A systematic review of the economic value proposition for commercially available nonsurgical weight-loss interventions.

OBJECTIVE: The study aim was to review the economic evaluation literature of commercially available and effective nonsurgical weight-loss interventions to investigate whether there is evidence to support claims of cost-effectiveness (i.e., good value for money) or cost savings (i.e., a positive return on investment). METHODS: Relevant databases were systematically reviewed to identify economic evaluations of commercially available weight-loss products and services shown to result in clinically significant weight loss. Five weight-loss medications (orlistat, liraglutide, naltrexone-bupropion, semaglutide, and phentermine-topiramate), two meal replacement programs (Jenny Craig, Optifast), and one behavioral intervention (Weight Watchers [WW]) that met inclusion criteria were identified. After screening, 32 relevant comparisons of cost-effectiveness or cost savings across 20 studies were identified. RESULTS: Ten of twenty pharmaceutical comparisons showed evidence of cost-effectiveness based on established thresholds. Four of twelve nonpharmaceutical comparisons provided evidence of cost-effectiveness, and five made claims of cost savings. However, methodological concerns cast doubt on the robustness of these claims. CONCLUSIONS: Evidence of cost-effectiveness for commercially available, evidence-based, nonsurgical weight-loss interventions is mixed. There is no evidence for cost-saving weight-loss medications and only weak evidence for behavioral and weight-loss interventions. Results provide a call to action to generate more robust evidence of the economic value proposition for these interventions.

Long-term outcomes of aortic root replacement for endocarditis.

BACKGROUND: Infective endocarditis (IE) involving the aortic valve and root is associated with high risk requiring thoughtful surgical decision-making. The impact of valve and conduit choices and patient factors on long-term outcomes in this patient population is poorly documented. METHODS: From January 1976 to December 2013, 485 patients underwent aortic root and valve replacement at a single institution. Cox's proportional hazard model identified predictors of long-term survival and cumulative incidence functions were compared to assess need for reoperation with death as a competing risk. RESULTS: Median age at time of operation was 56.6 years (interquartile range: 23.1) with the indication for operation being endocarditis in 14.6% (n = 71). Stentless root replacement was used in 70% IE versus 34% non-IE (p < .001). Endocarditis at time of root replacement did not have a significant impact on survival through 15 years (IE: 37.3% vs. non-IE: 42.5%; log-rank; p = .13). After multivariable adjustment, survival was similar between patients with and without endocarditis (hazard ratio: 1.1; 95% confidence interval: [0.77, 1.62]; p = .57). Freedom from reoperation at 15 years did not vary significantly by endocarditis status (IE: 95.9% vs. non-IE: 73.6%; p = .07). Among endocarditis patients, freedom from reoperation at 10 years was similar between homograft and stentless bioprosthetic conduits (95.3% vs. 88.5%; log-rank; K-sample; p = .46). CONCLUSIONS: In a sample with frequent use of stentless prostheses, aortic root replacement for infective endocarditis had acceptable risk and long-term survival similar to root replacement for other indications. In the setting of endocarditis, root replacement with homograft or stentless bioprosthetic root has excellent durability through 15 years.

Synergy between early-incorporation immunotherapy and extracranial radiotherapy in metastatic non-small cell lung cancer.

BACKGROUND: Combining radiotherapy (RT) and immunotherapy (IT) may enhance outcomes for metastatic non-small cell lung cancer (mNSCLC). However, data on the immunomodulatory effects of extracranial RT remains limited. This retrospective database analysis examined real-world practice patterns, predictors of survival, and comparative effectiveness of extracranial radioimmunotherapy (RT + IT) versus early-incorporation immunotherapy (eIT) in patients with mNSCLC. METHODS: Patients diagnosed with mNSCLC between 2004-2016 treated with eIT or RT + IT were identified in the National Cancer Database. Practice patterns were assessed using Cochrane-Armitrage trend test. Cox proportional hazards and Kaplan-Meier method were used to analyze overall survival (OS). Propensity score matching was performed to account for baseline imbalances. Biologically effective doses (BED) were stratified based on the median (39 Gy10). Stereotactic body radiotherapy (SBRT) was defined as above median BED in ≤5 fractions. RESULTS: eIT utilization increased from 0.3% in 2010 to 13.2% in 2016 (P<0.0001). Rates of RT + eIT increased from 38.8% in 2010 to 49.1% in 2016 among those who received eIT (P<0.0001). Compared to eIT alone, RT + eIT demonstrated worse median OS (11.2 vs. 13.2 months) while SBRT + eIT demonstrated improved median OS (25 vs. 13.2 months) (P<0.0001). There were no significant differences in OS based on sequencing of eIT relative to RT (log-rank P=0.4415) or irradiated site (log-rank P=0.1606). On multivariate analysis, factors associated with improved OS included chemotherapy (HR 0.86, P=0.0058), treatment at academic facilities (HR 0.83, P<0.0001), and SBRT (HR 0.60, P=0.0009); after propensity-score multivariate analysis, SBRT alone showed improved OS (HR 0.28, P<0.0001). CONCLUSIONS: Utilization of RT + eIT in mNSCLC is increasing. SBRT + eIT was associated with improved OS on propensity-score matched analysis. There were no significant differences in OS based on RT + eIT sequencing or site irradiated. Whether these observations reflect patient selection or possible immunomodulatory benefits of RT is unclear and warrants further study.

Off-study utilization of experimental therapies: Analysis of GOG249-eligible cohorts using real world data.

OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.