Missed opportunities for treatment of inflammatory arthritis and factors associated with non-treatment: An observational cohort study in United States Veterans with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

OBJECTIVE: To identify factors associated with non-treatment with biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs) during the 12 months after initial inflammatory arthritis (IA) diagnosis. METHODS: We identified Veterans with incident IA diagnosed in 2007-2019. We assessed time to treatment with Kaplan-Meier curves. We identified associations between non-treatment and factors relating to patients, providers, and the health system with multivariate Generalized Estimation Equation (GEE) log-Poisson. Subgroup analyses included IA subtypes (rheumatoid arthritis [RA], psoriatic arthritis [PsA], and ankylosing spondylitis [AS]) and timeframes of the initial IA diagnosis (2007-11, 2012-15, and 2016-19). RESULTS: Of 18,318 study patients, 40.7 % did not receive treatment within 12 months after diagnosis. In all patients, factors associated with non-treatment included Black race (hazard ratio, 95 % confidence interval: 1.13, 1.08-1.19), Hispanic ethnicity (1.14, 1.07-1.22), Charlson Comorbidity Index ≥2, (1.15, 1.11-1.20), and opiate use (1.09, 1.05-1.13). Factors associated with higher frequency of DMARD treatment included married status (0.86, 0.81-0.91); erosion in joint imaging report (HR: 0.86, 0.81-0.91); female diagnosing provider (0.90, CI: 0.85-0.96), gender concordance between patient and provider (0.91, CI: 0.86-0.97), and diagnosing provider specialty of rheumatology (0.53, CI: 0.49-0.56). CONCLUSION: A high proportion of Veterans with IA were not treated with a biologic or non-biologic DMARD within one year after their initial diagnosis. A wide range of factors were associated with non-treatment of IA that may represent missed opportunities for improving the quality of care through early initiation of DMARDs.

Serum alarmins and the risk of incident interstitial lung disease in rheumatoid arthritis.

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.

Aortic Stenosis Risk in Rheumatoid Arthritis.

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.

Factors Associated With Unplanned Reoperation After 4-Corner Arthrodesis: A Study of 478 Wrists.

Purpose: The 4-corner arthrodesis (FCA) is a reliable, motion-sparing technique used to treat scapholunate advanced collapse and scaphoid nonunion advanced collapse arthritis, particularly in stage III wrists in which the capitolunate articulation is compromised. Surgical technique and patient-level variables may influence complications following FCA. We sought to evaluate the rate of complications in a large, combined database and manual chart review study. Methods: Current Procedural Terminology codes were used to search the United States Veteran's Health Administration corporate database to identify wrists treated with FCA over a 24-year period. A retrospective chart review was completed to collect data regarding scapholunate advanced collapse/scaphoid nonunion advanced collapse stage, implant used, the use of a bone graft, smoking status, and comorbidities for all patients undergoing an FCA. A multivariable cox proportional hazards regression was used to assess hazard ratios for reoperation. Incidence rates and the standard error of the mean for reoperation and conversion to total wrist fusion were calculated after grouping patients by 10-year age categories. Results: A total of 478 wrists underwent FCA during the study period, with a mean follow-up of 63 months. Seventy-three (16%) wrists required reoperation. The most frequent secondary procedures included unplanned implant removal (8.2%), total wrist arthrodesis (4.6%), and revision FCA (1.7%). Positive smoking history increased the risk of reoperation, whereas posterior interosseous nerve neurectomy, arthritis stage, and fixation type did not have a statistically significant association with reoperation. Younger age demonstrated an increased incidence of overall reoperation and wrist fusion. Conclusions: The most common reason for reoperation after FCA was implant removal. Smoking history is associated with increased rates of reoperation and wrist arthrodesis. Knowledge of these factors may assist with accurately counseling and indicating patients for FCA. Type of study/level of evidence: Therapeutic III.

Risk of Total Wrist Arthrodesis Following Proximal Row Carpectomy: An Analysis of 1,070 Patients.

PURPOSE: Proximal row carpectomy (PRC) is a motion-sparing procedure with good patient-reported and clinical outcomes. Although some studies have investigated the risk of conversion to total wrist arthrodesis (TWA) after PRC, additional larger studies evaluating the specific risk factors that lead to failure are required. This study aimed to investigate the patient and procedure factors that are associated with increased risk for conversion to TWA in a large cohort of patients who underwent PRC. METHODS: The current procedural technology codes identified patients in a National Veteran's Health database undergoing a PRC over a 26-year period. Risk factors of interest comprised age, posterior interosseous nerve neurectomy, wrist arthritis pattern, bilateral surgery, smoking, comorbidities, and preoperative opioid use. The primary outcome was the rate of conversion to TWA. Cox proportional hazard regression was used to create hazard ratios of selected factors for reoperation. RESULTS: There were 1,070 PRCs performed, with a mean follow-up of 79.8 ± 59.6 months. A total of 5.3% (57/1,070) wrists underwent conversion to TWA. Younger age at the time of PRC (<50 years) significantly increased the risk of TWA (hazard ratio, 3.8; 95% confidence interval, 2.2-6.6). With every 1-year increase in age, there was a reduction of 4% (hazard ratio, 0.96; 95% confidence interval: 0.94-0.98) in the hazard of conversion to TWA. No other factors, including concomitant posterior interosseous nerve neurectomy or bilateral PRC, increased the risk of conversion to TWA. CONCLUSIONS: Proximal row carpectomy is a motion-preserving salvage procedure with a low rate of conversion to wrist arthrodesis. Younger patient age increases the risk of conversion to arthrodesis, whereas posterior interosseous nerve neurectomy, bilateral PRCs, and comorbidity status do not appear to have an impact on the risk of arthrodesis. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Risk of Prostate Cancer in US Veterans With Rheumatoid Arthritis.

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.

A Narrowing Mortality Gap: Temporal Trends of Cause-Specific Mortality in a National Matched Cohort Study in US Veterans With Rheumatoid Arthritis.

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.

Scaphotrapeziotrapezoid Arthrodesis: A 10-Year Follow-up Study of Complications in 58 Wrists.

BACKGROUND: Scaphotrapeziotrapezoid (STT) arthrodesis is a procedure used for specific degenerative arthritis and instability patterns of the wrist. This study evaluates nonunion rate and risk factors for reoperation after STT arthrodesis in the Veterans Affairs Department patient population. The purpose of our study was to assess the long-term nonunion rate following STT arthrodesis and to identify factors associated with reoperation. METHODS: The national Veterans Health Administration Corporate Data Warehouse and Current Procedural Terminology codes identified STT arthrodesis procedures from 1995 to 2016. Frequencies of total wrist arthrodesis (TWA) and secondary operations were determined. Univariate analyses provided odds ratios for risk factors associated with complications. RESULTS: Fifty-eight STT arthrodeses were performed in 54 patients with a mean follow-up of 120 months. Kirschner wires (K-wires) were the most common fixation method (69%). Six wrists (10%) required secondary procedures: 5 TWAs and 1 revision STT arthrodesis. Four patients underwent additional procedures for nonunion (7%). Twenty-four patients required K-wire removal, 8 (14%) of these in the operating room, which were not included in regression analysis. Every increase in 1 year of age resulted in a 15% decrease in likelihood of reoperation (95% confidence interval: 0.77-0.93; P < .0001). Opioid use within 90 days before surgery (P = 1.00), positive smoking history (P = 1.00), race (P = .30), comorbidity count (P = .25), and body mass index (P = .19) were not associated with increased risk of reoperation. CONCLUSIONS: At a mean follow-up of 10 years, patients undergoing STT arthrodesis have a 10% risk of reoperation, and this risk decreases with older patient age. There was a symptomatic nonunion rate of 7%, similar to prior published rates. Patient demographics, comorbidity, smoking history, and opioid use did not appear to increase risk of reoperation.

Associations of serum cytokines and chemokines with the risk of incident cancer in a prospective rheumatoid arthritis cohort.

OBJECTIVES: We aimed to assess whether serum cytokine/chemokine concentrations predict incident cancer in RA patients. METHODS: Data from cancer-free enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked to a national VA oncology database and the National Death Index (NDI) to identify incident cancers. Seventeen serum cytokines/chemokines were measured from enrollment serum and an overall weighted cytokine/chemokine score (CK score) was calculated. Associations of cytokines/chemokines with all-site, lung, and lymphoproliferative cancers were assessed in Cox regression models accounting for relevant covariates including age, sex, RA disease activity, and smoking. RESULTS: In 1216 patients, 146 incident cancers (42 lung and 23 lymphoproliferative cancers) occurred over 10,072 patient-years of follow-up with a median time of 4.6 years from enrollment (cytokine/chemokine measurement) to cancer incidence. In fully adjusted models, CK score was associated with a higher risk of all-site (aHR 1.32, 95% CI 1.01-1.71, p < 0.001), lung (aHR 1.81, 1.40-2.34, p = 0.001), and lung/lymphoproliferative (aHR 1.54 [1.35-1.75], p < 0.001) cancer. The highest quartile of CK score was associated with a higher risk of all-site (aHR 1.91, 0.96-3.81, p = 0.07; p-trend = 0.005), lung (aHR 8.18, 1.63-41.23, p = 0.01; p-trend < 0.001), and lung/lymphoproliferative (aHR 4.56 [1.84-11.31], p = 0.001; p-trend < 0.001) cancer. Thirteen of 17 individual analytes were associated with incident cancer risk. CONCLUSION: Elevated cytokine/chemokine concentrations are predictive of future cancer in RA patients, particularly lung and lymphoproliferative cancers. These results suggest that the measurement of circulating cytokines/chemokines could be informative in cancer risk stratification and could provide insight into future cancer prevention strategies in RA, and possibly individuals without RA.

Predicting Survival in Veterans with Follicular Lymphoma Using Structured Electronic Health Record Information and Machine Learning.

The most accurate prognostic approach for follicular lymphoma (FL), progression of disease at 24 months (POD24), requires two years' observation after initiating first-line therapy (L1) to predict outcomes. We applied machine learning to structured electronic health record (EHR) data to predict individual survival at L1 initiation. We grouped 523 observations and 1933 variables from a nationwide cohort of FL patients diagnosed 2006-2014 in the Veterans Health Administration into traditionally used prognostic variables ("curated"), commonly measured labs ("labs"), and International Classification of Diseases diagnostic codes ("ICD") sets. We compared performance of random survival forests (RSF) vs. traditional Cox model using four datasets: curated, curated + labs, curated + ICD, and curated + ICD + labs, also using Cox on curated + POD24. We evaluated variable importance and partial dependence plots with area under the receiver operating characteristic curve (AUC). RSF with curated + labs performed best, with mean AUC 0.73 (95% CI: 0.71-0.75). It approximated, but did not surpass, Cox with POD24 (mean AUC 0.74 [95% CI: 0.71-0.77]). RSF using EHR data achieved better performance than traditional prognostic variables, setting the foundation for the incorporation of our algorithm into the EHR. It also provides for possible future scenarios in which clinicians could be provided an EHR-based tool which approximates the predictive ability of the most accurate known indicator, using information available 24 months earlier.

Treatment Patterns and Outcomes in a Nationwide Cohort of Older and Younger Veterans with Waldenström Macroglobulinemia, 2006-2019.

Little is known about real-world treatment patterns and outcomes in Waldenström macroglobulinemia (WM) following the recent introduction of newer treatments, especially among older adults. We describe patterns of first-line (1 L) WM treatment in early (2006-2012) and modern (2013-2019) eras and report outcomes (overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse event (AE)-related discontinuation) in younger (≤70 years) and older (>70 years) populations. We followed 166 younger and 152 older WM patients who received 1 L treatment between January 2006 and April 2019 in the Veterans Health Administration. Median follow-up was 43.5 months (range: 0.6-147.2 months). Compared to the early era, older patients in the modern era achieved improved ORRs (early: 63.8%, modern: 72.3%) and 41% lower risk of death/progression (hazard ratio (HR) for PFS: 0.59, 95% CI (confidence interval): 0.36-0.95), with little change in AE-related discontinuation between eras (HR: 0.82, 95% CI: 0.4-1.7). In younger patients, the AE-related discontinuation risk increased almost fourfold (HR: 3.9, 95% CI: 1.1-14), whereas treatment effects did not change between eras (HR for OS: 1.4, 95% CI: 0.66-2.8; HR for PFS: 1.1, 95% CI: 0.67-1.7). Marked improvements in survival among older adults accompanied a profound shift in 1 L treatment patterns for WM.

Heart Failure Hospitalization Risk associated with Iron Status in Veterans with CKD.

BACKGROUND AND OBJECTIVES: CKD is an independent risk factor for heart failure. Iron dysmetabolism potentially contributes to heart failure, but this relationship has not been well characterized in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a historical cohort study using data from the Veterans Affairs Corporate Data Warehouse to evaluate the relationship between iron status and heart failure hospitalization. We identified a CKD cohort with at least one set of iron indices between 2006 and 2015. The first available date of serum iron indices was identified as the study index date. The cohort was divided into four iron groups on the basis of the joint quartiles of serum transferrin saturation (shown in percent) and ferritin (shown in nanograms per milliliter): reference (16%-28%, 55-205 ng/ml), low iron (0.4%-16%, 0.9-55 ng/ml), high iron (28%-99.5%, 205-4941 ng/ml), and function iron deficiency (0.8%-16%, 109-2783 ng/ml). We compared 1-year heart failure hospitalization risk between the iron groups using matching weights derived from multinomial propensity score models and Poisson rate-based regression. RESULTS: A total of 78,551 veterans met the eligibility criteria. The covariates were well balanced among the iron groups after applying the propensity score weights (n=31,819). One-year adjusted relative rate for heart failure hospitalization in the iron deficiency groups were higher compared with the reference group (low iron: 1.29 [95% confidence interval, 1.19 to 1.41]; functional iron deficiency: 1.25 [95% confidence interval, 1.13 to 1.37]). The high-iron group was associated with lower 1-year relative rate of heart failure hospitalization (0.82; 95% confidence interval, 0.72 to 0.92). Furthermore, the association between iron deficiency and heart failure hospitalization risk remained consistent regardless of the diabetes status or heart failure history at baseline. CONCLUSIONS: Iron deficiency, regardless of cause, was associated with higher heart failure hospitalization risk in CKD. Higher iron status was associated with lower heart failure hospitalization risks.

Perioperative Continuation of Biologic Medications Increases Odds of Periprosthetic Joint Infection in Patients With Inflammatory Arthropathy.

BACKGROUND: Rates of prosthetic joint infection (PJI) are elevated among patients with inflammatory arthropathy (IA). The effect of continuing biologic drugs perioperatively with regard to PJI is unknown. The purpose of this study is to compare rates of perioperative biologic continuation in IA patients who did and did not develop PJI after primary total joint arthroplasty (TJA). METHODS: All cases of PJI within 1 year of primary TJA in IA patients on biologic medications were retrospectively reviewed from 2005 to 2018 in the US Veterans Affairs Corporate Data Warehouse. Matched controls who did not develop PJI after TJA were populated from the same database. Biologic suspension, defined as medication interruption prior to TJA with surgery occurring after the end of the dosing cycle and resumption after wound healing, was compared among cases and controls. RESULTS: Biologic medications were continued through surgery in 35% (9/26) of patients who developed PJI compared to 14% (8/58) of controls (P = .031; adjusted odds ratio of 3.46 [1.11-10.78]). No significant difference existed among cases (n = 26) and controls (n = 58) for age, gender, procedure, body mass index, rates of diabetes or chronic kidney disease, smoking status, or preoperative opioid use (all P > .05). CONCLUSION: With the limited sample sizes available in this study, we found an association with perioperative continuation of biologic medications and PJI. This data may provide support for current guidelines from the American Association of Hip and Knee Surgeons to withhold biologics before TJA with surgery scheduled at the end of the dosing cycle and medication resumption only after wound healing.

Pharmacist-led collaborative medication management programs for oral antineoplastic therapies: A systematic literature review.

OBJECTIVES: The aim of this systematic review is to summarize the structure, process, and outcomes of pharmacist-led collaborative medication management programs for oral antineoplastic therapies (OATs). METHODS: Included studies were peer-reviewed journal articles published in English, between January 2000 to May 2020, and reporting on pharmacist-led collaborative medication management programs for patients on OATs. To be included, studies had to report on the pharmacy practice model, pharmacist interventions, and outcomes of the medication management program. The Donabedian model informed the data extraction and summary. Two independent researchers assessed the risk of bias (confounding) for all included studies (n = 12) using the NIH tool and Cochrane ROBINS-I for observational research. RESULTS: There were 12 studies that met inclusion criteria. The structure of the programs included hiring oncology pharmacists to deliver interventions, standardized templates for electronic medical record documentation, and administrative workflow changes (e.g., automatic referrals). The most common pharmacist interventions (processes) were patient education and counseling, adverse event monitoring, and dose modifications. All studies reported one or more positive outcomes, including improved patient adherence, safety, cost savings, cost avoidance, and patient satisfaction. All included studies used an observational study designs, and the majority of studies had moderate to high risk of bias. CONCLUSION: The evidence suggests that pharmacist-led collaborative medication management programs may have beneficial clinical and economic outcomes. The implementation of these programs could be strengthened by using a conceptual framework to guide program development, implementation, and evaluation and effectiveness-hybrid study designs to assess clinical and implementation outcomes. The risk of bias should be addressed by using more robust study designs and rigorous data collection and analysis methods.

Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma.

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000-2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan-Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

Atrial Fibrillation and Bleeding in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib in the Veterans Health Administration.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. The introduction of novel oral agents, starting with ibrutinib in 2013, has revolutionized the therapeutic landscape; however, clinical trials have suggested an association between ibrutinib and the risk of bleeding-related adverse events and atrial fibrillation (Afib) in patients with CLL. METHODS: Patients diagnosed and treated for CLL at the Veterans Health Administration (VHA) from 2010 to 2014 were followed until December 31, 2016, death, or lack of utilization of hematology/oncology services for ≥ 18 months; or until incidence of another cancer. Treatments dispensed, evidence of VHA system use, bleeding events, and Afib were determined from the administrative records, laboratory records, pharmacy dispensation records, and clinical notes in the electronic healthcare record. RESULTS: From 2010 to 2014, 2,796 patients were diagnosed and received care for CLL within the VHA, of whom 172 patients received ibrutinib and 291 received bendamustine + rituximab (BR). The use of anticoagulants following induction therapy did not differ between BR and ibrutinib patients (9% vs 8%, respectively), nor did the use of antiplatelets agents (6% vs 2%, respectively). Of the 291 patients that received BR, 12 (4%) developed a bleeding event compared with 20 (12%) who received ibrutinib. Additionally, 13 (8%) ibrutinib patients developed Afib compared with 9 (3%) BR patients. CONCLUSIONS: Real-world evidence from a nationwide cohort of patients with CLL suggests that while ibrutinib is associated with increased bleeding-related adverse events and Afib, the risk is comparable to those reported in previous clinical trials. These findings suggest that patients in real-world clinical care settings with higher levels of comorbidities may be at an increased risk for bleeding events and Afib.

Maintenance rituximab in Veterans with follicular lymphoma.

Real-world practice patterns and clinical outcomes in patients with follicular lymphoma (FL), including the adoption of maintenance rituximab (MR) therapy in the United States (US), have been reported in few studies since the release of the National LymphoCare Study almost a decade ago. We analyzed data from the largest integrated healthcare system in the United States, the Veterans Health Administration (VHA), to identify rates of adoption and effectiveness of MR in FL patients after first-line (1L) treatment. We identified previously untreated patients with FL in the VHA between 2006 and 2014 who achieved at least stable disease after chemoimmunotherapy or immunotherapy. Among these patients, those who initiated MR within 238 days of 1L composed the MR group, whereas those who did not were classified as the non-MR group. We examined the effect of MR on progression-free survival (PFS) and overall survival (OS). A total of 676 patients met our inclusion criteria, of whom 300 received MR. MR was associated with significant PFS (hazard ratio [HR]=0.55, P < .001) and OS (HR = 0.53, P = .005) compared to the non-MR group, after adjusting by age, sex, ethnicity, geographic region, diagnosis period, stage, grade at diagnosis, hemoglobin, lactate dehydrogenase (LDH), Charlson comorbidity index (CCI), 1L treatment regimen, and response to 1L treatment. These results suggest that in FL patients who do not experience disease progression after 1L treatment in real-world settings, MR is associated with a significant improvement in both PFS and OS. Maintenance therapy should be considered in FL patients who successfully complete and respond to 1L therapy.

Risk of Total Wrist Arthrodesis or Reoperation Following 4-Corner Arthrodesis or Proximal Row Carpectomy for Stage-II SLAC/SNAC Arthritis: A Propensity Score Analysis of 502 Wrists.

BACKGROUND: For stage-II scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) patterns of wrist arthritis, the optimal method of surgical treatment remains unclear. Previous literature has demonstrated similar clinical outcomes between proximal row carpectomy (PRC) and 4-corner arthrodesis (FCA), making the risk of reoperation a focus of particular interest. In the present study, the primary null hypothesis was that there would be no difference in the rate of conversion to total wrist arthrodesis between PRC and FCA. Additionally, we hypothesized that the rate of secondary surgical procedures would be similar between the 2 procedures. METHODS: The national Veterans Health Administration Corporate Data Warehouse was utilized to identify 2,449 patients who underwent either PRC or FCA between 1992 and 2016. With use of operative reports to identify the arthritis pattern, only cases of stage-II SLAC/SNAC were included. All complications and subsequent surgical procedures were confirmed by manual chart review. Propensity score analyses with matching weights were utilized to balance the PRC and FCA cohorts. The rates of conversion to wrist arthrodesis and secondary surgical procedures were calculated. RESULTS: Of the 1,168 patients with stage-II SLAC/SNAC arthritis, 933 wrists underwent PRC and 257 wrists underwent FCA. Ten-year survival free of total wrist arthrodesis in the matching PRC (251 procedures) and FCA (251 procedures) cohorts was 94.3% (95% confidence interval [CI], 92.3% to 96.3%) and 94.1% (95% CI, 90.8% to 97.4%), respectively. Survival free of a secondary surgical procedure other than wrist arthrodesis was 99.7% (95% CI, 99.3% to 100.0%) for PRC and 83.5% (95% CI, 78.2% to 88.8%) for FCA. CONCLUSIONS: PRC and FCA demonstrated similarly low rates of conversion to total wrist arthrodesis. In contrast, the rate of secondary surgical procedures following FCA was significantly higher compared with PRC. Given the historically similar clinical outcomes between PRC and FCA, the results of the present study show that PRC may be a preferable treatment for stage-II SLAC/SNAC wrist arthritis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Performance of Administrative Algorithms to Identify Interstitial Lung Disease in Rheumatoid Arthritis.

OBJECTIVE: To determine the performance of administrative-based algorithms for classifying interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). METHODS: Participants in a large, multicenter RA registry were screened for ILD using codes from the International Classification of Diseases, Ninth Revision (ICD-9) and the ICD-10. Medical record review confirmed ILD among participants screening positive and a random sample of those screening negative. ICD and procedure codes, provider specialty, and dates were extracted from Veterans Affairs administrative data to construct ILD algorithms. Performance of these algorithms against medical record review was assessed by sensitivity, specificity, positive predictive value (PPV), negative predictive value, and kappa using inverse probability weighting to account for sampling methods. RESULTS: Medical records of 536 RA patients were reviewed, confirming 182 (stringent definition) and 203 (relaxed definition) cases of ILD. Initially, we identified ≥2 ICD codes from inpatient or outpatient encounters as optimal discriminating factors (specificity 96.0%, PPV 65.5%; κ = 0.70). Subsequently, we constructed a set of ICD-9 and ICD-10 codes that improved algorithm specificity (specificity 96.8%, PPV 69.5%; κ = 0.72). Algorithms that included a pulmonologist diagnosis or chest computed tomography plus pulmonary function testing or lung biopsy had improved performance (specificity 98.0%, PPV 77.4%; κ = 0.75). PPV increased with exclusion of other ILD causes (78.5%) in comparison with the relaxed ILD definition (82.4%) and in sensitivity analyses (83.4-86.3%). Gains in specificity and PPV with greater algorithm requirements were accompanied by declines in sensitivity. CONCLUSION: Administrative algorithms with optimal combinations of ICD codes, provider specialty, diagnostic testing, and exclusion of other ILD causes accurately classify ILD in RA.