Baker, Joshua F.

Objective Hospitalization, particularly for surgery, represents a period of heightened stress. We evaluated how frailty attenuates the association of rheumatoid arthritis (RA) with negative health outcomes after elective noncardiac surgery. Methods We conducted a cross‐sectional study using the National Inpatient Sample (2018 to 2020), including adults (aged ≥18 years) with elective hospitalizations with noncardiac surgery. Frailty was measured using the Hospital Frailty Risk Score (HFRS). Surgeries were categorized by risk level. Outcomes included discharge health resources need (DHRN), composite adverse clinical events (CACE), and death. Results Among 8,800,359 hospitalizations (2.14% among patients with RA), 73.36% underwent intermediate‐risk surgery and 62.25% had HFRS above 0. DHRN occurred in 28.9%, CACE occurred in 0.93%, and all‐cause mortality occurred in 0.17%. A 10‐point increase in HFRS was associated with a 3.8‐fold increased DHRN, 8.5‐fold increased CACE, and 22.8‐fold increased mortality. RA was not independently associated with CACE (adjusted odds ratio [aOR] 0.91; 95% confidence interval [CI] 0.82–1.01; P = 0.08) or death (aOR 0.90; 95% CI 0.71–1.15; P = 0.41) but was significantly associated with DHRN (aOR 1.28, 95% CI 1.25–1.31; P < 0.001) after adjusting for confounders and frailty. In sensitivity analysis, RA had 10% higher relative odds of DHRN following orthopedic (aOR 1.10; 95% CI 1.07–1.13; P < 0.001) but not nonorthopedic intermediate‐risk surgery (aOR 1.10; 95% CI 0.98–1.23; P = 0.11). Conclusion RA was associated with higher odds of DHRN after orthopedic intermediate‐risk surgery but not CACE or inpatient mortality. Moreover, HFRS was associated with DHRN, CACE, and death. These findings underscore the need for disease‐specific clinical considerations and highlight the potential utility of HFRS in discharge planning.

Objective Immune checkpoint inhibitor (ICI) myositis is a rare but a highly morbid condition, particularly with the ICI myositis triad syndrome of myositis, myocarditis, and myasthenia gravis. We report the clinical characteristics of ICI myositis and all‐cause mortality in these patients. Methods We performed a national retrospective cohort study of US veterans treated with an ICI between June 2011 and February 2022. Cases were identified by elevated creatinine kinase (CK) following ICI therapy and/or “myositis” in notes. Chart review determined if candidates had ICI‐associated myositis and were subsequently classified as isolated ICI myositis or ICI triad syndrome. Results Of 29,296 veterans treated with ICIs, 68 (0.2%) ICI‐induced myositis cases were identified, including 23 patients with ICI triad syndrome and 45 patients with isolated ICI myositis. Median survival duration for ICI triad syndrome was 2.5 (95% confidence interval [CI] 1.7–18.5) months in comparison to 20.4 (95% CI 6.2–60) months for isolated ICI myositis and 12.6 (95% CI 12.3–12.8) months median survival for patients treated with ICI without myositis. Patients with ICI triad syndrome had 60.0% mortality during the six months following initiation of ICI treatment, in comparison to 30.2% mortality in isolated ICI myositis and 31.5% mortality in patients without myositis. Six months after the first ICI treatment, subsequent mortality trends were similar in the three groups. Conclusion ICI triad syndrome is associated with higher overall mortality and shortened median survival times during the first six months after initial ICI therapy, whereas isolated ICI myositis is associated with similar mortality outcomes compared to patients treated with ICI who did not develop myositis. image

Objective The objective of the study was to determine risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) after reinduction of remission with rituximab and discontinuation of maintenance therapy. Methods This is a post hoc analysis of the RITAZAREM clinical trial. Patients aged 15 years or older with AAV and a positive test for anti–proteinase‐3 or anti‐myeloperoxidase‐ANCA who achieved remission after reinduction with rituximab and glucocorticoids were randomized at month 4 to receive continued rituximab or azathioprine for a maintenance period up to 24 months, followed by observation until relapse or up to 48 months. Generalized estimating equations logistic regression identified baseline and time‐varying risk factors for relapse by the next visit for the two study phases: maintenance (months 4–24) and off‐treatment (months 24–48). Results Among 170 patients (median [interquartile range] age 59 [48–68] years, disease duration 5 [2–10] years), 99 relapses occurred (46 during maintenance). During maintenance, musculoskeletal involvement (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.1–7.2; P = 0.03) and higher patient global assessment (OR: 1.1, 95% CI: 1.0–1.2; P = 0.04) were associated with relapse. During the off‐treatment phase, presence of CD19 + B cells (OR: 2.5, 95% CI: 1.2–5.1; P = 0.01) and reappearance of ANCA (OR: 3.2, 95% CI: 1.3–7.7; P = 0.01) were each associated with higher relapse risk. Multivariable analysis identified markers of inflammation (changes in platelets, white blood cells, and IgA) associated with relapse. Conclusion Risk factors for relapse in AAV vary by treatment phase. Monitoring markers of inflammation and immune reconstitution may identify patients at risk for relapse, particularly after treatment withdrawal.

Objective Cognitive impairment is prevalent in rheumatoid arthritis (RA), yet risk factors are not well understood. We explored associations between clinical characteristics and cognitive impairment in an RA cohort. Methods Data were from a longitudinal RA cohort at Veterans Affairs Puget Sound Health Care System. Cognition was evaluated using the Saint Louis University Mental Status (SLUMS) examination. Demographics and health factors, objectively measured physical function, participant‐reported symptoms, RA disease characteristics, and comorbidities were evaluated. Univariable linear regressions explored the association between clinical factors and SLUMS scores. Those with P < 0.1 in the univariable models were evaluated in separate multivariable linear regressions controlling for age, sex, and years of education. Results A total of 145 participants with RA were included, with a mean age of 64.5 (SD 11.6) years, and were predominantly male (74%). Using SLUMS, 42 participants (29%) had normal cognition, 83 (57%) had mild cognitive impairment, and 20 (14%) had dementia. Physical performance (aβ: 0.35, confidence interval [CI] 0.11 to 0.59), self‐reported exhaustion (aβ: −2.22, CI −3.44 to −0.99), pain (aβ: −0.25, CI −0.50 to −0.00), disability (aβ: −1.79, CI −3.16 to −0.42), and trouble falling asleep (aβ: −2.57, CI −4.00 to −1.14) were all independently associated with a lower SLUMS score (all P < 0.05). Conclusion Cognitive impairment was prevalent in our cohort of veterans with RA and was associated with several modifiable clinical factors. Future longitudinal studies are needed to determine the directionality of these associations and evaluate interventions for modifiable risk factors that may mitigate cognitive dysfunction. image

Objective The aim of this study was to determine whether pollutants such as fire smoke–related particulate matter <2.5 μm (PM 2.5 ) are associated with incident rheumatoid arthritis (RA) and RA‐associated interstitial lung disease (RA‐ILD). Methods This patient–control study used Veterans Affairs (VA) data from October 1, 2009, to December 31, 2018. We identified patients with incident RA and RA‐ILD using validated algorithms, matching each patient to ≤10 controls on age, sex, and VA enrollment year. We obtained pollutants including fire smoke PM 2.5 , carbon monoxide, nitrogen oxides (NOx), ozone, overall PM 2.5 , PM 10 , and sulfur dioxide (SO 2 ) at least one year before the index date. We fit conditional logistic regression models to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for incident RA and RA‐ILD, adjusted for confounders. Results We identified 9,701 patients with incident RA (mean age 65 years, 86% male), including 531 patients with RA‐ILD (mean age 69 years, 91% male), and 68,852 matched controls. Fire smoke PM 2.5 was not associated with RA (aOR 1.07, 95% CI 0.92–1.23) but was associated with RA‐ILD (aOR 1.98, 95% CI 1.08–3.62, per 1 μg/m 3 ). Increased levels of NOx were associated with RA (aOR 1.16, 95% CI 1.06–1.27, highest vs lowest quartile). The highest quartiles of ozone (aOR 1.19, 95% CI 1.06–1.34) and PM 10 (aOR 1.25, 95% CI 1.10–1.43) were associated with seronegative RA. Carbon monoxide, overall PM 2.5 , and SO 2 were not, or negatively, associated with RA and RA‐ILD. Conclusion Increased fire smoke PM 2.5 was associated with RA‐ILD, whereas NOx, ozone, and PM 10 were associated with RA risk. Thus, air pollution may increase the risk of RA and RA‐ILD. image

ObjectiveWe aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA‐interstitial lung disease (ILD).MethodsWe 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.ResultsWe 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]).ConclusionRA 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.

ObjectiveTo develop evidence‐based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient‐important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA).MethodsWe developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations.ResultsThe panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality.ConclusionThis guideline provides evidence‐based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient‐important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

ObjectiveTo develop evidence‐based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient‐important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA).MethodsWe developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations.ResultsThe panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality.ConclusionThis guideline provides evidence‐based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate‐to‐severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient‐important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.