Real-world utilization, patient characteristics, and treatment patterns among men with localized prostate cancer tested with the 17-gene genomic prostate score® (GPSTM) assay.

OBJECTIVES: Descriptive study focusing on real-world utilization and characteristics of men with prostate cancer tested with the 17-gene Genomic Prostate Score® (GPS™) assay by linking administrative claims and electronic health record (EHR) data with GPS results. METHODS: This retrospective, observational cohort study (January 1, 2013 to December 31, 2020) included men aged 40-80 years with localized prostate cancer claims, continuous enrollment in Optum's Integrated Claims data set, ≥1 day of EHR clinical activity, and a GPS result. Men were classified as undergoing definitive therapy (DT) (prostatectomy, radiation, or focal therapy) or active surveillance (AS). AS and DT distribution were analyzed across GPS results, National Comprehensive Cancer Network® (NCCN®) risk, and race. Costs were assessed 6 months after the first GPS result (index); clinical outcomes and AS persistence were assessed during the variable follow-up. All variables were analyzed descriptively. RESULTS: Of 834 men, 650 (77.9%) underwent AS and 184 (22.1%) DT. Most men had Quan-Charlson comorbidity scores of 1-2 and a tumor stage of T1c (index). The most common Gleason patterns were 3 + 3 (79.6%) (AS cohort) and 3 + 4 (55.9%) (DT cohort). The mean (standard deviation) GPS results at index were 23.2 (11.3) (AS) and 30.9 (12.9) (DT). AS decreased with increasing GPS result and NCCN risk. Differences between races were minimal. Total costs were substantially higher in the DT cohort. CONCLUSIONS: Most men with GPS-tested localized prostate cancer underwent AS, indicating the GPS result can inform clinical management. Decreasing AS with increasing GPS result and NCCN risk suggests the GPS complements NCCN risk stratification.

Identification of Patients with Statin Intolerance in a Managed Care Plan: A Comparison of 2 Claims-Based Algorithms.

BACKGROUND: While statins are safe and efficacious, some patients may experience statin intolerance or treatment-limiting adverse events. Identifying patients with statin intolerance may allow optimal management of cardiovascular event risk through other strategies. Recently, an administrative claims data (ACD) algorithm was developed to identify patients with statin intolerance and validated against electronic medical records. However, how this algorithm compared with perceptions of statin intolerance by integrated delivery networks remains largely unknown. OBJECTIVE: To determine the concurrent validity of an algorithm developed by a regional integrated delivery network multidisciplinary panel (MP) and a published ACD algorithm in identifying patients with statin intolerance. METHODS: The MP consisted of 3 physicians and 2 pharmacists with expertise in cardiology, internal medicine, and formulary management. The MP algorithm used pharmacy and medical claims to identify patients with statin intolerance, classifying them as having statin intolerance if they met any of the following criteria: (a) medical claim for rhabdomyolysis, (b) medical claim for muscle weakness, (c) an outpatient medical claim for creatinine kinase assay, (d) fills for ≥ 2 different statins excluding dose increases, (e) decrease in statin dose, or (f) discontinuation of a statin with a subsequent fill for a nonstatin lipid-lowering therapy. The validated ACD algorithm identified statin intolerance as absolute intolerance with rhabdomyolysis; absolute intolerance without rhabdomyolysis (i.e., other adverse events); or as dose titration intolerance. Adult patients (aged ≥ 18 years) from the integrated delivery network with at least 1 prescription fill for a statin between January 1, 2011, and December 31, 2012 (first fill defined the index date) were identified. Patients with ≥ 1 year pre- and ≥ 2 years post-index continuous enrollment and no statin prescription fills in the pre-index period were included. The MP and ACD algorithms were applied to the population, and concordance was examined using individual (i.e., sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) and overall performance measures (i.e., accuracy, Cohen's kappa coefficient, balanced accuracy, F-1 score, and phi coefficient). RESULTS: After applying the inclusion criteria, 7,490 patients were evaluated for statin intolerance. The mean (SD) age of the population was 51.1 (8.5) years, and 55.7% were male. The MP and ACD algorithms classified 11.3% and 5.4% of patients as having statin intolerance, respectively. The concordance of the MP algorithm was mixed, with negative classification of statin intolerance measures having high concordance (specificity 0.91, NPV 0.97) and positive classification of statin intolerance measures having poor concordance (sensitivity 0.45, PPV 0.21). Overall performance measures showed mixed agreement between the algorithms. CONCLUSIONS: Both algorithms used a mix of pharmacy and medical claims and may be useful for organizations interested in identifying patients with statin intolerance. By identifying patients with statin intolerance, organizations may consider a variety of options, including using nonstatin lipid-lowering therapies, to manage cardiovascular event risk in these patients. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals and Sanofi US. Boklage is employed by, and owns stock in, Regeneron, and Charland is employed by Sanofi. Bellows has received fees from Avenir for advisory board membership and grants from Myriad Genetics, Biogen, Janssen, and National Institutes of Health. Brixner reports advisory board and consultancy fees and grants from Sanofi. Mitchell reports consultancy fees from Sanofi. Study concept and design were contributed by Bellows, Boklage, Charland, and Brixner. Bellows, Sainski-Nguyen, and Olsen took the lead in data collection, along with Mitchell. Data interpretation was performed by Mitchell, along with the other authors. The manuscript was written by Bellows, Sainski-Nguyen, and Olsen and revised by all the authors.

Maintenance of the HIV Reservoir Is Antagonized by Selective BCL2 Inhibition.

Decay of the HIV reservoir is slowed over time in part by expansion of the pool of HIV-infected cells. This expansion reflects homeostatic proliferation of infected cells by interleukin-7 (IL-7) or antigenic stimulation, as well as new rounds of infection of susceptible target cells. As novel therapies are being developed to accelerate the decay of the latent HIV reservoir, it will be important to identify interventions that prevent expansion and/or repopulation of the latent HIV reservoir. Our previous studies showed that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and activate Bak to induce apoptosis of infected cells. In circumstances where expression of the anti-apoptotic protein BCL2 is high, Casp8p41 instead binds BCL2, and cell death does not occur. This effect can be overcome by treating cells with the clinically approved BCL2 antagonist venetoclax, which prevents Casp8p41 from binding BCL2, thereby allowing Casp8p41 to bind Bak and kill the infected cell. Here we assess whether the events that maintain the HIV reservoir are also antagonized by venetoclax. Using the J-Lat 10.6 model of persistent infection, we demonstrate that proliferation and HIV expression are countered by the use of venetoclax, which causes preferential killing of the HIV-expressing cells. Similarly, during new rounds of infection of primary CD4 T cells, venetoclax causes selective killing of HIV-infected cells, resulting in decreased numbers of HIV DNA-containing cells.IMPORTANCE Cure of HIV infection requires an intervention that reduces the HIV reservoir size. A variety of approaches are being tested for their ability to impact HIV reservoir size. Even if successful, however, these approaches will need to be combined with additional complementary approaches that prevent replenishment or repopulation of the HIV reservoir. Our previous studies have shown that the FDA-approved BCL2 antagonist venetoclax has a beneficial effect on the HIV reservoir size following HIV reactivation. Here we demonstrate that venetoclax also has a beneficial effect on HIV reservoir size in a model of homeostatic proliferation of HIV as well as in acute spreading infection of HIV in primary CD4 T cells. These results suggest that venetoclax, either alone or in combination with other approaches to reducing HIV reservoir size, is a compound worthy of further study for its effects on HIV reservoir size.

Analyzing the Area Under the Curve of Pharyngeal pH Probes in the Diagnosis of Reflux Disease.

OBJECTIVES: To analyze the area under the curve (AUC) from 24-hour pharyngeal pH probes and evaluate this parameter as a predictor of disease severity for laryngopharyngeal reflux. METHODS: Eighty patients met inclusion criteria of a completed 24-hour pharyngeal pH probe and Reflux Symptom Index (RSI) questionnaire. The AUC was calculated below a pH threshold of 5.5 using the trapezoidal rule. The RSI and RYAN scores were correlated with AUC values, and nonparametric tests were used for comparisons. RESULTS: The median AUC value was 18 007 pH-seconds with an interquartile range (IQR) of 63 156, the median RSI score was 21 (IQR = 16), and the median RYAN score was 15.3 (IQR = 78). There was a Spearman's correlation of .36 between the RSI scores and AUC values ( P = .001) and a moderate correlation between AUC values and RYAN scores (0.58, P < .001). An insignificant correlation of .19 between RYAN scores and RSI scores was observed ( P = .09). CONCLUSIONS: The AUC may be a useful objective value in establishing the diagnosis of laryngopharyngeal reflux. Prospective studies with larger patient populations are necessary to validate these findings and determine standardized thresholds for symptomatic patients.

Office-Based Buprenorphine Versus Clinic-Based Methadone: A Cost-Effectiveness Analysis.

The objective of this analysis was to compare the cost-effectiveness of clinic-based methadone maintenance therapy (MMT) and office-based buprenorphine maintenance therapy (BMT) from the perspective of third-party payers in the United States. The authors used a Markov cost-effectiveness model. A hypothetical cohort of 1000 adult, opioid-dependent patients was modeled over a 1-year time horizon. Patients were allowed to transition between the health states of in opioid dependence treatment and either abusing or not abusing opioids, or to have dropped out of treatment. Probabilities were derived from randomized clinical trials comparing methadone and buprenorphine. Costs included drug and administration, clinic visits, and therapy sessions. Effectiveness outcomes examined were (1) retention in the treatment program and (2) opioid abuse-free weeks. For retention in treatment at 1 year, MMT was more costly ($4,613 vs. $4,155) and more effective (20.3% vs. 15.9%) than BMT, resulting in an incremental cost-effectiveness ratio (ICER) of $10,437 per additional patient retained in treatment. MMT was also more effective than BMT in terms of opioid abuse-free weeks (9.2 vs. 9.1 weeks), resulting in an ICER of $8,515 per opioid abuse-free week gained. One-way sensitivity analyses found costs per week of MMT to have the largest impact on the retention-in-treatment outcome, whereas the probability of dropping out with MMT had the greatest impact on opioid abuse-free weeks. The authors conclude that MMT is cost-effective compared with BMT for the treatment of patients with opioid dependence. However, the treatment of substance abuse is complex, and decision makers should also consider individual patient characteristics when making coverage decisions.

Serial full-thickness excision of dysplastic vocal fold leukoplakia: Diagnostic or therapeutic?

OBJECTIVES/HYPOTHESIS: A previous study proposed that serial full-thickness excisional biopsies of vocal fold leukoplakia therapeutically decreased dysplasia grade. The current investigation aimed to 1) analyze the pathological evolution and natural history of these lesions and 2) re-examine the role of serial excisions in dysplasia grade regression in long-term follow-up. STUDY DESIGN: Retrospective case series. METHODS: Patients treated for vocal fold dysplasia (1994-2013) with serial full-thickness microflap-type excisions were identified and followed longitudinally. Excluded were those with one excision, invasive cancer at initial excision, or history of laryngeal cancer or radiation. Data from surgical procedures, associated pathology, and patient characteristics were recorded. Weighted repeated measures ordinal logistic regression measured associations with pathology findings. RESULTS: Of 55 patients (median age = 65 years, interquartile range = 54-73 years, 89% male, 63% ever smokers, 27% alcohol users), 31 met inclusion criteria. During the study period, patients had two to 44 excisions, with a median time between excisions of 4.0 months. Each additional excision increased odds of higher-grade pathology by 4% (odds ratio = 1.04, 95% confidence interval = 1.01-1.06; P = .007). A transition model demonstrated that patients with moderate dysplasia, severe dysplasia, or carcinoma in situ on a prior biopsy had 2.64-, 5.64-, and 8.73-times increased odds of the same or higher pathology grade at the next excision, respectively. CONCLUSIONS: Data do not support the hypothesis that serial full-thickness excisions decrease dysplasia grade. Progression of dysplasia appears to be nonlinear, but higher-grade dysplasia is more likely to progress to malignancy. LEVEL OF EVIDENCE: 4.

Salivary endoscopy in a pediatric patient with HLA-B27 seropositivity and recurrent submandibular sialadenitis.

Patients with human leukocyte antigen (HLA)-B27 seropositivity have a genetic predisposition to form spondyloarthropathies, especially ankylosing spondylitis. Other related inflammatory or autoimmune disorders include reactive arthritis, uveitis, psoriatic arthritis, and Crohn's disease. Although juvenile recurrent parotitis is not uncommon, recurrent submandibular sialadenitis is rare in pediatric patients. Sialadenitis is typically caused by salivary stones, infection, or duct stricture. To our knowledge, there has not been report of HLA-B27 positivity and recurrent sialadenitis described previously. We describe a patient with HLA-B27 seropositivity and multiple episodes of left submandibular sialadenitis who underwent diagnostic and therapeutic sialendoscopy. Previous treatment included antibiotics, sialogogues, warm compresses, and hydration before he underwent definitive sialendoscopy treatment at a tertiary care medical center. Salivary endoscopy showed salivary stasis and sludging within the left submandibular gland duct, with no salivary stones. Topical steroid was applied to the duct. At one year following his surgery, he has not had any recurrent episodes of sialadenitis. HLA-B27 seropositivity is associated with many inflammatory disorders; we report a case in which the patient had coexisting recurrent sialadenitis. In the pediatric population, sialadenitis is traditionally managed with antibiotics and supportive care, however our patient underwent salivary endoscopy. Sialendoscopy is an emerging modality that potentially avoids radiation exposure from CT or sialography and should be considered as another preferred treatment option. More investigation is required to prove a possible correlation between existing HLA-B27 and the propensity to develop this clinical problem.