Faculty Bibliography

Importance:State cannabis laws are changing rapidly. Research is inconclusive about their association with rates of self-harm and assault. Existing studies have not considered variations in cannabis commercialization across states over time. Objective:To evaluate the association of state medical and recreational cannabis laws with self-harm and assault, overall and by age and sex, while considering varying degrees of commercialization. Design, Setting, and Participants:Using a cohort design with panel fixed-effects analysis, within-state changes in claims for self-harm and assault injuries before and after changes in cannabis laws were quantified in all 50 US states and the District of Columbia. Comprehensive claims data on commercial and Medicare Advantage health plan beneficiaries from January 1, 2003, to December 31, 2017, grouped by state and month, were evaluated. Data analysis was conducted from January 31, 2020, to January 21, 2021. Exposures:Categorical variable that indexed the degree of cannabis legalization in each state and month based on law type (medical or recreational) and operational status of dispensaries (commercialization). Main Outcomes and Measures:Claims for self-harm and assault injuries based on International Classification of Diseases codes. Results:The analysis included 75 395 344 beneficiaries (mean [SD] age, 47 [22] years; 50% female; and median follow-up, 17 months [interquartile range, 8-36 months]). During the study period, 29 states permitted use of medical cannabis and 11 permitted recreational cannabis. Point estimates for populationwide rates of self-harm and assault injuries were higher in states legalizing recreational cannabis compared with states with no cannabis laws, but these results were not statistically significant (adjusted rate ratio [aRR] assault, recreational dispensaries: 1.27; 95% CI, 0.79-2.03;self-harm, recreational dispensaries aRR: 1.15; 95% CI, 0.89-1.50). Results varied by age and sex with no associations found except for states with recreational policies and self-harm among males younger than 40 years (aRR <21 years, recreational without dispensaries: 1.70; 95% CI, 1.11-2.61; aRR aged 21-39 years, recreational dispensaries: 1.46; 95% CI, 1.01-2.12). Medical cannabis was generally not associated with self-harm or assault injuries populationwide or among age and sex subgroups. Conclusions and Relevance:Recreational cannabis legalization appears to be associated with relative increases in rates of claims for self-harm among male health plan beneficiaries younger than 40 years. There was no association between cannabis legalization and self-harm or assault, for any other age and sex group or for medical cannabis. States that legalize but still constrain commercialization may be better positioned to protect younger male populations from unintended harms.

BACKGROUND:Altered postinjury platelet behavior is recognized in the pathophysiology of trauma-induced coagulopathy (TIC), but the mechanisms remain largely undefined. Studies suggest that soluble factors released by injury may inhibit signaling pathways and induce structural changes in circulating platelets. Given this, we sought to examine the impact of treating healthy platelets with plasma from injured patients. We hypothesized that healthy platelets treated ex-vivo with plasma from injured patients with shock would impair platelet aggregation, while treatment with plasma from injured patients with significant injury burden, but without shock, would enhance platelet aggregation. METHODS:Plasma samples were isolated from injured patients (pretransfusion) and healthy donors at a Level I trauma center and stored at -80°C. Plasma samples from four separate patients in each of the following stratified clinical groups were used: mild injury/no shock (injury severity score [ISS] 2-15, base excess [BE]>-6), mild injury/with shock (ISS 2-15, BE≤-6), severe injury/no shock (ISS>25, BE>-6), severe injury/with shock (ISS>25, BE≤-6), minimal injury (ISS 0/1, BE>-6), and healthy. Platelets were isolated from three healthy adult males and were treated with plasma for 30 min. Aggregation was stimulated with a thrombin receptor agonist and measured via multiple-electrode platelet aggregometry. Data were normalized to HEPES Tyrode's (HT) buffer-only treated platelets. Associations of plasma treatment groups with platelet aggregation measures were tested with Mann-Whitney U tests. RESULTS:Platelets treated with plasma from patients with shock (regardless of degree of injury) had significantly impaired thrombin-stimulated aggregation compared with platelets treated with plasma from patients without shock (P = 0.002). Conversely, platelets treated with plasma from patients with severe injury, but without shock, had amplified thrombin-stimulated aggregation (P = 0.030). CONCLUSION:Shock-mediated soluble factors impair platelet aggregation, and tissue injury-mediated soluble factors amplify platelet aggregation. Future characterization of these soluble factors will support development of novel treatments of TIC.

Background/UNASSIGNED:Latino people in the US are experiencing higher excess deaths during the COVID-19 pandemic than any other racial/ethnic group, but it is unclear which subgroups within this diverse population are most affected. Such information is necessary to target policies that prevent further excess mortality and reduce inequities. Methods/UNASSIGNED:Using death certificate data for January 1, 2016 through February 29, 2020 and time-series models, we estimated the expected weekly deaths among Latino people in California from March 1 through October 3, 2020. We quantified excess mortality as observed minus expected deaths and risk ratios (RR) as the ratio of observed to expected deaths. We considered subgroups defined by age, sex, place of birth, education, occupation, and combinations of these factors. Findings/UNASSIGNED:During the first seven months of the pandemic, Latino deaths in California exceeded expected deaths by 10,316, a 31% increase. Excess death rates were greatest for individuals born in Mexico (RR 1.44; 95% PI, 1.41, 1.48) or Central America (RR 1.49; 95% PI, 1.37, 1.64), with less than a high school degree (RR 1.41; 95% PI, 1.35, 1.46), or in food-and-agriculture (RR 1.60; 95% PI, 1.48, 1.74) or manufacturing occupations (RR 1.59; 95% PI, 1.50, 1.69). Immigrant disadvantages in excess death were magnified among working-age Latinos in essential occupations. Interpretation/UNASSIGNED:The pandemic has disproportionately impacted mortality among Latino immigrants and Latinos in unprotected essential jobs; Interventions to reduce these disparities should include early vaccination, workplace safety enforcement, and expanded access to medical care. Funding/UNASSIGNED:National Institute on Aging; UCSF. RESEARCH IN CONTEXT/UNASSIGNED:

BACKGROUND:Firearm dealer density is correlated with firearm interpersonal violence, but no quasi-experimental studies have assessed whether changes in dealer density lead to changes in firearm self-harm injuries and deaths. We assessed whether openings of firearm dealers are associated with short-term changes in local firearm self-harm injury rates. METHODS:We identified 718 openings of firearm dealers in California using licensing data, 2014-2016. We defined exposure regions based on aggregations of zip codes defined by proximity to firearm dealer openings and matched each opening to four control regions on time and determinants of firearm injury. We applied a differences-in-differences approach to compare rates of firearm self-harm, in the month before and after each opening, in places with and without openings. RESULTS:Firearm dealer openings were not associated with acute, local changes in firearm self-harm relative to places without openings (ratio of rate ratio: 0.90 [95% CI:0.68-1.19]). Results were robust to numerous sensitivity and secondary analyses. CONCLUSION:We found no associations of firearm dealer openings with acute, localized firearm self-harm deaths and injuries. Our focus on acute, local effects; broad availability of dealers and firearms; durability of firearms; or strong confounding-control may explain these null findings.

INTRODUCTION:Pooling (or combining) and analysing observational, longitudinal data at the individual level facilitates inference through increased sample sizes, allowing for joint estimation of study- and individual-level exposure variables, and better enabling the assessment of rare exposures and diseases. Empirical studies leveraging such methods when randomization is unethical or impractical have grown in the health sciences in recent years. The adoption of so-called "causal" methods to account for both/either measured and/or unmeasured confounders is an important addition to the methodological toolkit for understanding the distribution, progression, and consequences of infectious diseases (IDs) and interventions on IDs. In the face of the Covid-19 pandemic and in the absence of systematic randomization of exposures or interventions, the value of these methods is even more apparent. Yet to our knowledge, no studies have assessed how causal methods involving pooling individual-level, observational, longitudinal data are being applied in ID-related research. In this systematic review, we assess how these methods are used and reported in ID-related research over the last 10 years. Findings will facilitate evaluation of trends of causal methods for ID research and lead to concrete recommendations for how to apply these methods where gaps in methodological rigor are identified. METHODS AND ANALYSIS:We will apply MeSH and text terms to identify relevant studies from EBSCO (Academic Search Complete, Business Source Premier, CINAHL, EconLit with Full Text, PsychINFO), EMBASE, PubMed, and Web of Science. Eligible studies are those that apply causal methods to account for confounding when assessing the effects of an intervention or exposure on an ID-related outcome using pooled, individual-level data from 2 or more longitudinal, observational studies. Titles, abstracts, and full-text articles, will be independently screened by two reviewers using Covidence software. Discrepancies will be resolved by a third reviewer. This systematic review protocol has been registered with PROSPERO (CRD42020204104).

BACKGROUND:Though SARS-CoV-2 outbreaks have been documented in occupational settings and in-person essential work has been suspected as a risk factor for COVID-19, occupational differences in excess mortality have, to date, not been examined. Such information could point to opportunities for intervention, such as vaccine prioritization or regulations to enforce safer work environments. METHODS AND FINDINGS:Using autoregressive integrated moving average models and California Department of Public Health data representing 356,188 decedents 18-65 years of age who died between January 1, 2016 and November 30, 2020, we estimated pandemic-related excess mortality by occupational sector and occupation, with additional stratification of the sector analysis by race/ethnicity. During these first 9 months of the COVID-19 pandemic, working-age adults experienced 11,628 more deaths than expected, corresponding to 22% relative excess and 46 excess deaths per 100,000 living individuals. Sectors with the highest relative and per-capita excess mortality were food/agriculture (39% relative excess; 75 excess deaths per 100,000), transportation/logistics (31%; 91 per 100,000), manufacturing (24%; 61 per 100,000), and facilities (23%; 83 per 100,000). Across racial and ethnic groups, Latino working-age Californians experienced the highest relative excess mortality (37%) with the highest excess mortality among Latino workers in food and agriculture (59%; 97 per 100,000). Black working-age Californians had the highest per-capita excess mortality (110 per 100,000), with relative excess mortality highest among transportation/logistics workers (36%). Asian working-age Californians had lower excess mortality overall, but notable relative excess mortality among health/emergency workers (37%), while White Californians had high per-capita excess deaths among facilities workers (70 per 100,000). CONCLUSIONS:Certain occupational sectors are associated with high excess mortality during the pandemic, particularly among racial and ethnic groups also disproportionately affected by COVID-19. In-person essential work is a likely venue of transmission of coronavirus infection and must be addressed through vaccination and strict enforcement of health orders in workplace settings.

Directed acyclic graphs (DAGs), a prominent tool for expressing assumptions in epidemiologic research, are most useful when the hypothetical data generating structure is correctly encoded. Understanding a study's data generating structure and translating that data structure into a DAG can be challenging, but these skills are often glossed over in training. Campbell and Stanley's framework for causal inference has been extraordinarily influential in social science training programs but has received less attention in epidemiology. Their work, along with subsequent revisions and enhancements based on practical experience conducting empirical studies, presents a catalog of 37 threats to validity describing reasons empirical studies may fail to deliver causal effects. We interpret most of these threats to study validity as suggestions for common causal structures. Threats are organized into issues of statistical conclusion validity, internal validity, construct validity, or external validity. To assist epidemiologists in drawing the correct DAG for their application, we map the correspondence between threats to validity and epidemiologic concepts that can be represented with DAGs. Representing these threats as DAGs makes them amenable to formal analysis with d-separation rules and breaks down cross-disciplinary language barriers in communicating methodologic issues.

Population health researchers from different fields often address similar substantive questions but rely on different study designs, reflecting their home disciplines. This is especially true in studies involving causal inference, for which semantic and substantive differences inhibit interdisciplinary dialogue and collaboration. In this paper, we group nonrandomized study designs into two categories: those that use confounder-control (such as regression adjustment or propensity score matching) and those that rely on an instrument (such as instrumental variables, regression discontinuity, or differences-in-differences approaches). Using the Shadish, Cook, and Campbell framework for evaluating threats to validity, we contrast the assumptions, strengths, and limitations of these two approaches and illustrate differences with examples from the literature on education and health. Across disciplines, all methods to test a hypothesized causal relationship involve unverifiable assumptions, and rarely is there clear justification for exclusive reliance on one method. Each method entails trade-offs between statistical power, internal validity, measurement quality, and generalizability. The choice between confounder-control and instrument-based methods should be guided by these tradeoffs and consideration of the most important limitations of previous work in the area. Our goals are to foster common understanding of the methods available for causal inference in population health research and the tradeoffs between them; to encourage researchers to objectively evaluate what can be learned from methods outside one's home discipline; and to facilitate the selection of methods that best answer the investigator's scientific questions.

The Robert Wood Johnson Foundation (RWJF)'s Culture of Health Action Framework guides a movement to improve health and advance health equity across the nation. Action Area One of the Framework, Making Health a Shared Value, highlights the role of individual and community factors in achieving a societal commitment to health and health equity, centered around three drivers: Mindset and Expectations, Sense of Community, and Civic Engagement. To stimulate research about how Action Area One and its drivers may impact health, Evidence for Action (E4A), a signature research funding program of RWJF, developed and released a national Call for Proposals (CFP). The process of formulating the CFP and reviewing proposals surfaced important challenges for research on creating and sustaining shared values to foster and maintain a Culture of Health. In this essay, we describe these considerations and provide examples from funded projects regarding how challenges can be addressed.