Complex FFA1 receptor (in)dependent modulation of calcium signaling by free fatty acids.

The expression of free fatty acid 1 receptors (FFA1R), activated by long chain fatty acids in human pancreatic ß-cells and enhancing glucose-stimulated insulin secretion are an attractive target to treat type 2 diabetes. Yet several clinical studies with synthetic FFA1R agonists had to be discontinued due to cytotoxicity and/or so-called "liver concerns". It is not clear whether these obstructions are FFA1R dependent. In this context we used CHO-AEQ cells expressing the bioluminescent calcium-sensitive protein aequorin to investigate calcium signaling elicited by FFA1 receptor ligands α-linolenic acid (ALA), oleic acid (OLA) and myristic acid (MYA). This study revealed complex modulation of intracellular calcium signaling by these fatty acids. First these compounds elicited a typical transient increase of intracellular calcium via binding to FFA1 receptors. Secondly slightly higher concentrations of ALA substantially reduced ATP mediated calcium responses in CHO-AEQ cells and Angiotensin II responses in CHO-AEQ cells expressing human AT1 receptors. This effect was less pronounced with MYA and OLA and was not linked to FFA1 receptor activation nor to acute cytotoxicity as a result of plasma membrane perturbation. Yet it can be hypothesized that, in line with previous studies, unsaturated long chain fatty acids such as ALA and OLA are capable of inactivating the G-proteins involved in purinergic and Angiotensin AT1 receptor calcium signaling. Alternatively the ability of fatty acids to deplete intracellular calcium stores might underly the observed cross-inhibition of these receptor responses in the same cells.

Differences in Health Characteristics of Geographic Subgroups of Arab Americans in a Northern California Health Plan.

INTRODUCTION: Arab Americans are a diverse ethnic group originating from a large geographic area in the Middle East and North Africa (MENA). We aim to characterize differences in health between Arab Americans from different geographic subgroups within MENA. METHODS: We used cross-sectional electronic health record (EHR) data for a subset of 4913 Arab Americans aged 20-84 in a 2016 Northern California health plan study cohort who could be assigned to one of 4 geographic subgroups (Gulf, African, Levant, and Other) based on EHR ethnicity data. We calculated age-adjusted prevalence estimates for men and women and used generalized linear models to compare Gulf, African, and Other subgroups to Levant Arabs on risk factors (obesity and smoking), chronic conditions (diabetes, hypertension, hyperlipidemia, and asthma), and mental health (depression and anxiety). RESULTS: Among women, prevalence of smoking was lower among Gulf, African, and Other Arabs than Levant Arabs. Among men, prevalence of obesity, diabetes, and hyperlipidemia was lower among Gulf, African, and Other Arabs than Levant Arabs, while prevalence of depression was higher for these subgroups than Levant Arabs. DISCUSSION: We found substantial differences in health characteristics across Arab Americans from different geographic subgroups. Our results suggest that more detailed race and ethnicity information should be collected on Arab Americans to better understand their diverse health risks.

Understanding differences within ethnic group designation: comparing risk factors and health indicators between Iranian and Arab Americans in Northern California.

BACKGROUND: The Middle Eastern and North African (MENA) ethnic group is a diverse group composed of two primary subsets in the United States: Iranian and Arab Americans. We aimed to compare health risk factors, chronic health conditions, and mental health conditions of Iranian and Arab American adults in Northern California. METHODS: We used cross-sectional electronic health record (EHR) data from a 2016 Northern California health plan study cohort to compare adults classified as Iranian or Arab American based on ethnicity, language, or surname. We produced age-standardized prevalence estimates of obesity, smoking, hyperlipidemia, prediabetes, diabetes, hypertension, depression, and anxiety for Iranian and Arab American men and women by age group (35-44, 45-64, and 65-84) and overall (35-84). We used generalized linear models to calculate prevalence ratios (PR) to compare Iranian and Arab American adults ages 35-84 on all health indicators. RESULTS: Compared to Arab Americans, Iranian Americans had a lower prevalence of obesity (PR: 0.77, 95% confidence interval, CI: 0.73, 0.82), current smoking (PR: 0.80, 95% CI: 0.73, 0.89), and ever smoking (PR: 0.95, 95% CI: 0.91, 0.99), but a higher prevalence of hyperlipidemia (PR: 1.09, 95% CI: 1.06, 1.12), prediabetes (PR: 1.12, 95% CI: 1.09, 1.16), depression (PR; 1.41, 95% CI: 1.30, 1.52), and anxiety (PR: 1.52, 95% CI: 1.42, 1.63). Similar patterns were observed for men and women. CONCLUSION: This work supports the need to collect granular data on race and ethnicity within the MENA ethnic group to improve identification in clinical care settings and population health reporting to better address the physical and mental health needs of different MENA subgroups.

Health Risks and Chronic Health Conditions among Arab American and White Adults in Northern California.

Objectives: To characterize the prevalence of chronic cardiovascular conditions and risk factors among Arab American adults stratified by sex and compare these with non-Hispanic Whites. Design: Cross-sectional study using electronic health record data from visits between January 2015 and December 2016. Age-adjusted prevalence estimates were calculated for men and women and compared using generalized linear models. Setting: Kaiser Permanente health plan in Northern California. Participants: Non-Hispanic White (N=969,566) and Arab American (N=18,072) adult members. Main Outcome Measures: Sex-stratified prevalence and prevalence ratios of diabetes, pre-diabetes, hypertension, and hyperlipidemia diagnosed by December 2016 and of obesity, ever smoking, and current smoking status. Results: Arab American men had a significantly higher prevalence of ever smoking (41.8 vs 40.8%), diabetes (17.3 vs 12.5%), and hyperlipidemia (40.8 vs 34.7%) than White men, but a significantly lower prevalence of obesity (34.4 vs 37.8%) and hypertension (30.5 vs 33.3%). Arab American women had a significantly higher prevalence of diabetes (11.1 vs 8.7%) and hyperlipidemia (31.5 vs 28.3%) than White women but significantly lower prevalence of obesity (31.0 vs 34.2%), ever smoking (24.8 vs 34.5%), and hypertension (25.8 vs 28.4%). Conclusions: Hospital and health systems should intentionally collect data on Middle Eastern and North African ethnicity in electronic health records to identify and reduce the disparities this minority group faces.

Racial disparities in COVID-19 mortality across Michigan, United States.

BACKGROUND: Black populations in the United States are being disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and other demographic characteristics is not well understood. We examined characteristics of individuals who died from COVID-19 in Michigan by race stratified by their age, sex and comorbidity prevalence to illustrate and understand this disparity in mortality risk. METHODS: We evaluate COVID-19 mortality in Michigan by demographic and health characteristics, using individual-level linked death certificate and surveillance data collected by the Michigan Department of Health and Human Services from March 16 to October 26, 2020. We identified differences in demographics and comorbidity prevalence across race among individuals who died from COVID-19 and calculated mortality rates by age, sex, race, and number of comorbidities. FINDINGS: Among the 6,065 COVID-19 related deaths in Michigan, Black individuals are experiencing 3·6 times the mortality rate of White individuals (p<0.001), with a mortality rate for Black individuals under 65 years without comorbidities that is 12·6 times that of their White counterparts (p<0.001). After accounting for age, race, sex, and number of comorbidities, we find that Black individuals in all strata are at higher risk of COVID-19 mortality than their White counterparts. INTERPRETATION: Our findings demonstrate that Black populations are disproportionately burdened by COVID-19 mortality, even after accounting for demographic and underlying health characteristics. We highlight how disparities across race, which result from systemic racism, are compounded in crises. FUNDING: ASP, AP and APG were funded by NSF Expeditions grant 1918784, NIH grant 1R01AI151176-01, NSF Rapid Response Research for COVID-19 grant RAPID-2027755, and the Notsew Orm Sands Foundation. MCF was supported by NIH grant K01AI141576.

Association between county jail incarceration and cause-specific county mortality in the USA, 1987-2017: a retrospective, longitudinal study.

BACKGROUND: Mass incarceration has collateral consequences for community health, which are reflected in county-level health indicators, including county mortality rates. County jail incarceration rates are associated with all-cause mortality rates in the USA. We assessed the causes of death that drive the relationship between county-level jail incarceration and mortality. METHODS: In this retrospective, longitudinal study, we assessed the association between county-level jail incarceration rates and county-level cause-specific mortality using county jail incarceration data (1987-2017) for 1094 counties in the USA obtained from the Vera Institute of Justice and cause-specific mortality data for individuals younger than 75 years in the total county population (1988-2018) obtained from the US National Vital Statistics System. We fitted quasi-Poisson models for nine common causes of death (cerebrovascular disease, chronic lower respiratory disease, diabetes, heart disease, infectious disease, malignant neoplasm, substance use, suicide, and unintentional injury) with county fixed effects, controlling for all unmeasured stable county characteristics and measured time-varying confounders (county median age, county poverty rate, county percentage of Black residents, county crime rate, county unemployment rate, and state incarceration rate). We lagged county jail incarceration rates by 1 year to assess the short-term, by 5 years to assess the medium-term, and by 10 years to assess the long-term associations of jail incarceration with premature mortality. FINDINGS: A 1 per 1000 within-county increase in jail incarceration rate was associated with a 6·5% increase in mortality from infectious diseases (risk ratio 1·065, 95% CI 1·061-1·070), a 4·9% increase in mortality from chronic lower respiratory disease (1·049, 1·045-1·052), a 2·6% increase in mortality induced from substance use (1·026, 1·020-1·032), a 2·5% increase in suicide mortality (1·025, 1·020-1·029), and smaller increases in mortality from heart disease (1·021, 1·019-1·023), unintentional injury (1·015, 1·011-1·018), malignant neoplasm (1·014, 1·013-1·016), diabetes (1·013, 1·009-1·018), and cerebrovascular disease (1·010, 1·007-1·013) after 1 year. Associations between jail incarceration and cause-specific mortality rates weakened as time lags increased, but to a greater extent for causes of death with generally shorter latency periods (infectious disease and suicide) than for those with generally longer latency periods (heart disease, malignant neoplasm, and cerebrovascular disease). INTERPRETATION: Jail incarceration rates are potential drivers of many causes of death in US counties. Jail incarceration can be harmful not only to the health of individuals who are incarcerated, but also to public health more broadly. Our findings suggest important points of intervention, including disinvestment from carceral systems and investment in social and public health services, such as community-based treatment of substance-use disorders. FUNDING: US National Institute on Drug Abuse (National Institutes of Health).

Objective and subjective poor mental health indicators among Arab Americans in Michigan: a population-based study.

Background: Arab Americans are at high risk for poor mental health outcomes and are difficult to study at a population level due to a lack of racial/ethnic identifiers for this population.Methods: Using data from the standalone 2013 Michigan Arab Behavioral Risk Factor Survey (MI ABRFS) we aimed to understand whether the burden of mental health differed between Arab Americans and non-Arab, non-Hispanic Whites. Two measures of mental health were used: a subjective (number of poor mental health days experienced in the past 30 days) and an objective (being diagnosed with depression) measure. Additionally, we aimed to understand the sociodemographic, stress, and health-related variables associated with the objective and subjective measures of psychopathologies in the Arab American population in Michigan using population-weighted logistic regression models with survey design correction.Results: Arab Americans had increased odds of adverse mental health when compared to non-Arab, non-Hispanic Whites for the subjective measure of number of poor mental health days (OR: 1.62, 95% CI: 1.08, 2.41) and decreased odds of reporting the objective measure of diagnosed depression (OR: 0.54, 95% CI: 0.30, 0.98). Having more than one poor mental health day and being diagnosed with depression among Arab Americans was associated with being female, unmarried, unemployed, and having experienced abuse as a child.Discussion: Combining mental health screenings with primary care check-ups among Arab Americans may be an important step in identifying individuals with mental health needs and extending access to care.

Infant Health for Arab and Non-Arab Mothers Identifying as White, Black, or Other in Massachusetts.

INTRODUCTION: This study quantifies the differences in infant outcomes by mother's self-identified race among Arab Americans and by self-identified race and ethnicity for Arabs and non-Arabs. METHODS: This study used data from the Standard Certificate of Live Birth on 8,204 infants born to Arab and 325,354 infants born to non-Arab mothers between 2012 and 2016 in Massachusetts; data were analyzed between 2019 and 2020. Mothers' race was categorized as White, Black, or Other. Mothers' ethnicity was categorized as Arab or non-Arab. Outcomes included birth weight, preterm birth, low-birth weight, small for gestational age, and large for gestational age. Linear and logistic regression models assessed the association between race and infant health outcomes. RESULTS: Black Arab mothers had higher odds of preterm birth (AOR=1.37, 95% CI=1.07, 1.76) and low-birth weight (AOR=1.35, 95% CI=0.99, 1.84) than White Arab mothers. Arab mothers who self-identified as Other had babies that were 51.4 grams lighter than babies born to White Arab mothers. White Arab mothers had higher odds of low birth weight (AOR=1.19, 95% CI=1.06, 1.34) and small-for-gestational-age babies (AOR=1.22, 95% CI=1.11, 1.36) but lower odds of large-for-gestational-age babies (AOR=0.77, 95% CI=0.70, 0.86) than White non-Arab mothers. CONCLUSIONS: Both ethnicity and race are important determinants of the health of Arab American infants. Arab ethnicity may play a negative role in the infant health of Arab Americans who identify as White. A better understanding of the lived experiences of Arab American mothers, with regard to their racial and ethnic identity, may help better inform clinical practice.

County Jail Incarceration Rates and County Mortality Rates in the United States, 1987-2016.

Objectives. To evaluate the relationship between changes in county jail incarceration rates and subsequent county mortality rates across the United States.Methods. We analyzed county jail incarceration rates from the Bureau of Justice Statistics from 1987 to 2016 for 1884 counties and mortality rates from the National Vital Statistics System. We fit 1-year-lagged quasi-Poisson 2-way fixed-effects models, controlling for unmeasured stable county characteristics, and measured time-varying confounders, including county poverty and crime rates.Results. A within-county increase in jail incarceration rates from the first to second quartile was associated with a 2.5% increase in mortality rates, adjusting for confounders (risk ratio [RR] = 1.03; 95% confidence interval [CI] = 1.02, 1.03). This association followed a dose-response relationship and was stronger for mortality among those aged 15 to 34 years (RR = 1.07; 95% CI = 1.06, 1.09).Conclusions. Within-county increases in jail incarceration rates are associated with increases in subsequent mortality rates after adjusting for important confounders.Public Health Implications. Our findings add to the growing body of empirical evidence of the harms of mass incarceration. The criminal justice reform and decarceration movements can use these findings as they develop strategies to end mass incarceration.

Relevance of the "Immigrant Health Paradox" for the Health of Arab Americans in California.

Objectives. To assess the validity of the immigrant health paradox among Arab Americans in California.Methods. We used data from the 2003 to 2017 California Health Interview Survey (n = 1425). We used survey-weighted χ2 and logistic regression analyses to compare Arabs by immigrant generation on socioeconomic indicators, health behaviors, and health outcomes.Results. Second-generation Arab Americans had higher odds of binge drinking (adjusted odds ratio [AOR] = 3.26; 95% confidence interval [CI] = 1.53, 6.94) in the past year than did first-generation Arab Americans. Third-generation Arab Americans had greater odds of receiving the influenza vaccine in the past year (AOR = 3.29; 95% CI = 1.09, 9.98) than did second-generation Arab Americans. Third-generation Arab Americans had increased odds of being overweight or obese when compared with first- (AOR = 2.59; 95% CI = 1.02, 6.58) and second-generation Arab Americans (AOR = 3.22; 95% CI = 1.25, 8.29), respectively.Conclusions. Alcohol use increased across immigrant generations, and we observed no differences in health outcomes, other than obesity. The immigrant health paradox does not appear to apply to Arab Americans in California; mechanisms that generate health in this population should be studied further.

Differences in health behaviors and health outcomes among non-Hispanic Whites and Arab Americans in a population-based survey in California.

BACKGROUND: Few population-based studies of Arab American health behaviors and outcomes exist outside of Michigan. We aimed to provide prevalence estimates of health behaviors and outcomes for Arab Americans and compare them to non-Hispanic Whites in California. METHODS: We used data from the 2003-2016 California Health Interview Surveys. We determined Arab American ethnicity using an algorithm that considered place of birth of the respondent or parent and use of Arabic language at home. Survey-weighted frequencies, chi-squared statistics, and logistic regression analyses were used to compare Arab Americans and non-Hispanic Whites on socioeconomic indicators, health behaviors and health outcomes. Multivariable models were adjusted for age, education level, and insurance status. RESULTS: Arab Americans had higher prevalence of no insurance, living below the federal poverty level, and home ownership than non-Hispanic Whites despite high levels of education and low unemployment prevalence. Arab Americans had reduced odds of alcohol consumption (OR: 0.33, 95% CI: 0.24, 0.45), binge drinking (OR: 0.28, 95% CI: 0.19, 0.40), and suicidal ideation (OR: 0.41, 0.25, 0.66) when compared to non-Hispanic Whites in multivariable models. Arab Americans had decreased odds of hypertension (OR: 0.64, 95% CI: 0.50, 0.83) and increased odds of diabetes (OR: 2.03, 95% CI: 1.23, 3.34) when compared to non-Hispanic Whites in multivariable models. CONCLUSIONS: Arab Americans in California participate in less risky health behaviors and have better health outcomes than non-Hispanic Whites, except with regards to diabetes. Future work aiming to understand the health of Arab Americans should allow for self-identification and less reliance on country of origin and language use at home for sample selection.

The Health of Arab Americans in the United States: An Updated Comprehensive Literature Review.

Background: Arab Americans are a historically understudied minority group in the United States and their health needs and risks have been poorly documented. We aim to provide an updated comprehensive review of the literature on Arab American physical and mental health and provide suggestions for future work in this field. Methods: A comprehensive review of the English language medical and public health literature published prior to 2017 identified through multiple database searches was conducted with search terms describing Arab Americans and health outcomes and behaviors. The literature was qualitatively summarized by health behavior (vaccination, tobacco use, drug and alcohol use, and physical activity), health outcome (diabetes, mental health, cardiovascular disease, cancer, women's, and child health), and populations at increased risk of poor health outcomes (adolescents and the elderly). Results: The majority of studies identified exploring Arab American health have been published since 2009 with an increase in the number of longitudinal and intervention studies done with this population. The majority of research is being undertaken among individuals living in ethnic enclaves due to the lack of an ethnic or racial identifier that may help identify Arab Americans from population-based studies. Studies highlight the conflicting evidence in the prevalence of diabetes and cardiovascular disease based on study sample, an increased understanding of cancer incidence and barriers to identification, and an increased level of knowledge regarding mental health and sexual health needs in the population. Information on health behaviors has also increased, with a better understanding of physical activity, alcohol and drug use, and vaccination. Conclusion: More research on Arab American health is needed to identify risks and needs of this marginalized population given the current social and political climate in the United States, especially with regard to acculturation status and immigrant generation status. We provide recommendations on approaches that may help improve our understanding of Arab American health.

Ineffective insurance in lower and middle income countries is an obstacle to universal health coverage.

BACKGROUND: Recent health policy efforts have sought to promote universal health coverage (UHC) as a means of providing affordable access to health services to populations. However, insurance schemes are heterogeneous, and some schemes may not provide necessary services to those covered. We explored the prevalence and determinants of ineffective insurance across 42 lower and middle income countries (LMICs) from the 2002-2004 World Health Survey. METHODS: Respondents were defined as having ineffective health insurance if they reported being insured and: were forced to borrow or sell personal items to pay for health services; had an untreated chronic condition; or had recently delivered a child outside of a skilled health facility (women only). RESULTS: Among the insured, 13% had ineffective insurance, which was most commonly due to having to borrow or sell to pay for health care. The likelihood of ineffective insurance was lowest in upper-middle income countries and higher in other lower-middle and low-income countries. Ineffective insurance also decreased with family wealth and was higher among rural residents. CONCLUSIONS: Our findings suggest that a high proportion of insurance in LMICs is ineffective, particularly among those who need it most, and that attention should be paid to effectiveness when defining health insurance in policy conversations about UHC.

The association between neighborhood socioeconomic disadvantage and high-risk injection behavior among people who inject drugs.

BACKGROUND: Although much research has been conducted on the determinants of HIV risk behavior among people who inject drugs (PWID), the influence of the neighborhood context on high-risk injection behavior remains understudied. To address this gap in the literature, we measured associations between neighborhood socioeconomic disadvantage and high-risk injection behavior, and determined whether these associations were modified by drug-related police activity and syringe exchange program (SEP) accessibility. METHODS: Our sample was comprised of 484 pharmacy-recruited PWID in New York City. Measures of neighborhood socioeconomic disadvantage were created using data from the 2006-2010 American Community Survey. Associations with high-risk injection behavior were estimated using multivariable Poisson regression. Effect modification by drug-related police activity and SEP accessibility was assessed by entering cross-product terms into adjusted models of high-risk injection behavior. RESULTS: Neighborhood socioeconomic disadvantage was associated with decreased receptive syringe sharing and unsterile syringe use. In neighborhoods with high drug-related police activity, associations between neighborhood disadvantage and unsterile syringe use were attenuated to the null. In neighborhoods with high SEP accessibility, neighborhood disadvantage was associated with decreased acquisition of syringes from an unsafe source. CONCLUSIONS: PWID in disadvantaged neighborhoods reported safer injection behaviors than their counterparts in neighborhoods that were relatively better off. The contrasting patterns of effect modification by SEP accessibility and drug-related police activity support the use of harm reduction approaches over law enforcement-based strategies for the control of blood borne virus transmission among PWID in disadvantaged urban areas.

An Ounce of Prevention: Deaths Averted From Primary Prevention Interventions.

INTRODUCTION: The U.S. lags in the nationwide implementation of primary prevention interventions that have been shown to be efficacious. However, the potential population health benefit of widespread implementation of these primary prevention interventions remains unclear. METHODS: The meta-analytic literature from October 2013 to March 2014 of primary prevention interventions published between January 2000 and March 2014 was reviewed. The authors then estimated the number of deaths that could have been averted in the U.S. in 2010 if all rigorously studied, efficacious primary prevention interventions for which population attributable risk proportions could be estimated were implemented nationwide. RESULTS: A total of 372,054 (15.1%) of all U.S. deaths in 2010 would have been averted if all rigorously studied, efficacious primary prevention interventions were implemented. Two in three averted deaths would have been from cardiovascular disease or malignancy. CONCLUSIONS: A substantial proportion of deaths in the U.S. in 2010 could have been averted if efficacious primary prevention interventions were implemented nationwide. Further investment in the implementation of efficacious interventions is warranted to maximize population health in the U.S.

National income inequality and ineffective health insurance in 35 low- and middle-income countries.

Global health policy efforts to improve health and reduce financial burden of disease in low- and middle-income countries (LMIC) has fuelled interest in expanding access to health insurance coverage to all, a movement known as Universal Health Coverage (UHC). Ineffective insurance is a measure of failure to achieve the intended outcomes of health insurance among those who nominally have insurance. This study aimed to evaluate the relation between national-level income inequality and the prevalence of ineffective insurance. We used Standardized World Income Inequality Database (SWIID) Gini coefficients for 35 LMICs and World Health Survey (WHS) data about insurance from 2002 to 2004 to fit multivariable regression models of the prevalence of ineffective insurance on national Gini coefficients, adjusting for GDP per capita. Greater inequality predicted higher prevalence of ineffective insurance. When stratifying by individual-level covariates, higher inequality was associated with greater ineffective insurance among sub-groups traditionally considered more privileged: youth, men, higher education, urban residence and the wealthiest quintile. Stratifying by World Bank country income classification, higher inequality was associated with ineffective insurance among upper-middle income countries but not low- or lower-middle income countries. We hypothesize that these associations may be due to the imprint of underlying social inequalities as countries approach decreasing marginal returns on improved health insurance by income. Our findings suggest that beyond national income, income inequality may predict differences in the quality of insurance, with implications for efforts to achieve UHC.

Web-Based Antismoking Advertising to Promote Smoking Cessation: A Randomized Controlled Trial.

BACKGROUND: Although hundreds of millions of dollars are spent each year on public health advertising, the advertisement content, design, and placement are usually developed by intuition rather than research. OBJECTIVE: The objective of our study was to develop a methodology for testing Web-based advertisements to promote smoking cessation. METHODS: We developed 10 advertisements that varied by their content (those that empower viewers to quit, help viewers to quit, or discuss the effects of smoking). We then conducted a series of Web-based randomized controlled trials that explored the effects of exposing users of Microsoft's Bing search engine to antismoking advertisements that differed by content, placement, or other characteristics. Finally, we followed users to explore whether they conducted subsequent searches for smoking cessation products or services. RESULTS: The advertisements were shown 710,106 times and clicked on 1167 times. In general, empowering advertisements had the greatest impact (hazard ratio [HR] 2.6, standard error [SE] 0.09 relative to nonempowering advertisements), but we observed significant variations by gender. For instance, we found that men exposed to smoking cessation advertisements were less likely than women to subsequently conduct smoking cessation searches (HR 0.2, SE 0.07), but that this likelihood increased 3.5 times in men exposed to advertisements containing empowering content. Women were more influenced by advertisements that emphasized the health effects of smoking. We also found that appearing at the top right of the page (HR 2.1, SE 0.07) or at the bottom rather than the top of a list (HR 1.1, SE 0.02) can improve smoking cessation advertisements' effectiveness in prompting future searches related to smoking cessation. CONCLUSIONS: Advertising should be targeted to different demographic groups in ways that are not always intuitive. Our study provides a method for testing the effectiveness of Web-based antismoking advertisements and demonstrates the importance of advertisements that are tailored according to specific demographics.