Projecting long-term clinical outcomes with larotrectinib compared with immune checkpoint inhibitors in metastatic nonsmall cell lung cancer and differentiated thyroid cancer.

BACKGROUND: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Prior studies demonstrated promising results with larotrectinib compared with other systemic therapy. However, comparisons to checkpoint inhibitors, such as nivolumab or pembrolizumab, have not been done. OBJECTIVE: To estimate and compare expected life-years (LYs) and quality-adjusted LYs (QALYs) for patients with nonsmall cell lung cancer (NSCLC) eligible for larotrectinib vs patients with unknown NTRK gene fusion status on nivolumab or pembrolizumab. We also assessed patients with metastatic differentiated thyroid cancer (DTC), as pembrolizumab may be considered in certain circumstances. METHODS: We developed partitioned survival models to project long-term comparative effectiveness of larotrectinib vs nivolumab or pembrolizumab. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adult patients (≥18 years of age) with metastatic NTRK gene fusion-positive NSCLC and 21 with DTC. Survival inputs for nivolumab and pembrolizumab were obtained from published articles. Progression-free and overall survival were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal). Exponential fits were chosen based on goodness-of-fit and clinical plausibility. RESULTS: In NSCLC, larotrectinib resulted in gains of 5.87 and 5.91 LYs compared to nivolumab and pembrolizumab, respectively, which translated to gains of 3.53 and 3.56 QALYs. In DTC, larotrectinib resulted in a gain of 5.23 LYs and 4.24 QALYs compared to pembrolizumab. CONCLUSIONS: In metastatic NSCLC and DTC, larotrectinib may produce substantial life expectancy and QALY gains compared to immune checkpoint inhibitors. Additional data with longer follow-up will further inform this comparison.

Estimated Prevalence and Testing for Albuminuria in US Adults at Risk for Chronic Kidney Disease.

Importance: Albuminuria testing is crucial for guiding evidence-based treatments to mitigate chronic kidney disease (CKD) progression and cardiovascular morbidity, but it is widely underutilized among persons with or at risk for CKD. Objective: To estimate the extent of albuminuria underdetection from lack of testing and evaluate its association with CKD treatment in a large US cohort of patients with hypertension or diabetes. Design, Setting, and Participants: This cohort study examined adults with hypertension or diabetes, using data from the 2007 to 2018 National Health and Nutrition Examination Surveys (NHANES) and the Optum deidentified electronic health record (EHR) data set of diverse US health care organizations. Analyses were conducted from October 31, 2022, to May 19, 2023. Main Outcomes and Measures: Using NHANES as a nationally representative sample, a logistic regression model was developed to estimate albuminuria (urine albumin-creatinine ratio ≥30 mg/g). This model was then applied to active outpatients in the EHR from January 1, 2017, to December 31, 2018. The prevalence of albuminuria among those with and without albuminuria testing during this period was estimated. A multivariable logistic regression was used to examine associations between having albuminuria testing and CKD therapies within the subsequent year (prescription for angiotensin-converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB], prescription for sodium-glucose cotransporter 2 inhibitor [SGLT2i], and blood pressure control to less than 130/80 mm Hg or less than 140/90 mm Hg on the latest outpatient measure). Results: The total EHR study population included 192 108 patients (mean [SD] age, 60.3 [15.1] years; 185 589 [96.6%] with hypertension; 50 507 [26.2%] with diabetes; mean [SD] eGFR, 84 [21] mL/min/1.73 m2). There were 33 629 patients (17.5%) who had albuminuria testing; of whom 11 525 (34.3%) had albuminuria. Among 158 479 patients who were untested, the estimated albuminuria prevalence rate was 13.4% (n = 21 231). Thus, only 35.2% (11 525 of 32 756) of the projected population with albuminuria had been tested. Albuminuria testing was associated with higher adjusted odds of receiving ACEi or ARB treatment (OR, 2.39 [95% CI, 2.32-2.46]), SGLT2i treatment (OR, 8.22 [95% CI, 7.56-8.94]), and having blood pressure controlled to less than 140/90 mm Hg (OR, 1.20 [95% CI, 1.16-1.23]). Conclusions and Relevance: In this cohort study of patients with hypertension or diabetes, it was estimated that approximately two-thirds of patients with albuminuria were undetected due to lack of testing. These results suggest that improving detection of CKD with albuminuria testing represents a substantial opportunity to optimize care delivery for reducing CKD progression and cardiovascular complications.

Migration of Hospital Total Hip and Knee Arthroplasty Procedures to an Ambulatory Surgery Center Setting and Postsurgical Opioid Use: A Private Practice Experience.

Background: An enhanced recovery pathway using individualized multimodal pain management with scheduled nonopioid and opioid regimens previously enabled reproducible same-day discharge of Medicare beneficiaries and commercially insured patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) procedures in the hospital or in ambulatory surgery center settings. Objective: To analyze the migration trends for TKA and THA procedures from a hospital to an ambulatory surgery center facility and to assess perioperative outcomes before and after incorporating liposomal bupivacaine into a multimodal pain management regimen for these procedures. Methods: This retrospective medical chart review study included patients undergoing THA or TKA with an enhanced recovery pathway in a hospital or an ambulatory surgery center between 2013 and 2019. The outcome measures included length of stay at the hospital or the ambulatory center, and opioid consumption. We compared the outcomes before and after the addition of liposomal bupivacaine to surgeon-applied periarticular intraoperative local anesthetic field blocks between in-hospital patients who received and patients who did not receive liposomal bupivacaine in 2013 and 2014, and the impact of liposomal bupivacaine use in the hospital versus the ambulatory center from 2015 to 2019. Results: In 2013 and 2014, the addition of liposomal bupivacaine increased the same-day hospital discharge rate to 32% versus 4% without liposomal bupivacaine (odds ratio, 14.3; 95% confidence interval, 5.9-33.3; P <.0001); the same-day hospital discharge rates increased to 73% in 2015. From 2015 through 2019, 89% of all patients were discharged on the same day from the hospital. In-hospital opioid use was 22% lower in the liposomal bupivacaine cohort than in the patients who did not receive this medication (P = .0035). In 2018 and 2019, same-day discharge from the hospital or the ambulatory surgery center rates were 96% and 100%, respectively, and 84% of the patients used postsurgical opioid prescriptions of 30 or fewer tablets. The complication rates and healthcare resource utilization did not increase with the incorporation of liposomal bupivacaine into the enhanced recovery pathway and increased same-day discharge rates. Conclusion: An enhanced recovery pathway using individualized, scheduled multimodal pain management protocol in patients undergoing THA or TKA facilitated reproducible, high same-day discharge rates and low postoperative opioid consumption. These results suggest that the use of liposomal bupivacaine for intraoperative field blocks supports predictable same-day discharge rates after THA or TKA. This protocol could facilitate same-day hospital discharge and the migration of THA and TKA procedures from the hospital to lower-cost ambulatory surgery centers.

Economic Outcomes and Incidence of Postsurgical Hypotension With Liposomal Bupivacaine vs Epidural Analgesia in Abdominal Surgeries.

Background: Epidural analgesia can be associated with high costs and postsurgical risks such as hypotension, despite its widespread use and value in providing opioid-sparing pain management. We tested the hypothesis that liposomal bupivacaine (LB) might be a reliable alternative to epidural analgesia in this real-world study. Objectives: To compare economic outcomes and hypotension incidence associated with use of LB and epidural analgesia for abdominal surgery. Methods: This retrospective analysis identified records of adults who underwent abdominal surgeries between January 2016 and September 2019 with either LB administration or traditional epidural analgesia using the Premier Healthcare Database. Economic outcomes included length of stay, hospital costs, rates of discharge to home, and 30-day hospital readmissions. Secondary outcomes included incidence of postsurgical hypotension and vasopressor use. Subgroup analyses were stratified by surgical procedure (colorectal, abdominal) and approach (endoscopic, open). A generalized linear model adjusted for patient and hospital characteristics was used for all comparisons. Results: A total of 5799 surgical records (LB, n=4820; epidural analgesia, n=979) were included. Compared with cases where LB was administered, cases of epidural analgesia use were associated with a 1.6-day increase in length of stay (adjusted rate ratio [95% confidence interval (CI), 1.2 [1.2-1.3]]; P<.0001) and $6304 greater hospital costs (adjusted rate ratio [95% CI], 1.2 [1.2-1.3]]; P<.0001). Cost differences were largely driven by room-and-board fees. Epidural analgesia was associated with reduced rates of discharge to home (P<.0001) and increased 30-day readmission rates (P=.0073) compared with LB. Epidural analgesia was also associated with increased rates of postsurgical hypotension (30% vs 11%; adjusted odds ratio [95% CI], 2.8 [2.3-3.4]; P<.0001) and vasopressor use (22% vs 7%; adjusted odds ratio [95% CI], 3.1 [2.5-4.0]; P<.0001) compared with LB. Subgroup analyses by surgical procedure and approach were generally consistent with overall comparisons. Discussion: Our results are consistent with previous studies that demonstrated epidural analgesia can be associated with higher utilization of healthcare resources and complications compared with LB. Conclusions: Compared with epidural analgesia, LB was associated with economic benefits and reduced incidence of postsurgical hypotension and vasopressor use.