Air Pollution Exposures and Child Executive Function: A U.S. Multi-Cohort Study.

BACKGROUND: Executive function, which develops rapidly in childhood, enables problem solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited. METHODS: We examined associations between early childhood air pollution exposure and school-aged executive function in 1,235 children from three U.S. pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2), and ozone (O3) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains -- cognitive flexibility, working memory, and inhibitory control -- using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution - child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity. RESULTS: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO2 exposure and working memory by neighborhood education opportunity were present (P interaction = 0.05), with inverse associations more pronounced in the "High" and "Very high" categories. Associations of interest did not differ by child sex or maternal education. CONCLUSIONS: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.

Two or more significant life-events in 6-months are associated with lower rates of HIV treatment and virologic suppression among youth with HIV in Uganda and Kenya.

Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15-24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa.Trial registration: ClinicalTrials.gov identifier: NCT03848728..

SARS-CoV-2 Variant Exposures Elicit Antibody Responses With Differential Cross-Neutralization of Established and Emerging Strains Including Delta and Omicron.

The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.

Estimation of Secondary Household Attack Rates for Emergent Spike L452R Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Detected by Genomic Surveillance at a Community-Based Testing Site in San Francisco.

BACKGROUND: Sequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities. METHODS: SARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants. RESULTS: A total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%). CONCLUSIONS: The increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.

Performance Characteristics of a Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco.

We evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3-28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct <30, indicating high viral load; of these, 40% (6 of 15) were asymptomatic. Using this Ct threshold (<30) for Binax-CoV2 evaluation, the sensitivity of Binax-CoV2 was 93.3% (95% confidence interval, 68.1%-99.8%) (14 of 15) and the specificity was 99.9% (99.4%-99.9%) (855 of 856).

Field Performance and Public Health Response Using the BinaxNOWTM Rapid Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen Detection Assay During Community-Based Testing.

Among 3302 persons tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by BinaxNOWTM and reverse transcription polymerase chain reaction (RT-PCR) in a community setting, rapid assay sensitivity was 100%/98.5%/89% using RT-PCR cycle thresholds of 30, 35, and no threshold. The specificity was 99.9%. Performance was high across ages and those with and without symptoms. Rapid resulting permitted immediate public health action.

SEARCH Human Immunodeficiency Virus (HIV) Streamlined Treatment Intervention Reduces Mortality at a Population Level in Men With Low CD4 Counts.

BACKGROUND: We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing. METHODS: In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk. RESULTS: Among 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58). CONCLUSIONS: After population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths.

Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Disproportionately Affects the Latinx Population During Shelter-in-Place in San Francisco.

BACKGROUND: There is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates. METHODS: We offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. RESULTS: We tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income <$50 000/year. Five SARS-CoV-2 phylogenetic lineages were detected. CONCLUSIONS: SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco's shelter-in-place ordinance.

Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda.

BACKGROUND: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. METHODS AND FINDINGS: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. CONCLUSIONS: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP. METHODS AND FINDINGS: During population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49-1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09-0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07-0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12-3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP ≤30 days before HIV diagnosis, and 24/25 (96%) started ART. Of those with repeat HIV RNA after ART start, 18/19 (95%) had <1,000 c/ml. One participant with viral non-suppression was found to have transmitted viral resistance, as well as emtricitabine resistance possibly related to PrEP use. Limitations include the lack of contemporaneous controls to assess HIV incidence without PrEP and that plasma samples were not archived to assess for baseline acute infection. CONCLUSIONS: Population-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

Plasticity of the lettuce infectious yellows virus minor coat protein (CPm) in mediating the foregut retention and transmission of a chimeric CPm mutant by whitefly vectors.

Transmission of the crinivirus, lettuce infectious yellows virus (LIYV), is determined by a minor coat protein (CPm)-mediated virion retention mechanism located in the foregut of its whitefly vector. To better understand the functions of LIYV CPm, chimeric CPm mutants engineered with different lengths of the LIYV CPm amino acid sequence and that of the crinivirus, lettuce chlorosis virus (LCV), were constructed based on bioinformatics and sequence alignment data. The 485 amino acid-long chimeric CPm of LIYV mutant, CPmP-1, contains 60 % (from position 3 to 294) of LCV CPm amino acids. The chimeric CPm of mutants CPmP-2, CPmP-3 and CPmP-4 contains 46 (position 3 to 208), 51 (position 3 to 238) and 41 % (position 261 to 442) of LCV CPm amino acids, respectively. All four mutants moved systemically, expressed the chimeric CPm and formed virus particles. However, following acquisition feeding of the virus preparations, only CPmP-1 was retained in the foreguts of a significant number of vectors and transmitted. In immuno-gold labelling transmission electron microscopy (IGL-TEM) analysis, CPmP-1 particles were distinctly labelled by antibodies directed against the LCV but not LIYV CPm. In contrast, CPmP-4 particles were not labelled by antibodies directed against the LCV or LIYV CPm, while CPmP-2 and -3 particles were weakly labelled by anti-LIYV CPm but not anti-LCV CPm antibodies. The unique antibody recognition and binding pattern of CPmP-1 was also displayed in the foreguts of whitefly vectors that fed on CPmP-1 virions. These results are consistent with the hypothesis that the chimeric CPm of CPmP-1 is incorporated into functional virions, with the LCV CPm region being potentially exposed on the surface and accessible to anti-LCV CPm antibodies.

No change in substance use disorders or overdose after implementation of state Earned Income Tax Credit (EITC).

BACKGROUND: Inadequate income is associated with higher likelihood of experiencing a substance use disorder (SUD). This study tests whether the earned income tax credit (EITC), which issues supplemental income for workers with children in the U.S., is associated with lower rates of SUD and fatal overdose. METHODS: We examined the effects of state-level refundable EITC presence and generosity (i.e., state EITC rate as a % of federal rate) on SUD-related outcomes (SUD prevalence and intentional and unintentional fatal overdose) using a difference-in-difference methodology, with both two-way fixed-effects models and event study plots. Several sensitivity analyses were conducted to assess the robustness of findings. Five data sources were used to create a combined state-level longitudinal dataset. RESULTS: We did not find significant effects of refundable EITC presence or generosity on unintentional or intentional fatal overdose or SUD prevalence in two-way models. Event study models detected a very slight upward shift in SUD prevalence following refundable EITC implementation (not seen in sensitivity analyses) and no significant effects of EITC implementation on any of the fatal overdose outcomes. CONCLUSIONS: Evidence regarding income support programs is being highly sought by policy makers as income support programs have become increasingly popular policy levers since the start of the COVID-19 pandemic. Our study indicates EITC policies likely have no impact on SUD or overdose, however, other income support programs without family restrictions are important to investigate further.

Prenatal exposures to phthalates and life events stressors in relation to child behavior at age 4-6: A combined cohort analysis.

Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4-6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother-child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms.

Using Location Intelligence to Evaluate the COVID-19 Vaccination Campaign in the United States: Spatiotemporal Big Data Analysis.

BACKGROUND: Highly effective COVID-19 vaccines are available and free of charge in the United States. With adequate coverage, their use may help return life back to normal and reduce COVID-19-related hospitalization and death. Many barriers to widespread inoculation have prevented herd immunity, including vaccine hesitancy, lack of vaccine knowledge, and misinformation. The Ad Council and COVID Collaborative have been conducting one of the largest nationwide targeted campaigns ("It's Up to You") to communicate vaccine information and encourage timely vaccination across the United States. More than 300 major brands, digital and print media companies, and community-based organizations support the campaigns to reach distinct audiences. OBJECTIVE: The goal of this study was to use aggregated mobility data to assess the effectiveness of the campaign on COVID-19 vaccine uptake. METHODS: Campaign exposure data were collected from the Cuebiq advertising impact measurement platform consisting of about 17 million opted-in and deidentified mobile devices across the country. A Bayesian spatiotemporal hierarchical model was developed to assess campaign effectiveness through estimating the association between county-level campaign exposure and vaccination rates reported by the Centers for Disease Control and Prevention. To minimize potential bias in exposure to the campaign, the model included several control variables (eg, age, race or ethnicity, income, and political affiliation). We also incorporated conditional autoregressive residual models to account for apparent spatiotemporal autocorrelation. RESULTS: The data set covers a panel of 3104 counties from 48 states and the District of Columbia during a period of 22 weeks (March 29 to August 29, 2021). Officially launched in February 2021, the campaign reached about 3% of the anonymous devices on the Cuebiq platform by the end of March, which was the start of the study period. That exposure rate gradually declined to slightly above 1% in August 2021, effectively ending the study period. Results from the Bayesian hierarchical model indicate a statistically significant positive association between campaign exposure and vaccine uptake at the county level. A campaign that reaches everyone would boost the vaccination rate by 2.2% (95% uncertainty interval: 2.0%-2.4%) on a weekly basis, compared to the baseline case of no campaign. CONCLUSIONS: The "It's Up to You" campaign is effective in promoting COVID-19 vaccine uptake, suggesting that a nationwide targeted mass media campaign with multisectoral collaborations could be an impactful health communication strategy to improve progress against this and future pandemics. Methodologically, the results also show that location intelligence and mobile phone-based monitoring platforms can be effective in measuring impact of large-scale digital campaigns in near real time.

A multilevel health system intervention for virological suppression in adolescents and young adults living with HIV in rural Kenya and Uganda (SEARCH-Youth): a cluster randomised trial.

BACKGROUND: Social and cognitive developmental events can disrupt care and medication adherence among adolescents and young adults living with HIV in sub-Saharan Africa. We hypothesised that a dynamic multilevel health system intervention helping adolescents and young adults and their providers navigate life-stage related events would increase virological suppression compared with standard care. METHODS: We did a cluster randomised, open-label trial of young individuals aged 15-24 years with HIV and receiving care in eligible clinics (operated by the government and with ≥25 young people receiving care) in rural Kenya and Uganda. After clinic randomisation stratified by region, patient population, and previous participation in the SEARCH trial, participants in intervention clinics received life-stage-based assessment at routine visits, flexible clinic access, and rapid viral load feedback. Providers had a secure mobile platform for interprovider consultation. The control clinics followed standard practice. The primary, prespecified endpoint was virological suppression (HIV RNA <400 copies per mL) at 2 years of follow-up among participants who enrolled before Dec 1, 2019, and received care at the study clinics. This trial is registered with ClinicalTrials.gov, NCT03848728, and is closed to recruitment. FINDINGS: 28 clinics were enrolled and randomly assigned (14 control, 14 intervention) in January, 2019. Between March 14, 2019, and Nov 26, 2020, we recruited 1988 participants at the clinics, of whom 1549 were included in the analysis (785 at intervention clinics and 764 at control clinics). The median participant age was 21 years (IQR 19-23) and 1248 (80·6%) of 1549 participants were female. The mean proportion of participants with virological suppression at 2 years was 88% (95% CI 85-92) for participants in intervention clinics and 80% (77-84) for participants in control clinics, equivalent to a 10% beneficial effect of the intervention (risk ratio [RR] 1·10, 95% CI 1·03-1·16; p=0·0019). The intervention resulted in increased virological suppression within all subgroups of sex, age, and care status at baseline, with greatest improvement among those re-engaging in care (RR 1·60, 95% CI 1·00-2·55; p=0·025). INTERPRETATION: Routine and systematic life-stage-based assessment, prompt adherence support with rapid viral load testing, and patient-centred, flexible clinic access could help bring adolescents and young adults living with HIV closer towards a goal of universal virological suppression. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health.

A community-based dynamic choice model for HIV prevention improves PrEP and PEP coverage in rural Uganda and Kenya: a cluster randomized trial.

INTRODUCTION: Optimizing HIV prevention may require structured approaches for providing client-centred choices as well as community-based entry points and delivery. We evaluated the effect of a dynamic choice model for HIV prevention, delivered by community health workers (CHWs) with clinician support, on the use of biomedical prevention among persons at risk of HIV in rural East Africa. METHODS: We conducted a cluster randomized trial among persons (≥15 years) with current or anticipated HIV risk in 16 villages in Uganda and Kenya (SEARCH; NCT04810650). The intervention was a client-centred HIV prevention model, including (1) structured client choice of product (pre-exposure prophylaxis [PrEP] or post-exposure prophylaxis [PEP]), service location (clinic or out-of-clinic) and HIV testing modality (self-test or rapid test), with the ability to switch over time; (2) a structured assessment of patient barriers and development of a personalized support plan; and (3) phone access to a clinician 24/7. The intervention was delivered by CHWs and supported by clinicians who oversaw PrEP and PEP initiation and monitoring. Participants in control villages were referred to local health facilities for HIV prevention services, delivered by Ministry of Health staff. The primary outcome was biomedical prevention coverage: a proportion of 48-week follow-up with self-reported PrEP or PEP use. RESULTS: From May to July 2021, we enrolled 429 people (212 intervention; 217 control): 57% women and 35% aged 15-24 years. Among intervention participants, 58% chose PrEP and 58% chose PEP at least once over follow-up; self-testing increased from 52% (baseline) to 71% (week 48); ≥98% chose out-of-facility service delivery. Among 413 (96%) participants with the primary outcome ascertained, average biomedical prevention coverage was 28.0% in the intervention versus 0.5% in the control: a difference of 27.5% (95% CI: 23.0-31.9%, p<0.001). Impact was larger during periods of self-reported HIV risk: 36.6% coverage in intervention versus 0.9% in control, a difference of 35.7% (95% CI: 27.5-43.9, p<0.001). Intervention effects were seen across subgroups defined by sex, age group and alcohol use. CONCLUSIONS: A client-centred dynamic choice HIV prevention intervention, including the option to switch between products and CHW-based delivery in the community, increased biomedical prevention coverage by 27.5%. However, substantial person-time at risk of HIV remained uncovered.

Abnormal end-tidal carbon dioxide levels on emergency department arrival in adult and pediatric intubated patients.

BACKGROUND: The utility of prehospital intubation is controversial, as uncontrolled studies in trauma patients suggest adverse outcomes with prehospital intubation, perhaps secondary to inappropriate ventilation once intubation is accomplished. OBJECTIVES: The objectives were 1) to establish, immediately upon arrival to the emergency department (ED), the prevalence of abnormal end-tidal carbon dioxide (ETCO(2)) levels in patients with prehospital intubation and 2) to describe the relationship between abnormal ETCO(2) levels on ED arrival and mortality. METHODS: This was a prospective, observational cohort study of patients with prehospital intubation. Patients were excluded if they underwent prehospital cardiopulmonary resuscitation (CPR). On ED arrival, the initial ETCO(2) measurement from the patient's endotracheal tube was immediately obtained prior to purposeful intervention in the patient's ventilation by using an Oridion Surestream Sure VentLine H Set with a Welch Allyn Propaq CS monitor. For each patient, the treating physician documented the ETCO(2) measurement, patient demographics, and details of the transport. The primary outcome was an abnormal ETCO(2) value (<30 mmHg or >45 mmHg). The secondary outcome was mortality. RESULTS: One hundred eligible patients were enrolled, with a median age of 30 years (interquartile range [IQR] 15, 48 years). Esophageal intubations were identified in four cases, and those cases were excluded from further analysis. Mechanisms included trauma, 74; medical, 12; and burn, 10. The median ETCO(2) value was 32 mmHg (IQR 27, 38 mmHg), range 18-80 mmHg. Forty-six of 96 (48%, 95% confidence interval [CI] 38%, 58%) patients had abnormal ETCO(2) values, including 37 (39%, 95% CI 29%, 49%) with low ETCO(2) levels and nine (9%, 95% CI 4%, 17%) with high ETCO(2) levels. Death was higher in those trauma patients with abnormal ETCO(2) levels (10/33, 30%, 95% CI 16%, 49%) than in those with normal ETCO(2) levels (2/41, 5%, 95% CI 0.6%, 17%), relative risk = 6.2 (95% CI 1.5, 26.4), p = 0.004. CONCLUSION: Nearly half of all patients transported by prehospital providers had abnormal ETCO(2) measurements on initial ED presentation, suggesting an area for potential improvement. Trauma patients with abnormal initial ETCO(2) levels were more likely to die.

Comparative analysis identifies amino acids critical for citrus tristeza virus (T36CA) encoded proteins involved in suppression of RNA silencing and differential systemic infection in two plant species.

Complementary (c)DNA clones corresponding to the full-length genome of T36CA (a Californian isolate of Citrus tristeza virus with the T36 genotype), which shares 99.1% identity with that of T36FL (a T36 isolate from Florida), were made into a vector system to express the green fluorescent protein (GFP). Agroinfiltration of two prototype T36CA-based vectors (pT36CA) to Nicotiana benthamiana plants resulted in local but not systemic GFP expression/viral infection. This contrasted with agroinfiltration of the T36FL-based vector (pT36FL), which resulted in both local and systemic GFP expression/viral infection. A prototype T36CA systemically infected RNA silencing-defective N. benthamiana lines, demonstrating that a genetic basis for its defective systemic infection was RNA silencing. We evaluated the in planta bioactivity of chimeric pT36CA-pT36FL constructs and the results suggested that nucleotide variants in several open reading frames of the prototype T36CA could be responsible for its defective systemic infection. A single amino acid substitution in each of two silencing suppressors, p20 (S107G) and p25 (G36D), of prototype T36CA facilitated its systemic infectivity in N. benthamiana (albeit with reduced titre relative to that of T36FL) but not in Citrus macrophylla plants. Enhanced virus accumulation and, remarkably, robust systemic infection of T36CA in N. benthamiana and C. macrophylla plants, respectively, required two additional amino acid substitutions engineered in p65 (N118S and S158L), a putative closterovirus movement protein. The availability of pT36CA provides a unique opportunity for comparative analysis to identify viral coding and noncoding nucleotides or sequences involved in functions that are vital for in planta infection.

High Likelihood of Accepting COVID-19 Vaccine in a Latinx Community at High SARS-CoV-2 Risk in San Francisco.

Of 4133 persons surveyed at a low-barrier coronavirus disease 2019 (COVID-19) test site with high positivity in an urban Latinx community in January 2021, 86% indicated that they would accept a COVID-19 vaccination. The top reasons for vaccine hesitancy included concerns around side effects and safety and distrust of health care systems.

Uptake and outcomes of a novel community-based HIV post-exposure prophylaxis (PEP) programme in rural Kenya and Uganda.

INTRODUCTION: Antiretroviral-based HIV prevention, including pre-exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high-risk sexual exposures. Non-occupational post-exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient-centred PEP programme with options for facility- or community-based service delivery. METHODS: After population-level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in-country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out-of-facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful "PEP completion" was defined as self-reported adherence over four weeks of therapy with post-PEP HIV testing. RESULTS: Community leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28-day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out-of-facility community-based sites; 35% of participants had ≥1 out-of-facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions. CONCLUSIONS: Among individuals with elevated-risk exposures in rural East African communities, patient-centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.