SWOG 1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers

Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Gemcitabine-based regimens are the standard of care in advanced disease, but median overall survival (OS) is roughly 12 months. The addition of albumin-bound paclitaxel to gemcitabine and cisplatin (GAP) demonstrated promising efficacy in a 60 patient, single-arm phase II study (Shroff et al, JAMA Oncol 2019), with observed median OS of 19.2 months. Methods: SWOG 1815 is a randomized, open-label, phase III trial comparing GAP to gemcitabine/cisplatin (GC). The study included newly diagnosed advanced BTC patients (pts), randomized 2:1 to GAP vs. GC. GAP included gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2 and albumin-bound paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. GC included standard dosing of gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of a 21-day cycle. Pts were treated until progression. The primary endpoint was overall survival (OS) with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025; randomization was stratified by disease site (intrahepatic cholangiocarcinoma [CCA] vs gallbladder adenocarcinoma [GBC] vs extrahepatic CCA), disease stage (locally advanced vs metastatic), and Zubrod PS 0 vs 1. Results: Of 441 eligible pts randomized, 55% were female. 67% of patients had intrahepatic CCA, 16% had GBC and 17% had extrahepatic CCA. Most pts had metastases (73%). Median OS with GAP vs. GC was 14 vs. 12.7 mo respectively (HR 0.93, 95% CI 0.74-1.19, p=0.58), ORR (confirmed and unconfirmed) 34% vs25% (p=0.11) and median PFS 8.2 vs 6.4 mo (HR 0.92, 95% CI 0.72-1.16, p=0.47), respectively. Grade 3 and 4 treatment related adverse events (TRAEs) in ≥10% of pts for GAP and GC were anemia, neutropenia, and thrombocytopenia. GAP had more ≥ grade 3 hematologic AEs compared to the GC arm (60% vs. 45%, p=0.003). Discontinuation due to toxicity was at 24% vs 19% (p=0.26) with GAP vs GC. In exploratory subset analyses, GAP vs GC improved OS in pts with locally advanced disease (medians 19.2 vs 13.7 mo; HR 0.67, 95% CI 0.42- 1.06, p=0.09) and in GBC pts (medians 17.0 vs 9.3 mo; HR 0.74, 95% CI 0.41-1.35, p=0.33). ORR for GAP vs GC in GBC was 50% vs 24% (p=0.09) and for locally advanced disease 28 vs 21% p=0.74. Conclusions: SWOG 1815 did not result in a statistically significant improvement in median OS with GAP vs. GC. The GAP regimen had higher rates of TRAEs without a statistically significant difference in discontinuation rates. Pts with locally advanced disease and GBC may benefit from the use of GAP. Further analyses are ongoing to understand potential benefit of GAP in subsets of BTC pts. Funding: NIH/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, and CA180868; and in part by Celgene Corporation, Summit, NJ (subsidiary of Bristol Myer Squibb)

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Longitudinal trends in enrollees’ employment and student status after Medicaid expansion

Abstract Background Medicaid community engagement requirements previously received federal approval in 12 states, despite limited data on their impact on enrollees’ employment-related activities. Our objective was to assess longitudinal changes in enrollees’ employment and student status after implementation of Michigan’s Medicaid expansion. Methods Longitudinal telephone survey of Michigan Medicaid expansion enrollees in 2016 (response rate [RR] = 53.7%), 2017 (RR = 83.4%), and 2018 (N = 2,608, RR = 89.4%) serially assessing self-reported employment or student status. Survey responses were benchmarked against statewide changes in assessed similar low-income adults in the U.S. Census Bureau Current Population Survey. We used mixed models with individual random effects to assess changes in the proportion of enrollees who were employed or students by year. Results Most respondents had incomes < 100% FPL (61.7% with 0–35% of the federal poverty level [FPL], 22.9% with 36–99% FPL, and 15.4% with 100–133% FPL), 89.3% had at least a high school diploma/equivalent, and they ranged in age (39.6% age 19–34, 34.5% age 35–50, 25.9% age 51–64). Employment or student status increased significantly among Michigan Medicaid expansion respondents, from 54.5% in 2016 to 61.4% in 2018 (P < 0.001), including among those with a chronic condition (47.8% to 53.8%, P < 0.001) or mental health/substance use disorder (48.5% to 56.0%, P < 0.001). In contrast, the statewide proportion of low-income non-elderly adults who were employed or students did not change significantly (from 42.7% in 2016 to 46.0% in 2018, P = 0.57). Conclusions Medicaid expansion, absent a community engagement requirement, was associated with increased employment and related activities. The role of Medicaid in providing safety-net coverage to individuals during times of economic stress is likely to grow.http://deepblue.lib.umich.edu/bitstream/2027.42/173785/1/12913_2022_Article_7599.pd

Morphological Comparison of the Maxillary Arch in Buccal and Palatal Canine Impaction among Asian Population of Gujarati Origin: A Hospital-Based Study

Aim: To estimate the differences in the maxillary arch morphology in buccal and palatal canine impaction in an Asian population of Gujarati origin. Methodology: An institutional ethics committee’s approval was acquired before the commencement of this study. Sixty subjects were enrolled in the study. Thirty subjects (20 females and 10 males) had a maxillary impacted canine either buccal or palatal and thirty control group participants were selected aged 13 to 18 years who sought orthodontic treatment at the tertiary health care center in Ahmedabad, Gujarat, in western India. Routine pre-treatment radiographs and dental plaster models with good anatomic details were recorded. Measurements of the inter-molar width, palatal depth, arch length, sum of the mesio-distal width of the upper incisors, and available arch space were recorded from prepared orthodontic study models using digital vernier calipers with an accuracy of 0.01 mm and brass wire. The ratio of palatal depth to inter-molar width (Ratio 1), arch length to inter-molar width (Ratio 2), and width of the maxillary incisors to available arch space (Ratio 3) were also secondarily calculated. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 21, IBM Inc. The normality of the data was assessed by the Shapiro–Wilk test. As the data was found to be normally distributed, bivariate analyses were also performed (one-way ANOVA test, Bonferroni post hoc correction). The level of statistical significance was set at a p-value less than 0.05. Results: The comparison of the inter-molar width, palatal depth, arch length, sum of the mesio-distal width of the upper incisors, available arch space, Ratio 1, Ratio 2, and Ratio 3 among controls and subjects with buccal and palatal canine impaction showed overall significant differences in the inter-molar width, palatal depth, arch length, sum of the mesio-distal width of the upper incisors, and available arch space when compared using one-way ANOVA as p p p p p < 0.0001) with a clinically reduced mesiodistal width of the sum of maxillary incisors may be considered as risk factors for palatal maxillary canine impaction in an Asian population of Gujarati origin

Beneficiaries’ perspectives on improved oral health and its mediators after Medicaid expansion in Michigan: a mixed methods study

ObjectiveTo investigate self-reported improved oral health and its mediators, and job-related outcomes, of Medicaid expansion beneficiaries in Michigan.MethodsThis cross-sectional mixed-methods study of adult “Healthy Michigan Plan” (HMP) Medicaid expansion beneficiaries included qualitative interviews with a convenience sample of 67 beneficiaries enrolled for ≥6 months, a stratified random sample survey of 4,090 beneficiaries enrolled for ≥12 months; and Medicaid claims data. We examined unadjusted associations between demographic variables and awareness of dental coverage, self-reported dental care access, dental visits, and self-reported oral health; and between improved oral health and job seeking and job performance. Multivariate analysis examined factors associated with self-reported oral health improvement, adjusting for sociodemographic characteristics, prior health insurance, and having at least one dental visit claim.ResultsAmong surveyed beneficiaries, 60 percent received ≥1 dental visit and 40 percent reported improved oral health. Adjusted odds ratios (aOR) for improved oral health were higher for African-American beneficiaries [aOR = 1.61; confidence interval (CI) = 1.28-2.03] and those previously uninsured for ≥12 months (aOR = 1.96; CI = 1.58-2.43). Beneficiaries reporting improved oral health were more likely to report improved job seeking (59.9 percent vs 51 percent; P = 0.04) and job performance (76.1 percent vs 65.0 percent; P < 0.001) due to HMP. Interviewees described previously unmet oral health needs, and treatments that improved oral health, functioning, appearance, confidence, and employability.ConclusionMichigan’s Medicaid expansion contributed to self-reported improved oral health, which was associated with improved job outcomes. Policymakers should consider the importance of Medicaid dental coverage in reducing oral health disparities and improving the health and socioeconomic well-being of low-income adults and communities when considering this optional benefit.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171987/1/jphd12447_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171987/2/jphd12447.pd

RNAi modulation of placental sFLT1 for the treatment of preeclampsia

Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1mRNA. Full chemical stabilization in the context of hydrophobic modifications enabled productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduced circulating sFLT1 in pregnant mice (up to 50%). In a baboon preeclampsia model, a single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of preeclampsia. Our results demonstrate RNAi-based extrahepatic modulation of gene expression with nonformulated siRNAs in nonhuman primates and establish a path toward a new treatment paradigm for patients with preterm preeclampsia