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Opportunities and challenges in using instrumental variables to study causal effects in nonrandomized stress and trauma research

Matthay, Ellicott C; Smith, Meghan L; Glymour, M Maria; White, Justin S; Gradus, Jaimie L
OBJECTIVE:Researchers are often interested in assessing the causal effect of an exposure on an outcome when randomization is not ethical or feasible. Estimating causal effects by controlling for confounders can be unconvincing because important potential confounders remain unmeasured. Study designs leveraging instrumental variables (IVs) offer alternatives to confounder-control methods but are rarely used in stress and trauma research. METHOD/METHODS:We review the conceptual foundations and implementation of IV methods. We discuss strengths and limitations of IV approaches, contrasting with confounder-control methods, and illustrate the relevance of IVs for stress and trauma research. RESULTS:IV approaches leverage an external or exogenous source of variation in the exposure. Instruments are variables that meet three conditions: relevance (variation in the IV is associated with variation in the chance of exposure), exclusion (the IV only affects the outcome through the exposure), and exchangeability (no unmeasured confounding of the IV-outcome relationship). Interpreting estimates from IV analyses requires an additional assumption, such as monotonicity (the instrument does not change the chance of exposure in different directions for any two individuals). Valid IVs circumvent the need to correctly identify, measure, and control for all confounders of the exposure-outcome relationship. The primary challenge is identifying a valid instrument. CONCLUSIONS:IV approaches have strengths and weaknesses compared with confounder-control approaches. IVs offers a promising complementary study design to improve evidence about the causal effects of exposures on outcomes relevant to stress and trauma. Collaboration with scientists who are experienced with identifying and analyzing IVs will support this work. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
PMID: 36227293
ISSN: 1942-969x
CID: 5386492

Commentary: Quantifying the impact of bias to inform quality assessments in systematic reviews: The case of perchloroethylene and Non-Hodgkin's lymphoma

Fox, Matthew P; Mathur, Maya B; Matthay, Ellicott C
PMCID:10445960
PMID: 37637019
ISSN: 2590-1133
CID: 5618512

Excess Mortality in California by Education During the COVID-19 Pandemic

Chen, Yea-Hung; Matthay, Ellicott C; Chen, Ruijia; DeVost, Michelle A; Duchowny, Kate A; Riley, Alicia R; Bibbins-Domingo, Kirsten; Glymour, M Maria
INTRODUCTION/BACKGROUND:Understanding educational patterns in excess mortality during the coronavirus disease 2019 (COVID-19) pandemic may help to identify strategies to reduce disparities. It is unclear whether educational inequalities in COVID-19 mortality have persisted throughout the pandemic, spanned the full range of educational attainment, or varied by other demographic indicators of COVID-19 risks, such as age or occupation. METHODS:This study analyzed individual-level California Department of Public Health data on deaths occurring between January 2016 and February 2021 among individuals aged ≥25 years (1,502,202 deaths). Authors applied ARIMA (autoregressive integrated moving average) models to subgroups defined by the highest level of education and other demographics (age, sex, race/ethnicity, U.S. nativity, occupational sector, and urbanicity). Authors estimated excess deaths (the number of observed deaths minus the number of deaths expected to occur under the counterfactual of no pandemic) and excess deaths per 100,000 individuals. RESULTS:Educational inequalities in excess mortality emerged early in the pandemic and persisted throughout the first year. The greatest per-capita excess occurred among people without high-school diplomas (533 excess deaths/100,000), followed by those with a high-school diploma but no college (466/100,000), some college (156/100,000), and bachelor's degrees (120/100,000), and smallest among people with graduate/professional degrees (101/100,000). Educational inequalities occurred within every subgroup examined. For example, per-capita excess mortality among Latinos with no college experience was 3.7 times higher than among Latinos with at least some college experience. CONCLUSIONS:Pervasive educational inequalities in excess mortality during the pandemic suggest multiple potential intervention points to reduce disparities.
PMCID:9325680
PMID: 36114132
ISSN: 1873-2607
CID: 5336572

Equity in Coverage of Local Cannabis Control Policies in California, 2020‒2021

Matthay, Ellicott C; Mousli, Leyla M; Fu, Cynthia; Zhang, Serena; Ponicki, William R; Gruenewald, Paul; Apollonio, Dorie E; Schmidt, Laura A
PMID: 36075009
ISSN: 1541-0048
CID: 5337102

When Effects Cannot be Estimated: Redefining Estimands to Understand the Effects of Naloxone Access Laws

Rudolph, Kara E; Gimbrone, Catherine; Matthay, Ellicott C; Díaz, Iván; Davis, Corey S; Keyes, Katherine; Cerdá, Magdalena
Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world threats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effects of Naloxone Access Laws on opioid overdose rates.
PMCID:9373236
PMID: 35944151
ISSN: 1531-5487
CID: 5310592

A Spatiotemporal Analysis of the Association of California City and County Cannabis Policies with Cannabis Outlet Densities

Matthay, Ellicott C; Mousli, Leyla; Ponicki, William R; Glymour, M Maria; Apollonio, Dorie E; Schmidt, Laura A; Gruenewald, Paul
BACKGROUND:Cannabis outlets may affect health and health disparities. Local governments can regulate outlets, but little is known about the effectiveness of local policies in limiting outlet densities and discouraging disproportionate placement of outlets in vulnerable neighborhoods. METHODS:For 241 localities in California, we measured seven policies pertaining to density or location of recreational cannabis outlets. We geocoded outlets using web-scraped data from the online finder Weedmaps between 2018 and 2020. We applied Bayesian spatiotemporal models to evaluate associations of local cannabis policies with Census block group-level outlet counts, accounting for confounders and spatial autocorrelation. We assessed whether associations differed by block group median income or racial-ethnic composition. RESULTS:Seventy-six percent of localities banned recreational cannabis outlets. Bans were associated with fewer outlets, particularly in block groups with higher median income, fewer Hispanic residents, and more White and Asian residents. Outlets were disproportionately located in block groups with lower median income [posterior RR (95% credible interval): 0.76 (0.70, 0.82) per $10,000], more Hispanic residents [1.05 (1.02, 1.09) per 5%], and fewer Black residents [0.91 (0.83, 0.98) per 5%]. For the six policies in jurisdictions permitting outlets, two policies were associated with fewer outlets and two with more; two policy associations were uninformative. For these policies, we observed no consistent heterogeneity in associations by median income or racial-ethnic composition. CONCLUSIONS:Some local cannabis policies in California are associated with lower cannabis outlet densities, but are unlikely to deter disproportionate placement of outlets in racial-ethnic minority and low-income neighborhoods.
PMCID:9345518
PMID: 35944153
ISSN: 1531-5487
CID: 5286882

A descriptive analysis of 2020 California Occupational Safety and Health Administration covid-19-related complaints

Thomas, Marilyn D; Matthay, Ellicott C; Duchowny, Kate A; Riley, Alicia R; Khela, Harmon; Chen, Yea-Hung; Bibbins-Domingo, Kirsten; Glymour, M Maria
COVID-19 mortality has disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred, and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.
PMID: 34977326
ISSN: 2352-8273
CID: 5252692

Heterogeneous treatment effects in social policy studies: An assessment of contemporary articles in the health and social sciences

Cintron, Dakota W; Adler, Nancy E; Gottlieb, Laura M; Hagan, Erin; Tan, May Lynn; Vlahov, David; Glymour, Madellena Maria; Matthay, Ellicott C
PURPOSE/OBJECTIVE:Social policies are important determinants of population health but may have varying effects on subgroups of people. Evaluating heterogeneous treatment effects (HTEs) of social policies is critical to determine how social policies will affect health inequities. Methods for evaluating HTEs are not standardized. Little is known about how often and by what methods HTEs are assessed in social policy and health research. METHODS:A sample of 55 articles from 2019 on the health effects of social policies were evaluated for frequency of reporting HTEs; for what subgroupings HTEs were reported; frequency of a priori specification of intent to assess HTEs; and methods used for assessing HTEs. RESULTS:A total of 24 (44%) studies described some form of HTE assessment, including by age, gender, education, race/ethnicity, and/or geography. Among studies assessing HTEs, 63% specified HTE assessment a priori, and most (71%) used descriptive methods such as stratification; 21% used statistical tests (e.g., interaction terms in a regression); and no studies used data-driven algorithms. CONCLUSIONS:Although understanding HTEs could enhance policy and practice-based efforts to reduce inequities, it is not routine research practice. Increased evaluation of HTEs across relevant subgroups is needed.
PMID: 35483641
ISSN: 1873-2585
CID: 5252732

Systematic Review Reveals Lack of Causal Methodology Applied to Pooled Longitudinal Observational Infectious Disease Studies

Hufstedler, Heather; Rahman, Sabahat; Danzer, Alexander M; Goymann, Hannah; de Jong, Valentijn M T; Campbell, Harlan; Gustafson, Paul; Debray, Thomas P A; Jaenisch, Thomas; Maxwell, Lauren; Matthay, Ellicott C; Bärnighausen, Till
OBJECTIVES/OBJECTIVE:Among ID studies seeking to make causal inferences and pooling individual-level longitudinal data from multiple infectious disease cohorts, we sought to assess what methods are being used, how those methods are being reported, and whether these factors have changed over time. STUDY DESIGN AND SETTING/METHODS:Systematic review of longitudinal observational infectious disease studies pooling individual-level patient data from 2+ studies published in English in 2009, 2014, or 2019. This systematic review protocol is registered with PROSPERO (CRD42020204104). RESULTS:Our search yielded 1,462 unique articles. Of these, 16 were included in the final review. Our analysis showed a lack of causal inference methods and of clear reporting on methods and the required assumptions. CONCLUSION/CONCLUSIONS:There are many approaches to causal inference which may help facilitate accurate inference in the presence of unmeasured and time-varying confounding. In observational ID studies leveraging pooled, longitudinal IPD, the absence of these causal inference methods and gaps in the reporting of key methodological considerations suggests there is ample opportunity to enhance the rigor and reporting of research in this field. Interdisciplinary collaborations between substantive and methodological experts would strengthen future work.
PMID: 35045316
ISSN: 1878-5921
CID: 5252702

Sociodemographic and geographic disparities in excess fatal drug overdoses during the COVID-19 pandemic in California: A population-based study

Kiang, Mathew V; Acosta, Rolando J; Chen, Yea-Hung; Matthay, Ellicott C; Tsai, Alexander C; Basu, Sanjay; Glymour, M Maria; Bibbins-Domingo, Kirsten; Humphreys, Keith; Arthur, Kristen N
Background/UNASSIGNED:The coronavirus disease 2019 (COVID-19) pandemic is co-occurring with a drug addiction and overdose crisis. Methods/UNASSIGNED:We fit overdispersed Poisson models, accounting for seasonality and secular trends, to estimate the excess fatal drug overdoses (i.e., deaths greater than expected), using data on all deaths in California from 2016 to 2020. Findings/UNASSIGNED:Between January 5, 2020 and December 26, 2020, there were 8605 fatal drug overdoses-a 44% increase over the same period one year prior. We estimated 2084 (95% CI: 1925 to 2243) fatal drug overdoses were excess deaths, representing 5·28 (4·88 to 5·68) excess fatal drug overdoses per 100,000 population. Excess fatal drug overdoses were driven by opioids (4·48 [95% CI: 4·18 to 4·77] per 100,000), especially synthetic opioids (2·85 [95% CI: 2·56 to 3·13] per 100,000). The non-Hispanic Black and Other non-Hispanic populations were disproportionately affected with 10·1 (95% CI: 7·6 to 12·5) and 13·26 (95% CI: 11·0 to 15·5) excess fatal drug overdoses per 100,000 population, respectively, compared to 5·99 (95% CI: 5.2 to 6.8) per 100,000 population in the non-Hispanic white population. There was a steep, nonlinear educational gradient with the highest rate among those with only a high school degree. There was a strong spatial patterning with the highest levels of excess mortality in the southernmost region and consistently lower levels at progressively more northern latitudes (7·73 vs 1·96 per 100,000). Interpretation/UNASSIGNED:Fatal drug overdoses disproportionately increased in 2020 among structurally marginalized populations and showed a strong geographic gradient. Local, tailored public health interventions are urgently needed to reduce growing inequities in overdose deaths. Funding/UNASSIGNED:US National Institutes of Health and Department of Veterans Affairs.
PMCID:8934030
PMID: 35342895
ISSN: 2667-193x
CID: 5252712