Using Bayesian hierarchical modeling for performance evaluation of clinical trial accrual for a cancer center.

Introduction: Slow patient accrual in cancer clinical trials is always a concern. In 2021, the University of Kansas Comprehensive Cancer Center (KUCC), an NCI-designated comprehensive cancer center, implemented the Curated Cancer Clinical Outcomes Database (C3OD) to perform trial feasibility analyses using real-time electronic medical record data. In this study, we proposed a Bayesian hierarchical model to evaluate annual cancer clinical trial accrual performance. Methods: The Bayesian hierarchical model uses Poisson models to describe the accrual performance of individual cancer clinical trials and a hierarchical component to describe the variation in performance across studies. Additionally, this model evaluates the impacts of the C3OD and the COVID-19 pandemic using posterior probabilities across evaluation years. The performance metric is the ratio of the observed accrual rate to the target accrual rate. Results: Posterior medians of the annual accrual performance at the KUCC from 2018 to 2023 are 0.233, 0.246, 0.197, 0.150, 0.254, and 0.340. The COVID-19 pandemic partly explains the drop in performance in 2020 and 2021. The posterior probability that annual accrual performance is better with C3OD in 2023 than pre-pandemic (2019) is 0.935. Conclusions: This study comprehensively evaluates the annual performance of clinical trial accrual at the KUCC, revealing a negative impact of COVID-19 and an ongoing positive impact of C3OD implementation. Two sensitivity analyses further validate the robustness of our model. Evaluating annual accrual performance across clinical trials is essential for a cancer center. The performance evaluation tools described in this paper are highly recommended for monitoring clinical trial accrual.

Incidence of breakthrough fungal infections on isavuconazole prophylaxis compared to posaconazole and voriconazole.

BACKGROUND: Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication. The comparative prophylactic efficacy of antifungals in this patient population has not been reported, and an analysis is warranted. METHODS: This retrospective, matched cohort, single-center study, included AML, MDS, or HCT patients who began treatment or underwent transplant between January 1, 2015 and July 31, 2021. Isavuconazole patients were matched 1:2 with patients receiving posaconazole or voriconazole prophylaxis. RESULTS: A total of 126 patients were included, 42 received isavuconazole, 81 received posaconazole, and three received voriconazole. The majority of patients were male receiving secondary IFI prophylaxis while receiving steroids for treatment of GVHD. The incidence of possible, probable or proven IFI was 16.7% in the isavuconazole group compared to 10.7% in the posaconazole and voriconazole group (OR 1.28, 95% CI -0.9-1.4; p = .67). Hepatotoxicity occurred in 16 total patients, 14 receiving posaconazole and two receiving isavuconazole. CONCLUSION: Patients who received isavuconazole prophylaxis during AML induction therapy or post-HCT experienced a similar incidence of breakthrough fungal infections compared to those who received posaconazole or voriconazole. These results suggest no difference in antifungal prophylactic efficacy; however larger prospective comparative studies are needed.

Bolstering the complex study start-up process at NCI cancer centers using technology.

Background: The study startup process for interventional clinical trials is a complex process that involves the efforts of many different teams. Each team is responsible for their startup checklist in which they verify that the necessary tasks are done before a study can move on to the next team. This regulatory process provides quality assurance and is vital for ensuring patient safety [10]. However, without having this startup process centralized and optimized, study approval can take longer than necessary as time is lost when it passes through many different hands. Objective: This manuscript highlights the process and the systems that were developed at The University of Kansas Comprehensive Cancer Center regarding the study startup process. To facilitate this process the regulatory management, site development, cancer center administration, and the Biostatistics & Informatics Shared Resources (BISR) teams came together to build a platform aimed at streamlining the startup process and providing a transparent view of where a study is in the startup process. Process: Ensuring the guidelines are clearly articulated for the review criteria of each of the three review boards, i.e., Disease Working Group (DWG), Executive Resourcing Committee (ERC), and Protocol Review and Monitoring Committee (PRMC) along with a system that can track every step and its history throughout the review process. Results: Well-defined processes and tracking methodologies have allowed the operations teams to track each study closely and ensure the 90-day and 120-day deadlines are met, this allows the operational team to dynamically prioritize their work daily. It also provides Principal investigators a transparent view of where their study stands within the study startup process and allows them to prepare for the next steps accordingly. Conclusion/future work: The current process and technology deployment has been a significant improvement to expedite the review process and minimize study startup delays. There are still a few opportunities to fine-tune the study startup process; an example of which includes automatically informing the operational managers or the study teams to act upon deadlines regarding study review rather than the current manual communication process which involves them looking it up in the system which can add delays.

Long-term microtensile bond strength of surface modified zirconia.

OBJECTIVE: To compare long-term microtensile bond strength of zirconia, surface-modified via a novel treatment, to current surface conditioning methods for zirconia, when resin bonded to dental composite. METHODS: Two ProCAD (porcelain) and 10 sintered ZirCAD (ZrO(2)) blocks (18 mm × 14 mm × 12 mm) were obtained from manufacturers. Twelve Herculite XRV composite blocks were fabricated (18 mm × 14 mm × 12 mm). Bonding surface of blocks was polished through 1200-grit SiC and air-abraded (50 µm alumina, 0.28MPa, 20s). Blocks were then separated into six groups: (1) porcelain (control), HF-etched/silane-treated, (2) ZrO(2), tribochemical-coated/silane-treated, (3) ZrO(2), primer-treated, (4) ZrO(2), modified via novel 3.2 nm silica layer/silane-treated, (5) ZrO(2), modified via novel 5.8nm silica layer/silane-treated, and (6) ZrO(2), modified via novel 30.4 nm silica layer/silane-treated. Blocks were bonded to composite using Clearfil Esthetic cement. Blocks were stored in distilled water (37°C, 24h), then cut into microtensile bars (n=8/gp), then bond strengths were measured using a universal testing machine at 0, 1, 3, and 6 months. All groups were statistically analyzed (ANOVA, Tukey's, p<0.05). RESULTS: At 6 months (aging), all silica seed layer specimens displayed microtensile bond strength similar to CoJet specimens but less than that of silane-modified dental porcelain. CONCLUSION: The deposition of a silica layer on zirconia resulted in similar or superior long-term resin bond strength when compared to traditional silanation and bonding techniques for zirconia but lower than that for silane-treated dental porcelain.

Dietary soy supplement on fibromyalgia symptoms: a randomized, double-blind, placebo-controlled, early phase trial.

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

Surface roughness in ceramics with different finishing techniques using atomic force microscope and profilometer.

This study assessed the finishing and polishing of 3 ceramic materials: Vitadur Alpha, IPS Empress 2 and AllCeram. Surface modification techniques were selected to simulate dental practice. Forty-five specimens of each ceramic were divided into 5 groups of 9 specimens, which were finished using the following procedures: Group 1--glaze; Group 2--glaze, grinding and subsequent polishing with the Eve system; Group 3--glaze, grinding and subsequent polished with the Identoflex system; Group 4--glaze followed by polishing with Identoflex; Group 5--glaze, grinding and subsequent polishing with Shofu kit. Two roughness-measuring instruments were used: a stylus profilometer and an atomic force microscope (AFM). The 135 specimens were evaluated quantitatively with respect to Ra (average roughness) and Ry (maximum roughness height), and the results were examined statistically by ANOVA and Tukey's test, with a significance level of 0.05. The roughness parameter (Ra), measured by the profilometer, and AFM showed that some of the commercial intraoral polishing kits tested achieved a finish equal in smoothness to the glazed surface. According to Pearson's test, no correlation was found between the parameter Ry, measured with the profilometer, and AFM. The profilometer results for Ry demonstrated no significant differences between the final polished surfaces and the initial glazed ones. On the other hand, the Ry values obtained by AFM indicated the tested polishing kits incapability of producing smoothness comparable to the glazed surfaces.

Surface finish produced on three resin composites by new polishing systems.

This study evaluated the surface finish of three direct resin composites polished with three different systems. Disk-shaped specimens (n=16 per material; phi=8.0 mm x h=2.0 mm) were formed in a stainless steel mold by packing uncured material, either a hybrid composite (Z250, 3M ESPE) or two micro-hybrid composites (Point 4, Kerr; Esthet-X, Dentsply), and light-cured from the top and the bottom surfaces with a light-emitting diode (LED) curing unit (NRG, Dentsply). After storing the specimens in deionized water at 37 degrees C for seven days, one side of each specimen was finished through 1200-grit SiC abrasive (Buehler). Five specimens of each resin composite were randomly assigned to one of the three polishing systems (Identoflex, Kerr; Pogo, Dentsply; Sof-Lex, 3M ESPE). Manufacturers' instructions were followed during the polishing procedures. The average surface roughness (Ra) was determined by generating tracings across the polished surface of each disk using a scanning profilometer (Surfanalyzer System 5000, Federal Products Co). The results were analyzed by Kruskal-Wallis and Mann and Whitney tests (p < or = 0.05). The smoothest surfaces were produced with the celluloid strip (control group) on all the resin composites tested. The aluminum oxide disks (Sof-Lex) produced a statistically equivalent surface finish (Ra) on the three resin composites. The lowest mean roughness values were recorded with diamond micropolisher disks (PoGo) on the hybrid composite (Z250). Overall, the two new polishing systems, Identoflex and PoGo, created a comparable surface finish to that produced by the Sof-Lex system on all three resin composites.

Use of complementary and alternative medical therapies by patients referred to a fibromyalgia treatment program at a tertiary care center.

OBJECTIVE: To evaluate the frequency and pattern of complementary and alternative medicine (CAM) use in patients referred to a fibromyalgia treatment program at a tertiary care center. PATIENTS AND METHODS: Patients referred to the Mayo Fibromyalgia Treatment Program between February 2003 and July 2003 were invited on their initial visit to participate in a survey regarding CAM use during the previous 6 months. An 85-question survey that addressed different CAM domains was used. RESULTS: Of the 304 patients invited to participate, 289 (95%) completed the survey (263 women and 26 men). Ninety-eight percent of the patients had used some type of CAM therapy during the previous 6 months. The 10 most frequently used CAM treatments were exercise for a specific medical problem (48%), spiritual healing (prayers) (45%), massage therapy (44%), chiropractic treatments (37%), vitamin C (35%), vitamin E (31%), magnesium (29%), vitamin B complex (25%), green tea (24%), and weight-loss programs (20%). CONCLUSION: CAM use is common in patients referred to a fibromyalgia treatment program.