Prior authorization for FDA-approved PARP inhibitors in ovarian cancer.

Objectives: PARP inhibitors (PARP-I) improve survival in ovarian cancer, especially in patients with germline or somatic BRCA mutations or other homologous recombination deficiency (HRD). With high efficacy and costs, insurers may enact barriers or facilitators to PARP-I. Our objective was to examine the prevalence of prior authorization for PARP-I in ovarian cancer. Methods: We performed a retrospective cross-sectional study of patients with ovarian cancer prescribed a PARP-I within the University of Pennsylvania practices from December 2018 through May 2021. We assessed prevalence of prior authorization for PARP-I overall, by frontline or recurrent maintenance, and by genetic status. We then assessed approval and appeal rates and time to PARP-I start. Results: Of 180 patients with a PARP-I prescription and information regarding prior authorization, 116 (64 %, 95 % CI 57-71) experienced prior authorization. Of patients in the frontline setting, 60 of 90 (67 %, 95 % CI 56-76) experienced prior authorization. Of patients prescribed PARP-I in recurrence, 55 of 85 (65 %, 95 % CI 54-74) experienced prior authorization. Having a germline or somatic genetic mutation was associated with higher risk of prior authorization (adjusted risk ratio 1.35, 95 %CI 1.09-1.67). 102 patients (89 %, 95 % CI 83-94) required one appeal, 8 required two appeals and 5 cases required 3 appeals. Five patients were denied. Mean time from PARP-I prescription to PARP-I start was 10 days longer for patients who experienced prior authorization. Conclusions: 64% of patients experienced prior authorization for PARP-I. Risk of prior authorization was increased for patients with BRCA, despite greater clinical benefit. Prior authorization contributes to delays in care, and reform is needed.

The prevalence of hyperglycemia and its association with perioperative outcomes in gynecologic surgery: a retrospective cohort study.

BACKGROUND: Preoperative hyperglycemia has been associated with perioperative morbidity in general surgery patients. Additionally, preoperative hyperglycemia may indicate underlying impaired glucose metabolism. Thus, identification of preoperative hyperglycemia may provide an opportunity to mitigate both short-term surgical and long-term health risk. We aimed to study this phenomenon specifically in the gynecologic surgery population. Specifically, we aimed to evaluate the association between preoperative hyperglycemia and perioperative complications in gynecologic surgery patients and to characterize adherence to diabetes screening guidelines. METHODS: This retrospective cohort study included 913 women undergoing major gynecologic surgery on an enhanced recovery pathway from January 2018 to July 2019. The main exposure was day of surgery glucose ≥ 140 g/dL. Multivariate regression identified risk factors for hyperglycemia and composite and wound-specific complications. RESULTS: Sixty-seven (7.3%) patients were hyperglycemic. Diabetes (aOR 24.0, 95% CI 12.3-46.9, P < .001) and malignancy (aOR 2.3, 95% CI 1.2-4.5, P = .01) were associated with hyperglycemia. Hyperglycemia was not associated with increased odds of composite perioperative (aOR 1.3, 95% CI 0.7-2.4, P = 0.49) or wound-specific complications (aOR 1.1, 95% CI 0.7-1.5, P = 0.76). Of nondiabetic patients, 391/779 (50%) met the USPSTF criteria for diabetes screening; 117 (30%) had documented screening in the preceding 3 years. Of the 274 unscreened patients, 94 (34%) had day of surgery glucose levels suggestive of impaired glucose metabolism (glucose ≥ 100 g/dL). CONCLUSION: In our study cohort, the prevalence of hyperglycemia was low and was not associated with higher risk of composite or wound-specific complications. However, adherence to diabetes screening guidelines was poor. Future studies should aim to develop a preoperative blood glucose testing strategy that balances the low utility of universal glucose screening with the benefit of diagnosing impaired glucose metabolism in at-risk individuals.

Prevalence of and Risk Factors for Emergency Department Visits After Outpatient Gynecologic Surgery.

STUDY OBJECTIVE: To identify the prevalence of and risk factors for emergency department (ED) visits within 30 days of outpatient gynecologic surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical institution. PATIENTS: Adult patients who underwent outpatient surgery (≤1 midnight in the hospital) between January 2018 and September 2019 (N = 2373). INTERVENTIONS: Scheduled outpatient gynecologic surgery for a benign indication. MEASUREMENTS AND MAIN RESULTS: A total of 109 patients (5%) visited the ED within 30 days of surgery. Patients who visited the ED were significantly younger (median age 37 years vs 42 years, p = .02) and had a higher prevalence of abdominal surgical history (67% vs 56%, p = .02) and cardiopulmonary comorbidities (53% vs 40%, p = .007). They were more likely to have undergone a hysterectomy (26% vs 20%) and less likely to have undergone prolapse surgery (4% vs 12%, p = .05). Pain related to the surgical site (42% of ED visits), nausea and/or vomiting (14%), and fever (12%) were the most common surgery-related reasons for ED visits. Medical issues not directly related to surgery accounted for 31% of ED visits. A total of 36% of ED visits resulted in admission. When adjusted for age, insurance status, American Society of Anesthesiologists class, chronic pain and cardiopulmonary comorbidities, abdominal surgical history, primary procedure performed, and surgical route, the following factors were associated with significantly increased risk of visiting the ED: decreasing age (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1-1.3, p <.001), history of abdominal surgery (aOR 1.7, 95% CI 1.1-2.6, p = .017), cardiopulmonary comorbidities (aOR 1.9, 95% CI 1.2-3.0, p = .003), undergoing hysterectomy (aOR 2.0, 95% CI 1.1-3.8, p = .032), and a vulvovaginal surgical route as opposed to abdominal surgical route (aOR 2.4, 95% CI 1.2-5.1, p = .015). CONCLUSION: ED visits after outpatient gynecologic surgery were uncommon, although approximately one-third of visits resulted in admission. Strategies that target our identified risk factors of younger patient age and cardiopulmonary comorbidities may help reduce the ED burden generated by patients undergoing gynecologic surgery.

Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults.

Use of race adjustment in estimating glomerular filtration rate (eGFR) has been challenged given concerns that it may negatively impact the clinical care of Black patients, as it results in Black patients being systematically assigned higher eGFR values than non-Black patients. We conducted a systematic review to assess how well eGFR, with and without race adjustment, estimates measured GFR (mGFR) in Black adults globally. A search across multiple databases for articles published from 1999 to May 2021 that compared eGFR to mGFR and reported outcomes by Black race was performed. We included studies that assessed eGFR using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr) creatinine equations. Risk of study bias and applicability were assessed with the QUality Assessment of Diagnostic Accuracy Studies-2. Of 13,167 citations identified, 12 met the data synthesis criteria (unique patient cohorts in which eGFR was compared to mGFR with and without race adjustment). The studies included patients with and without kidney disease from Africa (n = 6), the United States (n = 3), Europe (n = 2), and Brazil (n = 1). Of 11 CKD-EPI equation studies, all assessed bias, 8 assessed accuracy, 6 assessed precision, and 5 assessed correlation/concordance. Of 7 MDRD equation studies, all assessed bias, 6 assessed accuracy, 5 assessed precision, and 3 assessed correlation/concordance. The majority of studies found that removal of race adjustment improved bias, accuracy, and precision of eGFR equations for Black adults. Risk of study bias was often unclear, but applicability concerns were low. Our systematic review supports the need for future studies to be conducted in diverse populations to assess the possibility of alternative approaches for estimating GFR. This study additionally provides systematic-level evidence for the American Society of Nephrology-National Kidney Foundation Task Force efforts to pursue other options for GFR estimation.

Abdominal Wall Thickness at Palmer's Point and Distance to Adjacent Structures across the Body Mass Index Spectrum.

STUDY OBJECTIVE: Studies delineating left upper quadrant (LUQ) anatomy across a range of body mass indices are lacking. We aimed primarily to compare, between nonobese and obese women, abdominal wall thickness and the distance from the LUQ to key structures. In addition, we aimed to characterize LUQ anatomy in underweight women. DESIGN: A retrospective cohort study. SETTING: A tertiary academic medical institution. PATIENTS: Sixty women (30 nonobese, 30 obese) aged 18 years and older who underwent abdominal imaging from October 1, 2018, to December 31, 2018. INTERVENTIONS: Computed tomography imaging of the chest, abdomen, and pelvis. MEASUREMENTS AND MAIN RESULTS: Abdominal wall thickness at the LUQ was significantly greater in obese (4.3 ± 1.7 cm) than nonobese patients (2.4 ± 1.7 cm) (p <.001), as were distances to all key structures (aorta, vena cava, spleen, stomach, pancreas, liver, left kidney, and pelvis) (p ≤.02). On average, all structures, with the exception of stomach and liver, were >10 cm (the length of a typical insufflation needle) away from the LUQ insertion point in obese women. In underweight women, the aorta, spleen, stomach, pancreas, and liver were all within 10 cm of the LUQ insertion point. Within the obese and nonobese group, abdominal wall thickness at the LUQ was significantly greater than at the umbilicus (p <.001). Body mass index was more strongly correlated with abdominal wall thickness at the LUQ (r = 0.84; p <.001) than at the umbilicus (r = 0.69; p <.001) (p = .007 for comparison). CONCLUSION: This study highlights special anatomic considerations for LUQ access in obese and underweight patients. In obese women, abdominal wall thickness may be greater at this site than at the umbilicus and the liver and stomach remain within reach of an insufflation needle. The increased working distance from the LUQ to the pelvis in obese patients may necessitate specialized instruments if this site is used during surgery. In underweight women, the aorta, in addition to many other structures, is within reach of commonly used entry devices.

Provider education program on the Khorana score to promote venous thromboembolism chemoprophylaxis in patients with gynecologic cancer.

OBJECTIVE: To evaluate the efficacy of a healthcare improvement initiative to improve provider compliance with the American Society of Clinical Oncology (ASCO) guidelines for venous thromboembolism chemoprophylaxis in patients with gynecologic cancer receiving chemotherapy. METHODS: A healthcare improvement initiative was implemented at our institution to improve compliance with American Society of Clinical Oncology venous thromboembolism chemoprophylaxis guidelines in patients receiving chemotherapy with a Khorana score ≥2. Baseline Khorana score and venous thromboembolism data were retrospectively collected for chemotherapy-naïve patients with gynecologic cancer initiating chemotherapy between December 2018 and November 2019. Data for the post-intervention period from December 2019 to December 2020 were captured prospectively. Primary outcome was compliance with American Society of Clinical Oncology guidelines. Secondary outcomes were incidence of venous thromboembolism and complications surrounding venous thromboembolism chemoprophylaxis. RESULTS: We identified 62 patients in the pre-implementation cohort. Approximately half had a Khorana score of ≥2 (52%). Median Khorana score was 2 (range 1-4). None of these patients received prophylactic chemoprophylaxis. Seven (11%) of these patients were diagnosed with venous thromboembolism. Multivariate logistic regression showed increasing Khorana score was associated with increased venous thromboembolism risk (OR 4.9, p=0.01). With cut-off Khorana score of 2, there was no significant increase in venous thromboembolism. However, with a cut-off Khorana score of 3, patients were 15 times more likely to have venous thromboembolism (OR 15.2, p=0.04). In the post-intervention cohort, 22 patients were eligible for chemoprophylaxis and 11 patients were given anticoagulation (50% compliance with guidelines), with no incidence of venous thromboembolism or adverse effects of therapy noted among those receiving chemoprophylaxis. CONCLUSION: Notifying providers of a patient's Khorana score improves compliance with American Society of Clinical Oncology guidelines for venous thromboembolism chemoprophylaxis among chemotherapy patients.

Stopping the revolving door: An exploratory analysis of health care super-utilization in gynecologic oncology.

The objective of this study was to determine the prevalence of and risk factors for health care super-utilization among gynecologic oncology patients at a single academic hospital. A retrospective cohort study of gynecologic oncology patients with an index unplanned encounter between January and December 2018 was performed. Super-utilizers were defined as patients with 3 or more unplanned hospital encounters during a 12-month period starting at the time of the index unplanned encounter. We identified 553 patients with gynecologic cancer. Of those, 37(7%) met inclusion criteria for super-utilizers accounting for 193/310(62%) of unplanned visits. The median number of unplanned visits was 4 (range 3-24). The most common cancers were uterine (N = 15 (41%)) and ovarian (N = 11 (30%)). Nineteen (51%) super-utilizers had advanced stage disease. Phases of oncologic care at index unplanned encounter included primary diagnosis (N = 24 (65%)), recurrence (N = 10 (27%)), and surveillance (N = 2 (5%)). Twelve super-utilizers (32%) had new diagnoses of cancer without prior therapy, 19(51%) had prior chemotherapy, 17(46%) had prior surgery, and 10(27%) had prior radiation therapy at the time of initial encounter. Fifteen super-utilizers (41%) were in the last year of life. The most common reasons for unplanned encounters were pain (66%) and gastrointestinal symptoms (61%). Multivariable analysis adjusting for key variables demonstrated that Medicaid insurance, ASA classification, and disease status are risk factors for health care super-utilization. The majority of health care utilization occurred during the first year of diagnosis. This exploratory analysis suggests an opportunity to decrease health care utilization, particularly during upfront treatment.

Changes in FXR1 expression after Chemotherapy for Rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) arises from abnormal muscle development. We reported previously that Fragile-X-Related 1 (FXR1), essential to normal myogenesis, was highly expressed in RMS relative to other embryonal tumors. This current study explored FXR1 expression across RMS disease characteristics and treatment response. METHODS: RMS patients ≤18 years (1980-2019; n = 152) were categorized according to tumor histology, PAX/FOXO1 translocation, and vital status. FXR1 protein expression was compared before and after chemotherapy. Impact of FXR1 expression on relapse-free (RFS) and overall survival (OS) was analyzed. RESULTS: FXR1 was most intensely expressed in the cytosol of undifferentiated rhabdomyoblasts. At diagnosis, FXR1 expression was ubiquitous and strong across all disease characteristics and foremost associated with worse RFS in translocation-positive patients (p = 0.0411). Among embryonal and translocation-negative RMS, survivors showed a significantly greater decrease in FXR1 expression after chemotherapy (p < 0.001) compared to decedents (p = 0.8). In contrast, alveolar and translocation-positive RMS specimens showed insignificant changes in FXR1 expression across therapy. As expected, alveolar histology, translocation presence, stage, and clinical group associated with worse survival. CONCLUSIONS: FXR1 was expressed strongly across RMS specimens at diagnosis regardless of disease or patient characteristics, and particularly in undifferentiated cells. Reduction in FXR1 expression after chemotherapy associated with improved survival for embryonal and translocation-negative RMS patients.

Race disparities in genetic alterations within Wilms tumor specimens.

BACKGROUND: Wilms tumor (WT) affects Black children disproportionately. Genetic aberrations within WT specimens that contribute to this disparity have not been reported. METHODS: The Therapeutically Applied Research to Generate Effective Treatments (TARGET) database was queried for WT patient and genomic features. Clinical and genetic variables were compared by race. RESULTS: Within the discovery set (enriched for adverse events; N = 94 White, 19 Black, 14 Other/unreported patients), Black children were more likely to present with advanced stage disease (p = 0.019). Within the validation set (primarily a random sampling of NWTS-5; N = 360 White, 92 Black, 72 Other/Unreported), Black children appeared older at diagnosis (p = 0.050), had decreased median follow-up time (p<0.0005) and were over-represented (17.4%) relative to the concurrent U.S. Census (12.8%). Among the 37 target genes sequenced, ACTB (p = 0.030) and DICER1 (p = 0.026) mutations were more common in Black patient specimens, whereas DGCR8 (p = 0.041) mutations were more common in White patient specimens. White patient specimens were more likely to contain one or multiple targeted mutations (p = 0.026). CONCLUSION: Within the TARGET database, Black children were over-represented and harbored WT specimens containing more frequent ACTB and DICER1 mutations. In contrast, WT from White children contained overall more mutations in targeted genes and specifically in DGCR8. LEVEL OF EVIDENCE: III.

Wilms Tumor in Sub-Saharan Africa: Molecular and Social Determinants of a Global Pediatric Health Disparity.

Wilms tumor (WT) is the most common renal malignancy of childhood. Global disparities in WT have been reported with the highest incidence and lowest overall survival occurring in sub-Saharan African nations. After a detailed search of PubMed, we reviewed available literature on WT in sub-Saharan Africa and summarized findings that explore biologic and social factors contributing to this alarming cancer health disparity. Access to care and treatment abandonment are the most frequently reported factors associated with decreased outcomes. Implementation of multidisciplinary teams, collaborative networks, and financial support has improved overall survival in some nations. However, treatment abandonment remains a challenge. In high-income countries globally, WT therapy now is risk-stratified according to biology and histology. To a significantly lesser extent, biologic features have been studied only recently in sub-Saharan African WT, yet unique molecular and genetic signatures, including congenital anomaly-associated syndromes and biomarkers associated with treatment-resistance and poor prognosis have been identified. Together, challenges with access to and delivery of health care in addition to adverse biologic features likely contribute to increased burden of disease in sub-Saharan African children having WT. Publications on biologic features of WT that inform treatment stratification and personalized therapy in resource-limited regions of sub-Saharan Africa have lagged in comparison to publications that discuss social determinants of health. Further efforts to understand both WT biology and social factors relevant to appropriate treatment delivery should be prioritized in order to reduce health disparities for children residing in resource-limited areas of sub-Saharan Africa battling this lethal childhood cancer.

Using OCT Fixation Shift to Assess Eccentric Fixation in Children With Residual Amblyopia.

Purpose: Eccentric fixation in amblyopia is often estimated grossly without precision. Although the usefulness of optical coherence tomography (OCT) fixation shift in the quantification of eccentric fixation in a small cohort of amblyopic children was recently reported, there is a lack of understanding of characteristics of OCT fixation shift. In a retrospective cohort study, we evaluated eccentric fixation with OCT in a large cohort of children with residual amblyopia. Methods: Children, age 4 to 17 years, with residual amblyopia (amblyopic, n = 56) and without amblyopia (control, n = 75) were enrolled. Amblyopia was associated with anisometropia alone (anisometropia subtype, n = 28) and strabismus without or with anisometropia (strabismic subtype, n = 28). Spectral domain OCT was used to estimate fixation. The OCT fixation shift, defined as the distance between the fovea and the fixation point, was measured and adjusted with calculated axial length and converted into visual degrees. Fixation shift in amblyopic eyes, fellow nonamblyopic eyes, and right eyes of the control group were compared. Fixation shift between the anisometropic and strabismic amblyopia subtypes was also compared. Its correlation with visual acuity was estimated. Results: The mean fixation shift was significantly different: 0.17° ± 0.29° for control right eyes, 0.94° ± 1.24° for amblyopic eyes, and 0.34° ± 0.57° for fellow eyes (χ2 = 23.3; P < 0.001). There was no significant difference between fellow eyes and control eyes (P = 0.11). Fixation shift in amblyopic eyes was significantly correlated with visual acuity (R = 0.44; P < 0.001), and it was significantly smaller in the anisometropic subtype than in the strabismic subtypes (0.34° ± 0.46° vs. 1.54° ± 1.48°, W = 338, P < 0.001). Conclusions: OCT fixation shift can be used both in detection and quantification of eccentric fixation in children with residual amblyopia, especially in those with strabismus. Translational Relevance: OCT fixation shift offers a convenient clinical approach in quantitative evaluation of eccentric fixation in children with strabismic amblyopia.

Health disparities among tennessee pediatric renal tumor patients.

BACKGROUND/PURPOSE: Wilms tumor (WT) poses a cancer health disparity to black children globally, which has not been evaluated thoroughly for other pediatric renal cancers. We aimed to characterize health disparities among Tennessee children treated for any renal cancer. METHODS: The Tennessee Cancer Registry (TCR) was queried for patients ≤18 years having any renal cancer (n = 160). To clarify treatment and outcomes, we performed a retrospective cohort study of pediatric renal cancer patients in our institutional cancer registry (ICR; n = 121). Diagnoses in both registries included WT, Sarcoma/Other, and Renal Cell Carcinoma. Wilcoxon/Pearson, Kaplan-Meier, and logistic regression were completed. RESULTS: In both registries, WT comprised the most common renal cancer and youngest median age. Sarcoma was intermediate in frequency and age, and RCC was least common, having the oldest age (p < 0.001). In the TCR, black patients comprised 26% of all patients, presented more commonly with distant disease than white patients (37% v. 16%; p = 0.021), and showed worse overall survival (73% v. 89%; p = 0.018), while the ICR showed similar survival between race groups (92% v. 93%, p = 0.868). Sarcoma and metastases were independent predictors of death in both registries (p ≤ 0.002). CONCLUSIONS: Black children in Tennessee presented with more advanced disease and experienced worse survival when combining all renal cancer types, particularly RCC and Sarcoma. When treated at a comprehensive pediatric cancer center, these survival disparities appear diminished. TYPE OF STUDY: Prognostic study. LEVEL OF EVIDENCE: Level II (retrospective cohort).

An Integrated Clinic-Community Partnership for Child Obesity Treatment: A Randomized Pilot Trial.

BACKGROUND AND OBJECTIVES: Effective treatment of childhood obesity remains elusive. Integration of clinical and community systems may achieve effective and sustainable treatment. However, the feasibility and effectiveness of this integrated model are unknown. METHODS: We conducted a randomized clinical trial among children aged 5 to 11 presenting for obesity treatment. We randomized participants to clinical care or clinical care plus community-based programming at a local parks and recreation facility. Primary outcomes were the change in child BMI at 6 months and the intensity of the program in treatment hours. Secondary outcomes included health behaviors, fitness, attrition, and quality of life. RESULTS: We enrolled 97 children with obesity, and retention at 6 months was 70%. Participants had a mean age of 9.1 years and a mean baseline BMI z score of 2.28, and 70% were living in poverty. Intervention participants achieved more treatment hours than controls (11.4 vs 4.4, SD: 15.3 and 1.6, respectively). We did not observe differences in child BMI z score or percent of the 95th percentile at 6 months. Intervention participants had significantly greater improvements in physical activity (P = .010) and quality of life (P = .008). CONCLUSIONS: An integrated clinic-community model of child obesity treatment is feasible to deliver in a low-income and racially diverse population. As compared with multidisciplinary treatment, the integrated model provides more treatment hours, improves physical activity, and increases quality of life. Parks and recreation departments hold significant promise as a partner agency to deliver child obesity treatment.