Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.

Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases. Using chromatin interaction sequencing, massively parallel reporter assays (MPRA), and transgenic mice, we identified disease-linked, biallelic HAR mutations in active enhancers for CUX1, PTBP2, GPC4, CDKL5, and other genes implicated in neural function, ASD, or both. Our data provide genetic evidence that specific HARs are essential for normal development, consistent with suggestions that their evolutionary changes may have altered social and/or cognitive behavior. PAPERCLIP.

Densely interconnected transcriptional circuits control cell states in human hematopoiesis.

Though many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of cis-elements in gene promoters to decipher the general organization of their regulatory circuitry. We identified modules of highly coexpressed genes, some of which are restricted to a single lineage but most of which are expressed at variable levels across multiple lineages. We found densely interconnected cis-regulatory circuits and a large number of transcription factors that are differentially expressed across hematopoietic states. These findings suggest a more complex regulatory system for hematopoiesis than previously assumed.

Combined Treatment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-Human Primates.

BACKGROUND: Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs. METHODS: We generated 3 lines of hiPSC-derived endothelial cells (ECs) and hiPSC-CMs from 3 independent donors and tested hiPSC-CM sarcomeric length, gap junction protein, and calcium-handling ability in coculture with ECs. Next, we examined the therapeutic effect of the cotransplantation of hiPSC-ECs and hiPSC-CMs in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice undergoing myocardial infarction (n≥4). Cardiac function was assessed by echocardiography, whereas arrhythmic events were recorded using 3-lead ECGs. We further used healthy non-human primates (n=4) with cell injection to study the cell engraftment, maturation, and integration of transplanted hiPSC-CMs, alone or along with hiPSC-ECs, by histological analysis. Last, we tested the cell therapy in ischemic reperfusion injury in non-human primates (n=4, 3, and 4 for EC+CM, CM, and control, respectively). Cardiac function was evaluated by echocardiography and cardiac MRI, whereas arrhythmic events were monitored by telemetric ECG recorders. Cell engraftment, angiogenesis, and host-graft integration of human grafts were also investigated. RESULTS: We demonstrated that human iPSC-ECs promote the maturity and function of hiPSC-CMs in vitro and in vivo. When cocultured with ECs, CMs showed more mature phenotypes in cellular structure and function. In the mouse model, cotransplantation augmented the EC-accompanied vascularization in the grafts, promoted the maturity of CMs at the infarct area, and improved cardiac function after myocardial infarction. Furthermore, in non-human primates, transplantation of ECs and CMs significantly enhanced graft size and vasculature and improved cardiac function after ischemic reperfusion. CONCLUSIONS: These results demonstrate the synergistic effect of combining iPSC-derived ECs and CMs for therapy in the postmyocardial infarction heart, enabling a promising strategy toward clinical translation.

Use patterns of flavored non-cigarette tobacco products among US adults, 2010-2019.

OBJECTIVE: Flavored non-cigarette tobacco product (NCTP) use is common among US adult tobacco users. To update the estimates of use patterns of flavored NCTPs, this study assessed current NCTP use among adults by flavor use and flavor categories from 2010 to 2019. METHODS: We analyzed data from the 2010-2019 Tobacco Use Supplement to the Current Population Survey to estimate the weighted proportion of adult NCTP users by flavor use across survey waves. Flavor use was defined as past 30-day use of any menthol/mint or fruit/other flavors. We used the 2018-2019 data to examine the differences in demographic characteristics and tobacco use patterns among users of menthol/mint or fruit/other flavors compared to exclusive users of tobacco flavor, by product type. RESULTS: Compared to 2014-2015, electronic nicotine delivery system (ENDS) users were more likely (79.0% vs. 66.6%, p < 0.001) to report flavor use in 2018-2019, whereas cigar (26.9% vs. 31.2%, p = 0.030) and pipe (56.3% vs. 65.5%, p = 0.015) smokers were less likely to report flavor use in 2018-2019. In 2018-2019, the most prevalent flavor categories were exclusive use of tobacco flavor among cigar (73.1%) and smokeless tobacco (48.3%) users, and use of fruit/other flavors among ENDS (64.9%) and pipe (48.4%) users. Flavored users were more likely to be young adults aged 18-24 years (cigars, ENDS, smokeless tobacco) and Non-Hispanic Black or Hispanic persons (cigars, ENDS, pipes) compared to tobacco-flavored users. CONCLUSIONS: Flavored product use increased among adult ENDS users but decreased among cigar and pipe smokers. These findings could inform tobacco regulatory efforts concerning flavored NCTPs.

Cigar Cessation Prevalence and Trends by Demographic Characteristics Among US Adults, TUS-CPS, 2010-2019.

INTRODUCTION: Disproportionate rates of cigar smoking across demographic groups can contribute to tobacco-related health disparities in the United States. We assessed overall and demographic-specific cigar cessation rates from 2010 to 2019. AIMS AND METHODS: To characterize cessation prevalence among selected demographic groups over time, we analyzed data from the 2010-2011, 2014-2015, and 2018-2019 Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Individuals who reported either (1) current cigar smoking for at least 2 years or (2) quitting cigar smoking within the past 12 months were included in the study (n = 5262 in 2010-2011; n = 4741 in 2014-2015; n = 3741 in 2018-2019). Among this group, individuals who reported not smoking a cigar within the past 6 months were considered cigar quitters. Chi-square tests were used to test differences in cessation prevalence between the two survey waves within demographic groups as well as between different groups within survey waves. RESULTS: The prevalence of cigar cessation decreased from 2010-2011 to 2018-2019 for non-Hispanic (NH) White individuals, Hispanic individuals, and both males and females. (p < .05 for all groups). NH White individuals had significantly higher cessation prevalence than individuals who identified as NH Black (33.8% vs. 25.0%, respectively, in 2010-2011; 33.4% vs. 20.4% in 2014-2015; 31.1% vs. 22.3% in 2018-2019; p < .05 for all differences). CONCLUSIONS: Overall cigar cessation prevalence significantly decreased from 2010-2011 to 2018-2019. Findings from the study could provide an opportunity to implement strategies that promote cessation strategies targeting certain subpopulations. IMPLICATIONS: Cigar cessation patterns are starkly different across different demographic groups, which leads to a disproportionate burden of health-related effects of continued use of these products. These results can inform policy actions around cigar cessation efforts. Future research to close this disparity should be focused on populations that have lower cessation prevalence.

Initial Assessment and Management of Select Musculoskeletal Injuries: A Team Physician Consensus Statement.

ABSTRACT: Musculoskeletal injuries occur frequently in sport during practice, training, and competition. Injury assessment and management are common responsibilities for the team physician. Initial Assessment and Management of Musculoskeletal Injury-A Team Physician Consensus Statement is title 23 in a series of annual consensus documents written for the practicing team physician. This statement was developed by the Team Physician Consensus Conference, an annual project-based alliance of six major professional associations. The goal of this document is to help the team physician improve the care and treatment of the athlete by understanding the initial assessment and management of selected musculoskeletal injuries.

Smoke exposure associated with higher urinary benzene biomarker muconic acid (MUCA) in Golestan Cohort Study participants.

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

Randomized Comparative Effectiveness Trial of 2 Federally Recommended Strategies to Reduce Excess Body Fat in Overweight, Low-Income Patients: MyPlate.gov vs Calorie Counting.

PURPOSE: Since 2011, US authorities have supported the following 2 approaches to healthier body fat composition: the Centers for Disease Control and Prevention National Diabetes Prevention Program's calorie counting (CC) approach and the US Department of Agriculture's MyPlate (adherence to federal nutrition guidelines). The purpose of this study was to compare the effect of CC vs MyPlate approaches on satiety/satiation and on achieving healthier body fat composition among primary care patients. METHODS: We conducted a randomized controlled trial comparing the CC and MyPlate approaches from 2015 to 2017. The adult participants were overweight, of low income, and were mostly Latine (n = 261). For both approaches, community health workers conducted 2 home education visits, 2 group education sessions, and 7 telephone coaching calls over a period of 6 months. Satiation and satiety were the primary patient-centered outcome measures. Waist circumference and body weight were the primary anthropometric measures. Measures were assessed at baseline, 6 months, and 12 months. RESULTS: Satiation and satiety scores increased for both groups. Waist circumference was significantly decreased in both groups. MyPlate, but not CC, resulted in lower systolic blood pressure at 6 months but not at 12 months. Participants for both MyPlate and CC reported greater quality of life and emotional well-being and high satisfaction with their assigned weight-loss program. The most acculturated participants showed the greatest decreases in waist circumference. CONCLUSIONS: A MyPlate-based intervention might be a practical alternative to the more traditional CC approach to promoting satiety and facilitating decreases in central adiposity among low-income, mostly Latine primary care patients.

The Management of Children and Youth With Pediatric Mental and Behavioral Health Emergencies.

Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.

Characteristics and Patterns of Cigarette Smoking and Vaping By Past-Year Smokers Who Reported Using Electronic Nicotine Delivery System to Help Quit Smoking in the Past Year: Findings From the 2018-2019 Tobacco Use Supplement to the Current Population Survey.

INTRODUCTION: Cigarette smoking has declined, while electronic nicotine delivery system (ENDS) use has increased in the United States. Understanding the role of ENDS in adult smoking quit attempts and cessation is important for estimating their population health impact. AIMS AND METHODS: We used data from 2018 to 2019 tobacco use supplement to the current population survey to examine demographic characteristics and ENDS use patterns among adult ENDS users who reported quitting smoking in the past year by trying to switch to ENDS ("switchers") and smokers who did or did not make a quit attempt in the past year. χ2 tests of proportions and t-tests were used to compare characteristics between groups. RESULTS: In 2018-2019, about three-quarters of switchers reported daily use of ENDS compared to only one-third of dual users with a recent quit attempt by trying to switch to ENDS. Compared to dual users who made a quit attempt by trying to switch to ENDS, switchers were more likely to use menthol/mint-flavored ENDS exclusively (5.6% vs. 13.1%; p = .004) but less likely to use tobacco-flavored ENDS exclusively (21.2% vs. 13.7%; p = .01). CONCLUSIONS: ENDS users who quit smoking in the past year and reported trying to quit by switching to ENDS were more likely to use menthol/mint flavors exclusively and use ENDS daily compared to dual users who made a quit attempt by trying to switch to ENDS. Longer-term prospective data may better clarify the role of ENDS in smoking quit attempts and cessation. IMPLICATIONS: This study provides information on patterns of ENDS use in former smokers and current smokers who tried to quit smoking by switching to ENDS in a national sample of U.S. adults. These results can inform policy actions concerning ENDS products.

Variability in Urinary Nicotine Exposure Biomarker Levels Between Waves 1 (2013-2014) and 2 (2014-2015) in the Population Assessment of Tobacco and Health Study.

INTRODUCTION: To date, no studies have evaluated the consistency of biomarker levels in people who smoke over a long-time period in real-world conditions with a large number of subjects and included use behavior and measures of nicotine metabolism. We evaluated the variability of biomarkers of nicotine exposure over approximately a 1-year period in people who exclusively smoke cigarettes, including intensity and recency of use and brand switching to assess impact on understanding associations with product characteristics. AIMS AND METHODS: Multivariate regression analysis of longitudinal repeated measures of urinary biomarkers of nicotine exposure from 916 adults in the Population Assessment of Tobacco and Health (PATH) Study with demographic characteristics and use behavior variables. Intraclass correlation coefficients (ICCs) were calculated to examine individual variation of nicotine biomarkers and the uncertainty of repeat measures at two time points (Waves 1 and 2). RESULTS: Age, race, and urinary creatinine were significant covariates of urinary cotinine. When including use behavior, recency, and intensity of use were highly significant and variance decreased to a higher extent between than within subjects. The ICC for urinary cotinine decreased from 0.7530 with no use behavior variables in the model to 0.5763 when included. Similar results were found for total nicotine equivalents. CONCLUSIONS: Urinary nicotine biomarkers in the PATH Study showed good consistency between Waves 1 and 2. Use behavior measures such as time since last smoked a cigarette and number of cigarettes smoked in the past 30 days are important to include when assessing factors that may influence biomarker concentrations. IMPLICATIONS: The results of this study show that the consistency of the nicotine biomarkers cotinine and total nicotine equivalents in spot urine samples from Waves 1 to 2 of the PATH Study is high enough that these data are useful to evaluate the association of cigarette characteristics with biomarkers of exposure under real-world use conditions.

Transitions to smokeless tobacco use among adult cigarette smokers in the Population Assessment of Tobacco and Health (PATH) Study, Waves 3-5 (2015-2019).

OBJECTIVE: Examine patterns of dual use of cigarettes and smokeless tobacco and complete switching over time among adult current cigarette smokers using data from the Population Assessment of Tobacco and Health Study Wave 3 (2015-2016), Wave 4 (2016-2018) and Wave 5 (2018-2019). METHODS: We examined four tobacco use states among 6834 exclusive smokers and 372 dual users at Wave 3 with two waves of follow-up data: exclusive cigarette use, exclusive smokeless tobacco use, dual use and use of neither product. RESULTS: Among exclusive smokers at Wave 3, only 1.6% (95% CI: 1.3% to 2.1%) transitioned to dual use at Wave 4, and 0.1% (95% CI: 0.07% to 0.2%) switched to exclusive smokeless tobacco use. Among exclusive smokers who switched to dual use, 53.1% (95% CI: 40.9% to 64.9%) returned to exclusive cigarette smoking, 34.3% (95% CI: 23.8% to 46.6%) maintained dual use and 12.6% (95% CI: 7.0% to 21.7%) did not smoke cigarettes after an additional wave of follow-up. Dual users at Wave 3 were likely to maintain their dual use status at Wave 4, 51.2% (95% CI: 46.1% to 56.3%) and Wave 5, 47.9% (95% CI: 40.1% to 55.8%). CONCLUSIONS: Very few cigarette smokers transition to smokeless tobacco use, and among those who do, dual use is more common than exclusive smokeless tobacco use. Further, the majority of exclusive cigarette smokers who transition to dual use at Wave 4 continue smoking cigarettes at Wave 5, either as dual users or as exclusive smokers.

Suicide Safety Plan Self-knowledge in Serious Mental Illness: Psychiatric Symptom Correlates and Effects of Brief Intervention.

Psychiatric symptoms experienced by people with serious mental illness (SMI; schizophrenia, bipolar and other psychotic disorders) may impact suicide safety planning. This study examined safety plan self-knowledge, or an individual's own knowledge and awareness of their safety plan, in a sample of people with SMI. Participants (N = 53) with SMI at elevated risk of suicide completed a 4-session intervention that included safety plans, with one intervention group that included mobile augmentation. Self-knowledge was assessed from previous safety plans at 4-, 12- and 24-weeks. Fewer warning signs generated was correlated with greater psychiatric symptoms (r = - .306, p = .026) and suicidal ideation (r = - .298, p = .030). Fewer coping strategies generated was correlated with greater suicidal ideation (r = .- 323, p = .018). Preliminarily, there was greater self-knowledge of warning signs over time among participants in the mobile intervention. These preliminary findings highlight the relationship of safety plan self-knowledge to symptoms and suggest that mobile augmentation of safety planning may be beneficial. Trial Registration: NCT03198364.

Nutritional Strategies for Endurance Cyclists - Periodized Nutrition, Ketogenic Diets, and Other Considerations.

ABSTRACT: Cycling is a growing sport worldwide since the COVID-19 pandemic. With the growing availability and interest in long distance events, professional and amateur cyclists are pushing themselves further and harder than ever before. Training and nutrition should be understood by the sports medicine professional in order to guide counseling toward proper fueling to avoid health consequences. This article reviews macronutrients and micronutrients, periodized training and nutrition, and the relevance of the ketogenic diet for endurance cyclists riding greater than 90 min.

PrEP Stigma and logistical barriers remain significant challenges in curtailing HIV transmission among Black and Hispanic/Latinx cisgender sexual minority men and transgender women in the US.

Despite advancements in HIV prevention, such as pre-exposure prophylaxis (PrEP), there remain inequities in accessing PrEP among Black and Hispanic/Latinx cisgender sexual minority men and transgender women (SMMTW). Researchers have documented multiple barriers to PrEP uptake, yet the relative impacts of PrEP internalized stigma and logistical barriers (e.g., Cost; time) to PrEP use are understudied. It may be meaningful to investigate potential interactions between internalized stigma and logistical barriers to PrEP use. We utilized data from 827 Black and Hispanic/Latinx SMMTW (Mage = 25.09) in the US and found that greater PrEP-related internalized stigma and greater PrEP logistical barriers were independently significantly associated with lower likelihood of current PrEP use, but PrEP-related internalized stigma became a non-significant predictor when included in a multivariable model. We found a significant interaction between PrEP-related internalized stigma and logistical barriers to PrEP use, such that the association between internalized stigma and likelihood of current PrEP use was only significant at lower levels of logistical barriers to PrEP use. Findings highlight the need to reduce logistical barriers to PrEP use, and for clinicians to acknowledge the role of stigma for individuals who otherwise do not report logistical barriers.

Health Mindsets in Pediatric Chronic Headache.

OBJECTIVE: Given how frequently youth with chronic headache and migraine experience setbacks in treatment, identifying factors that promote coping and resilience is critical. Mindsets have gained attention as predictors of behavior and targets of intervention across contexts, including health. Health mindsets may help to explain how children with chronic pain interpret and respond to treatment. This study evaluated whether growth health mindsets might relate to adaptive outcomes in patients with chronic pediatric headache. METHODS: Participants were 88 children and adolescents (ages 10-17 years) with headache or migraine contacted following an appointment at a pediatric headache clinic, and their parent. Patients rated their beliefs about health as more fixed versus growth-oriented. They were presented with vignettes depicting hypothetical treatment setbacks and instructed to reflect upon real-life setbacks. Patients completed questionnaires about their cognitive appraisals of setbacks, coping, quality of life, life satisfaction, and functional impairment. RESULTS: The higher children rated their growth health mindsets, the less likely they were to appraise setbacks as threatening and endorse quality-of-life problems. Children with higher growth mindsets reported higher life satisfaction and lower functional disability. There was also an indirect relation between children's mindsets and coping through cognitive appraisals of setbacks as a threat, but not challenge. CONCLUSION: This research extends the health mindsets literature by contributing preliminary evidence of health mindsets as tied to adaptive outcomes in youth with chronic headache. These findings may be of interest to clinicians and parents, as health mindsets may offer an avenue by which resilience is promoted and maladaptive appraisals are minimized.

Willingness to Prescribe PrEP to Bisexual Men Depends on Genders of Their Past Partners: A Study of Medical Students in the USA.

Bisexual men are at increased risk for HIV compared to heterosexual men but unlikely to use pre-exposure prophylaxis (PrEP). Given that biases may influence whether bisexual men are prescribed PrEP, we examined whether medical students' decision-making was influenced by the genders of a bisexual male patient's partners. Medical students (N = 718) were randomized to one of nine conditions where they answered questions about a bisexual male patient after reviewing his electronic medical record. We manipulated the gender of his current partner (none, male, female) and the genders of his past partners (male, female, both). Current partners were described as living with HIV and not yet virally suppressed, past partners were described as being of unknown HIV-status, and condom use was described as intermittent with all partners. When the patient was not in a current relationship, perceived HIV risk and likelihood of prescribing PrEP were lowest if he only had female partners in the past. When he was in a current relationship, perceived HIV risk and likelihood of prescribing PrEP did not differ based on current or past partners' genders. In addition, identification as a PrEP candidate, perceived likelihood of adherence, and perceived likelihood of engaging in condomless sex if prescribed were lower when the patient was not in a current relationship. Medical students appropriately prioritized the status of the partner living with HIV, but their decision-making was influenced by past partner genders when the patient was not in a current relationship. Medical students may require additional education to ensure they understand PrEP eligibility criteria and make decisions based on patients' individual presentations.

ACSM-AMSSM Call to Action: Adapting Preparticipation Cardiovascular Screening to the COVID-19 Pandemic.

ABSTRACT: Preparticipation cardiovascular screening, designed to identify cardiovascular pathology responsible for sudden unexpected death, is recommended by all major professional medical organizations overseeing the clinical care of competitive athletes. Data from several large, prospective, cohort studies indicate that cardiac imaging findings consistent with inflammatory heart disease following COVID-19 infection are more common than most forms of heart disease associated with sudden death during exercise. This call-to-action document is intended to provide recommendations about how routine preparticipation cardiovascular screening for young competitive athletes - which has the capacity to detect both COVID-19 cardiovascular complications and pathology unrelated to infection - should be altered to account for recent scientific advances.

The contribution of smoking-attributable mortality to differences in mortality and life expectancy among US African-American and white adults, 2000-2019.

BACKGROUND: The role of smoking in racial disparities in mortality and life expectancy in the United States has been examined previously, but up-to-date estimates are generally unavailable, even though smoking prevalence has declined in recent decades. OBJECTIVE: We estimate the contribution of smoking-attributable mortality to observed differences in mortality and life expectancy for US African-American and white adults from 2000-2019. METHODS: The indirect Preston-Glei-Wilmoth method was used with national vital statistics and population data and nationally representative never-smoker lung cancer death rates to estimate the smoking-attributable fraction (SAF) of deaths in the United States by sex-race group from 2000-2019. Mortality rates without smoking-attributable mortality were used to estimate life expectancy at age 50 (e 50) by group during the period. RESULTS: African-American men had the highest estimated SAF during the period, beginning at 26.4% (95% CI:25.0%-27.8%) in 2000 and ending at 12.1% (95% CI:11.4%-12.8%) in 2019. The proportion of the difference in e 50 for white and African-American men that was due to smoking decreased from 27.7% to 14.8%. For African-American and white women, the estimated differences in e 50 without smoking-attributable mortality were similar to observed differences. CONCLUSIONS: Smoking continues to contribute to racial disparities in mortality and life expectancy among men in the United States. CONTRIBUTION: We present updated estimates of the contribution of smoking to mortality differences in the United States using nationally representative data sources.

Cigarette Smoking Reduction and Health Risks: A Systematic Review and Meta-analysis.

INTRODUCTION: Studies have shown the health benefits of cigarette smoking cessation. However, the literature remains unclear about the relationship between smoking reduction and health risks. This comprehensive review and meta-analysis updates previous reviews with the newest estimates. AIMS AND METHODS: We conducted a systematic review and meta-analysis evaluating the association between smoking reduction and some health risks in observational studies. We defined the following smoking categories: heavy smokers smoked ≥15-20 cigarettes per day (CPD), moderate smokers smoked 10-19 CPD, and light smokers smoked <10 CPD. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effect models. RESULTS: We identified 19 studies including four case-control and 15 cohort studies. Compared with continuing heavy smokers, we found decreased lung cancer risk for those who reduced CPD by more than 50% (RR = 0.72, 95% CI: 0.52, 0.91), from heavy to moderate (RR = 0.66, 95% CI: 0.46, 0.85), and from heavy to light (RR = 0.60, 95% CI: 0.49, 0.72). We also found lower risk of cardiovascular disease (CVD) for those who reduced from heavy to light smoking (RR = 0.78, 95% CI: 0.67, 0.89) but not those who reduced by more than 50% and reduced smoking from heavy to moderate. We did not find any significant difference in all-cause mortality, all-cancer risks, and smoking-/tobacco-related cancer risk among those who reduced. CONCLUSIONS: Substantial smoking reduction may decrease lung cancer risk but results on CVD (coronary heart disease and stroke combined) risk were mixed. The relationships between smoking reduction and other endpoints examined were not significant. IMPLICATIONS: This meta-analysis helps clarify our understanding of various smoking reduction levels on some health risks. While smoking reduction may decrease risks of lung cancer, the relationships between smoking reduction and other endpoints, including all-cause mortality and cardiovascular disease, remain unclear. Although smoking reduction may decrease lung cancer risks, the magnitude of lung cancer risk remain high. Among smokers, complete cessation remains the most effective approach for cancer and CVD prevention.