Population-Level Disparities in Exposure to COVID-19 Mitigation Policies, April 2020-April 2021.

CONTEXT: Studies have found that COVID-19 stay-at-home orders (SHOs) and face mask policies (FMPs) were associated with reduced COVID-19 transmission and deaths. But it is unknown whether exposure to these policies varied by sociodemographic characteristics across the US population. OBJECTIVE: The goal of this study was to quantify and characterize the sociodemographic characteristics and geographic distribution of populations exposed to evidence-based COVID-19 mitigation policies. DESIGN: We obtained statewide SHOs and FMPs for all US counties from April 10, 2020, to April 10, 2021, calculated median policy lengths, and categorized counties into 4 groups based on length of policy exposure: low SHO-low FMP, high SHO-low FMP, low SHO-high FMP, and high SHO-high FMP. We described exposure groups by COVID-19 cumulative case/death and vaccination rates and county sociodemographic characteristics. SETTING: In total, 3142 counties from all 50 states and Washington, District of Columbia, were included in the analysis. MAIN OUTCOME MEASURES: County-level sociodemographic factors and county cumulative rates for COVID-19 cases, deaths, and vaccinations. RESULTS: The largest percentage of the US population lived in counties with high exposure to SHOs and FMPs. However, populations living in high SHO-high FMP counties had the lowest percent non-Hispanic Black (NHB) and highest percent non-Hispanic White (NHW) populations. Populations living in high SHO-low FMP counties had the highest percent NHB and Hispanic populations and the lowest percent NHW population. CONCLUSION: This study identified county-level racial, ethnic, and sociodemographic disparities in exposure to evidence-based statewide COVID-19 mitigation policies. POLICY IMPLICATIONS: Exposure to evidence-based policies is an important consideration for studies evaluating the root causes of health inequities.

Natural carbazole alkaloid murrayafoline A displays potent anti-neuroinflammatory effect by directly targeting transcription factor Sp1 in LPS-induced microglial cells.

Neuroinflammation is a leading cause for neurological disorders. Carbazole alkaloids, isolated from the medicinal plants of Murraya species (Rutaceae), have exhibited wide pharmacological activities particularly for neuroinflammation. However, its underlying cellular targets and molecular mechanisms still remain unclear. In current study, we found that murrayafoline A (MA), a carbazole alkaloid obtained from Murraya tetramera, potently inhibited the production of neuroinflammation mediators, such as nitric oxide (NO), TNF-α, IL-6 and IL-1ß in LPS-induced BV-2 microglial cells. Then, we performed thermal proteome profiling (TPP) strategy to identify Specificity protein 1 (Sp1) as a potential cellular target of MA. Moreover, we performed surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DRATS) assays to confirm the direct interaction between MA and Sp1. Furthermore, we downregulated Sp1 expression in BV2 cells using siRNA transfection, and observed that Sp1 knockdown significantly antagonized MA-mediated inhibition of neuroinflammation mediator production. Meanwhile, Sp1 knockdown also markedly reversed MA-mediated inactivation of IKKß/NF-κB and p38/JNK MAPKs pathways. Finally, in vivo studies revealed that MA significantly suppressed the expression of Iba-1, TNF-α, and IL-6, while increased the number of Nissl bodies in the brains of LPS-induced mice. Taken together, our study demonstrated that MA exerted obvious anti-neuroinflammation effect by directly targeting Sp1, thereby inhibiting NF-κB and MAPK signaling pathways. Our findings also provided a promising direction of pharmacological targeting Sp1 for anti-neuroinflammation therapeutics as well as novel agent development.

Measuring State-Level Racial Inequity in Severe Maternal Morbidity in the Medicaid Population.

OBJECTIVE: Severe maternal morbidity represents a "near miss" mortality and is an important measure of quality and safety. Racial inequity in maternal morbidity is stark and the reasons for this disparity are poorly understood. We aimed to identify states achieving racial equity in maternal morbidity in order to identify policies that may promote racial equity. METHODS: We analyzed Medicaid deliveries from 2008 to 2009 in a sample that included 28 states and the District of Columbia. This dataset included approximately 80% of all Medicaid enrollees and 90% of minority Medicaid enrollees in the US. We determined the Non-Hispanic Black/Non-Hispanic white SMMI rate ratio for each state and categorized the states into groups by rate ratio. We described demographic features of both the general population and study population for these groups of states. RESULTS: In a sample that included a total of 1,489,134 births, we found that no state/district is achieving equity in severe maternal morbidity. The severe maternal morbidity rate is higher for Non-Hispanic Black than Non-Hispanic white patients in every state included. With a rate ratio ranging from 1.14 to 2.66, there are varying degrees of inequity. States in the group with the most equitable maternal morbidity rates had less inequity across racial subgroups with respect to educational attainment and poverty. CONCLUSIONS: Identifying geographic areas with varying degrees of inequity may be key to identifying policies to promote equity. Socioecological disparities and inadequate access to care may be factors in racial inequity in maternal morbidity.

Hyaluronic Acid-Functionalized Hollow Mesoporous Silica Nanoparticles as pH-Sensitive Nanocarriers for Cancer Chemo-Photodynamic Therapy.

Hollow mesoporous silica nanoparticles (HMSNs) served as nanocarriers for transporting doxorubicin hydrochloride (DOX) and indocyanine green (ICG) and were incorporated into a pH-sensitive targeted drug delivery system (DDS). Boronate ester bonds were employed to link HMSNs and dopamine-modified hyaluronic acid (DA-HA), which acted as both the "gatekeeper" and targeting agents (HMSNs-B-HA). Well-dispersed HMSNs-B-HA with a diameter of about 170 nm was successfully constructed. The conclusion was drawn from the in vitro drug release experiment that ICG and DOX (ID) co-loaded nanoparticles (ID@HMSNs-B-HA) with high drug loading efficiency could sustain drug release under acidic conditions. More importantly, in vitro cell experiments perfectly showed that ID@HMSNs-B-HA could well inhibit murine mammary carcinoma (4T1) cells via chemotherapy combined with photodynamic therapy and accurately target 4 T1 cells. In summary, all test results sufficiently demonstrated that the prepared ID@HMSNs-B-HA was a promising nano-DDS for cancer photodynamic combined with chemotherapy.

Variation in Reporting of the Race and Ethnicity of COVID-19 Cases and Deaths Across US States: April 12, 2020, and November 9, 2020.

Despite growing evidence that COVID-19 is disproportionately affecting communities of color, state-reported racial/ethnic data are insufficient to measure the true impact.We found that between April 12, 2020, and November 9, 2020, the number of US states reporting COVID-19 confirmed cases by race and ethnicity increased from 25 to 50 and 15 to 46, respectively. However, the percentage of confirmed cases reported with missing race remained high at both time points (29% on April 12; 23% on November 9). Our analysis demonstrates improvements in reporting race/ethnicity related to COVID-19 cases and deaths and highlights significant problems with the quality and contextualization of the data being reported.We discuss challenges for improving race/ethnicity data collection and reporting, along with opportunities to advance health equity through more robust data collection and contextualization. To mitigate the impact of COVID-19 on racial/ethnic minorities, accurate and high-quality demographic data are needed and should be analyzed in the context of the social and political determinants of health.

Food Access and Cardiovascular Outcomes in Metropolitan Atlanta Census Tracts With Residents at Low Risk and High Risk of Cardiovascular Disease: The Morehouse-Emory Cardiovascular Center for Health Equity Study.

INTRODUCTION: Perceived and actual access to healthy foods may differ in urban areas, particularly among Black people. We assessed the effect of objective and perceived neighborhood food access on self-reported cardiovascular disease (CVD) among Black people living in areas of high risk and low risk for the disease in Atlanta, Georgia. We hypothesized that perceived and objective food access would independently predict self-reported CVD. METHODS: We used survey data from the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity Study. Study participants consisted of 1,402 Black adults, aged 35 to 64, residing in urban Atlanta census tracts with high rates or low rates of CVD. We assessed perceived neighborhood healthy food access by self-reported selection and quality of produce and low-fat food options. We assessed objective food access by the 2015 US Department of Agriculture Food Access Research Atlas. Low access was defined as census tracts with at least 500 people living more than 1 mile from a large food retailer. Self-reported CVD included related conditions and/or procedures. We used multilevel logistic models adjusted for demographic characteristics to examine the association between objective and perceived food access and self-reported CVD. RESULTS: Overall, self-reported CVD was not significant for perceived (odds ratio = 0.87; 95% CI, 0.59-1.29) or objective (odds ratio = 0.74; 95% CI, 0.48-1.12) healthy food access. Similar results were obtained among adults living in areas with higher-than-expected rates of CVD. CONCLUSION: Results of this study suggest the odds for self-reported CVD events were not significantly affected by perceived or objective access to healthy foods.

Percentage of Black Population and Primary Care Shortage Areas Associated with Higher COVID-19 Case and Death Rates in Georgia Counties.

OBJECTIVES: We hypothesized that the proportion of Black individuals in a county would be associated with higher rates of coronavirus disease 2019 (COVID-19) cases and deaths, even after accounting for other high-risk socioecologic factors such as poverty, population density, and household crowding, and uninsured rates. We also expected that counties designated as primary care health professional shortage areas (PCHPSAs) would be associated with higher COVID-19 death rates, and the lack of primary care access would exacerbate racial disparities in death rates. We undertook this study to test these hypotheses and discern the independent effects of racial composition, socioecologic characteristics, and healthcare system factors on COVID-19 cases and deaths in Georgia counties. METHODS: We used county-level COVID-19 cases and deaths on April 23, 2020 from the Johns Hopkins Coronavirus Resource Center and estimates of 2019 county-level populations from the US Census Bureau to calculate the cumulative event rates for the state of Georgia. We used multiple regression models to examine crude and adjusted associations of socioecologic and health system variables with county-level COVID-19 case and mortality rates. RESULTS: After adjustment, a 1% increase in the proportion of Black people in the county resulted in a 2.3% increase in the county COVID-19 confirmed case rate and a 3.0% increase in the death rate (relative risk 1.03, 95% confidence interval 1.01-1.05, P < 0.001). Primary care shortage areas had a 74% higher death rate (relative risk 1.74, 95% confidence interval 1.00-3.00, P = 0.049). CONCLUSIONS: These results highlight the impact of racial disparities on the spatial patterns of COVID-19 disease burden in Georgia, which can guide interventions to mitigate racial disparities. The results also support the need for robust primary care infrastructure throughout the state.

Population-Level Disparities in COVID-19: Measuring the Independent Association of the Proportion of Black Population on COVID-19 Cases and Deaths in US Counties.

CONTEXT: There is a need to understand population race and ethnicity disparities in the context of sociodemographic risk factors in the US experience of the COVID-19 pandemic. OBJECTIVE: Determine the association between county-level proportion of non-Hispanic Black (NHB) on county COVID-19 case and death rates and observe how this association was influenced by county sociodemographic and health care infrastructure characteristics. DESIGN AND SETTING: This was an ecologic analysis of US counties as of September 20, 2020, that employed stepwise construction of linear and negative binomial regression models. The primary independent variable was the proportion of NHB population in the county. Covariates included county demographic composition, proportion uninsured, proportion living in crowded households, proportion living in poverty, population density, state testing rate, Primary Care Health Professional Shortage Area status, and hospital beds per 1000 population. MAIN OUTCOME MEASURES: Outcomes were exponentiated COVID-19 cases per 100 000 population and COVID-19 deaths per 100 000 population. We produced county-level maps of the measures of interest. RESULTS: In total, 3044 of 3142 US counties were included. Bivariate relationships between the proportion of NHB in a county and county COVID-19 case (Exp ß = 1.026; 95% confidence interval [CI], 1.024-1.028; P < .001) and death rates (rate ratio [RR] = 1.032; 95% CI, 1.029-1.035; P < .001) were not attenuated in fully adjusted models. The adjusted association between the proportion of NHB population in a county and county COVID-19 case was Exp ß = 1.025 (95% CI, 1.023-1.027; P < .001) and the association with county death rates was RR = 1.034 (95% CI, 1.031-1.038; P < .001). CONCLUSIONS: The proportion of NHB people in a county was positively associated with county COVID-19 case and death rates and did not change in models that accounted for other socioecologic and health care infrastructure characteristics that have been hypothesized to account for the disproportionate impact of COVID-19 on racial and ethnic minority populations. Results can inform efforts to mitigate the impact of structural racism of COVID-19.

Effect of Parity on Pregnancy-Associated Hypertension Among Asian American Women in the United States.

OBJECTIVES: Pregnancy-associated hypertension (PAH) includes gestational hypertension, preeclampsia and eclampsia. Although a protective effect of multi-parity on PAH has been reported in previous studies, the association has not been examined among Asian American women in the U.S. METHODS: Using data from 2014 U.S. National Vital Statistics System, we examined the prevalence of PAH among Asian American women who had singleton live births (N = 235,303), and its association with parity (number of previous pregnancies including live births and fetal deaths) controlling for potential confounders. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using multivariable logistic regression analysis. RESULTS: Overall, 2.72% (95% CI 2.66%, 2.79%) of Asian American women were recorded to have PAH during pregnancy. Parity was inversely associated with PAH in our study, where Asian American women who had 1-2 and 3 or more previous pregnancies had significantly lower odds of PAH (aOR 0.61, 95% CI 0.58, 0.65; and aOR 0.62, 95% CI 0.57, 0.68, respectively) compared to nulliparous women, after controlling for potential confounders. CONCLUSIONS: Recent U.S. vital statistics data revealed that nulliparity is significantly associated with PAH among Asian American women. Future studies should identify specific factors that are associated with PAH and factors contributing to disparities in PAH risk among Asian American women.

Identifying County-Level All-Cause Mortality Rate Trajectories and Their Spatial Distribution Across the United States.

INTRODUCTION: All-cause mortality in the United States declined from 1935 through 2014, with a recent uptick in 2015. This national trend is composed of disparate local trends. We identified distinct groups of all-cause mortality rate trajectories by grouping US counties with similar temporal trajectories. METHODS: We used all-cause mortality rates in all US counties for 1999 through 2016 and estimated discrete mixture models by using county level mortality rates. Proc Traj in SAS was used to detect how county trajectories clustered into groups on the basis of similar intercepts, slopes, and higher order terms. Models with increasing numbers of groups were assessed on the basis of model fit. We created county-level maps of mortality trajectory groups by using ArcGIS. RESULTS: Eight unique trajectory groups were detected among 3,091 counties. The average mortality rate in the most favorable trajectory group declined 29.4%, from 592.3 deaths per 100,000 in 1999 to 418.2 in 2016. The least favorable mortality trajectory group declined 3.4% over the period, from 1,280.3 deaths per 100,000 to 1,236.9. We saw significant differences in the demographic and socioeconomic profiles and geographic patterns across the trajectory categories, with favorable mortality trajectories in the Northeast, Midwest, and on the West Coast and unfavorable trajectories concentrated in the Southeast. CONCLUSIONS: County-level disparities in all-cause mortality rates widened over the past 18 years. Further investigation of the determinants of the trajectory groupings and the geographic outliers identified by our research could inform interventions to achieve equitable distribution of county mortality rates.

Identification of Resilient and At-Risk Neighborhoods for Cardiovascular Disease Among Black Residents: the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity Study.

INTRODUCTION: Despite the growing interest in place as a determinant of health, areas that promote rather than reduce cardiovascular disease (CVD) in blacks are understudied. We performed an ecologic analysis to identify areas with high levels of CVD resilience and risk among blacks from a large southern, US metropolitan area. METHODS: We obtained census tract-level rates of cardiovascular deaths, emergency department (ED) visits, and hospitalizations for black adults aged 35 to 64 from 2010 through 2014 for the Atlanta, Georgia, metropolitan area. Census tracts with substantially lower rates of cardiovascular events on the basis of neighborhood socioeconomic status were identified as resilient and those with higher rates were identified as at risk. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) of being classified as an at-risk versus resilient tract for differences in census-derived measures. RESULTS: We identified 106 resilient and 121 at-risk census tracts, which differed in the rates per 5,000 person years of cardiovascular outcomes (mortality, 8.13 vs 13.81; ED visits, 32.25 vs 146.3; hospitalizations, 26.69 vs 130.0), despite similarities in their median black income ($46,123 vs $45,306). Tracts with a higher percentage of residents aged 65 or older (odds ratio [OR], 2.29; 95% CI, 1.41-3.85 per 5% increment) and those with incomes less than 200% of the federal poverty level (OR, 1.19; 95% CI, 1.02-1.39 per 5% increment) and greater Gini index (OR, 1.56; 95% CI, 1.19- 2.07 per 0.05 increment) were more likely to be classified as at risk than resilient neighborhoods. DISCUSSION: Despite matching on median income level, at-risk neighborhoods for CVD among black populations were associated with a higher prevalence of socioeconomic indicators of inequality than resilient neighborhoods.

In vitro antibacterial effects of Tanreqing injection combined with vancomycin or linezolid against methicillin-resistant Staphylococcus aureus.

BACKGROUND: Combining conventional drugs and traditional medicine may represent a useful approach to combating antibiotic resistance, which has become a serious threat to global public health. This study aimed to evaluate the potential synergistic interactions between Tanreqing (TRQ) injection, a commercial traditional Chinese medicine formula used for the treatment of upper respiratory tract infection, and selected antibiotics used against methicillin-resistant Staphylococcus aureus (MRSA). METHODS: The minimum inhibitory concentrations (MICs) of TRQ, vancomycin and linezolid against planktonic MRSA strain were determined by the broth microdilution method. The combined effects of TRQ and antibiotics were studied by the checkerboard method and the time-kill curve assay. The 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay was employed to determine the inhibitory effect of the test compounds alone and in combination against MRSA embedded in biofilms. RESULTS: MRSA strain was found to be susceptible to TRQ formula with MIC value 4125 µg/ml, while the MIC values for antibiotics, vancomycin and linezolid, were 2.5 µg/ml. The checkerboard analysis revealed that TRQ markedly enhanced activities of the tested antibiotics by reducing their MICs. In the time-kill analysis, TRQ at 1/2 × MIC in combination with vancomycin at 1/2 × MIC, as well as TRQ at 1/8 × MIC in combination with linezolid at 1/2 × MIC decreased the viable colonies by ≥2log10 CFU/ml, resulting in a potent synergistic effect against planktonic MRSA. In contrast to the tested antibiotics, which did not affect mature MRSA biofilms at subinhibitory concentrations, TRQ alone showed strong ability to disrupt preformed biofilms and induce biofilm cell death. The combination of TRQ with vancomycin or linezolid at sub-MIC concentrations resulted in a synergistic antibiofilm effect significantly higher than for each single agent. CONCLUSIONS: This study provides the first in vitro evidence on the synergistic effects of TRQ and vancomycin or linezolid against planktonic and biofilm MRSA, and revealed their optimal combination doses, thereby providing a rational basis for the combination therapies against MRSA.

A de novo germline mutation of APC for inheritable colon cancer in a Chinese family using multigene next generation sequencing.

Inheritable colorectal cancers (CRC) accounted for about 20% of the CRC cases, such as hereditary nonpolyposis colorectal cancer (HNPCC), Gardner syndrome and familial adenomatous polyposis (FAP). A four-generation Han Chinese family was found affected with polyposis in colons. Inferred from the pedigree structure, the disease in this family showed an autosomal dominant inheritance model. To locate the causal mutations in this family, genomic DNAs were extracted and the next generation sequencing for 5 genes relating to colon cancer performed by Ion Torrent Personal Genome Machine with a 314 chip. The reads were aligned with human reference genome hg19 to call variants in the 5 genes. After analysis, 14 variants were detected in the sequenced sample and 13 been collected in dbSNP database and assigned with a rs identification number. In these variants, 9 were synonymous, 4 missense and 1 non-sense. In them, 2 rare variants (c.694C>T in APC and c.1690A>G in MSH2) might be the putative causal mutations for familial adenomatous polyposis (FAP) since the rarity of the mutated allele in normal controls. c.694C>T was detected in only affected members and generated a premature stop codon in APC. It should be a de novo germline mutation making APC containing this stop codon as targets for nonsense-mediated mRNA decay (NMD). c.1690A>G in MSH2 was not only detected in affected members, but also in normal ones in the family. Functional prediction revealed that the amino acid affected by this variant had no effect on the function of MSH2. Here, we report a de novo germline mutation of APC as the causal variant in a Chinese family with inheritable colon cancer by the next generation sequencing.

Rapid growth of a hepatocellular carcinoma and the driving mutations revealed by cell-population genetic analysis of whole-genome data.

We present the analysis of the evolution of tumors in a case of hepatocellular carcinoma. This case is particularly informative about cancer growth dynamics and the underlying driving mutations. We sampled nine different sections from three tumors and seven more sections from the adjacent nontumor tissues. Selected sections were subjected to exon as well as whole-genome sequencing. Putative somatic mutations were then individually validated across all 9 tumor and 7 nontumor sections. Among the mutations validated, 24 were amino acid changes; in addition, 22 large indels/copy number variants (>1 Mb) were detected. These somatic mutations define four evolutionary lineages among tumor cells. Separate evolution and expansion of these lineages were recent and rapid, each apparently having only one lineage-specific protein-coding mutation. Hence, by using a cell-population genetic definition, this approach identified three coding changes (CCNG1, P62, and an indel/fusion gene) as tumor driver mutations. These three mutations, affecting cell cycle control and apoptosis, are functionally distinct from mutations that accumulated earlier, many of which are involved in inflammation/immunity or cell anchoring. These distinct functions of mutations at different stages may reflect the genetic interactions underlying tumor growth.

A second generation human haplotype map of over 3.1 million SNPs.

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.

Genome-wide detection and characterization of positive selection in human populations.

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders.

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200-3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2alpha, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.

Opportunities and Challenges to Advance Health Equity Using Digital Health Tools in Underserved Communities in Southeast US: A Mixed Methods Study.

INTRODUCTION: Over the last 30 years, the adoption of health information technology and digital health tools (DHTs) into the US health system has been instrumental to improving access to care, especially for people living in rural, underserved, and underrepresented communities. Despite widespread adoption of DHTs by primary care clinicians, documented challenges have contributed to inequitable use and benefit. The COVID-19 pandemic necessitated rapid adoption of DHTs, accelerated by state and federal policy changes, in order to meet patient needs and ensure access to care. METHODS: The Digital Health Tools Study employed a mixed methods approach to assess adoption and use of DHTs by primary care clinicians in southeastern states and identify individual- and practice-level barriers and facilitators to DHT implementation. A survey was conducted using a multi-modal recruitment strategy: newsletters, meeting/conference presentations, social media, and emails/calls. Focus groups were conducted to assess priorities, barriers, and facilitators and were recorded/transcribed verbatim. Descriptive statistics were calculated for survey results, produced for the whole sample, and stratified by state. Thematic analysis was conducted of focus group transcripts. RESULTS: There were 1215 survey respondents. About 55 participants who had missing demographic information were excluded from the analysis. About 99% of clinicians used DHTs in the last 5 years, modalities included: telehealth (66%), electronic health records (EHRs; 66%), patient portals (49%), health information exchange (HIE; 41%), prescription drug monitoring programs (39%), remote/home monitoring (27%), and wearable devices (22%). Time (53%) and cost (51%) were identified as barriers. About 61% and 75% of clinicians reported being "satisfied" to "very satisfied" with telemedicine and EHRs, respectively. Seven focus groups with 25 clinicians were conducted and indicated COVID-19 and the use of supplemental tools/apps to connect patients to resources as major motivators for adopting DHTs. Challenges included incomplete and difficult-to-utilize HIE interfaces for providers and internet/broadband access and poor connectivity for patients. CONCLUSIONS: This study describes the impact adopting DHTs by primary care clinicians has on expanded access to healthcare and reducing health disparities in regions with longstanding health and social inequities. The findings identify opportunities to leverage DHTs to advance health equity and highlight opportunities for policy improvement.

Space-time trends of community-onset Staphylococcus aureus infections in children: a group-based trajectory modeling approach.

PURPOSE: Staphylococcus aureus (S. aureus) remains a serious cause of infections in the United States and worldwide. In the United States, methicillin-resistant S. aureus (MRSA) is the leading cause of skin and soft tissue infections. This study identifies 'best' to 'worst' infection trends from 2002 to 2016, using group-based trajectory modeling approach. METHODS: Electronic health records of children living in the southeastern United States with S. aureus infections from 2002 to 2016 were retrospectively studied, by applying a group-based trajectory model to estimate infection trends (low, high, very high), and then assess spatial significance of these trends at the census tract level; we focused on community-onset infections and not those considered healthcare acquired. RESULTS: Three methicillin-susceptible S. aureus (MSSA) infection trends (low, high, very high) and three MRSA trends (low, high, very high) were identified from 2002 to 2016. Among census tracts with community-onset S. aureus cases, 29% of tracts belonged to the best trend (low infection) for both methicillin-resistant S. aureus and methicillin-susceptible S. aureus; higher proportions occurring in the less densely populated areas. Race disparities were seen with the worst methicillin-resistant S. aureus infection trends and were more often in urban areas. CONCLUSIONS: Group-based trajectory modeling identified unique trends of S. aureus infection rates over time and space, giving insight into the associated population characteristics which reflect these trends of community-onset infection.

Interpersonal Primary Care Continuity for Chronic Conditions Is Associated with Fewer Hospitalizations and Emergency Department Visits Among Medicaid Enrollees.

BACKGROUND: Interpersonal primary care continuity or chronic condition continuity (CCC) is associated with improved health outcomes. Ambulatory care-sensitive conditions (ACSC) are best managed in a primary care setting, and chronic ACSC (CACSC) require management over time. However, current measures do not measure continuity for specific conditions or the impact of continuity for chronic conditions on health outcomes. The purpose of this study was to design a novel measure of CCC for CACSC in primary care and determine its association with health care utilization. METHODS: We conducted a cross-sectional analysis of continuously enrolled, nondual eligible adult Medicaid enrollees with a diagnosis of a CACSC using 2009 Medicaid Analytic eXtract files from 26 states. We conducted adjusted and unadjusted logistic regression models of the relationship between patient continuity status and emergency department (ED) visits and hospitalizations. Models were adjusted for age, sex, race/ethnicity, comorbidity, and rurality. We defined CCC for CACSC as at least 2 outpatient visits with any primary care physician for a CACSC in the year, and (2) more than 50% of outpatient CACSC visits with a single PCP. RESULTS: There were 2,674,587 enrollees with CACSC and 36.3% had CCC for CACSC visits. In fully adjusted models, enrollees with CCC were 28% less likely to have ED visits compared with those without CCC (aOR = 0.71, 95% CI = 0.71 - 0.72) and were 67% less likely to have hospitalization than those without CCC (aOR = 0.33, 95% CI = 0.32-0.33). CONCLUSIONS: CCC for CACSCs was associated with fewer ED visits and hospitalizations in a nationally representative sample of Medicaid enrollees.