Inselman, Jonathan

Background: Patients with atrial fibrillation and severely decreased kidney function were excluded from the pivotal non–vitamin K antagonist oral anticoagulants (NOAC) trials, thereby raising questions about comparative safety and effectiveness in patients with reduced kidney function. The study aimed to compare oral anticoagulants across the range of kidney function in patients with atrial fibrillation. Methods and Results: Using a US administrative claims database with linked laboratory data, 34 569 new users of oral anticoagulants with atrial fibrillation and estimated glomerular filtration rate ≥15 mL/(min·1.73 m 2 ) were identified between October 1, 2010 to November 29, 2017. The proportion of patients using NOACs declined with decreasing kidney function—73.5%, 69.6%, 65.4%, 59.5%, and 45.0% of the patients were prescribed a NOAC in estimated glomerular filtration rate ≥90, 60 to 90, 45 to 60, 30 to 45, 15 to 30 mL/min per 1.73 m 2 groups, respectively. Stabilized inverse probability of treatment weighting was used to balance 4 treatment groups (apixaban, dabigatran, rivaroxaban, and warfarin) on 66 baseline characteristics. In comparison to warfarin, apixaban was associated with a lower risk of stroke (hazard ratio [HR], 0.57 [0.43–0.75]; P <0.001), major bleeding (HR, 0.51 [0.44–0.61]; P <0.001), and mortality (HR, 0.68 [0.56–0.83]; P <0.001); dabigatran was associated with a similar risk of stroke but a lower risk of major bleeding (HR, 0.57 [0.43–0.75]; P <0.001) and mortality (HR, 0.68 [0.48-0.98]; P =0.04); rivaroxaban was associated with a lower risk of stroke (HR, 0.69 [0.51–0.94]; P =0.02), major bleeding (HR, 0.84 [0.72–0.99]; P =0.04), and mortality (HR, 0.73 [0.58–0.91]; P =0.006). There was no significant interaction between treatment and estimated glomerular filtration rate categories for any outcome. When comparing one NOAC to another NOAC, there was no significant difference in mortality, but some differences existed for stroke or major bleeding. No relationship between treatments and falsification end points was found, suggesting no evidence for substantial residual confounding. Conclusions: Relative to warfarin, NOACs are used less frequently as kidney function declines. However, NOACs appears to have similar or better comparative effectiveness and safety across the range of kidney function.

SummaryBackgroundGastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood.AimTo compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .MethodsPropensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1‐year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).ResultsWe identified 37 019 patients with ACS (non‐ST elevation ACS [NSTE‐ACS] and ST‐elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54–0.81) in GIB overall and with NSTE‐ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42–0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64–0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49–0.85) in STEMI patients but no reduction of GIB risk in NSTE‐ACS patients.ConclusionsIn the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.

Objective To identify the relationships between county-level area deprivation and patterns of both opioid prescriptions and drug-poisoning mortality. Design, setting and participants For this retrospective cross-sectional study, we used the IQVIA Xponent data to capture opioid prescriptions and Centres for Disease Control and Prevention National Vital Statistics System to assess drug-poisoning mortality. The Area Deprivation Index (ADI) is a composite measure of social determinants of health comprised of 17 US census indicators, spanning four socioeconomic domains. For all US counties with available opioid prescription (2712 counties) and drug-poisoning mortality (3133 counties) data between 2012 and 2017, we used negative binomial regression to examine the association between quintiles of county-level ADI and the rates of opioid prescriptions and drug-poisoning mortality adjusted for year, age, race and sex. Primary outcome measures County-level opioid prescription fills and drug-poisoning mortality. Results Between 2012 and 2017, overall rates of opioid prescriptions decreased from 96.6 to 72.2 per 100 people, while the rates of drug-poisoning mortality increased from 14.3 to 22.8 per 100 000 people. Opioid prescription and drug-poisoning mortality rates were consistently higher with greater levels of deprivation. The risk of filling an opioid prescription was 72% higher, and the risk of drug-poisoning mortality was 36% higher, for most deprived compared with the least deprived counties (both p<0.001). Discussion Counties with greater area-level deprivation have higher rates of filled opioid prescriptions and drug-poisoning mortality. Although opioid prescription rates declined across all ADI quintiles, the rates of drug-poisoning mortality continued to rise proportionately in each ADI quintile. This underscores the need for individualised and targeted interventions that consider the deprivation of communities where people live.

e20077 Background: Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancers among women and men. Though heavily associated with smoking, its incidence in women is rapidly increasing despite a decline in cigarette exposure. Given the changing demographics of SCLC and hormonal factors associated with other forms of lung cancer, we studied differences between sexes in SCLC. Methods: Utilizing the National Cancer Database, we identified all incident SCLC cases from 2004 to 2014. Patients were classified as limited stage (LS) or extensive stage (ES). Women were stratified by menopausal status (≥55 years = postmenopausal). Kaplan-Meier method and Cox regression were used for overall survival (OS) and multivariable analysis. Results: 161,978 patients were identified. No significant sociodemographic differences were observed between sexes. The majority of patients were non-Hispanic whites (89.1%), followed by non-Hispanic blacks (7.5%). Men were more likely to be diagnosed with ES disease than women (63% vs. 56%). Both sexes initiated treatment within a similar time frame from diagnosis (chemotherapy, median: 18 days, IQR 8-32). Women had better median OS compared to men in both LS (15.2 vs. 12.7 months, HR: 0.85, 95% CI 0.83-0.86, p < 0.0001) and ES (6.4 vs. 5.7 months, HR: 0.88, 95% CI 0.87-0.90, p < 0.0001). No racial or ethnic disparities in OS were observed, overall and when examined within sex and disease stage groups. Differences between sexes in OS were also observed when comparing patients within the same racial/ethnic group (women having better OS). When divided by menopausal status, postmenopausal women with LS and ES had worse OS than premenopausal women (14.7 vs. 22 months, HR: 1.50, 95% CI 1.44-1.56; 6.1 vs. 9.8 months, HR: 1.41, 95% CI: 1.37-1.46, respectively). We also observed worse OS in older men when divided by age ( < 55 years and ≥55 years). In multivariable analysis, older age, postmenopausal status, and Medicaid as primary insurance were associated with worse OS for both LS and ES. Conclusions: In this large cohort, women with SCLC had better OS compared to men. Post-menopausal women had worse OS compared to pre-menopausal women. Since older men had a similar trend of worse survival compared to younger men, age might exert a more significant influence on survival than hormonal status in SCLC. Further studies with data on sexual hormone levels are necessary to better understand their role in women with SCLC.

AbstractObjectiveTo test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.MethodsThis was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy‐two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.ResultsThe decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint] = 0.14) or physician trust more in parents with low health literacy (Pint = 0.34). The decision aid decreased decisional conflict more in non‐white parents (decisional conflict scale, −8.14, 95% CI: −12.33 to −3.95; Pint = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35‐14.83; Pint = 0.04).ConclusionsUse of the Head CT Choice decision aid resulted in less decisional conflict in non‐white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.

BackgroundPrior studies in oncology have shown that a higher annual facility patient volume is associated with reduced mortality. Because classic Hodgkin lymphoma is uncommon but highly curable, this study used the National Cancer Database (2003‐2014) to analyze whether such a relationship exists for this disease.MethodsThe facilities were classified by quartiles, and random intercepts were used to account for clustering of patients within facilities. A Cox regression model was used to determine the volume‐outcome relationship.ResultsThere were 47,633 patients with classic Hodgkin lymphoma treated at 1310 facilities. The first quartile (Q1), which included 58.4% of the facilities, treated 3 or fewer patients per year, whereas the fourth quartile (Q4), which included 5.9% of the facilities, treated more than 9 patients per year. Compared with the patients treated at Q4 facilities, those treated at lower quartile facilities had a higher risk of death (hazard ratio for the third quartile [HR], 1.19; 95% confidence interval [CI], 1.1‐1.29; HR for the second quartile, 1.28; 95% CI, 1.19‐1.38; HR for Q1, 1.29; 95% CI, 1.2‐1.39) after adjustments for all other factors (P < .0001). Compared with facilities treating 10 patients per year, facilities treating 40 patients per year had approximately 27% lower overall mortality rates.ConclusionsPatients with classic Hodgkin lymphoma treated at high‐volume centers had lower overall mortality than those treated at lower volume centers. Because this is a highly curable malignancy, such differences may suggest a benefit from referral to higher volume facilities or the emulation of their care models.

144 Background: Small cell lung cancer (SCLC) is highly responsive to cytotoxic therapy and can be cured in early stages of disease. In this setting, disparities in patient refusal despite provider recommendations are unknown. Methods: All incident limited stage (LS)-SCLC cases from the National Cancer Database were identified from 2004 to 2014. Logistic regression was used to determine factors associated with treatment refusal. Results: 65,664 patients (pts) were identified with LS-SCLC: 44% male, median age 68 years. 3.4% of pts refused radiation and 3.8% refused chemotherapy. The proportion of chemotherapy refusal increased over the study period: 3% in 2004-2006 compared to 5.4% in 2013-2014 [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.55-2.01]; this was not observed for radiation. In multivariate analysis, women were more likely to refuse radiation (OR 1.18, 95% CI 1.06-1.32) and chemotherapy (OR 1.30, 95% CI 1.19-1.43) than men. Women who accepted treatment had higher overall survival compared to those who refused radiation (19.8 vs 5.2 months) or chemotherapy (17.4 vs 3.9 months) (both p < 0.001). Hispanic, Black, and Asian pts were not more likely to refuse treatment than White pts. Older pts were more likely to refuse radiation (OR 1.09 per year, 95% CI 1.08-1.09) and chemotherapy (OR 1.10 per year, 95% CI 1.09-1.11). Charlson comorbidity index (CCI) of 2 was associated with more frequent treatment refusal compared to CCI of 0 (radiation OR 1.96, 95% CI 1.68-2.30; chemotherapy OR 1.54, 95% CI 1.34-1.76). Medicaid as primary insurance predicted a higher risk of refusal compared to private insurance for radiation (OR 2.36, 95% CI 1.81-3.07) and chemotherapy (OR 2.23, 95% CI 1.78-2.80). Treatment at an academic facility predicted a lower risk of radiation refusal (OR 0.71, 95% CI 0.59-0.84) but not chemotherapy refusal. Conclusions: Female sex, comorbidities, and Medicaid insurance were predictors of treatment refusal in LS-SCLC, suggesting that socioeconomic and sex disparities may affect treatment decisions in this life-threatening disease. Further research to identify reasons for refusal via patient and provider interviews can improve care of vulnerable populations with potentially curable cancer.