18F-Fluciclovine PET/CT performance in biochemical recurrence of prostate cancer: a systematic review.

BACKGROUND: A systematic literature review of the performance of 18Fluorine-fluciclovine PET/CT for imaging of men with recurrent prostate cancer was performed. METHODS: Scientific literature databases (MEDLINE, ScienceDirect and Cochrane Libraries) were searched systematically during Oct 2020 using PRISMA criteria. No limit was put on the date of publication. Prospective studies reporting a patient-level 18F-fluciclovine detection rate (DR) from ≥25 patients with recurrent prostate cancer were sought. Proceedings of relevant meetings held from 2018 through Oct 2020 were searched for abstracts meeting criteria. RESULTS: Searches identified 321 unique articles. In total, nine articles (six papers and three conference abstracts), comprising a total of 850 patients met inclusion criteria. Most studies (n = 6) relied on ASTRO-Phoenix Criteria, EAU-ESTRO-SIOG, and/or ASTRO-AUA guidelines to identify patients with biochemical recurrence. Patients' PSA levels ranged from 0.02-301.7 ng/mL (median level per study, 0.34-4.10 ng/mL [n = 8]). Approximately 64% of patients had undergone prostatectomy, but three studies focused solely on post-prostatectomy patients. Adherence to imaging protocol guidelines was heterogeneous, with variance seen in administered activity, uptake and scan times. Overall patient-level DR varied between studies from 26% to 83%, with 78% of studies reporting a DR > 50%. DR was proportional to PSA, but even at PSA < 0.5 ng/mL DR of up to 53% were reported. Prostate/bed DR (n = 7) ranged from 18% to 78% and extra-prostatic rates (n = 6) from 8% to 72%. Pelvic node and bone lesion DR ranged from 8% to 47% and 0% to 26%, respectively (n = 5). 18F-Fluciclovine PET/CT was shown to impact patient management and outcomes. Two studies reported 59-63% of patients to have a management change post-scan. A further study showed significant increase in failure-free survival following 18F-fluciclovine-guided compared with conventional imaging-guided radiotherapy planning. CONCLUSIONS: 18F-Fluciclovine PET/CT shows good performance in patients with recurrent prostate cancer leading to measurable clinical benefits. Careful adherence to recommended imaging protocols may help optimize DR.

Converting from Transdermal to Buccal Formulations of Buprenorphine: A Pharmacokinetic Meta-Model Simulation in Healthy Volunteers.

Objective: To develop a model to predict buprenorphine plasma concentrations during transition from transdermal to buccal administration. Design: Population pharmacokinetic model-based meta-analysis of published data. Methods: A model-based meta-analysis of available buprenorphine pharmacokinetic data in healthy adults, extracted as aggregate (mean) data from published literature, was performed to explore potential conversion from transdermal to buccal buprenorphine. The time course of mean buprenorphine plasma concentrations following application of transdermal patch or buccal film was digitized from available literature, and a meta-model was developed using specific pharmacokinetic parameters (e.g., absorption rate, apparent clearance, and volumes of distribution) derived from analysis of pharmacokinetic data for intravenously, transdermally, and buccally administered buprenorphine. Results: Data from six studies were included in this analysis. The final transdermal absorption model employed a zero-order input rate that was scaled to reflect a nominal patch delivery rate and time after patch application (with decline in rate over time). The transdermal absorption rate constant became zero following patch removal. Buccal absorption was a first-order process with a time lag and bioavailability term. Simulations of conversion from transdermal 20 mcg/h and 10 mcg/h to buccal administration suggest that transition can be made rapidly (beginning 12 hours after patch removal) using the recommended buccal formulation titration increments (75-150 mcg) and schedule (every four days) described in the product labeling. Conclusions: Computer modeling and simulations using a meta-model built from data extracted from publications suggest that rapid and straightforward conversion from transdermal to buccal buprenorphine is feasible.

Prediction model for penile prosthesis implantation for erectile dysfunction management.

OBJECTIVE: Penile prosthesis surgery is indicated based on undesirability, contraindication or ineffectiveness of non-surgical options for erectile dysfunction. This definitive treatment is often delayed after initial diagnosis. Our objective was to develop a prediction tool based on a patient's clinical history to determine likelihood of ultimately receiving a penile prosthesis. RESEARCH DESIGN AND METHODS: This retrospective analysis used claims data from Commercial and Medicare supplemental databases. Inclusion criteria were 18 years of age with 1 year of continuous enrollment at the first diagnosis of erectile dysfunction. Patients' demographics, co-morbidities and erectile dysfunction therapy were derived based on enrollment, medical and prescription histories. MAIN OUTCOME MEASURES: The Cox proportional hazards model with stepwise selection was used to identify and quantify (using relative risk) factors associated with a future penile prosthesis implant. Co-morbidities and therapies present prior to the index erectile dysfunction diagnosis were analyzed as fixed covariates. RESULTS: Approximately 1% of the dataset's population (N = 310,303 Commercial, N = 74,315 Medicare, respectively) underwent penile prosthesis implantation during the study period (3928 patients in the overall population: 2405 patients [0.78%] in the Commercial and 1523 patients [2.05%] in the Medicare population). Factors with the greatest predictive strength of penile prosthesis implantation included prostate cancer diagnosis (relative risk: 3.93, 2.29; 95% CI, 3.57-4.34, 2.03-2.6), diabetes mellitus (2.31, 1.23; 2.12-2.52, 1.1-1.37) and previous treatment with first-line therapy (1.39, 1.33; 1.28-1.5, 1.2-1.47) (all P < 0.01). CONCLUSION: The presence and extent of specific medical history factors at the time of erectile dysfunction diagnosis predict an individual's future likelihood of penile prosthesis. Calculating the likelihood of penile prosthesis implantation based on the weight of these factors may assist clinicians with the definition of a care plan and patient counseling. The precision of the model may be limited by factors beyond medical history information that possibly influence the decision to proceed to surgery.

Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model.

The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.