort study within a national pain research registry from April 2016 through August 2022. METHODS: A total of 1111 participants with chronic low back pain, but without CWP, were included. Participants were followed at quarterly intervals for up to 48 months to measure CWP risk. Survival analyses involved Kaplan-Meier plots and the Cox proportional hazards model to measure CWP risk according to pain catastrophizing and subscale scores for rumination, magnification, and helplessness. RESULTS: Crude CWP risks for moderate pain catastrophizing (HR, 2.13; 95% CI, 1.54-2.95; P < 0.001) and high pain catastrophizing (HR, 3.98; 95% CI, 2.95-5.35; P < 0.001) were each elevated in comparison with low pain catastrophizing. Adjusted CWP risks for moderate pain catastrophizing (HR, 1.80; 95% CI, 1.27-2.53; P < 0.001) and high pain catastrophizing (HR, 2.82; 95% CI, 1.98-4.02; P < 0.001) remained elevated in analyses that controlled for potential confounders. Corresponding results were observed in the survival analyses involving rumination, magnification, and helplessness. CONCLUSIONS: Pain catastrophizing appears to be an independent risk factor for progression to CWP among patients with chronic low back pain. These findings provide a rationale for interventions aimed at reducing pain catastrophizing, including rumination, magnification, and helplessness, among patients with chronic low back pain.


Assuntos
Dor Crônica , Dor Lombar , Humanos , Dor Lombar/complicações , Estudos Retrospectivos , Dor Crônica/complicações , Catastrofização , Fatores de Risco
7.
Arthritis Care Res (Hoboken) ; 76(4): 463-469, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37909392

RESUMO

OBJECTIVE: The objective of this study was to determine the impact of emerging safety data on practice patterns by describing the characteristics of patients initiating and discontinuing advanced therapies for rheumatoid arthritis (RA) before and after January 2021. METHODS: This cohort study evaluated US veterans with RA between April 2019 and September 2022. This period was divided into two 664-day periods before and after January 2021. Eligible patients had ≥1 diagnosis code for RA and initiated a tumor necrosis factor inhibitor (TNFi), non-TNFi biologic, or JAK inhibitor (JAKi). We tested for interaction within regression models to determine whether changes in patient characteristics for tofacitinib recipients were different from changes observed for other therapies. We also evaluated factors associated with therapy discontinuation in Cox models adjusted for age, sex, and duration on therapy, including assessment for effect modification. RESULTS: When comparing patients with RA initiating tofacitinib before (n = 2,111) with those initiating tofacitinib after (n = 1,664) January 2021, there was a decrease in mean age (64.1 vs 63.0 years) and in the proportion with cardiovascular comorbidities (all P < 0.01). These changes were significantly different from those observed for patients initiating TNFi or non-TNFi biologics. Among active advanced therapy recipients, the likelihood of discontinuation was higher for tofacitinib than TNFi (hazard ratio 1.18, 95% confidence interval 1.10-1.26, P < 0.001). The higher rate of tofacitinib discontinuation was more pronounced in the presence of cardiovascular comorbidities (P < 0.05). CONCLUSION: Recent safety data significantly affected prescribing practices for advanced therapies, with a reduction in JAKi initiation and an increase in JAKi discontinuation among older patients and those at high cardiovascular risk.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Pessoa de Meia-Idade , Antirreumáticos/efeitos adversos , Estudos de Coortes , Fator de Necrose Tumoral alfa , Resultado do Tratamento , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico
8.
Arthritis Care Res (Hoboken) ; 76(5): 627-635, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38116680

RESUMO

OBJECTIVE: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs. METHODS: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class. RESULTS: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]). CONCLUSION: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.


Assuntos
Antirreumáticos , Artrite Reumatoide , Fragilidade , Humanos , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Fragilidade/epidemiologia , Fragilidade/diagnóstico , Adulto , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Fatores de Risco , Medição de Risco , Infecções/epidemiologia , Infecções/induzido quimicamente , Infecções/etiologia , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Estudos Retrospectivos , Estados Unidos/epidemiologia , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Hospitalização , Fatores de Tempo , Bases de Dados Factuais
9.
Rheum Dis Clin North Am ; 50(1): 103-111, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37973278

RESUMO

Dr Schumacher was a force in rheumatology for more than half a century through his multiple roles as a researcher, clinician, mentor, and educator. He is not likely to be soon forgotten by the rheumatology community; however, it is hoped that this chapter can provide a faithful recollection that will help bring his memory to life for some and that rings true to those who knew him and learned from him.


Assuntos
Reumatologia , Masculino , Humanos , Mentores
10.
Artigo em Inglês | MEDLINE | ID: mdl-37812235

RESUMO

OBJECTIVES: To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Using serum collected at enrolment, three alarmins (interleukin [IL]-33, thymic stromal lymphopoietin [TSLP], and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score, and anti-cyclic citrullinated antibody positivity. RESULTS: Of 2,835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (HR 0.73 per log-fold increase; 95% CI 0.57-0.95; p= 0.018) and adjusted (HR 0.77; 95% CI 0.59-1.00, p= 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. CONCLUSIONS: In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA.

11.
ACR Open Rheumatol ; 5(10): 563-567, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37658632

RESUMO

OBJECTIVE: To determine whether prescribing practices for Janus kinase inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic agents changed after the results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance trial were released in January 2021. METHODS: This is a retrospective study in adult patients with rheumatoid arthritis (RA) receiving advanced therapies within the Veterans Affairs Health System from January 2012 through September 2022. Eligible patients were required to have at least one diagnosis code for RA and to have received a biologic disease-modifying antirheumatic drug or JAKi. Treatment courses were defined from pharmacy dispensing data and the number of new courses of each advanced therapy was quantified over time. We assessed changes in the use of each therapy before and after the release of safety data (January 2021). RESULTS: A total of 88,253 individual drug courses (in 34,656 unique patients) were included in the study. There was a consistent increase in the number and proportion of new courses of JAKi leading up to January 2021, which was followed by a significant net decrease in JAKi use through September 2022. There was significantly less tofacitinib use after the release of safety data, with a significant difference in the slope of change in use with time. In contrast, whereas TNFi use declined leading up to 2021, its use significantly increased after January 2021. CONCLUSION: Changes in prescribing in response to new evidence emphasize the impact that safety trials have on prescribing practices. Ongoing study in this area, with attention to specific patient characteristics and risk profiles, will help characterize these changes in practice.

12.
JAMA Intern Med ; 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37523173

RESUMO

Importance: Although an increased risk of ischemic cardiovascular disease has been associated with rheumatoid arthritis (RA), the risk of aortic stenosis (AS) is unknown. Objective: To examine the risk of incident AS, aortic valve intervention, AS-related death, and risk factors for AS development in patients with RA. Design, Setting, and Participants: This cohort study linked data from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services from 2000 to 2019. Patients with RA were matched by age, sex, and VHA enrollment year with up to 10 patients without RA. The cohort was followed until incident AS, aortic valve intervention, or death. Data were analyzed from August 23, 2022, to March 3, 2023. Exposures: the primary exposure was the presence of RA, defined using validated RA algorithms. Main Outcomes and Measures: Aortic stenosis was defined as a composite of inpatient or outpatient diagnoses, surgical or transcatheter aortic valve replacement, or AS-related death using diagnostic and procedural codes. Risk of AS development was assessed with multivariable Cox proportional hazards models adjusted for race, ethnicity, smoking status, body mass index, rurality, comorbidities, and health care use. Results: The cohort included 73 070 patients with RA (64 008 [87.6%] males; mean [SD] age, 63.0 [11.9] years) matched with 639 268 patients without RA (554 182 [86.7%] males; mean [SD] age, 61.9 [11.7] years) and 16 109 composite AS outcomes that occurred over 6 223 150 person-years. The AS incidence rate was 3.97 (95% CI, 3.81-4.13) per 1000 person-years in patients with RA and 2.45 (95% CI, 2.41-2.49) per 1000 person-years in the control patients (absolute difference, 1.52 per 1000 person-years). Rheumatoid arthritis was associated with an increased risk of composite AS (adjusted hazard ratio [AHR], 1.48; 95% CI, 1.41-1.55), aortic valve intervention (AHR, 1.34; 95% CI, 1.22-1.48), and AS-related death (AHR, 1.26; 95% CI, 1.04-1.54). Conclusions and Relevance: In this cohort study, RA was associated with a higher risk of developing AS and the subsequent risks of undergoing aortic valve intervention and suffering from AS-related death. Future studies are needed to confirm whether valvular heart disease, specifically AS, may be an overlooked cardiovascular disease complication in RA.

13.
Artigo em Inglês | MEDLINE | ID: mdl-37394710

RESUMO

OBJECTIVE: To determine whether unique multimorbidity patterns are associated with long-term rheumatoid arthritis (RA) disease severity. METHODS: We conducted a cohort study within the Veterans Affairs Rheumatoid Arthritis registry. We applied previously derived multimorbidity patterns based on the presence of diagnostic codes for relevant conditions prior to enrollment using linked administrative data. Disease activity and functional status were assessed longitudinally up to 5 years after enrollment. The association of multimorbidity patterns with disease activity and functional status were assessed using generalized estimating equations models adjusting for relevant confounders. RESULTS: We studied 2,956 participants, of which 88.2% were male, 76.9% reported white race, and 79.3% had a smoking history. Mental health and substance abuse (ß 0.12 [95% confidence interval {CI} 0.00, 0.23]), cardiovascular (ß 0.25 [95% CI 0.12, 0.38]), and chronic pain (ß 0.21 [95% CI 0.11, 0.31]) multimorbidity were associated with higher Disease Activity Score in 28 joints (DAS28) scores. Mental health and substance abuse (ß 0.09 [0.03, 0.15]), cardiovascular (ß 0.11 [95% CI 0.04, 0.17]), and chronic pain multimorbidity (ß 0.15 [95% CI 0.10, 0.20]) were also associated with higher Multidimensional Health Assessment Questionnaire (MDHAQ) scores. The metabolic pattern of multimorbidity was not associated with DAS28 or MDHAQ. The number of multimorbidity patterns present was highly associated with DAS28 and MDHAQ (P trend < 0.001), and patients with all four multimorbidity patterns had the highest DAS28 (ß 0.59 [95% CI 0.36, 0.83]) and MDHAQ (ß 0.27 [95% CI 0.16, 0.39]) scores. CONCLUSION: Mental health and substance abuse, chronic pain, and cardiovascular multimorbidity patterns are associated with increased RA disease activity and poorer functional status. Identifying and addressing these multimorbidity patterns may facilitate achieving RA treatment targets.

14.
JAMA Netw Open ; 6(5): e2314660, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37256623

RESUMO

Importance: Involvement of palliative care specialists in the care of medical oncology patients has been repeatedly observed to improve patient-reported outcomes, but there is no analogous research in surgical oncology populations. Objective: To determine whether surgeon-palliative care team comanagement, compared with surgeon team alone management, improves patient-reported perioperative outcomes among patients pursuing curative-intent surgery for high morbidity and mortality upper gastrointestinal (GI) cancers. Design, Setting, and Participants: From October 20, 2018, to March 31, 2022, a patient-randomized clinical trial was conducted with patients and clinicians nonblinded but the analysis team blinded to allocation. The trial was conducted in 5 geographically diverse academic medical centers in the US. Individuals pursuing curative-intent surgery for an upper GI cancer who had received no previous specialist palliative care were eligible. Surgeons were encouraged to offer participation to all eligible patients. Intervention: Surgeon-palliative care comanagement patients met with palliative care either in person or via telephone before surgery, 1 week after surgery, and 1, 2, and 3 months after surgery. For patients in the surgeon-alone group, surgeons were encouraged to follow National Comprehensive Cancer Network-recommended triggers for palliative care consultation. Main Outcomes and Measures: The primary outcome of the trial was patient-reported health-related quality of life at 3 months following the operation. Secondary outcomes were patient-reported mental and physical distress. Intention-to-treat analysis was performed. Results: In total, 359 patients (175 [48.7%] men; mean [SD] age, 64.6 [10.7] years) were randomized to surgeon-alone (n = 177) or surgeon-palliative care comanagement (n = 182), with most patients (206 [57.4%]) undergoing pancreatic cancer surgery. No adverse events were associated with the intervention, and 11% of patients in the surgeon-alone and 90% in the surgeon-palliative care comanagement groups received palliative care consultation. There was no significant difference between study arms in outcomes at 3 months following the operation in patient-reported health-related quality of life (mean [SD], 138.54 [28.28] vs 136.90 [28.96]; P = .62), mental health (mean [SD], -0.07 [0.87] vs -0.07 [0.84]; P = .98), or overall number of deaths (6 [3.7%] vs 7 [4.1%]; P > .99). Conclusions and Relevance: To date, this is the first multisite randomized clinical trial to evaluate perioperative palliative care and the earliest integration of palliative care into cancer care. Unlike in medical oncology practice, the data from this trial do not suggest palliative care-associated improvements in patient-reported outcomes among patients pursuing curative-intent surgeries for upper GI cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT03611309.


Assuntos
Neoplasias Gastrointestinais , Cuidados Paliativos , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Qualidade de Vida , Neoplasias Gastrointestinais/cirurgia , Pacientes , Saúde Mental
15.
J Cachexia Sarcopenia Muscle ; 14(4): 1648-1656, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37254658

RESUMO

BACKGROUND: This study aimed to determine if greater variability in body mass index (BMI) is associated with declines in physical functioning and incident disability in older adults. METHODS: Included were participants from the Health, Aging and Body Composition Study who had semi-annual BMI data during the first 3 years of follow-up. Participants were categorized into quintiles of BMI variability, using two methods. The first method used average successive variability, whereas the second method adjusted these values to remove the variability due to net change in BMI over the 3-year period. Linear regression was used to assess the relationship between the two measures of BMI variability and net changes in BMI, fat mass index, appendicular lean mass index, and Health, Aging and Body Composition Physical Performance Score during the first 3 years of the study. Cox proportional hazard models were used to assess the relationship of BMI variability with the subsequent incidence of new disability, adjusting for confounding factors. RESULTS: Among 2121 participants, those in the highest BMI variability quintile were more likely to lose both body mass (ß: -0.086 [95% confidence interval, CI: -0.133, -0.040], P < 0.01) and fat mass (ß: -0.059 [95% CI: -0.117, -0.002], P = 0.04) and had greater declines in physical performance score (ß: -0.094 [95% CI: -0.162, -0.026], P < 0.01) compared to participants with the least variability in BMI. Participants with high BMI variability also had higher rates of incident disability (hazard ratio: 1.36 [95% CI: 1.07, 1.72], P = 0.01), independent of net BMI change. CONCLUSIONS: BMI variability in older adults is associated with decline in physical performance and incident disability. This relationship cannot be explained by net weight loss alone, supporting it as an independent feature of frailty.


Assuntos
Pessoas com Deficiência , Fragilidade , Humanos , Idoso , Envelhecimento , Índice de Massa Corporal , Composição Corporal
16.
Genet Med ; 25(6): 100314, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36305855

RESUMO

PURPOSE: This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and determine the role of cysteine supplementation in its treatment. METHODS: Individuals with biallelic (likely) pathogenic variants in TRMU were studied within an international retrospective collection of de-identified patient data. RESULTS: In 62 individuals, including 30 previously unreported cases, we described 47 (likely) pathogenic TRMU variants, of which 17 were novel, and 1 intragenic deletion. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow-up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals; 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. CONCLUSION: In most patients, TRMU-associated ALF was a transient, reversible disease and cysteine supplementation improved survival.


Assuntos
Falência Hepática Aguda , Falência Hepática , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Adulto Jovem , Acetilcisteína/uso terapêutico , Falência Hepática/tratamento farmacológico , Falência Hepática/genética , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/genética , Proteínas Mitocondriais/genética , Mutação , Estudos Retrospectivos , tRNA Metiltransferases/genética
17.
Arthritis Care Res (Hoboken) ; 75(8): 1648-1658, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36331101

RESUMO

OBJECTIVE: To examine temporal trends in all-cause and cause-specific mortality in patients with rheumatoid arthritis (RA) in the Veterans Health Administration (VHA). METHODS: We conducted a matched cohort study in the VHA from January 1, 2000 to December 31, 2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non-RA patients, then followed until death or end of study period. Cause of death was obtained from the National Death Index. Multivariable Cox regression models stratified by RA diagnosis years were used to examine trends in RA-related risk of all-cause and cause-specific mortality. RESULTS: Among 29,779 incident RA patients (matched to 245,226 non-RA patients), 9,565 deaths occurred. RA patients were at increased risk of all-cause (adjusted hazard ratio [HRadj ] 1.23 [95% confidence interval (95% CI) 1.20-1.26]), cardiovascular (HRadj 1.19 [95% CI 1.14-1.23]), cancer (HRadj 1.19 [95% CI 1.14-1.24]), respiratory (HRadj 1.46 [95% CI 1.38-1.55]), and infection-related mortality (HRadj 1.59 [95% CI 1.41-1.80]). Interstitial lung disease was the cause of death most strongly associated with RA (HRadj 3.39 [95% CI 2.88-3.99]). Nearly 70% of excess deaths in RA were attributable to cardiopulmonary disease. All-cause mortality risk related to RA was lower among those diagnosed during 2012-2017 (HRadj 1.10 [95% CI 1.05-1.15]) compared to 2000-2005 (HRadj 1.31 [95% CI 1.26-1.36]), but still higher than for non-RA controls (P < 0.001). Cause-specific mortality trends were similar. CONCLUSION: Excess RA-related mortality was driven by cardiovascular, cancer, respiratory, and infectious causes, particularly cardiopulmonary diseases. Although our findings support that RA-related mortality risk is decreasing over time, a mortality gap remains for all-cause and cause-specific mortality in RA.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Neoplasias , Veteranos , Humanos , Estudos de Coortes , Causas de Morte , Artrite Reumatoide/complicações , Neoplasias/complicações , Fatores de Risco
18.
Arthritis Care Res (Hoboken) ; 75(4): 785-792, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35612872

RESUMO

OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of select cancers, including lymphoma and lung cancer. Whether RA influences prostate cancer risk is uncertain. We aimed to determine the risk of prostate cancer in patients with RA compared to patients without RA in the Veterans Health Administration (VA). METHODS: We performed a matched (up to 1:5) cohort study of male patients with and without RA in the VA from 2000 to 2018. RA status, as well as covariates, were obtained from national VA databases. Prostate cancer was identified through linked VA cancer databases and the National Death Index. Multivariable Cox models compared prostate cancer risk between patients with RA and patients without RA, including models that accounted for retention in the VA system. RESULTS: We included 56,514 veterans with RA and 227,284 veterans without RA. During 2,337,104 patient-years of follow-up, 6,550 prostate cancers occurred. Prostate cancer incidence (per 1,000 patient-years) was 3.50 (95% confidence interval [95% CI] 3.32-3.69) in patients with RA and 2.66 (95% CI 2.58-2.73) in patients without RA. After accounting for confounders and censoring for attrition of VA health care, RA was modestly associated with a higher prostate cancer risk (adjusted HR [HRadj ] 1.12 [95% CI 1.04-1.20]). There was no association between RA and prostate cancer mortality (HRadj 0.92 [95% CI 0.73-1.16]). CONCLUSION: RA was associated with a modestly increased risk of prostate cancer, but not prostate cancer mortality, after accounting for relevant confounders and several potential sources of bias. However, even minimal unmeasured confounding could explain these findings.


Assuntos
Artrite Reumatoide , Neoplasias Pulmonares , Veteranos , Humanos , Masculino , Estudos de Coortes , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Modelos de Riscos Proporcionais , Neoplasias Pulmonares/complicações , Fatores de Risco , Incidência
19.
Rheum Dis Clin North Am ; 48(4): 799-811, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36332996

RESUMO

Although there is a substantial body of literature focused on understanding noninhalational risk-factors for rheumatoid arthritis, the data are mixed and often conflicting. Given the other health benefits for certain lifestyle modifications, it seems reasonable for clinicians to promote healthy lifestyle habits related to diet, exercise, maintenance of health weight, and maintenance of good dental hygiene. Overall, however, these lifestyle modifications may be expected to have modest benefit, and other strategies to prevent rheumatoid arthritis in high-risk patients are needed.


Assuntos
Artrite Reumatoide , Estilo de Vida , Humanos , Exercício Físico , Artrite Reumatoide/etiologia , Artrite Reumatoide/prevenção & controle , Dieta , Fatores de Risco
20.
Best Pract Res Clin Rheumatol ; 36(3): 101773, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36208961

RESUMO

People with rheumatoid arthritis (RA) have both disease-specific risk factors for osteoporosis and fractures in addition to those that affect the general population. Disease specific risks include directly pathogenic auto-antibodies, chronic exposure to systemic inflammation, and joint damage causing early disability. Risk factors that affect the general population which may have a higher prevalence in RA include smoking, calcium and vitamin D deficiency as well as hypogonadism. Additionally, chronic exposure to glucocorticoids results in reduced bone mineral density and body composition changes which can further increase fracture risk. In this review we discuss these risk-factors for osteoporosis as well as factors that may impact fall and fracture risk in people with RA.


Assuntos
Artrite Reumatoide , Fraturas Ósseas , Osteoporose , Humanos , Densidade Óssea , Osteoporose/epidemiologia , Osteoporose/etiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Fraturas Ósseas/etiologia , Fatores de Risco
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