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Browsing by Author "Austin, Peter C."
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Item Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids(American Medical Association, 2022-12-01) Keyhani, Salomeh; Leonard, Samuel; Byers, Amy L.; Zaman, Tauheed; Krebs, Erin; Austin, Peter C.; Moss-Vazquez, Tristan; Austin, Charles; Sandbrink, Friedhelm; Bravata, Dawn M.; Medicine, School of MedicineImportance: Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids. Objective: To examine the risks associated with cannabis use among adults prescribed opioid analgesic medications. Design, setting, and participants: This cohort study was conducted among individuals aged 18 years and older who had urine drug screening in 2014 to 2019 and received any prescription opioid in the prior 90 days or long-term opioid therapy (LTOT), defined as more than 84 days of the prior 90 days, through the Veterans Affairs health system. Data were analyzed from November 2020 through March 2022. Exposures: Biologically verified cannabis use from a urine drug screen. Main outcomes and measures: The main outcomes were 90-day and 180-day all-cause mortality. A composite outcome of all-cause emergency department (ED) visits, all-cause hospitalization, or all-cause mortality was a secondary outcome. Weights based on the propensity score were used to reduce confounding, and hazard ratios [HRs] were estimated using Cox proportional hazards regression models. Analyses were conducted among the overall sample of patients who received any prescription opioid in the prior 90 days and were repeated among those who received LTOT. Analyses were repeated among adults aged 65 years and older. Results: Among 297 620 adults treated with opioids, 30 514 individuals used cannabis (mean [SE] age, 57.8 [10.5] years; 28 784 [94.3%] men) and 267 106 adults did not (mean [SE] age, 62.3 [12.3] years; P < .001; 247 684 [92.7%] men; P < .001). Among all patients, cannabis use was not associated with increased all-cause mortality at 90 days (HR, 1.07; 95% CI, 0.92-1.22) or 180 days (HR, 1.00; 95% CI, 0.90-1.10) but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.01-1.07) and 180 days (HR, 1.04; 95% CI, 1.01-1.06). Among 181 096 adults receiving LTOT, cannabis use was not associated with increased risk of all-cause mortality at 90 or 180 days but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.02-1.09) and 180 days (HR, 1.05; 95% CI, 1.02-1.09). Among 77 791 adults aged 65 years and older receiving LTOT, cannabis use was associated with increased 90-day mortality (HR, 1.55; 95% CI, 1.17-2.04). Conclusions and relevance: This study found that cannabis use among adults receiving opioid analgesic medications was not associated with any change in mortality risk but was associated with a small increased risk of adverse outcomes and that short-term risks were higher among older adults receiving LTOT.Item Comparative Effectiveness of Carotid Endarterectomy vs Initial Medical Therapy in Patients With Asymptomatic Carotid Stenosis(American Medical Association, 2020-03-06) Keyhani, Salomeh; Cheng, Eric M.; Hoggatt, Katherine J.; Austin, Peter C.; Madden, Erin; Hebert, Paul L.; Halm, Ethan A.; Naseri, Ayman; Johanning, Jason M.; Mowery, Danielle; Chapman, Wendy W.; Bravata, Dawn M.; Medicine, School of MedicineImportance Carotid endarterectomy (CEA) among asymptomatic patients involves a trade-off between a higher short-term perioperative risk in exchange for a lower long-term risk of stroke. The clinical benefit observed in randomized clinical trials (RCTs) may not extend to real-world practice. Objective To examine whether early intervention (CEA) was superior to initial medical therapy in real-world practice in preventing fatal and nonfatal strokes among patients with asymptomatic carotid stenosis. Design, Setting, and Participants This comparative effectiveness study was conducted from August 28, 2018, to March 2, 2020, using the Corporate Data Warehouse, Suicide Data Repository, and other databases of the US Department of Veterans Affairs. Data analyzed were those of veterans of the US Armed Forces aged 65 years or older who received carotid imaging between January 1, 2005, and December 31, 2009. Patients without a carotid imaging report, those with carotid stenosis of less than 50% or hemodynamically insignificant stenosis, and those with a history of stroke or transient ischemic attack in the 6 months before index imaging were excluded. A cohort of patients who received initial medical therapy and a cohort of similar patients who received CEA were constructed and followed up for 5 years. The target trial method was used to compute weighted Kaplan-Meier curves and estimate the risk of fatal and nonfatal strokes in each cohort in the pragmatic sample across 5 years of follow-up. This analysis was repeated after restricting the sample to patients who met RCT inclusion criteria. Cumulative incidence functions for fatal and nonfatal strokes were estimated, accounting for nonstroke deaths as competing risks in both the pragmatic and RCT-like samples. Exposures Receipt of CEA vs initial medical therapy. Main Outcomes and Measures Fatal and nonfatal strokes. Results Of the total 5221 patients, 2712 (51.9%; mean [SD] age, 73.6 [6.0] years; 2678 men [98.8%]) received CEA and 2509 (48.1%; mean [SD] age, 73.6 [6.0] years; 2479 men [98.8%]) received initial medical therapy within 1 year after the index carotid imaging. The observed rate of stroke or death (perioperative complications) within 30 days in the CEA cohort was 2.5% (95% CI, 2.0%-3.1%). The 5-year risk of fatal and nonfatal strokes was lower among patients randomized to CEA compared with patients randomized to initial medical therapy (5.6% vs 7.8%; risk difference, −2.3%; 95% CI, −4.0% to −0.3%). In an analysis that incorporated the competing risk of death, the risk difference between the 2 cohorts was lower and not statistically significant (risk difference, −0.8%; 95% CI, −2.1% to 0.5%). Among patients who met RCT inclusion criteria, the 5-year risk of fatal and nonfatal strokes was 5.5% (95% CI, 4.5%-6.5%) among patients randomized to CEA and was 7.6% (95% CI, 5.7%-9.5%) among those randomized to initial medical therapy (risk difference, −2.1%; 95% CI, −4.4% to −0.2%). Accounting for competing risks resulted in a risk difference of −0.9% (95% CI, −2.9% to 0.7%) that was not statistically significant. Conclusions and Relevance This study found that the absolute reduction in the risk of fatal and nonfatal strokes associated with early CEA was less than half the risk difference in trials from 20 years ago and was no longer statistically significant when the competing risk of nonstroke deaths was accounted for in the analysis. Given the nonnegligible perioperative 30-day risks and the improvements in stroke prevention, medical therapy may be an acceptable therapeutic strategy.Item Comparative Effectiveness of Carotid Stenting to Medical Therapy Among Patients With Asymptomatic Carotid Stenosis(Wolters Kluwer, 2022) Keyhani, Salomeh; Cheng, Eric M.; Hoggatt, Katherine; Austin, Peter C.; Madden, Erin; Hebert, Paul L.; Halm, Ethan A.; Naseri, Ayman; Johanning, Jason; Abraham, Ann; Bravata, Dawn M.; Medicine, School of MedicineBackground: No completed trials have compared carotid artery stenting (CAS) to medical therapy (MT). We examined the effectiveness of CAS compared with MT in patients with asymptomatic carotid stenosis. Methods: We conducted a retrospective cohort study of 219 979 Veterans ≥65 years who received carotid imaging for asymptomatic carotid stenosis between 2005 and 2009 in the US Veterans Health Administration. We constructed a sample of patients who received MT (n=2509) and comparable patients who received CAS (n=551) and followed them for 5 years. Using target trial methodology, we computed weighted Kaplan-Meier curves and estimated the risk of fatal and nonfatal stroke in each group over 5 years of follow-up. We also estimated the cumulative incidence functions for fatal and nonfatal stroke accounting for nonstroke deaths as competing risks. Results: Five hundred fifty-one patients received CAS, and 2509 patients received MT. The observed rate of stroke or death (perioperative complications) within 30 days in the CAS arm was 2.2%. Using the target trial methodology, the 5-year risk of fatal and nonfatal stroke was similar among patients assigned to CAS (6.9%) compared with patients assigned to MT (7.1%; risk difference, -0.1% [95% CI, -2.6% to 2.7%]). In an analysis that incorporated the competing risk of death, the risk difference between the two arms remained nonsignificant (risk difference, -1.5% [95% CI, -3.0% to 0.3%]). Conclusions: In this sample of older male adults, we found no difference between MT and CAS in the treatment of asymptomatic carotid stenosis. Future studies in other settings are needed to confirm these findings.Item Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations(Springer Nature, 2023-05-23) Kelly, J. Daniel; Leonard, Samuel; Boscardin, W. John; Hoggatt, Katherine J.; Lum, Emily N.; Austin, Charles C.; Byers, Amy; Tien, Phyllis C.; Austin, Peter C.; Bravata, Dawn M.; Keyhani, Salomeh; Medicine, School of MedicineStudies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.Item Comparison of Troponin Elevation, Prior Myocardial Infarction, and Chest Pain in Acute Ischemic Heart Failure(Elsevier, 2020-05) Freitas, Cassandra; Wang, Xuesong; Ge, Yin; Ross, Heather J.; Austin, Peter C.; Pang, Peter S.; Ko, Dennis T.; Farkouh, Michael E.; Stukel, Therese A.; McMurray, John J.V.; Lee, Douglas S.; Emergency Medicine, School of MedicineBackground: Patients with heart failure (HF) with concomitant ischemic heart disease (IHD) have not been well characterized. We examined survival of patients with ischemic HF syndrome (IHFS), defined as presentation with acute HF and concomitant features suggestive of IHD. Methods: Patients were included if they presented with acute HF to hospitals in Ontario, Canada. IHD was defined by any of the following criteria: angina/chest pain, prior myocardial infarction (MI), or troponin elevation that was above the upper limit of normal (mild) or suggestive of cardiac injury. Deaths were determined after hospital presentation. Results: Of 5353 patients presenting with acute HF, 4088 (76.4%) exhibited features of IHFS. Patients with IHFS demonstrated a higher rate of 30-day (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.33-2.68) and 1-year death (HR, 1.16, 95% CI, 1.00-1.35) compared with those with nonischemic HF. Troponin elevation demonstrated the strongest association with mortality. Mildly elevated troponin was associated with increased hazard over 30-day (HR, 1.77; 95% CI, 1.12-2.81) and 1-year (HR, 1.63; 95% CI, 1.38-1.93) mortality. Troponins indicative of cardiac injury were associated with increased hazard of death over 30 days (HR, 2.33; 95% CI, 1.63-3.33) and 1 year (HR, 1.40; 95% CI, 1.21-1.61). The association between elevated troponin and higher mortality at 30 days was similar in left ventricular ejection fraction subcategories of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, or HF with preserved ejection fraction (P interaction = 0.588). After multivariable adjustment, prior MI and angina were not associated with higher mortality risk. Conclusions: In acute HF, elevated troponin, but not prior MI or angina, was associated with a higher risk of 30-day and 1-year mortality irrespective of left ventricular ejection fraction.Item Risk Prediction Tools to Improve Patient Selection for Carotid Endarterectomy Among Patients With Asymptomatic Carotid Stenosis(American Medical Association, 2019-04-01) Keyhani, Salomeh; Madden, Erin; Cheng, Eric M.; Bravata, Dawn M.; Halm, Ethan; Austin, Peter C.; Ghasemiesfe, Mehrnaz; Abraham, Ann S.; Zhang, Alysandra J.; Johanning, Jason M.; Medicine, School of MedicineImportance: Randomized clinical trials have demonstrated that patients with asymptomatic carotid stenosis are eligible for carotid endarterectomy (CEA) if the 30-day surgical complication rate is less than 3% and the patient's life expectancy is at least 5 years. Objective: To develop a risk prediction tool to improve patient selection for CEA among patients with asymptomatic carotid stenosis. Design, Setting, and Participants: In this cohort study, veterans 65 years and older who received both carotid imaging and CEA in the Veterans Administration between January 1, 2005, and December 31, 2009 (n = 2325) were followed up for 5 years. Data were analyzed from January 2005 to December 2015. A risk prediction tool (the Carotid Mortality Index [CMI]) based on 23 candidate variables identified in the literature was developed using Veterans Administration and Medicare data. A simpler model based on the number of 4 key comorbidities that were prevalent and strongly associated with 5-year mortality was also developed (any cancer in the past 5 years, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease [the 4C model]). Model performance was assessed using measures of discrimination (eg, area under the curve [AUC]) and calibration. Internal validation was performed by correcting for optimism using 500 bootstrapped samples. Main Outcome and Measure: Five-year mortality. Results: Among 2325 veterans, the mean (SD) age was 73.74 (5.92) years. The cohort was predominantly male (98.8%) and of white race/ethnicity (94.4%). Overall, 29.5% (n = 687) of patients died within 5 years of CEA. On the basis of a backward selection algorithm, 9 patient characteristics were selected (age, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, any cancer diagnosis in the past 5 years, congestive heart failure, atrial fibrillation, remote stroke or transient ischemic attack, and body mass index) for the final logistic model, which yielded an optimism-corrected AUC of 0.687 for the CMI. The 4C model had slightly worse discrimination (AUC, 0.657) compared with the CMI model; however, the calibration curve was similar to the full model in most of the range of predicted probabilities. Conclusions and Relevance: According to results of this study, use of the CMI or the simpler 4C model may improve patient selection for CEA among patients with asymptomatic carotid stenosis.Item The Heart and Cannabis (THC) Cohort: Differences in Baseline Health and Behaviors by Cannabis Use(Springer, 2022) Keyhani, Salomeh; Cohen, Beth E.; Vali, Marzieh; Hoggatt, Katherine J.; Bravata, Dawn M.; Austin, Peter C.; Lum, Emily; Hasin, Deborah S.; Grunfeld, Carl; Shlipak, Michael G.; Medicine, School of MedicineBackground: Evidence on the cardiovascular health effects of cannabis use is limited. We designed a prospective cohort study of older Veterans (66 to 68 years) with coronary artery disease (CAD) to understand the cardiovascular consequences of cannabis use. We describe the cohort construction, baseline characteristics, and health behaviors that were associated with smoking cannabis. Objective: To understand the cardiovascular consequences of cannabis use. Design: We designed a prospective cohort study of older Veterans (66 to 68 years) with CAD. Participants: A total of 1,015 current cannabis smokers and 3,270 non-cannabis smokers with CAD. Main measures: Using logistic regression, we examined the association of baseline variables with smoking cannabis in the past 30 days. Results: The current cannabis smokers and non-current smokers were predominantly male (97.2% vs 97.1%, p=0.96). Characteristics associated with recent cannabis use in multivariable analyses included lack of a high school education (odds ratio [OR] 2.15, 95% confidence interval [CI]: 1.10 to 4.19), financial difficulty (OR 1.47, 95% CI: 1.02 to 2.11), tobacco use (OR 3.02, 95% CI: 1.66 to 5.48), current drug use (OR 2.82, 95% CI: 1.06 to 7.46), and prior drug use (OR 2.84, 95% CI: 2.11 to 3.82). In contrast, compared to individuals with 0 to 1 comorbid conditions, those with 5 chronic conditions or more (OR 0.43, 95% CI: 0.27 to 0.70) were less likely to smoke cannabis. Conclusions: In this older high-risk cohort, smoking cannabis was associated with higher social and behavioral risk, but with fewer chronic health conditions.