Comparing Catastrophic Costs: Active vs. Passive Tuberculosis Case Finding in Urban Vietnam.

Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO's End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded.

Information fraction estimation: Strategies for a phase 3 non-inferiority maximum duration design with time to event outcome.

There is considerable debate surrounding the choice of methods to estimate information fraction for futility monitoring in a randomized non-inferiority maximum duration trial. This question was motivated by a pediatric oncology study that aimed to establish non-inferiority for two primary outcomes. While non-inferiority was determined for one outcome, the futility monitoring of the other outcome failed to stop the trial early, despite accumulating evidence of inferiority. For a one-sided trial design for which the intervention is inferior to the standard therapy, futility monitoring should provide the opportunity to terminate the trial early. Our research focuses on the Total Control Only (TCO) method, which is defined as a ratio of observed events to total events exclusively within the standard treatment regimen. We investigate its properties in stopping a trial early in favor of inferiority. Simulation results comparing the TCO method with alternative methods, one based on the assumption of an inferior treatment effect (TH0), and the other based on a specified hypothesis of a non-inferior treatment effect (THA), were provided under various pediatric oncology trial design settings. The TCO method is the only method that provides unbiased information fraction estimates regardless of the hypothesis assumptions and exhibits a good power and a comparable type I error rate at each interim analysis compared to other methods. Although none of the methods is uniformly superior on all criteria, the TCO method possesses favorable characteristics, making it a compelling choice for estimating the information fraction when the aim is to reduce cancer treatment-related adverse outcomes.

Evaluating novel engagement mechanisms, yields and acceptability of tuberculosis screening at retail pharmacies in Ho Chi Minh City, Viet Nam.

Pharmacies represent a key health system entry point for people with TB in Viet Nam, but high fragmentation hinders their broader engagement. Professional networking apps may be able to facilitate pharmacy engagement for systematic TB screening and referral. Between September and December 2019, we piloted the use of a social networking app, SwipeRx, to recruit pharmacists for a TB referral scheme across four districts of Ho Chi Minh City, Viet Nam. We measured chest X-ray (CXR) referrals and TB detection yields at participating pharmacies and fielded 100 acceptability surveys, divided into pharmacists who did and did not make a CXR referral. We then fitted mixed-effect odds proportional models to explore acceptability factors that were associated with making a CXR referral. 1,816 push notifications were sent to pharmacists via the SwipeRx app and 78 indicated their interest in participating; however, only one was within the pilot's intervention area. Additional in-person outreach resulted in the recruitment of 146 pharmacists, with 54 (37.0%) making at least one CXR referral. A total of 182 pharmacy customers were referred, resulting in a total of 64 (35.2%) CXR screens and seven people being diagnosed with TB. Compared to pharmacists who did not make any CXR referrals, pharmacists making at least one CXR referral understood the pilot's objectives more clearly (aOR = 2.6, 95% CI: 1.2-5.8) and they believed that TB screening increased customer trust (aOR = 2.7, 95% CI: 1.2-5.8), benefited their business (aOR = 2.8, 95% CI: 1.3-6.2) and constituted a competitive advantage (aOR = 4.4, 95% CI: 1.9-9.9). They were also more confident in using mHealth apps (aOR = 3.1, 95 CI%: 1.4-6.8). Pharmacies can play an important role in early and increased TB case finding. It is critical to highlight the value proposition of TB referral schemes to their business during recruitment. Digital networking platforms, such as SwipeRx, can facilitate referrals for TB screening by pharmacists, but their ability to identify and recruit pharmacists requires optimization, particularly when targeting specific segments of a nation-wide digital network.

Outcome of patients with relapsed or progressive Ewing sarcoma enrolled on cooperative group phase 2 clinical trials: A report from the Children's Oncology Group.

SevenChildren's Oncology Group phase 2 trials for patients with relapsed/progressive solid tumors were analyzed to estimate the event-free survival (EFS) for relapsed/progressive Ewing sarcoma. One hundred twenty-eight Ewing sarcoma patients were enrolled and 124 events occurred. The 6-month EFS was 12.7%, demonstrating the poor outcome of these patients. Only docetaxel achieved its protocol-specified radiographic response rate for activity; however, the EFS for docetaxel was similar to other agents, indicating that a higher radiographic response rate may not translate into superior disease control. This EFS benchmark could be utilized as an additional endpoint in trials for recurrent Ewing sarcoma.

Information fraction estimation based on the number of events within the standard treatment regimen.

For a Phase III randomized trial that compares survival outcomes between an experimental treatment versus a standard therapy, interim monitoring analysis is used to potentially terminate the study early based on efficacy. To preserve the nominal Type I error rate, alpha spending methods and information fractions are used to compute appropriate rejection boundaries in studies with planned interim analyses. For a one-sided trial design applied to a scenario in which the experimental therapy is superior to the standard therapy, interim monitoring should provide the opportunity to stop the trial prior to full follow-up and conclude that the experimental therapy is superior. This paper proposes a method called total control only (TCO) for estimating the information fraction based on the number of events within the standard treatment regimen. Based on theoretical derivations and simulation studies, for a maximum duration superiority design, the TCO method is not influenced by departure from the designed hazard ratio, is sensitive to detecting treatment differences, and preserves the Type I error rate compared to information fraction estimation methods that are based on total observed events. The TCO method is simple to apply, provides unbiased estimates of the information fraction, and does not rely on statistical assumptions that are impossible to verify at the design stage. For these reasons, the TCO method is a good approach when designing a maximum duration superiority trial with planned interim monitoring analyses.

Association of hot flushes with ghrelin and adipokines in early versus late postmenopausal women.

OBJECTIVE: Vasomotor flushing (hot flushes) is a common menopausal symptom experienced by most women going through the menopausal transition; flushing continues for a variable period in postmenopause. Primarily due to lack of ovarian estrogen, other biomarkers of hot flushes have not been clearly identified. We examined the relationship of hot flushes with ghrelin and adipokines. METHODS: Baseline data from two clinical trials, the Women's Isoflavone Soy Health (WISH) trial and Early versus Late Intervention Trial of Estrogen (ELITE), were used in this post hoc cross-sectional study. Both WISH and ELITE had similar study designs, inclusion criteria, and data collection processes. Study participants were healthy postmenopausal women not taking estrogen-based hormone therapy, free of cardiovascular disease, or any other chronic diseases. Both trials used the same hot flush diary in which participants recorded the number of daily hot flushes by severity over a month on average. Serum concentrations of ghrelin, leptin, adiponectin, and resistin were assessed in stored fasting blood samples using highly specific radioimmunoassay. In this analysis, self-reported flushing experience was tested for an association with leptin, adiponectin, resistin, and ghrelin concentrations using logistic regression and mean comparisons. RESULTS: A total of 898 postmenopausal women from the ELITE and WISH trials contributed to this analysis. Mean (SD) age was 60.4 (7.0) years, body mass index (BMI) 27 (5.3) kg/m, 67% were white, and 47% were within 10 years of menopause. Reported flushing was significantly associated with younger age, lower education, lower BMI, being married, and more recent menopause. Adjusted for these factors other than BMI, women in the highest quartile of ghrelin had significantly greater likelihood of experiencing hot flushes (OR [95% CI] = 1.84 [1.21-2.85]) compared to women in the lowest quartile. The association was more pronounced among overweight or obese women (OR [95% CI] = 2.36 [1.28-4.35]) compared to those with normal BMI (1.24 [0.54, 2.86]; interaction P value = 0.46). The association between ghrelin and hot flushes was similar among early (within 10 y) and late (over 10 y) postmenopausal women. Blood levels of adiponectin and resistin were not associated with hot flushes. CONCLUSIONS: Higher concentrations of ghrelin were associated with greater likelihood of hot flushes in both early- and late-postmenopausal women. Leptin, adiponectin, and resistin levels were not associated with hot flushes in postmenopausal women.

Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration.

During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.