Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?

PURPOSE: The accuracy of target delineation in radiation treatment planning of high-grade gliomas (HGGs) is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Magnetic resonance imaging (MRI) represents the standard imaging modality for delineation of gliomas with inherent limitations in accurately determining the microscopic extent of tumors. The purpose of this study was to assess the survival impact of multi-observer delineation variability of multiparametric MRI (mpMRI) and [18F]-FET PET/CT. MATERIALS AND METHODS: Thirty prospectively included patients with histologically confirmed HGGs underwent a PET/CT and mpMRI including diffusion-weighted imaging (DWI: b0, b1000, ADC), contrast-enhanced T1-weighted imaging (T1-Gado), T2-weighted fluid-attenuated inversion recovery (T2Flair), and perfusion-weighted imaging with computation of relative cerebral blood volume (rCBV) and K2 maps. Nine radiation oncologists delineated the PET/CT and MRI sequences. Spatial similarity (Dice similarity coefficient: DSC) was calculated between the readers for each sequence. Impact of the DSC on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and the log-rank test. RESULTS: The highest DSC mean values were reached for morphological sequences, ranging from 0.71 +/- 0.18 to 0.84 +/- 0.09 for T2Flair and T1Gado, respectively, while metabolic volumes defined by PET/CT achieved a mean DSC of 0.75 +/- 0.11. rCBV variability (mean DSC0.32 +/- 0.20) significantly impacted PFS (p = 0.02) and OS (p = 0.002). CONCLUSIONS: Our data suggest that the T1-Gado and T2Flair sequences were the most reproducible sequences, followed by PET/CT. Reproducibility for functional sequences was low, but rCBV inter-reader similarity significantly impacted PFS and OS.

The Effect of Eccentric or Isometric Training on Strength, Architecture, and Sprinting across an Australian Football Season.

PURPOSE: This study aimed to investigate the effect of an isometric (ISO) or Nordic hamstring exercise (NHE) intervention, alongside a sprint training program on hamstring strength, architecture, and sprinting performance in Australian footballers. METHODS: Twenty-five male athletes undertook NHE ( n = 13) or ISO ( n = 12) training across a 38-wk period (including preseason and in season). Biceps femoris long head (BFlh) architecture, ISO, and eccentric knee flexor strength were assessed at baseline, at the end of preseason (14 wk), and at the conclusion of the intervention. Sprint times and force-velocity profiles were determined at baseline and at the end of preseason. RESULTS: After the intervention, both groups had significant improvements in BFlh fascicle length (NHE: 1.16 cm, 95% CI = 0.68 to 1.63 cm, d = 1.88, P < 0.001; ISO: 0.82 cm, 95% CI = 0.57 to 1.06 cm, d = 1.70, P < 0.001), muscle thickness (NHE: 0.11 cm, 95% CI = 0.01 to 0.21 cm, d = 0.51, P = 0.032; ISO: 0.21 cm, 95% CI = 0.10 to 0.32 cm, d = 0.86, P = 0.002), and eccentric strength (NHE: 83 N, 95% CI = 53 to 114 N, d = 1.79, P < 0.001; ISO: 83 N, 95% CI = 17 to 151 N, d = 1.17, P = 0.018). Both groups also finished the intervention weaker isometrically than they started (NHE: -45 N, 95% CI = -81 to -8 N, d = -1.03, P = 0.022; ISO: -80 N, 95% CI = -104 to -56 N, d = -3.35, P < 0.001). At the end of preseason, the NHE group had improved their 5-m sprint time by 3.3% ± 2.0%), and their maximum horizontal velocity was 3% ± 2.1% greater than the ISO group who saw no changes. CONCLUSIONS: Both ISO and NHE training with a periodized sprinting program can increase BFlh fascicle length, thickness, and eccentric strength in Australian footballers. NHE training also improves 5-m sprint time and maximum velocity. However, both interventions reduced ISO strength. These findings provide unique, contextually relevant insights into the adaptations possible in semiprofessional athletes.

Development of complexity categories for an investigational drug services complexity scoring tool to assess pharmacy effort in clinical trial initiation and maintenance.

PURPOSE: Research pharmacy effort required to safely and compliantly manage investigational products (IP) varies between studies. No validated tool exists in the United States to evaluate these differences in effort. The Vizient Pharmacy Research Committee Investigational Drug Services (IDS) Subcommittee previously developed a systematic complexity scoring tool (CST) through expert consensus to assign a complexity score for pharmacy effort. This project seeks to develop and validate complexity categories based on CST scores. METHODS: Vizient member institutions in IDS assigned a CST complexity score and a perceived complexity category (low, medium, or high) for study initiation and maintenance. Receiver operating characteristic (ROC) curve analysis defined the best CST score cutoff points for each complexity category. Comparing the CST-assigned to the user-perceived complexity category determined whether the CST-assigned complexity category aligned with practitioner assignment. RESULTS: A total of 322 responses were used to determine complexity score categories. The AUC values for study initiation and maintenance were 0.79 (P < 0.001) for the low/medium boundary and 0.80 (P < 0.001) for the medium/high boundary, suggesting the performance of the CST is good. The agreement between CST-assigned and user-perceived complexity categories was 60% for study initiation and 58% for maintenance. The Kendall rank correlation coefficient between the raters and ROC categories was strong, with a value of 0.48 for study initiation and 0.47 for maintenance. CONCLUSION: Development of the CST allows IDS pharmacies to objectively measure the complexity of clinical trials, which is a significant step towards assessing workload and guiding resource allocation.

Cost-effectiveness of overactive bladder treatments from a US commercial and payer perspective.

Aim: The cost-effectiveness of treatment options (anticholinergics, ß3-adrenoceptor agonists, onabotulinumtoxinA, sacral nerve stimulation and percutaneous tibial stimulation [the latter two including new rechargeable neurostimulators]) for the management of overactive bladder (OAB) were compared with best supportive care (BSC) using a previously published Markov model. Materials & methods: Cost-effectiveness was evaluated over a 15-year time horizon, and sensitivity analyses were performed using 2- and 5-year horizons. Discontinuation rates, resource utilization, and costs were derived from published sources. Results: Using Medicare and commercial costs over a 15-year time period, onabotulinumtoxinA 100U had incremental cost-effectiveness ratios (ICERs) gained of $39,591/quality-adjusted life-year (QALY) and $42,255/QALY, respectively, versus BSC, which were the lowest ICERs of all assessed treatments. The sensitivity analyses at 2- and 5-year horizons also showed onabotulinumtoxinA to be the most cost-effective of all assessed treatments versus BSC. Conclusion: OnabotulinumtoxinA 100U is currently the most cost-effective treatment for OAB.

Are Drugs Priced in Accordance With Value? A Comparison of Value-Based and Net Prices Using Institute for Clinical and Economic Review Reports.

OBJECTIVES: The Institute for Clinical and Economic Review (ICER) is an independent organization that reviews drugs and devices with a focus on emerging agents. As part of their evaluation, ICER estimates value-based prices (VBP) at $50 000 to $150 000 per quality-adjusted life-year (QALY) gained thresholds. We compared actual estimated net prices to ICER-estimated VBPs. METHODS: We reviewed ICER final evidence reports from November 2007 to October 2020. List prices were combined with average discounts obtained from SSR Health to estimate net prices. If a drug had been evaluated more than once for the same indication, only the more recent VBP was included. RESULTS: A total of 34 ICER reports provided unique VBPs for 102 drugs. The net price of 81% of drugs exceeded the $100 000 per QALY VBP and 71% exceeded the $150 000 per QALY VBP. The median change in net price needed to reach the $150 000 per QALY VBP was a 36% reduction. The median decrease in net price needed was highest for drugs targeting rare inherited disorders (n = 15; 62%) and lowest for cardiometabolic disorders (n = 6; 162% price increase). The reduction in net prices needed to reach ICER-estimated VBPs was higher for drugs evaluated for the first approved indication, rare diseases, less competitive markets, and if the drug approval occurred before the ICER report became available. CONCLUSION: Net prices are often above VBPs estimated by ICER. Although gaining awareness among decision makers, the long-term impact of ICER evaluations on pricing and access to new drugs continues to evolve.

Sprinting, Strength, and Architectural Adaptations Following Hamstring Training in Australian Footballers.

The aim of this study was to determine the sprinting, strength, and architectural adaptations following a hip-dominant flywheel (FLY) or Nordic hamstring exercise (NHE) intervention in Australian footballers. Twenty-seven male athletes were randomized to FLY (n = 13) or NHE (n = 14) training across a 39-week period (inclusive of pre-season and in-season). Biceps femoris long head (BFlh) architecture was assessed throughout. Eccentric hamstring strength and 40 m sprint times (with force-velocity profiling) were assessed at baseline, end of pre-season, and following the intervention. After the intervention, BFlh fascicle length was longer in both groups compared to baseline (FLY: 1.16 cm, 95%CI: 0.66 to 1.66 cm, d = 1.99, p < 0.001; NHE: 1.08 cm, 95%CI: 95%CI 0.54 to 1.61 cm, d = 1.73, p < 0.001). Both groups also increased their eccentric strength (FLY: mean change 82 N, 95%CI 12 to 152 N, d = 1.34, p = 0.026; NHE: mean change 97 N, 95%CI 47 to 146 N, d = 1.77, p = 0.001). After pre-season, the NHE group improved their 5 m sprint time by 3.5% (±1.2%) and were 3.7% (±1.4%) and 2.0% (±0.5%) faster than the FLY group across 5 m and 10 m, respectively. At the end of pre-season, the FLY group improved maximal velocity by 3.4% (±1.4%) and improved horizontal force production by 9.7% in-season (±2.2%). Both a FLY and NHE intervention increase BFlh fascicle length and eccentric strength in Australian Footballers. An NHE intervention led to enhanced acceleration capacity. A FLY intervention was suggested to improve maximal sprint velocity and horizontal force production, without changes in sprint times. These findings have implications for hamstring injury prevention but also programs aimed at improving sprint performance.

Cost-effectiveness of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis.

AIMS: Primary axillary hyperhidrosis (PAHH) is a condition characterized by excessive sweating that negatively impacts health-related quality of life, with significant psychological and social impacts. Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the United States for treatment of PAHH in patients 9 years of age and older. Our objective was to assess the cost-effectiveness of GT as first-line topical therapy compared to topical aluminum chloride from a United States commercial perspective. MATERIALS AND METHODS: A Markov model was developed consisting of four health states based on the Hyperhidrosis Disease Severity Scale (HDSS) over a time horizon of 5 years with discount rates of 3% for both costs and outcomes. Transitions between health states were driven by HDSS response, defined as an improvement of ≥2 points. Non-responders and those who discontinue could switch to later line treatments or no treatment. Health utility scores were based on HDSS scores, supported by published literature. RESULTS: Over 5 years, GT yielded 0.12 greater QALYs and 0.93 greater LYs with response compared to treatment with prescription aluminum chloride at an incremental cost of $10,584. Relative to prescription aluminum chloride, GT resulted in an incremental cost-effectiveness ratio (ICER) of $87,238 per QALY gained, $11,349 per LY with response. The ICER fell below $100,000 for 66% of probabilistic sensitivity analysis simulations and below $150,000 for 82% of simulations. LIMITATIONS: This analysis represents a simplified scenario of a hypothetical PAHH patient. Due to sparse data, assumptions were required for treatment patterns, efficacy, and persistence. CONCLUSION: Based on the analysis of incremental cost per QALY gained, GT may be cost-effective relative to prescription aluminum chloride at commonly accepted willingness to pay thresholds.

Evaluating the Presence of Cognitive Biases in Health Care Decision Making: A Survey of U.S. Formulary Decision Makers.

BACKGROUND: Behavioral economics is a field of economics that draws on insights from psychology to understand and identify patterns of decision making. Cognitive biases are psychological tendencies to process information in predictable patterns that result in deviations from rational decision making. Previous research has not evaluated the influence of cognitive biases on decision making in a managed care setting. OBJECTIVE: To assess the presence of cognitive biases in formulary decision making. METHODS: An online survey was conducted with a panel of U.S. pharmacy and medical directors who worked at managed care organizations and served on pharmacy and therapeutics committees. Survey questions assessed 4 cognitive biases: relative versus absolute framing effect, risk aversion, zero-risk bias, and delay discounting. Simulated data were presented in various scenarios related to adverse event profiles, drug safety and efficacy, and drug pricing for new hypothetical oncology products. Survey questions prompted participants to select a preferred drug based on the information provided. Survey answers were analyzed to identify decision patterns that could be explained by the cognitive biases. Likelihood of bias was analyzed via chi-square tests for framing effect, risk aversion, and zero-risk bias. The delay discounting section used a published algorithm to characterize discounting patterns. RESULTS: A total of 35 pharmacy directors and 19 medical directors completed the survey. In the framing effect section, 80% of participants selected the suboptimal choice in the relative risk frame, compared with 38.9% in the absolute risk frame (P < 0.0001). When assessing risk aversion, 42.6% and 61.1% of participants displayed risk aversion in the cost- and efficacy-based scenarios, respectively, but these were not statistically significant (P = 0.27 and P = 0.10, respectively). In the zero-risk bias section, results from each scenario diverged. In the first zero-risk bias scenario, 90.7% of participants selected the drug with zero risk (P < 0.001), but in the second scenario, only 32.1% chose the zero-risk option (P < 0.01). In the section assessing delay discounting, 54% of survey participants favored a larger delayed rebate over a smaller immediate discount. A shallow delay discounting curve was produced, which indicated participants discounted delayed rewards to a minimal degree. CONCLUSIONS: Pharmacy and medical directors, like other decision makers, appear to be susceptible to some cognitive biases. Directors demonstrated a tendency to underestimate risks when they were presented in relative risk terms but made more accurate appraisals when information was presented in absolute risk terms. Delay discounting also may be applicable to directors when choosing immediate discounts over delayed rebates. However, directors neither displayed a statistically significant bias for risk aversion when assessing scenarios related to drug pricing or clinical efficacy nor were there significant conclusions for zero-risk biases. Further research with larger samples using real-world health care decisions is necessary to validate these findings. DISCLOSURES: This research was funded by Xcenda. Mezzio, Nguyen, and O'Day are employees of Xcenda. Kiselica was employed by Xcenda at the time the study was conducted. The authors have nothing to disclose. A portion of the preliminary data was presented as posters at the 2017 AMCP Managed Care & Specialty Pharmacy Annual Meeting; March 27-30, 2017; in Denver, CO, and the 2017 International Society for Pharmacoeconomics and Outcomes Research 22nd Annual International Meeting; May 20-24, 2017; in Boston, MA.

Point-of-Care Ultrasound in General Surgery Residency Training: A Proposal for Milestones in Graduate Medical Education Ultrasound.

The use of point-of-care ultrasound (US) in the clinical setting has undergone massive growth, although its incorporation into training and practice is variable. Surgeons are interested in using point-of-care US and can incorporate it effectively into clinical practice. However, the current state of point-of-care US training in general surgery is inadequate. The Accreditation Council for Graduate Medical Education introduced the Milestones Project to evaluate resident and fellow performance. Emergency medicine is the only specialty with a point-of-care US milestone. We have successfully implemented a US training program into our general surgery residency curriculum and now propose milestones in point-of-care US for all general surgery residents.

Use of Radio Frequency Identification to Establish Emergency Medical Service Offload Times.

Emergency medical services (EMS) crews often wait for emergency department (ED) beds to become available to offload their patients. Presently there is no national benchmark for EMS turnaround or offload times, or method for objectively and reliably measuring this. This study introduces a novel method for monitoring offload times and identifying variance. We performed a descriptive, observational study in a large urban community teaching hospital. We affixed radio frequency identification (RFID) tags (Confidex Survivor™, Confidex, Inc., Glen Ellyn, IL) to 65 cots from 19 different EMS agencies and placed a reader (CaptureTech Weatherproof RFID Interpreter, Barcoding Inc., Baltimore, Maryland) in the ED ambulance entrance, allowing for passive recording of traffic. We recorded data for 16 weeks starting December 2009. Offload times were calculated for each visit and analyzed using STATA to show variations in individual and cumulative offload times based on the time of day and day of the week. Results are presented as median times, confidence intervals (CIs), and interquartile ranges (IQRs). We collected data on 2,512 visits. Five hundred and ninety-two were excluded because of incomplete data, leaving 1,920 (76%) complete visits. Average offload time was 13.2 minutes. Median time was 10.7 minutes (IQR 8.1 minutes to 15.4 minutes). A total of 43% of the patients (833/1,920, 95% CI 0.41-0.46) were offloaded in less than 10 minutes, while 27% (513/1,920, 95% CI 0.25-0.29) took greater than 15 minutes. Median times were longest on Mondays (11.5 minutes) and shortest on Wednesdays (10.3 minutes). Longest daily median offload time occurred between 1600 and 1700 (13.5 minutes), whereas the shortest median time was between 0800 and 0900 (9.3 minutes). Cumulative time spent waiting beyond 15 minutes totaled 72.5 hours over the study period. RFID monitoring is a simple and effective means of monitoring EMS traffic and wait times. At our institution, most squads are able to offload their patients within 15 minutes, with many in less than 10 minutes. Variations in wait times are seen and are a topic for future study.

Nonlinear relationship between length of residence and depression in a community-based sample of Vietnamese Americans.

BACKGROUND: Length of residence has been viewed as an indicator of acculturation among immigrants and refugees in their host society. This study aims to test an inverted U relationship between length of residence and depression in a community-based sample of Vietnamese Americans. METHODS: Data were collected from a community-based survey of adult Vietnamese Americans living in an East Coast metropolitan area consisting of 349 respondents aged 18 and older. However, due to missing data, the actual sample in our regression analysis using listwise deletion method is 311. Among the participants, 52.1% are female (n = 182), and 47.9% are male (n = 167). The age of the respondents ranges from 18 to 73 years with the average age being 38.76 (SD = 13.76). The average number of years that the participants lived within the United States was 7.01 years (SD = 5.22). RESULTS: Findings from a polynomial regression analysis support the hypothesis that depression levels tend to be high during the first decade of initial resettlement. However, after approximately 12.5 years, depression levels decrease. CONCLUSION: As revealed by the data and community experts, immigrants/ refugees tend to suffer from higher levels of psychological problems during their first decade of resettlement. It takes more than a decade for a non-English-speaking immigrant or refugee to adjust psychologically into his/her host society.