Mitigating time toxicity in lymphoma and multiple myeloma.

The concept of time toxicity in oncology refers to the presence of frequent healthcare-related interactions that can interfere with patient well-being. In this review, we examine several manifestations of time toxicity in non-Hodgkin lymphoma and multiple myeloma and discuss their impact on decision-making with patients. For example, time toxicity may influence the choice of chemoimmunotherapy versus lenalidomide-rituximab in follicular lymphoma. In myeloma, it may inform the optimal dosing schedule for proteasome inhibitors and bisphosphonates. In both malignancies, varying time toxicity profiles are a key distinction between chimeric antigen receptor T-cell therapies and bispecific antibodies. We outline the challenges with measuring time toxicity as a trial endpoint but discuss its importance as a consideration for patient care, both in standard-of-care settings and in clinical trials. Throughout the review, we highlight strategies to lower the time toxicity of therapies in lymphoma and myeloma without compromising their efficacy or patient safety.

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia.

BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. METHODS: We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. RESULTS: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups. CONCLUSIONS: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

Brentuximab vedotin plus AVD for Hodgkin lymphoma: incidence and management of peripheral neuropathy in a multisite cohort.

Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.

Functional status and therapy for older adults with diffuse large B-cell lymphoma in nursing homes: A population-based study.

OBJECTIVES: To characterize the prevalence of functional and cognitive impairments, and associations between impairments and treatment among older patients with diffuse large B cell lymphoma (DLBCL) receiving nursing home (NH) care. METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify beneficiaries diagnosed with DLBCL 2011-2015 who received care in a NH within -120 ~ +30 days of diagnosis. Multivariable logistic regression was used to compare receipt of chemoimmunotherapy (including multi-agent, anthracycline-containing regimens), 30-day mortality, and hospitalization between NH and community-dwelling patients, estimating odds ratios (OR) and 95% confidence interval (CI). We also examined overall survival (OS). Among NH patients, we examined receipt of chemoimmunotherapy based on functional and cognitive impairment. RESULTS: Of the eligible 649 NH patients (median age: 82 years), 45% received chemoimmunotherapy; among the recipients, 47% received multi-agent, anthracycline-containing regimens. Compared with community-dwelling patients, those in a NH were less likely to receive chemoimmunotherapy (OR: 0.34, 95%CI: 0.29-0.41), had higher 30-day mortality (OR: 2.00, 95%CI: 1.43-2.78) and hospitalization (OR: 1.51, 95%CI: 1.18-1.93), and poorer OS (hazard ratio: 1.36, 95%CI: 1.11-1.65). NH patients with severe functional (61%) or any cognitive impairment (48%) were less likely to receive chemoimmunotherapy. CONCLUSIONS: High rates of functional and cognitive impairment and low rates of chemoimmunotherapy were observed among NH residents diagnosed with DLBCL. Further research is needed to better understand the potential role of novel and alternative treatment strategies and patient preferences for treatment to optimize clinical care and outcomes in this high-risk population.

Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence.

Tyrosine kinase inhibitor (TKI) use is critical in the care of patients with chronic myeloid leukemia (CML). Quantitative polymerase chain reaction (qPCR) testing for BCR-ABL1 every 3 months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1192 patients aged ≥66 years (median age, 74 years) with newly diagnosed CML who were followed up for ≥13 months from TKI initiation. In total, 965 patients (81.0%) had ≥1 test, with 425 (35.7%) and 540 (45.3%) of the patients tested during 1, 2, and ≥3 quarters (optimal monitoring) of the first year from TKI initiation, respectively. In multivariable analysis, diagnosis in later years and influenza vaccination before diagnosis, a proxy for health care access, were associated with optimal qPCR monitoring. Use of low-income subsidy and residing in census tracts with the lowest socioeconomic status were associated with less optimal monitoring. Patients with optimal monitoring were 60% more likely to be TKI adherent (odds ratio, 1.60; 95% CI, 1.11-2.31; P = .01) and had improved 5-year survival (hazard ratio, 0.66; 95% CI, 0.49-0.90; P < .01) than those without such monitoring. In this large, real-world study of CML management patterns, many older patients had suboptimal molecular monitoring, which was associated with decreased TKI adherence and worse survival.

Cost-effectiveness of chimeric antigen receptor T-cell therapy in adults with relapsed or refractory follicular lymphoma.

Follicular lymphoma (FL) is traditionally considered treatable but incurable. In March 2021, the US Food and Drug Administration approved the use of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) FL after ≥2 lines of therapy. Priced at $373 000, CAR T-cell therapy is potentially curative, and its cost-effectiveness compared with other modern R/R FL treatment strategies is unknown. We developed a Markov model to assess the cost-effectiveness of third-line CAR T-cell vs standard of care (SOC) therapies in adults with R/R FL. We estimated progression rates for patients receiving CAR T-cell and SOC therapies from the ZUMA-5 trial and the LEO CReWE study, respectively. We calculated costs, discounted life years, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) of CAR T-cell vs SOC therapies with a willingness-to-pay threshold of $150 000 per QALY. Our analysis was conducted from a US payer's perspective over a lifetime horizon. In our base-case model, the cost of the CAR T-cell strategy was $731 682 compared with $458 490 for SOC therapies. However, CAR T-cell therapy was associated with incremental clinical benefit of 1.50 QALYs, resulting in an ICER of $182 127 per QALY. Our model was most sensitive to the utilities associated with CAR T-cell therapy remission and third-line SOC therapies and to the total upfront CAR T-cell therapy cost. Under current pricing, CAR T-cell therapy is unlikely to be cost-effective in unselected patients with FL in the third-line setting. Both randomized clinical trials and longer term clinical follow-up can help clarify the benefits of CAR T-cell therapy and optimal sequencing in patients with FL.

Hispanic Ethnicity Differences in Birth Characteristics, Maternal Birthplace, and Risk of Early-Onset Hodgkin Lymphoma: A Population-Based Case-Control Study.

BACKGROUND: Hispanic ethnicity differences in the risk of early-onset Hodgkin lymphoma diagnosed at <40 years are understudied. We conducted a population-based case-control study to evaluate associations between birth characteristics and early-onset Hodgkin lymphoma with a focus on potential ethnic differences. METHODS: This study included 1,651 non-Hispanic White and 1,168 Hispanic cases with Hodgkin lymphoma endorsing a range of races diagnosed at the age of 0 to 37 years during 1988-2015 and 140,950 controls without cancer matched on race/ethnicity and year of birth from the California Linkage Study of Early-Onset Cancers. OR and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. RESULTS: Having a foreign-born mother versus a United States-born mother (i.e., the reference group) was associated with an increased risk of early-onset Hodgkin lymphoma among non-Hispanic Whites (OR = 1.52; 95% CI, 1.31-1.76; P < 0.01) and a decreased risk among Hispanics (OR = 0.78; 95% CI, 0.69-0.88; P < 0.01). Among both race groups, risk of early-onset Hodgkin lymphoma increased with birthweight and maternal age (all Ptrends < 0.01). Among non-Hispanic Whites, each 5-year increase in maternal age (OR = 1.11; 95% CI, 1.04-1.18; Ptrend < 0.01) and paternal age (OR = 1.07; 95% CI, 1.02-1.13; Ptrend < 0.01) was associated with increased risk of early-onset Hodgkin lymphoma. Compared with female Hispanics, male Hispanics had an increased risk of early-onset Hodgkin lymphoma (OR = 1.26; 95% CI, 1.12-1.42; P < 0.01). CONCLUSIONS: Maternal birthplace may play a role in risk of early-onset Hodgkin lymphoma that differs by ethnicity. IMPACT: The ethnic differences observed between certain birth characteristics, maternal birthplace, and early-onset Hodgkin lymphoma raise questions about the underlying biological, generational, lifestyle, residential, and genetic contributions to the disease.

Global Risk Indicator and Therapy for Older Patients With Diffuse Large B-Cell Lymphoma: A Population-Based Study.

PURPOSE: To examine the impact of global risk, a measure comprising age, comorbidities, function, and cognitive statuses, on treatment selection and outcomes among older home care recipients with diffuse large B-cell lymphoma. METHODS: From SEER-Medicare, we selected home care recipients diagnosed with diffuse large B-cell lymphoma in 2011-2015, who had pretreatment Outcome and Assessment Information Set (OASIS) evaluations. We created a global risk indicator categorizing patients as low-, moderate-, or high-risk on the basis of OASIS assessments. We examined the association of global risk with receipt of therapy and among chemotherapy recipients, with mortality, emergency department visits, hospitalization, and intensive care unit admission within 30 days from first treatment in logistic models, reporting adjusted odds ratios (OR) with 95% CI. We compared overall survival across risk groups estimating adjusted hazard ratios. RESULTS: Of the 1,232 patients (median age, 80 years), 65% received chemotherapy. High-risk patients (v moderate-risk) were less likely to receive any chemotherapy (OR, 0.50; 95% CI, 0.39 to 0.64) and curative regimens (OR, 0.59; 95% CI, 0.40 to 0.86) if treated, although even in the moderate-risk group, only 61% received curative regimens. High-risk patients were more likely to experience acute mortality (OR, 2.24; 95% CI, 1.43 to 3.52), emergency department visits (OR, 1.35; 95% CI, 1.00 to 1.83), hospitalization (OR, 1.60; 95% CI, 1.19 to 2.17), or intensive care unit admission (OR, 1.52; 95% CI, 1.04 to 2.22) and had inferior overall survival (hazard ratio, 1.41; 95% CI, 1.11 to 1.78). CONCLUSION: Global risk on the basis of OASIS is easily available, suggesting a potential way to improve patient selection for curative treatment and institution of preventive measures.

Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis). METHODS: This was a pooled analysis of the Nurses' Health Study (NHS, n = 82,869), NHS II (n = 95,141), and UK Biobank (n = 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications. RESULTS: We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22-1.65; number needed to harm, 3770; 95% CI, 3668-4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16-1.65). CONCLUSIONS: Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.

Cost-effectiveness of once-weekly selinexor, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma.

The BOSTON trial showed that use of once-weekly selinexor, bortezomib, and dexamethasone (SVd) prolonged progression-free survival compared to twice-weekly bortezomib and dexamethasone (Vd) in patients with relapsed or refractory (R/R) multiple myeloma (MM). In this study, we constructed a Markov model to assess the cost-effectiveness of SVd versus Vd in R/R MM. We calculated the incremental cost-effectiveness ratio (ICER) of each treatment strategy from a US payer perspective, using a lifetime horizon and a willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY). Use of SVd was associated with an incremental cost of $170,002 compared to Vd alone ($1,015,120 vs. $845,118, respectively), an incremental effectiveness of 0.35 QALYs (3.43 vs. 3.08 QALYs, respectively), and an ICER of $487,361/QALY. These data suggest that use of once-weekly SVd for R/R M/M is unlikely to be cost-effective compared to twice-weekly Vd.

Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients.

Most patients with diffuse large B-cell lymphoma (DLBCL) are diagnosed at age 60 years or older. Challenges to effective therapy among older individuals include unfavorable biologic features of DLBCL, geriatric vulnerabilities, suboptimal treatment selection, and toxicities of cytotoxic chemotherapy. Wider application of geriatric assessments may help identify fit older patients who benefit from standard immunochemotherapy without unnecessary dose reductions. Conversely, attenuated regimens may provide a better balance of risk and benefit for selected unfit or frail patients. Supportive care with the use of corticosteroid-based prephase, prophylactic growth factors, and early institution of supportive and palliative care can help maximize treatment tolerance. Several novel or emerging therapies have demonstrated favorable toxicity profiles, thus facilitating effective treatment for elderly patients. In the relapsed or refractory setting, patients who are not candidates for stem cell transplantation can benefit from newly approved options including polatuzumab vedotin-based combinations or tafasitamab plus lenalidomide, which may have higher efficacy and/or lower toxicity than historical chemotherapy regimens. Chimeric antigen receptor T-cell therapy has been successfully applied to older patients outside of clinical trials. In the first-line setting, emerging immunotherapy options (bispecific antibodies) and targeted therapies (anti-CD20 antibodies combined with lenalidomide and/or B-cell receptor inhibitors) may provide chemotherapy-free approaches for DLBCL. Enrolling older patients in clinical trials will be paramount to fully examine potential efficacy and toxicity of these strategies. In this review, we discuss recent advances in fitness stratification and therapy that have expanded curative options for older patients, as well as future opportunities to improve outcomes in this population. IMPLICATIONS FOR PRACTICE: Management of diffuse large B-cell lymphoma in older patients poses challenges due to aggressive disease biology and geriatric vulnerability. Although R-CHOP remains standard first-line treatment, geriatric assessment may help evaluate patients' fitness for immunochemotherapy. Corticosteroid prephase, prophylactic growth factors, and early palliative care can improve tolerance of treatment. Novel salvage options (polatuzumab vedotin-based combinations, tafasitamab plus lenalidomide) or chimeric antigen receptor T-cell therapy should be considered in the relapsed or refractory setting for patients ineligible for stem cell transplantation. Emerging immunotherapies (bispecific antibodies) and targeted therapies provide potential first-line chemotherapy-free approaches, which need to be rigorously assessed in clinical trials that involve geriatric patients.

Adjuvant chemotherapy administration and survival outcomes of lymphoma survivors with common solid tumors: a population-based study†.

Using the Surveillance, Epidemiology, and End Results database (2004-2015), we compared adjuvant chemotherapy use and survival for three common solid tumors in patients with and without history of lymphoma (DLBCL: diffuse large B cell, HL: Hodgkin lymphoma). Among patients with breast (n = 531,243), colon (n = 108,196), and lung (n = 23,179) cancers, we identified 361, 134, and 37 DLBCL survivors, and 349, 73, and 25 HL survivors, respectively. We found no significant difference between lymphoma survivors and controls in the use of adjuvant chemotherapy, except HL survivors with colon cancer, who had a lower rate. Among chemotherapy recipients, OS was significantly worse among HL survivors with all three cancers, and DLBCL survivors with breast cancer (hazard ratio [HR] 1.57-2.28). HL survivors had significantly higher mortality from cardiovascular diseases in breast and lung cancers (sub-HR, 7.96-9.64), which suggests that worse survival in this population might be due to late or cumulative toxicities of cancer-directed treatment.

Lack of effects of evidence-based, individualised counselling on medication use in insured patients with mild hypertension in China: a randomised controlled trial.

OBJECTIVE: To evaluate whether evidence-based, individualised (EBI) counselling regarding hypertension and the treatment would affect medication use in insured patients with mild hypertension in China. METHODS: We conducted a parallel-group, randomised controlled trial in two primary care centres in Shenzhen, a metropolitan city in China. Patients with mild primary hypertension, 10-year risk of cardiovascular diseases (CVDs) lower than 20% and no history of CVDs were recruited and randomly allocated to two groups. EBI plus general counselling was provided to the intervention group and general counselling alone to the control group. EBI counselling included information on the 10-year CVD risk and treatment benefit in terms of absolute risk reduction estimated for each individual and information on average side effects and costs of antihypertensive drugs. The outcomes included use of antihypertensive drugs and adherence to the treatment at 6-month follow-up, with the former being primary outcome. RESULTS: Two hundred and ten patients were recruited, with 103 and 107 allocated to the intervention and control groups, respectively. At baseline, 62.4% of the patients were taking antihypertensive drugs that were all covered by health insurance. At the end of 6-month follow-up, there was no statistically significant difference in the rate of medication use between the intervention group and the control group (65.0% vs 57.9%; OR=1.35, 95% CI: 0.77 to 2.36). The difference in adherence rate between the two groups was not statistically significant either (43.7% vs 40.2%; OR=1.15, 95% CI 0.67 to 2.00]). The results were robust in sensitivity analyses that used different cutoffs to define the two outcomes. CONCLUSIONS: The EBI counselling by health educators other than the caring physicians had little impact on treatment choices and drug-taking behaviours in insured patients with mild primary hypertension in this study. It remains unclear whether EBI counselling would make a difference in uninsured patients, especially when conducted by the caring physicians. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-14004169.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C Virus Infection in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2018 Clinical Practice Guideline.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population. Methods: The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification. Recommendation: The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.

Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.

Comparative Effectiveness and Safety of Bariatric Procedures in Medicare-Eligible Patients: A Systematic Review.

Importance: The prevalence of obesity in patients older than 65 years is increasing. A substantial number of beneficiaries covered by Medicare meet eligibility criteria for bariatric procedures. Objective: To assess the comparative effectiveness and safety of bariatric procedures in the Medicare-eligible population. Evidence Review: This systematic review was conducted according to the PRISMA guidelines. Articles were identified through searches of PubMed, Embase, CINAHL, PsycINFO, Cochrane Central Trials Registry, Cochrane Database of Systematic Reviews, and scientific information packages from manufacturers, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and US Food and Drug Administration drugs and devices portals from January 1, 2000, to June 31, 2017. Randomized and nonrandomized comparative studies that evaluated bariatric procedures in the Medicare-eligible population were eligible. Six researchers extracted data on design, interventions, outcomes, and study quality. Findings were synthesized qualitatively; a planned meta-analysis was not undertaken owing to clinical heterogeneity. Findings: A total of 11 455 citations were screened for eligibility. Of those, 16 met the eligibility criteria. Compared with no surgery or conventional weight-loss treatment, bariatric surgery results in greater weight loss. Overall mortality after 30 days is lower among bariatric patients (hazard ratio, HR, 0.50; 95% CI, 0.31-0.79, in the study with the longest follow-up of 5.9 years), although, based on 1 study, mortality within 30 days of surgery was higher than in nonsurgically treated controls (1.55% vs 0.53%; P < .001). Bariatric surgery is associated with lower risk of cardiovascular disease (HR, 0.59; 95% CI, 0.44-0.79 in the largest study comparison) and with improvements in respiratory, musculoskeletal, metabolic, and renal outcomes (increase in estimated glomerular filtration rate, 9.84; 95% CI, 8.05-11.62 mL/min/1.73m2). Compared with sleeve gastrectomy (SG) and adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGB) appears to be associated with greater weight loss (percent excess weight loss, 23.8% [95% CI, 16.2%-31.4%] at the longest follow-up of 4 years) but the 3 procedures have similar associations with most non-weight loss outcomes. Overall postoperative complications are not statistically significantly different between RYGB and SG, although major and/or serious complications are more common after RYGB. However, these associations are susceptible to at least moderate risk of confounding, selection, or measurement biases. Conclusions and Relevance: In the Medicare population, there is low to moderate strength of evidence that bariatric surgery as a weight loss treatment improves non-weight loss outcomes. Well-designed comparative studies are needed to credibly determine the treatment effects for bariatric procedures in this patient population.