Development and Evaluation of a Multisource Approach to Extend Mortality Follow-Up for Older Adults With Advanced Cancer Enrolled in Randomized Trials.

PURPOSE: Mortality data can complement primary end points from cancer clinical trials. Yet, identifying deaths after trial completion is challenging, as timely and comprehensive vital status data are unavailable in the United States. We developed and evaluated a multisource approach to capture death data after clinical trial completion. METHODS: Individuals age 70 years and older with incurable solid tumors or lymphoma and ≥1 aging-related condition were enrolled from October 2014 to March 2019 (ClinicalTrials.gov identifier: NCT02107443 and NCT02054741). Participants provided consent to link trial information to external sources. We developed a stepped approach for extended death capture using (1) active trial follow-up up to 1 year, (2) linkage to the National Death Index (NDI), and (3) obituary searches, thus generating a 5-year survival curve. In a random sample of 50 participants who died during trial follow-up, we estimated sensitivity of death data using NDI and obituary sources and computed survival times by data source. RESULTS: The two trials enrolled 1,169 participants; mean age was 76 years; 46% were female; and gastrointestinal cancer (30%) and lung cancer (26%) were the most common cancer types. Across data sources, maximum follow-up was >7 years; 5-year survival was 18%. In total, there were 841 deaths: 603 identified during trial follow-up; 199 from the NDI; and 39 from obituary searches. The sensitivity for death capture was 92% for the NDI and 94% for the obituary searches compared with the trial data, and computed survival times were similar across data sources. CONCLUSION: Extending clinical trial mortality follow-up through linkage with external data sources was feasible and accurate. Future cancer clinical trials should collect necessary consent and patient identifiers for vital status linkages that can enhance understanding of longer-term outcomes.

Prevalence of Lung Cancer Screening in the US, 2022.

This cross-sectional study compares lung cancer screening prevalence in 2022 among individuals eligible by 2021 vs 2013 criteria by sociodemographics and state.

Nondifferential Treatment Misclassification Biases Toward the Null? Not a Safe Bet for Active Comparator Studies.

Active comparator studies are increasingly common, particularly in pharmacoepidemiology. In such studies, the parameter of interest is a contrast (difference or ratio) in the outcome risks between the treatment of interest and the selected active comparator. While it may appear treatment is dichotomous, treatment is actually polytomous as there are at least 3 levels: no treatment, the treatment of interest, and the active comparator. Because misclassification may occur between any of these groups, independent nondifferential treatment misclassification may not be toward the null (as expected with a dichotomous treatment). In this work, we describe bias from independent nondifferential treatment misclassification in active comparator studies with a focus on misclassification that occurs between each active treatment and no treatment. We derive equations for bias in the estimated outcome risks, risk difference, and risk ratio, and we provide bias correction equations that produce unbiased estimates, in expectation. Using data obtained from US insurance claims data, we present a hypothetical comparative safety study of antibiotic treatment to illustrate factors that influence bias and provide an example probabilistic bias analysis using our derived bias correction equations.

Delays in breast cancer care by race and sexual orientation: Results from a national survey with diverse women in the United States.

BACKGROUND: Despite known differences in breast cancer by both race and sexual orientation, data on the intersectional experiences of Black sexual minority women (BSMW) along the care continuum are scant. This study sought to understand delays in breast cancer care by examining the intersection of race and sexual orientation. METHODS: This online, cross-sectional survey enrolled racially and sexually diverse women aged ≥ 35 years who had been diagnosed with breast cancer within the prior 10 years or had an abnormal screening in the prior 24 months. The authors calculated summary statistics by race/sexual orientation categories, and they conducted univariate and multivariable modeling by using multiple imputation for missing data. RESULTS: BSMW (n = 101) had the highest prevalence of care delays with 5.17-fold increased odds of a care delay in comparison with White heterosexual women (n = 298) in multivariable models. BSMW reported higher intersectional stigma and lower social support than all other groups. In models adjusted for race, sexual orientation, and income, intersectional stigma was associated with a 2.43-fold increase in care delays, and social support was associated with a 32% decrease in the odds of a care delay. CONCLUSIONS: Intersectional stigma may be an important driver of breast cancer inequities for BSMW. Reducing stigma and ensuring access to appropriate social support that addresses known barriers can be an important approach to reducing inequities in the breast cancer care continuum.

Surveillance for Guillain-Barré syndrome after 2015-2016 and 2016-2017 influenza vaccination of Medicare beneficiaries.

BACKGROUND: Guillain-Barré syndrome (GBS) is a serious acute demyelinating disease, an increased risk of which was found after the 1976 swine flu vaccinations. The U.S. Food and Drug Administration, in collaboration with the Centers for Medicare & Medicaid Services, has been conducting active surveillance for GBS after influenza vaccinations of Medicare Fee-For-Service beneficiaries since 2009. METHODS: We conducted active surveillance for GBS claims in the 2015-2016 and 2016-2017 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT) to monitor for signals of GBS risk. We performed self-controlled risk interval (SCRI) analyses at the end of both seasons, including chart confirmation in the 2015-2016 season, to estimate the odds ratio of GBS risk. We used 1-42 and 8-21 days post-vaccination as primary and secondary risk windows, respectively, and 43-84 days post-vaccination as the control window. RESULTS: Over 13 million beneficiaries were vaccinated in each season. USPRT found a low magnitude signal for GBS in both seasons. SCRI analyses did not find excess GBS risk following any influenza vaccine for days 1-42 post-vaccination in either season. In the 2015-2016 season, for the 8-21 day window, our chart-confirmation showed an attributable GBS risk of 0.87 (95% CI: 0.16, 1.49) and 1.68 (95% CI: 0.69, 2.41) cases per million vaccinees after all seasonal and high dose (HD) vaccines, respectively, an elevated GBS risk for beneficiaries aged ≥75 years following all seasonal vaccines (OR: 2.25; 95% CI: 1.15, 4.39) and HD vaccine (OR: 3.67, 95% CI: 1.52, 8.85), and an elevated GBS risk for males who received seasonal vaccines (OR: 2.18; 95% CI: 1.15, 4.15) and HD vaccine (OR: 3.33; 95% CI: 1.35, 8.20). The finding of elevated GBS risk with advancing age and in males is consistent with literature; however, a distinction between HD and SD was a new finding. In the 2016-17 season, for the 8-21 day window, attributed cases showed an attributable GBS risk of 0.87 (95% CI: 0.03, 1.61) and 1.11 (95% CI: 0.00, 2.01) cases per million vaccinees after all seasonal and HD vaccines, respectively. We found no excess GBS risk for standard dose vaccines in the 8-21 day window in either season. CONCLUSIONS: Our primary analysis finding of no excess GBS risk during both seasons was reassuring. The slightly elevated GBS risk, although in the expected range, in the 8-21 day window after all seasonal and high dose vaccines, but not after standard dose vaccines is hypothesis-generating because the difference may be due to vaccine factors such as antigen amount or strains in various seasons or due to host factors.

Metformin Ameliorates Periapical Lesions through Suppression of Hypoxia-induced Apoptosis of Osteoblasts.

INTRODUCTION: Intramuscular injection of metformin has been shown to inhibit the progression of periapical lesions in rats by decreasing the number of receptor activator of nuclear factor-κß ligand- and tartrate-resistant acid phosphatase-positive cells. In this study, we investigated the effect of metformin on hypoxia-induced apoptosis of osteoblasts and the therapeutic activity of intracanal metformin in induced periapical lesions in rats. METHODS: The influence of metformin on hypoxia-induced mitochondrial superoxide production in human osteoblasts was examined by using MitoSOX (Invitrogen, Carlsbad, CA) fluorescence dye signaling. The release of cytochrome c from mitochondria and the cleavage of procaspase-9 and poly(adenosine diphosphate-ribose) polymerase were evaluated by Western blot analysis. Apoptotic cell fraction was assessed by DNA content flow cytometry. In a rat model of induced periapical lesions, the effect of intracanal metformin on disease progression was appraised by 2-dimensional radiography and micro-computed tomographic imaging. Oxidative lesions and apoptotic activity of osteoblasts in vivo were estimated, respectively, by 8-hydroxy-2'-deoxyguanosine staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: Metformin inhibited hypoxia-enhanced mitochondrial superoxide production in osteoblasts. Metformin suppressed hypoxia-induced cytochrome c release from mitochondria and the cleavage of procaspase-9 and poly(adenosine diphosphate-ribose) polymerase. Metformin repressed hypoxia-augmented apoptotic cell fraction. In a rat model, intracanal metformin diminished the size of periapical lesions and the oxidative damage and apoptotic activity in osteoblasts. CONCLUSIONS: Hypoxia increased oxidative stress in osteoblasts and enhanced cell death through activation of the mitochondrial pathway of apoptosis. Metformin attenuated the oxidative and cytotoxic action of hypoxia. The therapeutic effect of metformin on periapical lesions is partially caused by its antioxidative activity.

Evaluating a Cobalt-Tetraphenylporphyrin Complex, Functionalized with a Reduced Graphene Oxide Nanocomposite, for Improved Tooth Whitening.

OBJECTIVES: To study using cobalt-tetraphenylporphyrin/reduced graphene oxide (CoTPP/RGO), a nanocomposite highly catalytic both for oxidizing and for reducing hydrogen peroxide (H2 O2 ), to whiten teeth. METHODS: Dyes (D&C Red 34, Orange No. 4), tea, and betel nuts (Areca catechu) were used to stain the tooth specimens for three days and subsequently bleached using H2 O2 alone, H2 O2 plus CoTPP, or H2 O2 plus CoTPP/RGO for 0.5-70 hours. The process was photographed using an electronic chromometer and a camera. Color change was assessed after each session. The results of bleaching teeth with and without photoirradiation were compared. RESULTS: CoTPP/RGO increased the tooth-whitening efficacy of H2 O2 for specimens stained with dyes, tea, and betel nuts. Using lamps (photoactivation) (wavelengths: 254 nm and 310 nm) to catalyze the H2 O2 bleaching agent reduced the bleaching treatment time. CLINICAL SIGNIFICANCE: First, the Co/TPP/RGO complex allows improved tooth bleaching and shorter treatment times. Second, because the Co/TPP/RGO complex bleached D&C Red 34 at a similar rate and to a similar degree as tea and other natural agents stain teeth, it is a convenient staining agent for studying many vital aspects of tooth bleaching. (J Esthet Restor Dent 28:321-329, 2016).

Photocatalytic reduction of NO pollutant using an optical-fibre photoreactor at room temperature.

Photo-assisted catalytic reduction of nitric oxide (NO) was studied over different metal-loaded TiO2 catalysts at room temperature. The activities of metal-loaded (Pt, Ag, Cu) TiO2 photocatalysts, prepared by the sol-gel method, were compared in a batch system using CH4 as the reducing agent. The Pt/TiO2 catalyst showed the highest activity for NO reduction. Thus, Pt/TiO2 was coated on optical fibres and used in a continuous-flow optical-fibre photoreactor. The optical-fibre photoreactor provides light irradiation on the photocatalyst through the optical fibre, thus improving the efficiency ofphotoreactions. Ten per cent conversion of NO was found using CH4 as the reducing agent. The NO conversions increased to 90% in the presence of water vapour and oxygen. However, most NO was oxidized to NO2. Hydrogen had superior reducing capabilities over CH4 on Pt/TiO2 photocatalyst, and the conversion of NO reached 85%. But the conversion of NO was substantially decreased to less than 10% in the presence of water vapour and oxygen. Our research proposed an alternative way to reduce NO pollutant to N2 at room temperature using an optical-fibre photoreactor, which could possibly utilize sunlight in the future.