The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage.

OBJECTIVE: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH). METHODS: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC. RESULTS: Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P  = 0.14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC ( P  = 0.93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days [IQR 6 - 12] vs. 6 days [IQR 3-12], P  = 0.66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC ($15 000 [IQR 15 000-$27 000] vs. $11 650 [IQR $8567-$14 149]). CONCLUSION: Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.

Can magnetic resonance imaging differentiate muscle invasion (T2) and lamina propria invasion (T1) urothelial carcinoma of the bladder? A systematic review and meta-analysis of Vesical Imaging-Reporting and Data System accuracy.

Background: Vesical Imaging-Reporting and Data System (VI-RADS) was developed as a structured reporting tool to anticipate the possibility of muscle invasion. This study is aimed to investigate the diagnostic accuracy of VI-RADS for discriminating T2 from T1 bladder cancer. Materials and methods: Scopus, Web of Science, PubMed, and Embase were searched on October 4, 2021, for studies with the following characteristics: (1) bladder cancer patient population, (2) VI-RADS as an index test, (3) retransurethral resection of bladder tumor/cystectomy as a reference, and (4) adequate VI-RADS score data for T1 and T2 lesions. The analyses were performed using the binary regression model of MIDAS in Stata. Results: Six studies with 624 magnetic resonance imaging reports were included. The receiver operating characteristics curve for differentiation of T2 from T1 bladder cancer showed an area under the curve of 0.93 (95% confidence interval [CI], 0.91-0.95) for a VI-RADS ≥3 and 0.75 (95% CI, 0.71-0.79) for a VI-RADS ≥4. A VI-RADS ≥3 showed high sensitivity of 93% (95% CI, 85%-97%), specificity of 61% (95% CI, 30%-86%), positive likelihood ratio of 2.4 (95% CI, 1.1-5.3), and negative likelihood ratio of 0.11 (95% CI, 0.05-0.24). A total of 10.4% of T2 lesions were scored as VI-RADS 2, while 10% of T1 lesions were scored as VI-RADS 4 or 5. Conclusions: The VI-RADS ≥3 has high accuracy and sensitivity for detecting muscle invasion in borderline populations of T1 or T2 bladder cancer. Thus, the VI-RADS could be a good non-invasive screening test for the detection of T2 urothelial lesions.

Colorectal cancer screening completion by patients due or overdue for screening after reminders: a retrospective study.

BACKGROUND: Patient and clinician reminders were implemented as part of an adherence improvement project at University of Florida (UF) Internal Medicine Clinics. We sought to assess colorectal cancer (CRC) screening completion rates among patients not up-to-date with screening following distribution of reminders and to identify characteristics correlated with screening outcomes. METHODS: Retrospective chart review was performed for patients not up-to-date with CRC screening for whom at least one reminder (patient and/or clinician) was issued in June 2018. The primary endpoint, the completion of a CRC screening test, is characterized as the ratio of completed screening tests to the number of patients not up-to-date with screening. All analyses were performed using R 4.0 software. RESULTS: Of the 926 patients included, 403 (44%; 95% CI, 0.40-0.47) completed a CRC screening test within 24 months following a reminder. Family history of CRC (relative risk (RR) 1.33; P = 0.007), flu immunization within two years of the reminder (RR 1.23; P = 0.019), and receiving a patient reminder either alone (RR 1.62; P < 0.001) or in combination with a clinician reminder (RR 1.55; P = 0.006) were positively associated with CRC screening completion. Reporting being divorced, separated, or widowed was negatively associated with screening completion (RR 0.70; P = 0.004). CONCLUSION: Reminders, in particular patient reminders, seem to be an effective method to enhance screening among patients not up-to-date with CRC screening. This study suggests that reminder efforts should be focused at the level of the patients and provides insight on target populations for practical interventions to further increase CRC screening adherence.

The availability of gonadotropin therapy from FDA-approved pharmacies for men with hypogonadism and infertility.

Background: Recent changes to the Biologics Price Competition and Innovation Act of 2009 have created barriers to accessing therapy for men utilizing gonadotropins for hypogonadism and infertility. Aim: In this study we sought to investigate ways to decrease disparities in the treatment of male hypogonadism by increasing access to gonadotropin therapy by identifying 503b outsourcing pharmacies which currently provide gonadotropin therapy. Methods: A review of 503b compounding pharmacies was performed using the online published registry available from the US Food and Drug Administration (FDA). Each pharmacy was contacted regarding their ability to provide gonadotropin therapy. Pharmacies were also queried regarding the impact of FDA-related legal changes and cost considerations. Outcomes: The study outcomes were the number and location of FDA-approved 503b compounding pharmacies supplying human chorionic gonadotrophin (hCG) and/or follicle-stimulating hormone (FSH) for the treatment of male hypogonadism and infertility. Results: The 81 503b-compounding pharmacies approved by the FDA to produce hCG and FSH therapy were identified using the FDA registry. Seventy-five of the 81 pharmacies responded to the survey (response rate 92.6%). Of the contacted pharmacies, 5 provided hCG (6.67%). Of the pharmacies offering compounded hCG, 4 offered FSH. No additional pharmacies offered compounded FSH. Eight pharmacies had previously provided hCG and FSH. Six of the 8 pharmacies that stopped making hCG and FSH cited the 2020 FDA mandate as the reason for halting compounding services. Of the 75 pharmacies that responded, only 1 pharmacy provided the cost for FSH ($287 per 100-IU vial), and 3 pharmacies provided the cost for hCG ($50-$83 per 10 000-IU vial). Clinical Implications: There are few FDA-approved outsourcing pharmacies currently providing male gonadotropin therapy, and increasing awareness of these pharmacies may decrease barriers to care for patients with male hypogonadism and infertility. Strengths and Limitations: The strengths of this article are the clinical utility of the data presented, as this article may serve as a tool for clinicians to increase patient access to therapy. All FDA-approved 503b outsourcing pharmacies were contacted, and 92.6% participated in this project. Limitations of this article were the following: no non-FDA-approved compounding pharmacies such as 503a pharmacies were contacted, participant-reported outcomes were utilized, and only 3 contacted outsourcing pharmacies provided a cost for FSH or hCG, allowing for an unknown degree of cost variability between outsourcing pharmacies. Conclusions: There currently exists limited access to FDA-approved compounded gonadotropin therapies for hypogonadism and male infertility, and these results demonstrate the barriers to hCG and FSH access and the need for additional treatment options for this vulnerable patient population.

Glomerular hyperfiltration is a predictor of adverse outcomes following major urologic oncology surgery.

PURPOSE: Glomerular hyperfiltration (GHF) has been associated with cardiovascular disease and all-cause mortality. We aimed to evaluate whether preoperative GHF is associated with 30-day complications following major urologic oncology procedures. METHODS: We conducted a retrospective cohort study using subjects from the 2006 to 2019 American College of Surgeons National Surgical Quality Improvement Program database who underwent prostatectomy, cystectomy, or nephrectomy. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Patients were classified as having either low, normal, or high eGFR based on the 5th and 95th percentiles of age- and sex-specific quintiles for eGFR. Using multivariable logistic regression, we evaluated GHF as an independent predictor of postoperative complications. RESULTS: A total of 120,013 patients were eligible for analysis, of which 1706 (1.4%) were identified as having GHF, with a median eGFR of 105.37 ml/min per 1.73 m2 (IQR 94.84-116.77). Compared to patients with normal eGFR, patients with GHF were older (68 years, [IQR 60-71], p < 0.001), had a lower BMI (27.52 kg/m2 [IQR 23.71-31.95], p < 0.001), and greater 5-item modified frailty index scores (≥ 1, 70.6%, p < 0.001). Multivariable logistic regression demonstrated that GHF was associated with greater odds of any complication (OR 1.23, 95% CI 1.08-1.40, p = 0.002), non-home discharge (OR 1.86, 95% CI 1.50-2.30, p < 0.001), and prolonged LOS (OR 1.33, 95% CI 1.18-1.51, p < 0.001). CONCLUSION: GHF is associated with greater odds of 30-day complications following major urologic oncology surgery.

Inter-reader reliability of the vesical imaging-reporting and data system (VI-RADS) for muscle-invasive bladder cancer: a systematic review and meta-analysis.

To evaluate the diagnostic agreement between readers in VI-RADS interpretation to detect muscle-invasive bladder cancer (MIBC) preoperatively, we conducted a systematic review and meta-analysis of the available data. Scopus, PubMed, Web of Science, and Embase databases were systematically searched up to November 13, 2021. Case reports, review articles, editorials, and studies with insufficient data were eliminated. The Quality Appraisal of the Diagnostic Reliability Checklist was used to assess the risk of bias. The degree of agreement was determined by Cohen's kappa coefficient (κ) for comparison of data. The heterogeneity of these studies was explored using subgroup analysis and meta-regression analysis. The level of confidence was set at 0.05. All analyses were conducted in STATA 16.0. Overall, 19 eligible studies, consisting of 2439 participants, were included in this meta-analysis. The inter-reader agreement for VI-RADS in MIBC detection ranged from κ of 0.45 to 0.96 among included studies. The pooled inter-reader reliability was calculated as 0.76 [95% CI 0.73-0.80; I2 = 92.13%, Q(50) = 635.08, p < 0.01]. Sources of heterogeneity included magnetic strength, T2WI slice thickness, number of readers, sample size, study design, number of centers, year of publication, proportion of male patients, and mean age. There is substantial reliability in VI-RADS interpretation for MIBC among radiologists with various levels of expertise. The high degree of inter-reader agreement for MIBC detection supports the implementation of VI-RADS in routine clinical practice for the staging paradigm of bladder cancer.

Implementation of Cancer Plans in the United States: A Review.

State cancer plans facilitate prioritization and stakeholder engagement in preventing and controlling cancer. Implementation plans further help stakeholders prioritize efforts, reduce redundancy, and find opportunities for work synergies. A review of cancer plan implementations plans was performed in the development of an implementation plan for the Florida Cancer Plan. This review sought to identify, characterize, and summarize the use of implementation plans that support comprehensive cancer control activities. Although 100% of states and territories published a cancer plan and 78% of states provided funding for implementing their state cancer plans, only 32% published an implementation plan. Commonalities and unique features of state cancer plan implementations are presented and discussed. An example implementation plan is provided for states without a plan to model.