Epidemic outcomes following government responses to COVID-19: Insights from nearly 100,000 models.

Government responses to COVID-19 are among the most globally impactful events of the 21st century. The extent to which responses-such as school closures-were associated with changes in COVID-19 outcomes remains unsettled. Multiverse analyses offer a systematic approach to testing a large range of models. We used daily data on 16 government responses in 181 countries in 2020-2021, and 4 outcomes-cases, infections, COVID-19 deaths, and all-cause excess deaths-to construct 99,736 analytic models. Among those, 42% suggest outcomes improved following more stringent responses ("helpful"). No subanalysis (e.g. limited to cases as outcome) demonstrated a preponderance of helpful or unhelpful associations. Among the 14 associations with P values < 1 × 10-30, 5 were helpful and 9 unhelpful. In summary, we find no patterns in the overall set of models that suggests a clear relationship between COVID-19 government responses and outcomes. Strong claims about government responses' impacts on COVID-19 may lack empirical support.

Panel stacking is a threat to consensus statement validity.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members towards one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but non-financial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analysing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated towards COVID-19 elimination (zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases towards advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Sociodemographic and geographic variation in mortality attributable to air pollution in the United States.

There are large differences in premature mortality in the USA by racial/ethnic, education, rurality, and social vulnerability index groups. Using existing concentration-response functions, particulate matter (PM2.5) air pollution, population estimates at the tract level, and county-level mortality data, we estimated the degree to which these mortality discrepancies can be attributed to differences in exposure and susceptibility to PM2.5. We show that differences in mortality attributable to PM2.5 were consistently more pronounced between racial/ethnic groups than by education, rurality, or social vulnerability index, with the Black American population having by far the highest proportion of deaths attributable to PM2.5 in all years from 1990 to 2016. Over half of the difference in age-adjusted all-cause mortality between the Black American and non-Hispanic White population was attributable to PM2.5 in the years 2000 to 2011.

Global population profile of tropical cyclone exposure from 2002 to 2019.

Tropical cyclones have far-reaching impacts on livelihoods and population health that often persist years after the event1-4. Characterizing the demographic and socioeconomic profile and the vulnerabilities of exposed populations is essential to assess health and other risks associated with future tropical cyclone events5. Estimates of exposure to tropical cyclones are often regional rather than global6 and do not consider population vulnerabilities7. Here we combine spatially resolved annual demographic estimates with tropical cyclone wind fields estimates to construct a global profile of the populations exposed to tropical cyclones between 2002 and 2019. We find that approximately 560 million people are exposed yearly and that the number of people exposed has increased across all cyclone intensities over the study period. The age distribution of those exposed has shifted away from children (less than 5 years old) and towards older people (more than 60 years old) in recent years compared with the early 2000s. Populations exposed to tropical cyclones are more socioeconomically deprived than those unexposed within the same country, and this relationship is more pronounced for people exposed to higher-intensity storms. By characterizing the patterns and vulnerabilities of exposed populations, our results can help identify mitigation strategies and assess the global burden and future risks of tropical cyclones.

U.S. global health aid policy and family planning in sub-Saharan Africa.

The Trump administration reinstated and expanded the Mexico City Policy (MCP) in 2017 as the Protecting Life in Global Health Assistance (PLGHA) policy, forbidding international organizations receiving all U.S. health assistance from promoting abortion. Existing evidence suggests that abortion rates rise under the MCP, but the direct effect of U.S. funding restrictions on supply and use of family planning has received less attention. By studying PLGHA's impact on health service delivery providers and women in eight sub-Saharan African countries, we are able to fill this gap. We find that health facilities provide fewer family planning services, including emergency contraception, and that women are less likely to use contraception and more likely to have given birth recently under the policy. These findings suggest that PLGHA has important unintended consequences that are detrimental to reproductive health and the autonomous decision-making of health service providers and women.

Duration of SARS-CoV-2 Culturable Virus Shedding in Children.

This cohort study evaluates the duration of SARS-CoV-2 infectivity and its association with vaccination status in children after a positive COVID-19 test result.

Emergency department visits respond nonlinearly to wildfire smoke.

Air pollution negatively affects a range of health outcomes. Wildfire smoke is an increasingly important contributor to air pollution, yet wildfire smoke events are highly salient and could induce behavioral responses that alter health impacts. We combine geolocated data covering all emergency department (ED) visits to nonfederal hospitals in California from 2006 to 2017 with spatially resolved estimates of daily wildfire smoke PM[Formula: see text] concentrations and quantify how smoke events affect ED visits. Total ED visits respond nonlinearly to smoke concentrations. Relative to a day with no smoke, total visits increase by 1 to 1.5% in the week following low or moderate smoke days but decline by 6 to 9% following extreme smoke days. Reductions persist for at least a month. Declines at extreme levels are driven by diagnoses not thought to be acutely impacted by pollution, including accidental injuries and several nonurgent symptoms, and declines come disproportionately from less-insured populations. In contrast, health outcomes with the strongest physiological link to short-term air pollution increase dramatically in the week following an extreme smoke day: We estimate that ED visits for asthma, COPD, and cough all increase by 30 to 110%. Data from internet searches, vehicle traffic sensors, and park visits indicate behavioral changes on high smoke days consistent with declines in healthcare utilization. Because low and moderate smoke days vastly outweigh high smoke days, we estimate that smoke was responsible for an average of 3,010 (95% CI: 1,760-4,380) additional ED visits per year 2006 to 2017. Given the increasing intensity of wildfire smoke events, behavioral mediation is likely to play a growing role in determining total smoke impacts.

Infant and Neonatal Mortality During the Covid-19 Pandemic: An Interrupted Time Series Analysis From Five Low- and Middle-Income Countries.

Background: The Covid-19 pandemic led to widespread changes to health and social institutions. The effects of the pandemic on neonatal and infant health outcomes in low- and middle-income countries (LMICs) are poorly understood, and nationally representative data characterizing changes to health care and outcomes is only now emerging. Methods: We used nationally representative survey data with vital status and perinatal care information on 2,959,203 children born in India, Madagascar, Cambodia, Nepal, and the Philippines. Using interrupted time series models, we estimated the change in neonatal mortality (death in first 30 days of life) and infant mortality (death in first year of life) following the start of the Covid-19 pandemic, controlling for granular location fixed-effects and seasonality. Findings: We analyzed 2,935,052 births (146,820 deaths) before March 2020 and 24,151 births (799 deaths) after March 2020. We estimated that infant mortality increased by 9.9 deaths per 1,000 live births after March 2020 (95% CI 5.0, 15.0; p<0.01; 22% increase) and neonatal mortality increased by 6.7 deaths per 1,000 live births (95% CI 2.4, 11.1; p<0.01; 27% increase). We observe increased mortality in all study countries. We also estimated a 3.8 percentage point reduction in antenatal care use (95% CI -4.9, -2.7; p<0.01) and a 5.6 percentage point reduction in facility deliveries (95% CI -7.2, -4.0; p<0.01) during the pandemic. Interpretation: Since the start of the Covid-19 pandemic, neonatal and infant mortality are higher than expected in five LMICs. Helping LMICs resume pre-pandemic declines in neonatal and infant mortality should be a major global priority.

Exact inference for disease prevalence based on a test with unknown specificity and sensitivity.

To make informative public policy decisions in battling the ongoing COVID-19 pandemic, it is important to know the disease prevalence in a population. There are two intertwined difficulties in estimating this prevalence based on testing results from a group of subjects. First, the test is prone to measurement error with unknown sensitivity and specificity. Second, the prevalence tends to be low at the initial stage of the pandemic and we may not be able to determine if a positive test result is a false positive due to the imperfect test specificity. The statistical inference based on a large sample approximation or conventional bootstrap may not be valid in such cases. In this paper, we have proposed a set of confidence intervals, whose validity doesn't depend on the sample size in the unweighted setting. For the weighted setting, the proposed inference is equivalent to hybrid bootstrap methods, whose performance is also more robust than those based on asymptotic approximations. The methods are used to reanalyze data from a study investigating the antibody prevalence in Santa Clara County, California in addition to several other seroprevalence studies. Simulation studies have been conducted to examine the finite-sample performance of the proposed method.

Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection.

BACKGROUND: Guidelines widely recommend avoiding antibiotics for many acute upper respiratory infections (aURIs) to avert adverse events in the absence of likely benefit. However, the extent of harm from these antibiotics remains a subject of debate and could inform patient-centered decision-making. Prior estimates finding a number needed to harm (NNH) between 8 and 10 rely on patient-reported adverse events of any severity. In this analysis, we sought to estimate adverse events by only measuring comparatively severe events that require subsequent clinical evaluation. METHODS: We constructed a retrospective cohort, including 51 million patient encounters. Using logistic regression models, we determined the adjusted odds ratio (aOR) of clinically detectable adverse events following antibiotic use compared with events among unexposed individuals with aURIs. Our outcomes included candidiasis, diarrhea, Clostridium difficile infection (CDI), and a composite outcome. FINDINGS: From our analysis, 62.4% of the population received antibiotics in an aURI encounter. Observed adverse events in the antibiotic-exposed group were 54,279 and 46,936 for diarrhea and candidiasis, respectively, yielding an aOR of 1.24 and 1.61, and an NNH of 3,126 and 1,975. Observed events of CDI in the exposed group were 30,133, and aORs of isolated CDI and combined adverse events were 1.07 and 1.30, resulting in an NNH of 17,695 and 1,150, respectively. Females were more likely to be diagnosed with any adverse event. Overall antibiotics were found to result in 5.7 additional cases of CDI per 100,000 outpatient prescriptions following an upper respiratory tract infection. INTERPRETATION: Despite higher NNH than previous methods of analysis, we find substantial iatrogenic harm associated with prescribing antibiotics in aURIs.

Geographically resolved social cost of anthropogenic emissions accounting for both direct and climate-mediated effects.

The magnitude and distribution of physical and societal impacts from long-lived greenhouse gases are insensitive to the emission source location; the same is not true for major coemitted short-lived pollutants such as aerosols. Here, we combine novel global climate model simulations with established response functions to show that a given aerosol emission from different regions produces divergent air quality and climate changes and associated human system impacts, both locally and globally. The marginal global damages to infant mortality, crop productivity, and economic growth from aerosol emissions and their climate effects differ by more than an order of magnitude depending on source region, with certain regions creating global external climate changes and impacts much larger than those felt locally. The complex distributions of aerosol-driven societal impacts emerge from geographically distinct and region-specific aerosol-climate interactions, estimation of which is enabled by the full Earth System Modeling Framework used here.

The demographic and socioeconomic correlates of behavior and HIV infection status across sub-Saharan Africa.

Background: Predisposition to become HIV positive (HIV + ) is influenced by a wide range of correlated economic, environmental, demographic, social, and behavioral factors. While evidence among a candidate handful have strong evidence, there is lack of a consensus among the vast array of variables measured in large surveys. Methods: We performed a comprehensive data-driven search for correlates of HIV positivity in >600,000 participants of the Demographic and Health Survey across 29 sub-Saharan African countries from 2003 to 2017. We associated a total of 7251 and of 6,288 unique variables with HIV positivity in females and males respectively in each of the 50 surveys. We performed a meta-analysis within countries to attain 29 country-specific associations. Results: Here we identify 344 (5.4% out possible) and 373 (5.1%) associations with HIV + in males and females, respectively, with robust statistical support. The associations are consistent in directionality across countries and sexes. The association sizes among individual correlates and their predictive capability were low to modest, but comparable to established factors. Among the identified associations, variables identifying being head of household among females was identified in 17 countries with a mean odds ratio (OR) of 2.5 (OR range: 1.1-3.5, R2 = 0.01). Other common associations were identified, including marital status, education, age, and ownership of land or livestock. Conclusions: Our continent-wide search for variables has identified under-recognized variables associated with being HIV + that are consistent across the continent and sex. Many of the association sizes are as high as established risk factors for HIV positivity, including male circumcision.

Massive covidization of research citations and the citation elite.

Massive scientific productivity accompanied the COVID-19 pandemic. We evaluated the citation impact of COVID-19 publications relative to all scientific work published in 2020 to 2021 and assessed the impact on scientist citation profiles. Using Scopus data until August 1, 2021, COVID-19 items accounted for 4% of papers published, 20% of citations received to papers published in 2020 to 2021, and >30% of citations received in 36 of the 174 disciplines of science (up to 79.3% in general and internal medicine). Across science, 98 of the 100 most-cited papers published in 2020 to 2021 were related to COVID-19; 110 scientists received ≥10,000 citations for COVID-19 work, but none received ≥10,000 citations for non-COVID-19 work published in 2020 to 2021. For many scientists, citations to their COVID-19 work already accounted for more than half of their total career citation count. Overall, these data show a strong covidization of research citations across science, with major impact on shaping the citation elite.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study.

BACKGROUND: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. METHODS: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. FINDINGS: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished. INTERPRETATION: Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation. FUNDING: US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.

The Effect of Healthcare Worker Density on Maternal Health Service Utilization in Sub-Saharan Africa.

Facility births and antenatal care (ANC) are key to improving maternal health. This study evaluates the relationship between physician and nurse/midwife densities and the use of key maternal health services in sub-Saharan Africa (SSA). We matched individual-level maternal health service indicators from Demographic and Health Surveys between 2008 and 2017, to country-level physician and nurse/midwife per-capita densities, across 35 SSA countries. We performed univariate and multivariate probit regression analyses to evaluate the association between healthcare worker (HCW) densities and facility births as our primary outcome and additional ANC services as secondary outcomes. We controlled for established maternal health predictors, including literacy, child marriage, reported problems accessing healthcare, GDP per capita, political instability, and government effectiveness scores. HCW density across SSA was low at 0.13 physicians and 0.91 nurses/midwives per 1,000 people, compared with 2010 worldwide mean densities of 1.33 and 3.07, respectively. The probability of facility birth increased by 9.8% (95% CI: 2.1-17.5%) for every additional physician per 1,000 people and 8.9% (95% CI: 7.1-9.7%) for every additional nurse/midwife per 1,000 people. HCW densities were also associated with increased likelihood of ANC by the respective provider type, and with antenatal testing for preeclampsia (urine and blood pressure checks). Other ANC services demonstrated variable relationships with HCW densities based on provider type. In 35 SSA countries, HCW density was positively associated with many key measures of maternal health service utilization including facility birth and ANC testing for preeclampsia.