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e18845 Background: Glioblastoma (GBM) is the most common and aggressive of the primary malignant brain tumors in adults. Bevacizumab (beva) remains the only currently approved therapeutic for recurrent GBM (rGBM) patients who progress on prior therapy. Despite advances in care, rGBM has a median expected progression-free survival (PFS) of < 4 months and overall survival (OS) of ~8 months. NCCN guidelines [Version 2.2022], and other oncology medical societies unanimously recommend patients seek treatment by entering a clinical trial. Since the late 1990’s a number of studies have explored the use of convection-enhanced delivery (CED) of drugs, a well-accepted and widely published delivery option for the treatment of rGBM. This analysis compares the demographics, medical history and survival outcome of patients enrolled into recently completed clinical trials with beva monotherapy to those entered into CED studies. Methods: Data for this analysis was sourced from the Medidata Enterprise Data Store (MEDS), comprised of over 28,000 historical clinical trials for de-identified aggregate patient-level analyses and from the study and patient-level data in the CED studies referenced in D’Amico [J Neurooncol 2021]. Aggregate summary statistics comparing beva and CED patients were based on combined study- and patient-level data using weighted (by sample size) means, incidence and overall survival (OS) rates and median of medians. Results: 163 rGBM beva patients were identified from MEDS. The CED cohort included 636 patients from MEDS and studies referenced in D’Amico. Cohort comparisons (beva vs CED) found median age: 56 vs 55 years; Caucasian race: 91% vs 93%; male sex: 68% vs 65%; not Hispanic or Latino ethnicity: 90% vs 94%; median OS: 7.9 vs 8.4 months. Over the last 2 decades there was a 23% increase in patients with ECOG Performance Status = 0 and 25% decrease in tumor area size at study enrollment, whereas there was no clear temporal OS trend. Conclusions: Patient demographics and most tumor attribute variables were similarly distributed between the beva and CED cohorts. While there is some indication that recent CED studies have enrolled healthier patients with smaller tumors; as expected, this does not appear to have translated to a consistent survival benefit.

Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients. Patients not responding to siltuximab often require immediate therapeutic changes to avert life-threatening multi-organ failure, but no biomarkers exist to provide an early indication after treatment initiation whether siltuximab is likely to work. We analyzed 1,178 proteins in iMCD (N=88), healthy control (N=42), and related disease (N=60) patients’ sera to search for disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) was identified and validated as a top up-regulated protein in iMCD. CXCL13 also demonstrated early and significant decline in siltuximab responders compared to non-responders; a 17% reduction by day 8 following siltuximab initiation was predictive of response. Our discoveries suggest that CXCL13 is a predictive biomarker of response to siltuximab.

Objective: The comparative effectiveness of low-dose budesonide inhalation suspension (BIS) versus oral montelukast (MON) in managing asthma control among children with mild asthma was assessed in Korea.Methods: Claims from Korea’s national health insurance database for children (2–17 years) with mild asthma (GINA 1 or 2) who initiated BIS or MON during 2015 were retrospectively analyzed. Pre- and post-index windows were 1 year each. Adherence, persistency, asthma control, asthma-related health-care resource utilization, and costs were evaluated using unadjusted descriptive statistics and propensity score-matched regression analyses.Results: The number of children identified was 26,052 for unmatched (n = 1,221 BIS; n = 24,831 MON) and 2,290 for matched populations (n = 1,145 per cohort). Medication adherence, measured by proportion of days covered, was low for both cohorts but significantly higher for MON versus BIS (13.8% vs. 4.5%; p < .001). Time to loss of persistency was longer for MON versus BIS (82.3 vs. 78.4 days, respectively; p < .001). Mean number of post-index asthma-related office visits was 6.6 for BIS versus 8.3 for MON (p < .001). However, a greater proportion of patients in the BIS cohort had an asthma exacerbation-related office visit than the MON cohort (78.3% vs. 56.1%; p < .001). Asthma-related total health-care costs were higher with MON versus BIS (₩ 190,185 vs. ₩ 167,432, respectively; p < .001), likely driven by higher pharmaceutical costs associated with MON (₩ 69,113 vs. ₩ 49,225; p < .001).Conclusions: Montelukast patients had better adherence, a longer time to loss of persistency, and were less likely to experience an exacerbation-related office visit in the post-index period than BIS patients.

ObjectivesWe aimed to estimate the prevalence and correlates of QT interval prolongation in rural Uganda. BackgroundMajor electrocardiographic abnormalities, including prolonged QT interval, have been shown to be independently predictive of adverse cardiovascular events among Western populations. Cardiovascular diseases are on the rise in sub-Saharan Africa with poorly characterized context-specific risk factors. An important question is whether ECG screening might have value in cardiovascular disease risk stratification in SSA. MethodsWe conducted a cross-sectional survey in a sample of adults participating in an ongoing whole-population cohort in Mbarara, Uganda, in 2015. Of 1,814 subjects enrolled in the parent whole-population cohort, 856 (47%) participated in the study. Participants completed 12-lead electrocardiography and cardiovascular disease risk factors assessment. We summarized sex-specific, heart rate variation–adjusted QT (QTa) defining prolonged QTa as >460 ms in women and >450 ms in men. We fit linear and logistic regression models to estimate correlates of (continuous) QTa interval length and (dichotomous) prolonged QTa. Models included inverse probability of sampling weights to generate population-level estimates accounting for study nonparticipation. ResultsWe assessed data from 828 participants with electrocardiograms. The weighted population mean age was 38.4 years (95% confidence interval: 36.3–40.4). The weighted population was 50.4% female, 11.5% had elevated blood pressure, and 57.6% had a high-sensitivity C-reactive protein >1 mg/dl. The population mean QTa was 409.1 ms (95% confidence interval: 405.1–413.1), and 10.3% (95% confidence interval: 7.8–13.5) met criteria for prolonged QTa. Women had a higher mean QTa (421.6 ms vs. 396.3 ms; p < 0.001), and a higher proportion of women had a prolonged QTa (14.0% vs. 9.3%; p = 0.122) than did men. In multivariable-adjusted regression models, female sex and hypertension correlated with higher mean QTa and meeting criteria for prolonged QTa, respectively. ConclusionsQT interval prolongation is highly prevalent in rural Uganda and may be more common than in high-income settings. Female sex, age, and high blood pressure correlated with QT interval prolongation. Future work should assess whether genetic predisposition or environmental factors in sub-Saharan African populations contribute to prolonged QT and clarify consequences.

Objective:Patients in long-term care (LTC) are at increased risk for acquiring Clostridium difficile infection (CDI). We compared the characteristics and outcomes of matched cohorts with and without CDI in the LTC setting.Methods:Using a retrospective cohort design, demographic characteristics, Minimum Data Set (MDS 2.0) assessments (years 2007–2010), and pharmacy records of residents were analyzed. Residents were required to have a CDI diagnosis, ≥1 MDS 2.0 assessment ≤120 days pre- and post-index event, and receipt of metronidazole (MET) or vancomycin (VAN) within ±7 days of index date. Baseline characteristics were compared between cases and controls matched 1:3 on age, gender, and index year. Cox regression (CR) analysis evaluated the relationship between CDI status, and post-index mortality and hospitalization.Results:A total of 1145 CDI residents were matched with 3488 non-CDI residents. A second sample used propensity score methods. CDI vs. non-CDI residents had a higher baseline comorbidity burden (Charlson score: 3.0 ± 1.9 vs. 2.2 ± 1.8, respectively), and were more likely to have had a recent hospitalization (63% vs. 9%, respectively) and shorter mean pre-index continuous length of stay (cLOS) in the LTC (386.4 d ± 536.3 d vs. 568.3 d ± 567.4 d, respectively), all P < 0.0001. CR analyses of both samples indicated that CDI was strongly associated with shorter times to hospitalization and mortality (hazard ratio (HR) = 1.3, P = 0.023 and 2.2, P < 0.0001, respectively; propensity-matched group). Pre-index LTC cLOS also remained an important variable in the CR analysis and was the strongest predictor of post-index hospitalization and mortality (HR = 0.999 and 0.996, respectively, P < 0.0001), indicating that residents with longer pre-index LTC cLOS had longer times to post-index hospitalization and mortality. Our reliance on the MDS records for case identification was our chief limitation; misclassification was mitigated by our requirement to include CDI treatment as part of our inclusion criteria.Conclusions:Understanding factors that put LTC patients at risk for CDI can help guide better management and improvement of patient outcomes.

The Tufts Center for the Study of Drug Development analyzed 8,317 clinical trial protocols to benchmark protocol complexity by phase and therapeutic area and to characterize trends in clinical trial complexity and the burden placed on study staff to execute protocol procedures between 2000 and 2007. Wide variability in protocol complexity and work burden was observed across therapeutic areas, within and between clinical research phases. Phase 1 protocols are the most complex and the most demanding to execute. The mean number of total procedures per protocol in phase 4 studies and the work burden associated with phase 1 protocols grew the fastest between the periods 2000-2003 and 2004–2007. The complexity and work burden of phase 3 protocols also grew rapidly during this period. Protocols in anti-infectives, immunomodulation, CNS, and oncology are consistently the most complex and burdensome to execute. Reasons for the wide variability in protocol complexity and work burden by phase and therapeutic area are discussed. This study provides insight into areas where protocol design improvements should be targeted.