Screening for Severe Acute Respiratory Syndrome Coronavirus 2 in Close Contacts of Individuals With Confirmed Infection: Performance and Operational Considerations.

BACKGROUND: Point-of-care and decentralized testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies. METHODS: A prospective diagnostic accuracy study was conducted among close contacts of coronavirus disease 2019 (COVID-19) cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and 1 molecular method were evaluated for usability and performance against reference reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens. RESULTS: Fifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during ≥1 visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta variants emerged increasingly during implementation. The overall sensitivity of evaluated tests ranged from 33% to 76%. Performance was higher among symptomatic cases and those with cycle threshold (Ct) values <34 and lower among oligosymptomatic or asymptomatic cases. Assuming a 24-hour time to results for RT-PCR, the cumulative sensitivity of an anterior nares swab rapid antigen test was >70% and almost 90% after 4 days. CONCLUSIONS: The near-immediate time to results for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.

Politics and Universal Health Coverage--The Post-2015 Global Health Agenda.

What political, social, and economic factors allow a movement toward universal health coverage to take hold in some low- and middle-income countries? Can we use that knowledge to help other such countries achieve health care for all?

Large language models for preventing medication direction errors in online pharmacies.

Errors in pharmacy medication directions, such as incorrect instructions for dosage or frequency, can increase patient safety risk substantially by raising the chances of adverse drug events. This study explores how integrating domain knowledge with large language models (LLMs)-capable of sophisticated text interpretation and generation-can reduce these errors. We introduce MEDIC (medication direction copilot), a system that emulates the reasoning of pharmacists by prioritizing precise communication of core clinical components of a prescription, such as dosage and frequency. It fine-tunes a first-generation LLM using 1,000 expert-annotated and augmented directions from Amazon Pharmacy to extract the core components and assembles them into complete directions using pharmacy logic and safety guardrails. We compared MEDIC against two LLM-based benchmarks: one leveraging 1.5 million medication directions and the other using state-of-the-art LLMs. On 1,200 expert-reviewed prescriptions, the two benchmarks respectively recorded 1.51 (confidence interval (CI) 1.03, 2.31) and 4.38 (CI 3.13, 6.64) times more near-miss events-errors caught and corrected before reaching the patient-than MEDIC. Additionally, we tested MEDIC by deploying within the production system of an online pharmacy, and during this experimental period, it reduced near-miss events by 33% (CI 26%, 40%). This study shows that LLMs, with domain expertise and safeguards, improve the accuracy and efficiency of pharmacy operations.

Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types.

The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and initiation among young people in 204 countries and territories, 1990-2019.

BACKGROUND: Universally, smoking cessation rates among established smokers are poor. Preventing young people from starting use of and becoming addicted to tobacco products remains a key strategy to end the tobacco epidemic. Previous country-specific studies have found that initiation of smoking tobacco use occurs predominantly among young people and have found mixed progress in reducing the prevalence of smoking tobacco use among young people. Current and comparable estimates for all countries are needed to inform targeted interventions and policies. METHODS: We modelled two indicators: prevalence of current smoking tobacco use among young adults aged 15-24 years, and the age at which current smokers aged 20-54 years in 2019 began smoking regularly. We synthesised data from 3625 nationally representative surveys on prevalence of smoking and 254 on age at initiation. We used spatiotemporal Gaussian process regression to produce estimates of the prevalence of smoking and age of initiation by sex, for 204 countries and territories for each year between 1990 and 2019. FINDINGS: Globally in 2019, an estimated 155 million (95% uncertainty interval 150-160) individuals aged 15-24 years were tobacco smokers, with a prevalence of 20·1% (19·4-20·8) among males and 4·95% (4·64-5·29) among females. We estimated that 82·6% (82·1-83·1) of current smokers initiated between ages 14 and 25 years, and that 18·5% (17·7-19·3) of smokers began smoking regularly by age 15 years. Although some countries have made substantial progress in reducing the prevalence of smoking tobacco use among young people, prevalence in 2019 still exceeds 20% among males aged 15-24 years in 120 countries and among females aged 15-24 years in 43 countries. INTERPRETATION: The fact that most smokers start smoking regularly before age 20 years highlights the unique window of opportunity to target prevention efforts among young people and save millions of lives and avert health-care costs in the future. Countries can substantially improve the health of their populations by implementing and enforcing evidence-based tobacco control policies that prevent the next generation from initiating smoking. FUNDING: Bloomberg Philanthropies.

Reexamining Rates of Decline in Lung Cancer Risk after Smoking Cessation. A Meta-analysis.

Rationale: Prior studies have questioned whether prevailing eligibility criteria for lung cancer screening are sufficiently inclusive of former smokers who remain at elevated risk of disease outside current screening windows.Objectives: To characterize the percentage of the reducible relative risk (RR) remaining for lung cancer as a function of years since quitting (YSQ).Methods: MEDLINE and PubMed were searched from January 2011 to May 2018; key search terms included "smoking" and "cancer." Current smoker RRs were extracted to represent former smokers at 0 YSQ; data were transformed assuming a lognormal distribution.Results: The main review included 49 prospective cohorts across 18 studies comprising a total of 139 RRs from 20 countries and territories. At 1 year since quitting, the percentage of reducible RR remaining for lung cancer was 81.4% (64.1-98.2%). At 5 YSQ, the percentage of reducible RR remaining was 57.2% (45.7-67.3%); at 10 years, it was 36.9% (28.3-47.9%); at 15 years, it was 26.7% (20.2-34.3%); and at 20 years, it was 19.7% (13.3-26.4%). If eligibility criteria in the United States were broadened to screen former smokers at up to 20 YSQ, we estimate an additional 4.2 (3.9-4.5) million former smokers between 55 and 80 years of age would be eligible for lung cancer screening.Conclusions: At the critical screening threshold of 15 YSQ, the percentage of excess risk for lung cancer remains high and only marginally declines at time points afterward, excluding millions of former smokers who remain at elevated risk of malignancy. A risk-based algorithm for lung cancer screening that deemphasizes time after cessation as a key screening determinant would more likely capture these former smokers who remain at elevated risk of malignancy.

Have geopolitics influenced decisions on American health foreign assistance efforts during the Obama presidency?

BACKGROUND: This study sought to characterize the possible relationship between US geopolitical priorities and annual decisions on health foreign assistance among recipient nations between 2009 and 2016. METHODS: Data on total planned United States (US) foreign aid and health aid were collected for the 194 member nations of the World Health Organization (WHO) from publicly available databases. Trends in per-capita spending were examined between 2009 and 2016 across the six regions of the WHO (Africa, Americas, Eastern Mediterranean, Europe, Southeast Asia, and the Western Pacific). Data on US national security threats were obtained from the Council on Foreign Relations' annual Preventive Priorities Survey. Multivariable regression models were fitted specifying planned health aid as the dependent variable and threat level of a recipient aid nation as the primary independent variable. RESULTS: Across the aggregate 80 planned recipient countries of US health aid over the duration of the study period, cumulative planned per-capita spending was stable (US$ 0.65 in both 2009 and 2016). The number of annual planned recipients of this aid declined from 74 in 2009 to 56 in 2016 (24.3% decline), with planned allocations decreasing in the Americas, Eastern Mediterranean, and Europe; corresponding increases were observed in Africa, Southeast Asia, and the Western Pacific. Regression analyses demonstrated a dose-response, whereby higher levels of threat were associated with larger declines in planned spending (critical threat nations: b = -3.81; 95% confidence interval (CI) -5.84 to -1.78, P ≤ 0.001) and one-year lagged (critical threat nations: b = -3.91; 95% CI, -5.94 to -1.88, P ≤ 0.001) analyses. CONCLUSIONS: Higher threat levels are associated with less health aid. This is a novel finding, as prior studies have demonstrated a strong association between national security considerations and decisions on development aid.

Has development assistance for health facilitated the rise of more peaceful societies in sub-Saharan Africa?

Growing evidence suggests that health aid can serve humanitarian and diplomatic ends. This study utilised the Fragile States Index (FSI) for the 47 nations of the World Health Organizations' Africa region for the years 2005-2014 and data on health and non-health development aid spending from the United States (US) for those same years. Absolute amounts of health and non-health aid flows from the US were used as predictors of state fragility. We used time-lagged, fixed-effects multivariable regression modelling with change in FSI as the outcome of interest. The highest quartile of US health aid per capita spending (≥$4.00 per capita) was associated with a large and immediate decline in level of state fragility (b = -7.57; 95% CI, -14.6 to -0.51, P = 0.04). A dose-response effect was observed in the primary analysis, with increasing levels of spending associated with greater declines in fragility. Health per-capita expenditures were correlated with improved fragility scores across all lagged intervals and spending quartiles. The association of US health aid with immediate improvements in metrics of state stability across sub-Saharan Africa is a novel finding. This effect is possibly explained by our observations that relative to non-health aid, US health expenditures were larger and more targeted.

Analysis of results from the Joint External Evaluation: examining its strength and assessing for trends among participating countries.

BACKGROUND: The Joint External Evaluation (JEE) is part of the World Health Organization's (WHO) new process to help countries assess their ability to prevent, detect and respond to public health threats such as infectious disease outbreaks, as specified by the International Health Regulations (IHR). How countries are faring on these evaluations is not well known and neither is there any previous assessment of the performance characteristics of the JEE process itself. METHODS: We obtained JEE data for 48 indicators collectively across 19 technical areas of preparedness for 55 countries. The indicators are scored on a 1 to 5 scale with 4 indicating demonstrated capacity. We created a standardized JEE index score representing cumulative performance across indicators using principal components analysis. We examined the state of performance across all indicators and then examined the relationship between this index score and select demographic and health variables to better understand potential drivers of performance. RESULTS: Among our study cohort, the median performance on 43 of the 48 (89.6%) indicators was less than 4, suggesting that countries were failing to meet demonstrated capacity on these measures. The two weakest indicators were related to antimicrobial resistance (median score = 1.0, interquartile range = 1.0-2.0) and biosecurity response (median score = 2.0, interquartile range = 2.0-3.0). JEE index scores correlated with various metrics of health outcomes (life expectancy, under-five year mortality rate, disability-adjusted life years lost to communicable diseases) and with standard measures of social and economic development that enable public health system performance in the total sample, but in stratified analyses, these relationships were much weaker in the AFRO region. CONCLUSIONS: We find large variations in JEE scores among countries and WHO regions with many nations still unprepared for the next disease outbreak with pandemic potential The strong correlations between JEE performance and metrics of both health outcomes and health systems' performance suggests that the JEE is likely accurately measuring the strength of IHR-specific, public health capabilities.