Association of cancer diagnosis with disability status among older survivors of colorectal cancer: a population-based retrospective cohort study.

Background: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort. Methods: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff's method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS. Results: Among the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors. Conclusions: Our findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Deprescribing medications among patients with multiple prescribers: A socioecological model.

Deprescribing is the intentional dose reduction or discontinuation of a medication. The development of deprescribing interventions should take into consideration important organizational, interprofessional, and patient-specific barriers that can be further complicated by the presence of multiple prescribers involved in a patient's care. Patients who receive care from an increasing number of prescribers may experience disruptions in the timely transfer of relevant healthcare information, increasing the risk of exposure to drug-drug interactions and other medication-related problems. Furthermore, the fragmentation of healthcare information across health systems can contribute to the refilling of discontinued medications, reducing the effectiveness of deprescribing interventions. Thus, deprescribing interventions must carefully consider the unique characteristics of patients and their prescribers to ensure interventions are successfully implemented. In this special article, an international working group of physicians, pharmacists, nurses, epidemiologists, and researchers from the United States Deprescribing Research Network (USDeN) developed a socioecological model to understand how multiple prescribers may influence the implementation of a deprescribing intervention at the individual, interpersonal, organizational, and societal level. This manuscript also includes a description of the concept of multiple prescribers and outlines a research agenda for future investigations to consider. The information contained in this manuscript should be used as a framework for future deprescribing interventions to carefully consider how multiple prescribers can influence the successful implementation of the service and ensure the intervention is as effective as possible.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin Among Adults With Cancer and Atrial Fibrillation.

BACKGROUND: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin. METHODS: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death. RESULTS: Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92-2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70-1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59-0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69-0.94]) compared to warfarin users. CONCLUSIONS: Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

Effectiveness of COVID-19 Booster on the Risk of Hospitalization Among Medicare Beneficiaries.

OBJECTIVE: To determine the effectiveness of booster vaccinations on the risk of hospitalization with coronavirus disease 2019 (COVID-19) and how it varies by enrollee characteristics and interval from the initial vaccination to receipt of a booster. PATIENTS AND METHODS: This cohort study used 100% Medicare claims from January 1, 2020, through December 31, 2021, and matched 3,940,475 individuals who received boosters to 3,940,475 controls based on week and type of original COVID-19 vaccine and demographic and clinical characteristics. We compared the association of booster vs no booster with COVID-19 hospitalization using Cox proportional hazards regression models controlling for patient characteristics. We also determined the association of time from original vaccine to booster with COVID-19 hospitalization. RESULTS: Over a maximum of 130 days of follow-up, boosted enrollees had 8.20 (95% CI, 7.81 to 8.60) COVID-19 hospitalizations per million days vs 43.70 (95% CI, 42.79 to 44.64) for controls (81% effectiveness). Effectiveness varied by race, prior hospitalizations, and certain comorbidities, for example, leukemia/lymphoma (53% effectiveness), autoimmune disease (73%), and dementia (73%). Boosters received between 6 and 9 months after original vaccination varied between 81% and 85% effectiveness, while boosters received at 5 to 6 months (62%) or less than 5 months (58%) were less effective. CONCLUSION: Boosters are highly effective in the Medicare population. Approximately 69,225 hospitalizations would be prevented by boosters in the 15 million individuals aged 65 years or older currently not boosted in a period similar to the September 2020 through January 2021 period studied. Boosters provided the greatest benefits if they were received between 6 and 9 months following original vaccinations. However, boosters were associated with substantial decreases in COVID-19 hospitalizations in all categories of enrollees.

Use of oral anticoagulants among individuals with cancer and atrial fibrillation in the United States, 2010-2016.

BACKGROUND: Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF). METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively. RESULTS: Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA2DS2-VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.90 for score ≥6 vs. 1) or with lower HAS-BLED scores (HR 1.96, 95% CI 1.67-2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA2DS2-VASc scores (odds ratio [OR] 0.53, 95% CI 0.33-0.84 for score ≥6 vs. 1). CONCLUSIONS: Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

Real-World Effectiveness of Remdesivir in Adults Hospitalized With Coronavirus Disease 2019 (COVID-19): A Retrospective, Multicenter Comparative Effectiveness Study.

BACKGROUND: There is an urgent need to understand the real-world effectiveness of remdesivir in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This was a retrospective comparative effectiveness study. Individuals hospitalized in a large private healthcare network in the United States from 23 February 2020 through 11 February 2021 with a positive test for SARS-CoV-2 and ICD-10 diagnosis codes consistent with symptomatic coronavirus disease 2019 (COVID-19) were included. Remdesivir recipients were matched to controls using time-dependent propensity scores. The primary outcome was time to improvement with a secondary outcome of time to death. RESULTS: Of 96 859 COVID-19 patients, 42 473 (43.9%) received at least 1 remdesivir dose. The median age of remdesivir recipients was 65 years, 23 701 (55.8%) were male, and 22 819 (53.7%) were non-White. Matches were found for 18 328 patients (43.2%). Remdesivir recipients were significantly more likely to achieve clinical improvement by 28 days (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI], 1.16-1.22). Remdesivir patients on no oxygen (aHR 1.30, 95% CI, 1.22-1.38) or low-flow oxygen (aHR 1.23, 95% CI, 1.19-1.27) were significantly more likely to achieve clinical improvement by 28 days. There was no significant impact on the likelihood of mortality overall (aHR 1.02, 95% CI, .97-1.08). Remdesivir recipients on low-flow oxygen were significantly less likely to die than controls (aHR 0.85, 95% CI, .77-.92; 28-day mortality 8.4% [865 deaths] for remdesivir patients, 12.5% [1334 deaths] for controls). CONCLUSIONS: These results support the use of remdesivir for hospitalized COVID-19 patients on no or low-flow oxygen. Routine initiation of remdesivir in more severely ill patients is unlikely to be beneficial.

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

BACKGROUND: Many individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals. METHODS: We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology. FINDINGS: Among 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions. INTERPRETATION: Among this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined. FUNDING: None.

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.

Comparing Costs of Radical Versus Partial Cystectomy for Patients Diagnosed With Localized Muscle-Invasive Bladder Cancer: Understanding the Value of Surgical Care.

OBJECTIVE: To compare costs associated with radical versus partial cystectomy. Prior studies noted substantial costs associated with radical cystectomy, however, they lack surgical comparison to partial cystectomy. METHODS: A total of 2305 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 to December 31, 2011 were included. Total Medicare costs within 1 year of diagnosis following radical versus partial cystectomy were compared using inverse probability of treatment-weighted propensity score models. Cox regression and competing risks analysis were used to determine overall and cancer-specific survival, respectively. RESULTS: Median total costs were not significantly different for radical than partial cystectomy in 90 days ($73,907 vs $65,721; median difference $16,796, 95% CI $10,038-$23,558), 180 days ($113,288 vs $82,840; median difference $36,369, 95% CI $25,744-$47,392), and 365 days ($143,831 vs $107,359; median difference $34,628, 95% CI $17,819-$53,558), respectively. Hospitalization, surgery, pathology/laboratory, pharmacy, and skilled nursing facility costs contributed largely to costs associated with either treatment. Patients who underwent partial cystectomy had similar overall survival but had worse cancer-specific survival (Hazard Ratio 1.45, 95% Confidence Interval, 1.34-1.58, P < .001) than patients who underwent radical cystectomy. CONCLUSION: While treatments for bladder cancer are associated with substantial costs, we showed radical cystectomy had comparable total costs when compared to partial cystectomy among patients with muscle-invasive bladder cancer. However, partial cystectomy resulted in worse cancer-specific survival further supporting radical cystectomy as a high-value surgical procedure for muscle-invasive bladder cancer.

Proximity to Oil Refineries and Risk of Cancer: A Population-Based Analysis.

BACKGROUND: The association between proximity to oil refineries and cancer rate is largely unknown. We sought to compare the rate of cancer (bladder, breast, colon, lung, lymphoma, and prostate) according to proximity to an oil refinery in Texas. METHODS: A total of 6 302 265 persons aged 20 years or older resided within 30 miles of an oil refinery from 2010 to 2014. We used multilevel zero-inflated Poisson regression models to examine the association between proximity to an oil refinery and cancer rate. RESULTS: We observed that proximity to an oil refinery was associated with a statistically significantly increased risk of incident cancer diagnosis across all cancer types. For example, persons residing within 0-10 (risk ratio [RR] = 1.13, 95% confidence interval [CI] = 1.07 to 1.19) and 11-20 (RR = 1.05, 95% CI = 1.00 to 1.11) miles were statistically significantly more likely to be diagnosed with lymphoma than individuals who lived within 21-30 miles of an oil refinery. We also observed differences in stage of cancer at diagnosis according to proximity to an oil refinery. Moreover, persons residing within 0-10 miles were more likely to be diagnosed with distant metastasis and/or systemic disease than people residing 21-30 miles from an oil refinery. The greatest risk of distant disease was observed in patients diagnosed with bladder cancer living within 0-10 vs 21-30 miles (RR = 1.30, 95% CI = 1.02 to 1.65), respectively. CONCLUSIONS: Proximity to an oil refinery was associated with an increased risk of multiple cancer types. We also observed statistically significantly increased risk of regional and distant/metastatic disease according to proximity to an oil refinery.

Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

Impact of Alzheimer's disease and related dementia diagnosis following treatment for bladder cancer.

OBJECTIVES: Our objective was to assess the incidence of Alzheimer's Disease and related dementia diagnosis following treatment for muscle-invasive bladder cancer and impact on survival outcomes. MATERIALS AND METHODS: A total of 4814 patients diagnosed with clinical stage T2-T4a, N0, M0 bladder cancer between January 1, 2002 to December 31, 2011 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were identified. Alzheimer's disease and related dementia diagnosis was identified using International Statistical Classification of Disease-Ninth Edition outpatient and inpatient codes. Incidence of dementia following treatment were calculated and reported as dementia cases per 10,000 person-years. Cox proportional hazards models were used to assess the impact of dementia on survival outcomes. RESULTS: Of the 4814 patients, 2403 (49.9%) underwent radical cystectomy (RC) and 2411 (50.1%) underwent radiotherapy (RTX) and/or chemotherapy (CTX). Overall, 837 (17.4%) patients developed Alzheimer's disease and related dementia following bladder cancer treatment. There was no significant difference in the incidence of Alzheimer's disease and related dementia following either treatment. Patients diagnosed with Alzheimer's disease and related dementia had worse overall (Hazard Ratio (HR), 2.64; 95% Confidence Interval (CI), 2.41-2.89) and cancer-specific (HR, 2.45; 95% CI, 2.18-2.76) survival than those without a dementia diagnosis following treatment. CONCLUSION: While we observed no difference in new-onset Alzheimer's disease and related dementia diagnosis following RC or RTX and/or CTX, patients with a Alzheimer's and related dementia diagnosis was associated with worse overall and cancer-specific survival. These findings have important implications for screening and the development of targeted interventions for improving outcomes in older adults following complex cancer treatments, as observed in this bladder cancer population.

Pediatric firearm injuries: Racial disparities and predictors of healthcare outcomes.

BACKGROUND/PURPOSE: The U.S. has an alarming rate of firearm injuries. Racial disparities among victims and predictors of outcomes are not well established. Our objective was to assess costs, length of stay (LOS), and inpatient mortality among nonfatal and fatal pediatric firearm injuries that required hospitalization. METHODS: Pediatric (≤18 years of age) hospitalizations with a firearm injury discharge diagnosis were identified from the national Kids' Inpatient Databases (KID) for 2006 through 2012. Firearm injury intent, weapon type, and hospitalization rates by racial groups were examined. Inpatient mortality, costs, and length of stay were examined using regression models. RESULTS: Of 15,211 hospitalizations, the majority of injuries were due to assault (60%) and the intentions of firearm injury differed by race (p < 0.001). The median cost per hospitalization was $10,159 (interquartile range: $5071 to $20,565), totaling more than a quarter of a billion dollars. On regression analysis, Black (OR: 0.41; CI: 0.30-0.55) and Hispanic (OR: 0.47; CI: 0.34-0.66) patients were less likely to die than White patients. CONCLUSION: Pediatric firearm injury circumstances and survival vary by race with Whites being more likely to experience unintentional injury and suicide, while Blacks and Hispanics are more likely to experience inflicted injury. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Clinical Research Study.

Impact of Diagnosing Urologists and Hospitals on the Use of Radical Cystectomy.

BACKGROUND: One out of five patients with muscle-invasive bladder cancer undergo radical cystectomy-a guideline-recommended treatment. Previous studies have primarily evaluated patient characteristics associated with the use of radical cystectomy, ignoring potential nesting of data. OBJECTIVE: To determine the impact of patient, diagnosing urologist, and hospital characteristics on the variation in the use of radical cystectomy. DESIGN SETTING AND PARTICIPANTS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Registry (SEER)-Medicare linked database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 7097 muscle-invasive bladder cancer patients and 4601 diagnosing urologists affiliated to 822 hospitals from January 1, 2002 to December 31, 2012 were analyzed. Multilevel logistic regression analyses were used to determine variation and factors associated with the use of radical cystectomy. RESULTS AND LIMITATIONS: Of the 7097 patients, only 27% underwent radical cystectomy. The intraclass correlation coefficient for variation in the use of radical cystectomy attributed to the hospital level was 4.3%. Higher radical cystectomy volume by diagnosing urologists (more than five vs zero to one surgery: odds ratio [OR], 1.27; 95% confidence interval [CI], 1.00-1.62) and hospitals (more than five vs zero to four surgeries: OR,1.48; 95% CI, 1.14-1.93) was associated with increased use of radical cystectomy. Patients diagnosed by female rather than male urologists were more likely to undergo radical cystectomy (OR, 1.32; 95% CI, 1.07-1.62). CONCLUSIONS: We found that 4.3% variation in the use of radical cystectomy was attributed to the hospital level, leaving 95.7% variation in use unexplained. We identified significantly increased use among higher-volume and female diagnosing urologists. These findings support further investigation into measures beyond hospital volume, which largely impact the utilization of radical cystectomy. PATIENT SUMMARY: In this large population-based study, we found that 4.3% of variation in the use of radical cystectomy was attributed to the hospital level, leaving 95.7% variation in use unexplained. Higher radical cystectomy volume of diagnosing urologists and female urologists were independently associated with increased use of radical cystectomy. These findings support further investigation into measures beyond hospital volume, which largely impact the utilization of radical cystectomy.

Development of comorbidity score for patients undergoing major surgery.

OBJECTIVE: To develop and validate a claims-based comorbidity score for patients undergoing major surgery, and compare its performance with established comorbidity scores. DATA SOURCE: Five percent Medicare data from 2007 to 2014. STUDY DESIGN: Retrospective cohort study of patients aged ≥65 years undergoing six major operations (N = 99 250). DATA COLLECTION: One-year mortality was the primary outcome. Secondary outcomes were hospital mortality, 30-day mortality, 30-day readmission, and length of stay. The comorbidity score was developed in the derivation cohort (70 percent sample) using logistic regression model. The comorbidity score was calibrated and validated in the validation cohort (30 percent sample), and compared against the Charlson, Elixhauser, and Centers for Medicare and Medicaid Services Hierarchical Condition Categories (CMS-HCC) comorbidity scores using c-statistic, net reclassification improvement, and integrated discrimination improvement. PRINCIPAL FINDINGS: In the validation cohort, the surgery-specific comorbidity score was well calibrated and performed better than the Charlson, Elixhauser, and CMS-HCC comorbidity scores for all outcomes; the performance was comparable to the CMS-HCC for 30-day readmission. For example, the surgery-specific comorbidity score (c-statistic = 0.792; 95% CI, 0.785-0.799) had greater discrimination than the Charlson (c-statistic = 0.747; 95% CI, 0.739-0.755), Elixhauser (c-statistic = 0.747; 95% CI, 0.735-0.755), or CMS-HCC (c-statistic = 0.755; 95% CI, 0.747-0.763) scores in predicting 1-year mortality. The net reclassification improvement and integrated discrimination improvement were greater for surgery-specific comorbidity score compared to the Charlson, Elixhauser, and CMS-HCC scores. CONCLUSIONS: Compared to commonly used comorbidity measures, a surgery-specific comorbidity score better predicted outcomes in the surgical population.

Discerning Patterns and Quality of Neoadjuvant Chemotherapy Use Among Patients with Muscle-invasive Bladder Cancer.

BACKGROUND: Neoadjuvant chemotherapy is underutilized in bladder cancer patients who undergo radical cystectomy. However, the quality of regimens used in this setting remains largely unknown. OBJECTIVE: To determine utilization treatment patterns and survival outcomes according to regimens administered. DESIGN, SETTING, AND PATIENTS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify patients diagnosed with clinical stage TII-IV bladder cancer from January 1, 2001 to December 31, 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Temporal trends were assessed using the Cochran-Armitage test. Multivariable logistic regression models were used to identify predictors for neoadjuvant chemotherapy use. Cox proportional hazards models were used to compare overall survival according to regimens administered. RESULTS AND LIMITATIONS: Of 2738 patients treated with radical cystectomy, 344 (12.6%) received neoadjuvant chemotherapy. The agents most commonly used were gemcitabine (72.3%), cisplatin (55.2%), and carboplatin (31.1%). The regimens most commonly used were gemcitabine-cisplatin (45.3%), gemcitabine-carboplatin (24.1%), and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC; 6.7%). Use of neoadjuvant chemotherapy more than tripled during the study period, from 5.7% in 2001 to 17.3% in 2011 (p<0.001). The quality of the regimen administered impacted survival outcomes, as M-VAC use was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer (hazard ratio 0.24, 95% confidence interval 0.07-0.86; p=0.030]. Limitations include the limited ability of retrospective analysis to control for selection bias. CONCLUSIONS: Neoadjuvant chemotherapy was underused, and the quality of neoadjuvant chemotherapy regimens administered for bladder cancer was inconsistent with guideline recommendations. These findings are important when interpreting population-based data on the use of chemotherapy and extrapolating survival outcomes. PATIENT SUMMARY: In a large population-based study, 12.6% of patients undergoing radical cystectomy for bladder cancer received neoadjuvant chemotherapy, half of whom received guideline-recommended regimens. The quality of the regimen impacted survival outcomes, as use of cisplatin-based chemotherapy was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer. However, <1% of radical cystectomy patients received this regimen.

Comparison of Costs of Radical Cystectomy vs Trimodal Therapy for Patients With Localized Muscle-Invasive Bladder Cancer.

Importance: Earlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days. Objective: To compare the 1-year costs associated with trimodal therapy vs radical cystectomy, accounting for survival and intensity effects on total costs. Design, Setting, and Participants: This population-based cohort study used the US Surveillance, Epidemiology, and End Results-Medicare database and included 2963 patients aged 66 to 85 years who had received a diagnosis of clinical stage T2 to T4a muscle-invasive bladder cancer from January 1, 2002, through December 31, 2011. The data analysis was performed from March 5, 2018, through December 4, 2018. Main Outcomes and Measures: Total Medicare costs within 1 year of diagnosis following radical cystectomy vs trimodal therapy were compared using inverse probability of treatment-weighted propensity score models that included a 2-part estimator to account for intrinsic selection bias. Results: Of 2963 participants, 1030 (34.8%) were women, 2591 (87.4%) were white, 129 (4.4%) were African American, and 98 (3.3%) were Hispanic. Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83 754 vs $68 692; median difference, $11 805; 95% CI, $7745-$15 864), 180 days ($187 162 vs $109 078; median difference, $62 370; 95% CI, $55 581-$69 160), and 365 days ($289 142 vs $148 757; median difference, $109 027; 95% CI, $98 692-$119 363), respectively. Outpatient care, radiology, medication expenses, and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On inverse probability of treatment-weighted adjusted analyses, patients undergoing trimodal therapy had $136 935 (95% CI, $122 131-$152 115) higher mean costs compared with radical cystectomy 1 year after diagnosis. Conclusions and Relevance: Compared with radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. The differences in costs were largely attributed to medication and radiology expenses associated with trimodal therapy. Extrapolating cost figures resulted in a nationwide excess spending of $468 million for trimodal therapy compared with radical cystectomy for patients who received a diagnosis of bladder cancer in 2017.

Cost of benign versus oncologic colon resection among fee-for-service Medicare enrollees.

BACKGROUND AND OBJECTIVES: Reimbursement for colonic pathology by the Centers for Medicare and Medicaid Services (CMS) are grouped in the Medicare Severity-Diagnosis Related Groups (MS-DRG). With limited available data, we sought to compare the relative impact of malignant vs benign colonic pathology on reimbursement under the MS-DRG system. METHODS: We used 5% national Medicare data from 2011 to 2014. Patients were classified as having benign disease or malignancy. Descriptive statistics and multivariate regression analysis were used to evaluate the surgical approach and health resource utilization. RESULTS: Of 10 928 patients, most were Non-Hispanic White women. The majority underwent open colectomy in both cohorts (P < .001). Colectomy for benign disease was associated with higher total charges (P < .001) and a longer length of stay (P = .0002). Despite higher charges, payments were not significantly different between the cohorts (P = .434). Both inpatient mortality and discharge to a rehab facility were higher in the oncologic group (P < .001). CONCLUSION: Payment methodology for colectomy under the CMS MS-DRG system does not appear to accurately reflect the episode cost of care. The data suggest that inpatient costs are not fully compensated. A transition to value-based payments with expanded episode duration will require a better understanding of unique costs before adoption.

Diagnosis-Related Group in Colon Surgery: Identifying Areas of Improvement to Drive High-Value Care.

Diagnosis-related group (DRG) migration is defined as the reassignment of colectomy patients from DRG 331 to 330 based exclusively on postoperative complications. Strategic and comparative application of this metric has the potential to demonstrate baseline and excessive rates of complications related directly to patient care differences across institutions. The aim of this study was to report the variability of DRG migration across United States hospitals and its impact on overall cost and length of stay (LOS). This study investigated the variability of DRG migration rates across United States hospitals polling 5 per cent of the national Medicare data. The study endpoints were total cost, LOS, and DRG migration rate. Hospitals were classified into tertiles for low (0.1-16.6%), moderate (16.7-23.0%), and high (23.1-83.3%) DRG migration rates. The study included 5120 patients from 615 hospitals. DRG migration rates for hospitals ranged from 0.1 per cent to 83.3 per cent, with 157 in the low, 183 in the moderate, and 364 in the high tertile. DRG migration resulted in a progressively increased LOS and hospital costs from the lowest to highest tertile. Several diagnoses were identified which are suggestive of failure to integrate evidence-based processes of care across the tertiles. The data confirm a wide variation in DRG migration rates from DRG 331 to 330 based only on postoperative complications. These ranges allow for the potential definition of both best practice, and opportunities for quality improvement with respect to postoperative complications, identification of hospital outliers, and the economics of care as part of a value-based care program.

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer.

BACKGROUND: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. METHODS: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. RESULTS: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. CONCLUSIONS: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.