Efficacy and safety of maintenance therapy with pamiparib versus placebo for advanced gastric cancer responding to first-line platinum-based chemotherapy: Phase 2 study results.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for the treatment of various solid tumors. In gastric cancer, genes commonly harbor mutations in the homologous recombination DNA repair pathway, potentially increasing sensitivity to PARPi. Pamiparib (BGB-290) is a small molecule inhibitor of PARP1 and PARP2. METHODS: The PARALLEL-303 study (NCT03427814) investigated the efficacy and safety of pamiparib 60 mg orally (PO) twice daily (BID) versus placebo PO BID as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy. The primary endpoint of this double-blind, randomized, global phase 2 study was progression-free survival (PFS) (RECIST version 1.1; per investigator assessment). Secondary endpoints included overall survival (OS) and safety. RESULTS: In total, 136 patients were randomized 1:1 to receive pamiparib (n = 71) or placebo (n = 65). Median PFS was numerically longer with pamiparib versus placebo but did not reach statistical significance (3.7 months [95% confidence interval (CI): 1.9, 5.3] vs. 2.1 months [95% CI: 1.9, 3.8]; hazard ratio 0.8 [95% CI: 0.5, 1.2]; p = 0.1428). Median OS was 10.2 months (95% CI: 8.7, 16.3) in the pamiparib arm versus 12.0 months (95% CI: 8.2, not estimable) in the placebo arm. Overall, 8 patients (11.3%) in the pamiparib arm and 2 patients (3.1%) in the placebo arm experienced ≥1 TEAE leading to treatment discontinuation. CONCLUSIONS: Maintenance pamiparib did not meet statistical significance for superiority versus placebo for PFS, but was well tolerated with few treatment discontinuations; no unexpected safety signals were identified.

Association between Medicaid expansion status and lung cancer screening exam growth: findings from the ACR lung cancer registry.

PURPOSE: To determine if Medicaid expansion is associated with increased volumes of lung cancer screenings. METHODS: A quasi-experimental study was performed to compare the annual growth rates in lung cancer screenings between states that expanded Medicaid (n = 31) versus those that did not (n = 17). Using the American College of Radiology Lung Cancer Screening Registry, we calculated the average annual growth rate between 2016 and 2019 for both groups. Secondary analyses between these two groups also included calculations of the percentages of studies considered appropriate by USPSTF criteria. RESULTS: No significant difference was identified in the average annual growth in lung cancer screenings between Medicaid expanding and non-expanding states (57.6%, 50.3%, P = 0.51). No difference was observed in the percentage of studies considered appropriate (Medicaid expanding = 89.6%, non-expanding = 90.2%, P = 0.72). At baseline, there were socioeconomic differences between both groups of states. Medicaid expanding states had a more urban population (76.5% versus 67.9%, P = 0.05) and higher average incomes ($56,947, $49,876, P < 0.05). CONCLUSION: No association is found between Medicaid expansion and increasing volumes of lung cancer screening exams. Although no data is available in the registry for screening exams before the implementation of Medicaid expansion (2014), most nationwide estimates of lung screening rates report a low baseline (<5%). Furthermore, despite being advantaged in other ways, such as with a more urban population or with higher incomes, the Medicaid expansion cohort does not demonstrate a higher growth rate. These findings suggest Medicaid expansion alone will not increase lung cancer screenings.

High deductible health plans: does cost sharing stimulate increased consumer sophistication?

OBJECTIVE: To determine whether increased cost sharing in health insurance plans induces higher levels of consumer sophistication in a non-elderly population. STUDY DESIGN: This analysis is based on the collection of survey and demographic data collected from enrollees in the RAND health insurance experiment (HIE). During the RAND HIE, enrollees were randomly assigned to different levels of cost sharing (0, 25, 50 and 95%). METHODS: The study population compromises about 2000 people enrolled in the RAND HIE, between the years 1974 and 1982. Effects on health-care decision making were measured using the results of a standardized questionnaire, administered at the beginning and end of the experiment. Points of enquiry included whether or not enrollees' (i) recognized the need for second opinions (ii) questioned the effectiveness of certain therapies and (iii) researched the background/skill of their medical providers. Consumer sophistication was also measured for regular health-care consumers, as indicated by the presence of a chronic disease. PRINCIPAL FINDINGS: We found no statically significant changes (P < 0.05) in the health-care decision-making strategies between individuals randomized to high cost sharing plans and low cost sharing plans. Furthermore, we did not find a stronger effect for patients with a chronic disease. CONCLUSIONS: The evidence from the RAND HIE does not support the hypothesis that a higher level of cost sharing incentivizes the development of consumer sophistication. As a result, cost sharing alone will not promote individuals to become more selective in their health-care decision-making.

Preventing waterborne diseases: analysis of a community health worker program in rural Tamil Nadu, India.

Community health worker (CHW) programs have become popular tools in reducing the burden of childhood illnesses. However, the efficacy of CHWs in facilitating behavior change, as a means of preventing waterborne diseases, remains unclear. Using a household survey (n = 225),in rural Tamil Nadu, South India, we assessed the effects of a CHW program on knowledge, attitudes and practices related to diarrheal illness through comparison with a control population that was not enrolled in the program. The CHW program in the experimental village entailed behavior change aimed at preventing diarrheal illness through home visits, community events and health education. Correlates of four key variables on knowledge of drinking water contamination and behavior change were examined by using logistic regression models. We found that while the program was effective in raising awareness of drinking water contamination, it did not significantly increase hygiene and water sanitation practices in the village community in comparison to the control population. Furthermore, villagers enrolled in the CHW program were unable to recognize the connections between contaminated drinking water and disease. The results of our survey indicated the CHW program did not significantly affect behavior in the experimental village. Possible shortcomings in the program are discussed.

The organic preservation of fossil arthropods: an experimental study.

Modern arthropod cuticles consist of chitin fibres in a protein matrix, but those of fossil arthropods with an organic exoskeleton, particularly older than Tertiary, contain a dominant aliphatic component. This apparent contradiction was examined by subjecting modern cockroach, scorpion and shrimp cuticle to artificial maturation (350 degrees C/700 bars/24 h) following various chemical treatments, and analysing the products with pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Analysis of artificially matured untreated cuticle yielded moieties related to phenols and alkylated substituents, pyridines, pyrroles and possibly indenes (derived from chitin). n-Alkyl amides, C16 and C18 fatty acids and alkane/alk-1-ene homologues ranging from C9 to C19 were also generated, the last indicating the presence of an n-alkyl component, similar in composition to that encountered in fossil arthropods. Similar pyrolysates were obtained from matured pure C16 and C18 fatty acids. Py-GC/MS of cuticles matured after lipid extraction and hydrolysis did not yield any aliphatic polymer. This provides direct experimental evidence that lipids incorporated from the cuticle were the source of aliphatic polymer. This process of in situ polymerization appears to account for most of the fossil record of terrestrial arthropods as well as marine arthropods that lacked a biomineralized exoskeleton.