Did the Comprehensive Care for Joint Replacement Bundled Payment Program Impact Sex Disparities in Total Hip and Knee Arthroplasties?

BACKGROUND: Sex disparities have been noted across various aspects of total hip/knee arthroplasty (THA/TKA). Given incentives to standardize care, bundled payment initiatives including the Comprehensive Care for Joint Replacement (CJR) program may reduce disparities. This study aimed to assess the CJR program's impact on sex disparities in THA/TKA care and outcomes. METHODS: This retrospective cohort study included 259,673 THAs (61.7% women) and 506,311 TKAs (64.0% women) from a large national database (2013 to 2017). Sex disparities were assessed for care and outcomes related to the period (1) before surgery, (2) during hospitalization for THA/TKA, and (3) after discharge. Disparities were reported as women:men ratios. Difference-in-differences analyses estimated the impact of the CJR program on pre-existing sex disparities. RESULTS: For both THA and TKA, women were less likely than men to present with a Charlson-Deyo comorbidity index >0 (women:men ratio 0.88 to 0.92), but were more likely to require blood transfusions (women:men ratio 1.48 to 1.79) and be discharged to institutional postacute care (women:men ratio 1.50 to 1.66). Difference-in-differences models demonstrated that the CJR bundled payment program reduced sex disparities in institutional postacute care discharges (THA: -2.28%; 95% confidence interval [CI] -4.20 to -0.35%, P = .02; TKA: -2.07%; 95% CI -3.93 to -0.20%; P = .03) and THA 90-day readmissions (-1.00%, 95% CI -1.88 to -0.13%, P = .02), indicating a differential impact of CJR in women versus men for some outcomes. CONCLUSIONS: While sex disparities in THA/TKA persist, the CJR program demonstrates potential to impact such differences. Future research should focus on how potential mechanisms could be leveraged to reduce disparities.

Prostate cancer in transgender women: considerations for screening, diagnosis and management.

Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically masculine body of androgens and simultaneously provide oestrogen therapy for feminisation. In gender-confirming surgery (GCS) for transgender females, the prostate is usually not removed. Due to limitations of existing cohort studies, the true incidence of prostate cancer in transgender females is unknown but is thought to be less than the incidence among cis-gender males. It is unclear how prostate cancer develops in androgen-deprived conditions in these patients. Six out of eleven case reports in the literature presented with metastatic disease. It is thought that androgen receptor-mediated mechanisms or tumour-promoting effects of oestrogen may be responsible. Due to the low incidence of prostate cancer identified in transgender women, there is little evidence to drive specific screening recommendations in this patient subpopulation. The treatment of early and locally advanced prostate cancer in these patients warrants an individualised thoughtful approach with input from patients' reconstructive surgeons. Both surgical and radiation treatment for prostate cancer in these patients can profoundly impact the patient's quality of life. In this review, we discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in our knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients.

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer.

Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.

Changes in Epidemiology of Acetaminophen Overdoses in an Urban County Hospital After 20 Years.

INTRODUCTION: Acetaminophen (APAP) toxicity is the main cause of acute liver failure in the United States. A prior series (1992-1995) identified 71 hospitalized adults with APAP toxicity through the International Statistical Classification of Disease and Related Health Problems, 9th revision (ICD-9) code at Parkland Hospital, Dallas, TX. METHODS: We used a laboratory database search of serum APAP levels from 2011 to 2015 to identify patients with APAP toxicity in the same hospital. RESULTS: We identified 140 patients hospitalized for APAP toxicity from 27,143 APAP levels obtained; 35 required Intensive Care Unit (ICU) admission, and there were no deaths. APAP toxicity/100,000 admissions was similar between eras. DISCUSSION: APAP toxicity continues unabated after 20 years but with improved overall outcomes.

Association between chronic kidney disease and COVID-19-related mortality in New York.

PURPOSE: To evaluate mortality risk of CKD patients infected with COVID-19, and assess shared characteristics associated with health disparities in CKD outcome. METHODS: We extracted the data from a case series of 7624 patients presented at Mount Sinai Health System, in New York for testing between 3/28/2020 and 4/16/2020. De-identified patient data set is being produced by the Scientific Computing department and made available to the Mount Sinai research community at the following website: https://msdw.mountsinai.org/ . RESULTS: Of 7624 COVID-19 patients, 7.8% (n = 597) had CKD on hospital admission, and 11.2% (n = 856) died of COVID-19 infection. CKD patients were older, more likely to have diabetes, hypertension, and chronic obstructive pulmonary disease (COPD), were current or former smokers, had a longer time to discharge, and had worse survival compared to non-CKD patients (p < 0.05). COVID-19 mortality rate was significantly higher in CKD patients (23.1% vs 10.2%) with a 1.51 greater odds of dying (95% CI: 1.19-1.90). Controlling for demographic, behavioral, and clinical covariates, the logistic regression analysis showed significant and consistent effects of CKD, older age, male gender, and hypertension with mortality (p < 0.05). CONCLUSION: CKD was a significant independent predictor of COVID-19 mortality, along with older age, male gender, and hypertension. Future research will investigate the effects of COVID-19 on long-term renal function.

Racial Differences in Care and Outcomes After Total Hip and Knee Arthroplasties: Did the Comprehensive Care for Joint Replacement Program Make a Difference?

BACKGROUND: There is a paucity of literature on racial differences across a full total joint arthroplasty (TJA) "episode of care" and beyond. Given various incentives, the Comprehensive Care for Joint Replacement (CJR) program in the U.S. may have impacted preexisting racial differences across this care continuum. The purposes of the present study were (1) to assess trends in racial differences in care/outcome characteristics before, during, and after TJA surgery and (2) to assess if the CJR program coincided with reductions in these racial differences. METHODS: This retrospective cohort study includes data on 1,483,221 TJAs (based on Medicare claims data, 2013 to 2018). Racial differences between Black and White patients were assessed for (1) preoperative characteristics (Deyo-Charlson comorbidity index, patient sex, and age), (2) characteristics during hospitalization (length of stay, blood transfusions, and combined complications), and (3) postoperative characteristics (90 and 180-day readmission rates and institutional post-acute care). Additionally, Medicare payments for each period were assessed. Racial differences (Black versus White patients) were expressed in terms of odds ratios (ORs) and 95% confidence intervals (CIs) per year. A "difference-in-differences" analysis (comparing before and after CJR implementation, with non-CJR hospitals being used as controls) estimated the association of the CJR program with changes in racial differences. RESULTS: In both 2013 and 2018, Black patients (n = 74,390; 5.0%) were more likely than White patients to have a higher Deyo-Charlson comorbidity index (score of >0) (OR = 1.32 [95% CI = 1.28 to 1.36] and OR = 1.32 [95% CI = 1.28 to 1.37]), to require more transfusions (OR = 1.55 [95% CI = 1.49 to 1.62] and OR = 1.77 [95% CI = 1.56 to 2.01]), to be discharged to institutional post-acute care (OR = 1.40 [95% CI = 1.36 to 1.44] and OR = 1.49 [95% CI = 1.43 to 1.56]), and to be readmitted within 90 days (OR = 1.38 [95% CI = 1.32 to 1.44] and OR = 1.21 [95% CI = 1.13 to 1.29]) (p < 0.05 for all). Adjusted difference-in-differences analyses demonstrated that the CJR program coincided with reductions in racial differences in 90-day readmission (-1.24%; 95% CI, -2.46% to -0.03%) and 180-day readmission (-1.28%; 95% CI, -2.52% to -0.03%) (p = 0.044 for both). CONCLUSIONS: Racial differences persist among patients managed with TJA. The CJR program coincided with reductions in some racial differences, thus identifying bundle design as a potential novel strategy to target racial disparities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Understanding the link between kidney stones and cancers of the upper urinary tract and bladder.

Kidney stones are one of the most common renal pathologies. While emerging evidence has implicated a potential association between kidney stones and upper urinary tract cancers (including renal cancer), there is limited understanding as to the common underlying biological pathways functionally linking the etiology of kidney stone formation and the incidence, development, and progression of urinary tract cancers. From a clinical perspective, kidney stone disease can be a barrier to oncologic care due to renal obstruction. From the epidemiological perspective, risk factors associated with both conditions include smoking, alcohol consumption, diet, and gender. Herein, we review the association between renal calculi and malignancy of the upper urinary tract and discuss the current understanding of (a) potential shared mechanisms, and (b) the impact this has on shared therapeutic management of both conditions.

COVID-19 and Kidney Disease: Molecular Determinants and Clinical Implications in Renal Cancer.

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that erupted in December 2019 has affected more than a million people from over 200 countries, claiming over 70 000 lives (by April 7, 2020). As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19). OBJECTIVE: This study considers up-to-date information on the biological determinants shared by COVID-19 and renal disease, and aims to provide evidence-based recommendations for the clinical management of RCC patients with COVID-19. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science). As of March 31, 2020, the Center for Disease Control reported that of the adults hospitalized for COVID-19 with underlying conditions in the USA, 74.8% had chronic renal disease. EVIDENCE SYNTHESIS: Evidence is discussed from epidemiological studies on SARS-CoV-2 pandemic and molecular studies on the role of kidney in facilitating routes for SARS-CoV-2 entry, leading to increased virulence of SARS-CoV-2 and clinical manifestation of symptoms in RCC. CONCLUSIONS: This analysis will advance our understanding of (1) the molecular signatures shared by RCC and COVID-19 and (2) the clinical implications of overlapping signaling pathways in the therapeutic management of RCC and COVID-19 patients. PATIENT SUMMARY: Amid the coronavirus disease 2019 (COVID-19) pandemic, patients diagnosed with renal cell carcinoma and infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may receive complimentary treatment modalities to enhance therapeutic response.

The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients.

Coronavirus disease-2019 (COVID-19), a disease caused by Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages in the United States, and the highest incidence and mortality in adult men. As the pandemic evolves there is limited understanding of a potential association between symptomatic viral infection and age. To date, there is no knowledge of the role children (prepubescent, ages 9-13 years) play as "silent" vectors of the virus, with themselves being asymptomatic. Throughout different time frames and geographic locations, the current evidence on COVID-19 suggests that children are becoming infected at a significantly lower rate than other age groups-as low as 1%. Androgens upregulate the protease TMPRSS2 (type II transmembrane serine protease-2), which facilitates efficient virus-host cell fusion with the epithelium of the lungs, thus increasing susceptibility to SARS-CoV-2 infection and development of severe COVID-19. Owing to low levels of steroid hormones, prepubertal children may have low expression of TMPRSS2, thereby limiting the viral entry into host cells. As the world anticipates a vaccine against SARS-CoV-2, the role of prepubescent children as vectors transmitting the virus must be interrogated to prepare for a potential resurgence of COVID-19. This review discusses the current evidence on the low incidence of COVID-19 in children and the effect of sex-steroid hormones on SARS-CoV-2 viral infection and clinical outcomes of pediatric patients. On reopening society at large, schools will need to implement heightened health protocols with the knowledge that children as the "silent" viral transmitters can significantly affect the adult populations.

Repurposing of α1-Adrenoceptor Antagonists: Impact in Renal Cancer.

Renal cancer ranks twelfth in incidence among cancers worldwide. Despite improving outcomes due to better therapeutic options and strategies, prognosis for those with metastatic disease remains poor. Current systemic therapeutic approaches include inhibiting pathways of angiogenesis, immune checkpoint blockade, and mTOR inhibition, but inevitably resistance develops for those with metastatic disease, and novel treatment strategies are urgently needed. Emerging molecular and epidemiological evidence suggests that quinazoline-based α1-adrenoceptor-antagonists may have both chemopreventive and direct therapeutic actions in the treatment of urological cancers, including renal cancer. In human renal cancer cell models, quinazoline-based α1-adrenoceptor antagonists were shown to significantly reduce the invasion and metastatic potential of renal tumors by targeting focal adhesion survival signaling to induce anoikis. Mechanistically these drugs overcome anoikis resistance in tumor cells by targeting cell survival regulators AKT and FAK, disrupting integrin adhesion (α5ß1 and α2ß1) and engaging extracellular matrix (ECM)-associated tumor suppressors. In this review, we discuss the current evidence for the use of quinazoline-based α1-adrenoceptor antagonists as novel therapies for renal cell carcinoma (RCC) and highlight their potential therapeutic action through overcoming anoikis resistance of tumor epithelial and endothelial cells in metastatic RCC. These findings provide a platform for future studies that will retrospectively and prospectively test repurposing of quinazoline-based α1-adrenoceptor-antagonists for the treatment of advanced RCC and the prevention of metastasis in neoadjuvant, adjuvant, salvage and metastatic settings.

Review of malignant pleural mesothelioma survival after talc pleurodesis or surgery.

Malignant pleural mesothelioma (MPM) is an aggressive tumor and the prognosis is still dismal despite the various proposed multimodal treatment plans. Currently, new palliative treatments, such as talc pleurodesis, are being explored besides traditional surgery. This review reports survival rates after talc pleurodesis in comparison to surgery in patients with malignant pleural mesothelioma. A systematic literature search yielded 49 articles eligible for this review. The mean survival in the talc pleurodesis group was 14 months compared to 17 and 24 months for the pleurectomy decortication (P/D) group and extrapleural pneumonectomy (EPP) group, respectively. Few studies reported on the 1-, 2-year overall survival for the talc pleurodesis group and the results were very heterogeneous. The pooled 1-year overall survival for the P/D and EPP groups were 55% [credibility limits (CL): 21-87%] and 67% (CL: 3-89%), the pooled 2-year overall survival were 32% (CL: 8-63%) and 36% (CL: 8-54%), respectively. The pooled 1- and 2-year survival for surgery independently from the type of surgery were 62% (CL: 38-84%) and 34% (CL: 16-54%). There was significant heterogeneity in all the analyses. This review shows that there is limited research on the survival rate after talc pleurodesis compared to surgery in the treatment of malignant pleural mesothelioma. A comparison study is necessary to accurately assess the best way to treat MPM patients, including assessment of the quality of life after treatment as an outcome measure.