Identifying Population-Level and Within-Hospital Disparities in Surgical Care.

INTRODUCTION: The lack of consensus on equity measurement and its incorporation into quality-assessment programs at the hospital and system levels may be a barrier to addressing disparities in surgical care. This study aimed to identify population-level and within-hospital differences in the quality of surgical care provision. METHODS: The analysis included 657 National Surgical Quality Improvement Program participating hospitals with over 4 million patients (2014-2018). Multi-level random slope, random intercept modeling was used to examine for population-level and in-hospital disparities. Disparities in surgical care by Area Deprivation Index (ADI), race, and ethnicity were analyzed for five measures: all-case inpatient mortality, all-case urgent readmission, all-case postoperative surgical site infection, colectomy mortality, and spine surgery complications. RESULTS: Population-level disparities were identified across all measures by ADI, two measures for Black race (all-case readmissions and spine surgery complications), and none for Hispanic ethnicity. Disparities remained significant in the adjusted models. Prior to risk-adjustment, in all measures examined, within-hospital disparities were detected in: 25.8-99.8% of hospitals for ADI, 0-6.1% of hospitals for Black race, and 0-0.8% of hospitals for Hispanic ethnicity. Following risk-adjustment, in all measures examined, fewer than 1.1% of hospitals demonstrated disparities by ADI, race, or ethnicity. CONCLUSIONS: Following risk adjustment, very few hospitals demonstrated significant disparities in care. Disparities were more frequently detected by ADI than by race and ethnicity. The lack of substantial in-hospital disparities may be due to the use of postoperative metrics, small sample sizes, the risk adjustment methodology, and healthcare segregation. Further work should examine surgical access and healthcare segregation.

Predicting Peak Productivity in Urologic Medicare Practice via Work-Relative Value Units.

OBJECTIVE: To explore factors associated with productivity in urologic practice. Work-relative value units (wRVUs), the basis for Center for Medicare & Medicaid Services (CMS) and private payer reimbursements, commonly serve to estimate physician productivity. Limited data describes which practice factors predict increased wRVU productivity. METHODS: The 2017 and 2018 CMS databases were retrospectively queried for urologic Medicare provider demographics and procedural/service details. Medical school graduation year was used to estimate years in practice and generation (Millennial, Gen X, Baby Boomer, or Post-War). Treated patients' demographics were obtained. Adjusted and unadjusted linear mixed models were performed to predict wRVU production. RESULTS: Included were 6773 Medicare-participating urologists across the United States. Millennials produced 1115 wRVUs per year, while Gen X and Baby Boomers produced significantly more (1997 and 2104, respectively, P <.01). Post-War urologists produced numerically more (1287, P = .88). In adjusted analyses, predictors of Medicare wRVU productivity included female and pelvic medicine and reconstructive surgery (exponentiated beta estimate (ß) 1.46, 95% CI 1.32-1.60), men's health (ß 1.22, 95% CI 1.13-1.32), and oncologic subspecialization (ß 1.08, 95% CI 1.02-1.14), female gender (ß 0.87, 95% CI 0.82-0.92), wRVUs generated from inpatient procedures (ß 1.08, 95% CI 1.06-1.09) and office visits (ß 0.88, 95% CI 0.87-0.89), and the level of education (ß 1.10, 95% CI 1.07-1.14) and percent impoverished patients (ß 0.85, 95% CI 0.83-0.88) in provider's practice zip code. CONCLUSION: Urologic experience, specialization, demographics, practice patterns, and patient demographics are significantly associated with wRVU productivity in Medicare settings. Further work should incorporate quality metrics into wRVUs and ensure patient demographics do not affect reimbursement.

Impact of COVID-19 pandemic on ambulatory urologic oncology surgeries.

INTRODUCTION: Robot-assisted laparoscopic prostatectomy (RALP) and transurethral resection of bladder tumor (TURBT) are two common surgeries for prostate and bladder cancer. We aim to assess the trends in the site of care for RALP and TURBT before and after the COVID outbreak. MATERIALS AND METHODS: We identified adults who underwent RALP and TURBT within the California Healthcare Cost and Utilization Project State Inpatient Database and the State Ambulatory Surgery Database between 2018 and 2020. Multivariable analysis and spline analysis with a knot at COVID outbreak were performed to investigate the time trend and factors associated with ambulatory RALP and TURBT. RESULTS: Among 17,386 RALPs, 6,774 (39.0%) were ambulatory. Among 25,070 TURBTs, 21,573 (86.0%) were ambulatory. Pre-COVID, 33.5% of RALP and 85.3% and TURBT were ambulatory, which increased to 53.8% and 88.0% post-COVID (both p < 0.001). In multivariable model, RALP and TURBT performed after outbreak in March 2020 were more likely ambulatory (OR 2.31, p < 0.0001; OR 1.25, p < 0.0001). There was an overall increasing trend in use of ambulatory RALP both pre- and post-COVID, with no significant change of trend at the time of outbreak (p = 0.642). TURBT exhibited an increased shift towards ambulatory sites post-COVID (p < 0.0001). CONCLUSIONS: We found a shift towards ambulatory RALP and TURBT following COVID outbreak. There was a large increase in ambulatory RALP post-COVID, but the trend of change was not significantly different pre- and post-COVID - possibly due to a pre-existing trend towards ambulatory RALP which predated the pandemic.

In-hospital Outcomes for COVID-19 Patients in the Military Health System: Comparison of Military and Civilian Facility Treatment.

INTRODUCTION: Beneficiaries of TRICARE, an insurance program of the military health system, can choose to receive care within the private sector (fee-for-service) or direct (budget-based facilities with salaried providers) care setting. Previous studies in several specialties have shown that there are disparities in both resource utilization and outcomes between the two settings. In this study, we sought to determine differences in outcomes between coronavirus disease 2019 (COVID-19) patients treated in the private sector versus direct care. MATERIALS AND METHODS: Using TRICARE claims data, we identified patients admitted to the hospital for COVID-19 between March and September 2020. Cases were classified, according to the facility where they were admitted for treatment, as private sector or direct care. We abstracted patient sociodemographic characteristics, comorbid conditions, and outcomes including in-hospital mortality, intensive care unit (ICU) admission, ventilator use, in-hospital complications, and 30-day readmission. We used multivariable regression models, adjusted for covariates, to determine the association between health care settings and outcomes. RESULTS: A total of 3,177 patients were included. Of these, 2,147 (68%) and 1,030 (32%) received care in the private sector and direct care settings, respectively. The average age of the study cohort was 52 years (SD = 21), and 84% had at least one medical comorbidity. In adjusted analyses, we found significant differences in the rates of ICU admission, with patients treated in private sector care having lower odds of being admitted to the ICU (odds ratio, 0.64; 95% CI, 0.53-0.76). There were no significant differences in the rates of in-hospital mortality, ventilator use, in-hospital complications, and 30-day readmissions. CONCLUSION: With the exception of ICU admission rates, which are higher in the direct care setting, we encountered comparable hospital-based outcomes for patients treated for COVID-19 within the military health system, whether care was received under private sector or direct care.

Changes in Elective and Urgent Surgery Among TRICARE Beneficiaries During the COVID-19 Pandemic.

BACKGROUND: COVID-19 is known to have altered the capacity to perform surgical procedures in numerous health care settings. The impact of this change within the direct and private-sector settings of the Military Health System has not been effectively explored, particularly as it pertains to disparities in surgical access and shifting of services between sectors. We sought to characterize how the COVID-19 pandemic influenced access to care for surgical procedures within the direct and private-sector settings of the Military Health System. METHODS: We retrospectively evaluated claims for patients receiving urgent and elective surgical procedures in March-September 2017, 2019, and 2020. The pre-COVID period consisted of 2017 and 2019 and was compared to 2020. We adjusted for sociodemographic characteristics, medical comorbidities, and region of care using multivariable Poisson regression. Subanalyses considered the impact of race and sponsor rank as a proxy for socioeconomic status. RESULTS: During the period of the COVID-19 pandemic, there was no significant difference in the adjusted rate of urgent surgical procedures in direct (risk ratio, 1.00; 95% CI, 0.97-1.03) or private-sector (risk ratio, 0.99; 95% CI, 0.97-1.02) care. This was also true for elective surgeries in both settings. No significant disparities were identified in any of the racial subgroups or proxies for socioeconomic status we considered in direct or private-sector care. CONCLUSIONS: We found a similar performance of elective and urgent surgeries in both the private sector and direct care during the first 6 months of the COVID-19 pandemic. Importantly, no racial disparities were identified in either care setting.

Association of Outpatient Oral Macrolide Use With Sensorineural Hearing Loss in Children, Adolescents, and Young Adults.

Importance: Prior publications have reported the sporadic development of sensorineural hearing loss (SNHL) after intravenous or high-dose macrolide therapy for adults with comorbid conditions, but investigations of the auditory effect of oral outpatient dosing for children, adolescents, and young adults have been limited. Objective: To determine whether broad-based outpatient use of oral macrolide therapy is associated with increased risk of pediatric SNHL through nationally representative analyses. Design, Setting, and Participants: A retrospective case-control study of 875 matched pairs of children, adolescents, and young adults was performed, matching on age, sex, and the time elapsed since prescription date. All eligible pediatric patients were included, with matched control participants from the TRICARE US military health insurance system who were evaluated between October 1, 2009, and September 30, 2014. Exposures: Oral outpatient macrolide treatment compared with penicillin use among pediatric patients. Main Outcomes and Measures: The clinical outcome of interest was SNHL in children, adolescents, and young adults. Multivariable conditional logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders. Four time frames between exposure and diagnosis were additionally assessed. Results: There were 875 eligible matched pairs of children, adolescents, and young adults included. The mean (SD) age of the participants was 5.7 (4.9) years; 1082 participants were male (62%), 58 were Asian (3%), 254 were Black (15%), 1152 were White (66%), and 286 were of Native American and other (no further breakdown was available in the TRICARE database) race and ethnicity (16%). In multivariable analysis, participants who had SNHL had increased odds of having received a macrolide prescription compared with a penicillin prescription when all time frames from exposure were included (adjusted odds ratio, 1.31; 95% CI, 1.05-1.64). There were significantly higher odds of macrolide exposure than penicillin exposure when diagnosis and testing occurred more than 180 days after antibiotic exposure (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60). Conclusions and Relevance: In this case-control study of a nationally representative patient population, findings suggest that children, adolescents, and young adults with SNHL had increased odds of outpatient oral macrolide use compared with penicillin use, particularly when having received a diagnosis more than 180 days after exposure. Further study of the association of macrolides with SNHL in children, adolescents, and young adults is warranted.

Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance.

Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive tumors phenocopied resistance. MAMs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ER-mitochondria-associated membranes as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.

Health-Care Utilization and Expenditures Associated with Long-Term Treatment After Combat and Non-Combat-Related Orthopaedic Trauma.

BACKGROUND: The long-term consequences of musculoskeletal trauma can be profound and can extend beyond the post-injury period. The surveillance of long-term expenditures among individuals who sustain orthopaedic trauma has been limited in prior work. We sought to compare the health-care requirements of active-duty individuals who sustained orthopaedic injuries in combat and non-combat (United States) environments using TRICARE claims data. METHODS: We identified service members who sustained combat or non-combat musculoskeletal injuries between 2007 and 2011. Combat-injured personnel were matched to those in the non-combat-injured cohort on a 1:1 basis using biologic sex, year of the injury, Injury Severity Score (ISS), and age at the index hospitalization. Health-care utilization was surveyed through 2018. The total health-care expenditures over the post-injury period were the primary outcome. These were assessed as a total overall cost and then as costs adjusted per year of follow-up. We used negative binomial regression to identify the independent association between risk factors and health-care expenditures. RESULTS: We identified 2,119 individuals who sustained combat-related orthopaedic trauma and 2,119 individuals who sustained non-combat injuries. The most common mechanism of injury within the combat-injured cohort was blast-related trauma (59%), and 418 individuals (20%) sustained an amputation. The total costs were $156,886 for the combat-injured group compared with $55,873 for the non-combat-injured group (p < 0.001). Combat-related orthopaedic injuries were associated with a 43% increase in health-care expenditures (incidence rate ratio, 1.43 [95% confidence interval, 1.19 to 1.73]). Severe ISS at presentation, ≥2 comorbidities, and amputations were also significantly associated with health-care utilization, as was junior enlisted rank, our proxy for socioeconomic status. CONCLUSIONS: Health-care requirements and associated costs are substantial among service members sustaining combat and non-combat orthopaedic trauma. Given the sociodemographic characteristics of our cohort, we believe that these results are translatable to civilians who sustain similar types of musculoskeletal trauma.

Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response.

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline - an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their "dispositional endotype" at pre-vaccination baseline, could dictate response to vaccination.