Center for Effective Global Action

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

OBJECTIVE(S): Few HIV prevention interventions have been evaluated in randomized controlled trials (RCTs). We examined design, implementation, and contextual considerations that may limit detection of a positive or adverse effect in HIV prevention trials. DESIGN: A systematic review of late phase RCTs for prevention of sexual transmission of HIV that randomly allocated intervention and comparison groups; evaluated interventions to prevent sexual transmission in nonpregnant populations; and reported HIV incidence as the primary or secondary outcome. METHODS: PubMed/MEDLINE, other electronic databases, and electronic conference proceedings of recent HIV/AIDS-related conferences were searched to identify published or unpublished trials meeting the inclusion criteria. Descriptive, methodological, and contextual factors were abstracted from each trial. RESULTS: The review included 37 HIV prevention RCTs reporting on 39 unique interventions. Only six RCTs, all evaluating biomedical interventions, demonstrated definitive effects on HIV incidence. Five of the six RCTs significantly reduced HIV infection: all three male circumcision trials, one trial of sexually transmitted infection treatment and care, and one vaccine trial. One microbicide trial of nonoxynol-9 gel produced adverse results. Lack of statistical power, poor adherence, and diluted versions of the intervention in comparison groups may have been important issues for the other trials that demonstrated 'flat' results. CONCLUSION: Almost 90% of HIV prevention trials had 'flat' results, which may be attributable to trial design and/or implementation. The HIV prevention community must not only examine evidence from significant RCTs, but must also examine flat trials and address design and implementation issues that limit detection of an effect.

IMPORTANCE: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. OBJECTIVE: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONS: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURES: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. CONCLUSIONS AND RELEVANCE: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

During recent decades, antifungal susceptibility testing has become standardized and nowadays has the same role of the antibacterial susceptibility testing in microbiology laboratories. American and European standards have been developed, as well as equivalent commercial systems which are more appropriate for clinical laboratories. The detection of resistant strains by means of these systems has allowed the study and understanding of the molecular basis and the mechanisms of resistance of fungal species to antifungal agents. In addition, many studies on the correlation of in vitro results with the outcome of patients have been performed, reaching the conclusion that infections caused by resistant strains have worse outcome than those caused by susceptible fungal isolates. These studies have allowed the development of interpretative breakpoints for Candida spp. and Aspergillus spp., the most frequent agents of fungal infections in the world. In summary, antifungal susceptibility tests have become essential tools to guide the treatment of fungal diseases, to know the local and global disease epidemiology, and to identify resistance to antifungals.

How large economic stimuli generate individual and aggregate responses is a central question in economics, but has not been studied experimentally. We provided one‐time cash transfers of about USD 1000 to over 10,500 poor households across 653 randomized villages in rural Kenya. The implied fiscal shock was over 15 percent of local GDP. We find large impacts on consumption and assets for recipients. Importantly, we document large positive spillovers on non‐recipient households and firms, and minimal price inflation. We estimate a local transfer multiplier of 2.5. We interpret welfare implications through the lens of a simple household optimization framework.

In Sub-Saharan Africa, 600 million people live without electricity. Despite ambitions of governments and donors to invest in rural electrification, decisions about how to extend electricity access are being made in the absence of rigorous evidence. In this paper, we present high-resolution spatial data on electrification rates in rural Kenya in order to quantify and visualize energy poverty in a novel way. Using our dataset of 20,000 geo-tagged structures in Western Kenya, we provide descriptive evidence that electrification rates remain very low despite significant investments in nearby grid infrastructure. This pattern holds across time and for both poor and relatively well-off households and businesses. We argue that if governments wish to leverage existing infrastructure and economies of scale, subsidies and new approaches to financing connections are necessary.

How large economic stimuli generate individual and aggregate responses is a central question in economics, but has not been studied experimentally. We provided one-time cash transfers of about USD 1000 to over 10,500 poor households across 653 randomized villages in rural Kenya. The implied fiscal shock was over 15 percent of local GDP. We find large impacts on consumption and assets for recipients. Importantly, we document large positive spillovers on nonrecipient households and firms, and minimal price inflation. We estimate a local transfer multiplier of 2.4. We interpret welfare implications through the lens of a simple household optimization framework.

The rising prevalence of private cars in the developing world is causing serious congestion and pollution. In China, private cars started to emerge as an important travel mode in the past decade. Prospective research on the relationship between urban form and car ownership is relatively uncommon in the developing world, and China offers a unique study opportunity, given the tremendous increases in private cars and fast-paced urbanization over the past decade. This study investigates the influence of urban form on car ownership as well as the impact of other socioeconomic and demographic factors on private car ownership across megacities in China. Analysis was conducted through the use of data from 36 megacities and two household survey data sets collected in Beijing and the city of Chengdu, China. Ordinary least squares regression and discrete choice models were employed to execute the aggregate and disaggregate analysis of the urban form impact on private car ownership across cities. The statistical model results demonstrate that urban affluence, urban scale, and road infrastructure supply factors have significant positive effects on the city level of private car ownership across cities. Population density calculated at the subdistrict level, however, had a significant negative effect on private car ownership across cities. Households with private cars were found to prefer to live close to urban centers where amenities were readily available. The results provide evidence for urban planners and policy makers.

Two billion people are infected with intestinal worms. In many areas, the majority of schoolchildren are infected, and the World Health Organization (WHO) has called for school-based mass deworming. The key area for debate is not whether deworming medicine works—in fact, the medical literature finds that treatment is highly effective, and thus the standard of care calls for treating any patient known to harbor an infection. As the authors of the Cochrane systematic review point out, a critical issue in evaluating current soil-transmitted helminth policies is whether the benefits of deworming exceed the costs or whether it would be more prudent to use the money for other purposes. While in general we think the Cochrane approach is very valuable, we argue below that many of the underlying studies of deworming suffer from three critical methodological problems: treatment externalities in dynamic infection systems, inadequate measurement of cognitive outcomes and school attendance, and sample attrition. We then argue that the currently available evidence from studies that address these issues is consistent with the consensus view expressed by other reviews and by policymakers that deworming is a very cost-effective way to increase school participation and has a high benefit to cost ratio.

Vaccines are changing the course of the COVID-19 pandemic, but in grossly uneven ways. Low- and middle-income countries (LMICs) face considerable obstacles in both receiving and distributing doses. To limit virus transmission, its devastating impacts, and opportunities for further mutations, this must change. Until it does, nonpharmaceutical interventions such as masking must remain a priority. Science invited global experts to highlight research and innovations aimed at quickening the end of COVID-19 in LMICs.

Urban community gardens have increased in prevalence as a means to generate fresh fruits and vegetables, including in areas lacking access to healthy food options. However, urban soils may have high levels of toxic heavy metals, including lead and cadmium and the metalloid arsenic, which can lead to severe health risks. In this study, fruit and vegetable samples grown at an urban community garden in southeastern San Diego, the Ocean View Growing Grounds, were sampled repeatedly over a four-year time period in order to measure potential contamination of toxic heavy metals and metalloids and to develop solutions for this problem. Metal nutrient, heavy metal, and metalloid concentrations were monitored in the leaf and fruit tissues of fruit trees over the sampling period. Several of the fruit trees showed uptake of lead in the leaf samples, with Black Mission fig measuring 0.843-1.531 mg/kg dry weight and Mexican Lime measuring 1.103-1.522 mg/kg dry weight over the sampling period. Vegetables that were grown directly in the ground at this community garden and surrounding areas showed arsenic, 0.80 + 0.073 mg/kg dry weight for Swiss chard, and lead, 0.84 ± 0.404 mg/kg dry weight for strawberries, in their edible tissues. The subsequent introduction of raised beds with uncontaminated soil is described, which eliminated any detectable heavy metal or metalloid contamination in these crops during the monitoring period. Recommendations for facilitating the monitoring of edible tissues and for reducing risk are discussed, including introduction of raised beds and collaborations with local universities and research groups.

We randomly expose the owners of small retail businesses in Vietnam to scenarios that trigger financial worries and study the effect of this intervention on risk attitudes using an incentive-compatible elicitation method. We find that entrepreneurs exposed to financial worries behave less risk-averse than those assigned to a placebo treatment. This effect is stronger for owners of shops which are smaller and those less exposed to large income shocks in their everyday business. We further show that the effect of financial worries on risk attitudes is not explained by changes in the cognitive functioning of the treated. The findings are consistent with previous results from laboratory experiments with students in developed countries. As such, the paper provides evidence for the external validity of these findings in the context of micro-entrepreneurship in a developing country and points to financial worries as one understudied psychological channel for the effect of material deprivation on decision-making.

Celebrity endorsements are often sought to influence public opinion.We ask whether celebrity endorsement per se has an effect beyond the fact that their statements are seen by many, and whether on net their statements actually lead people to change their beliefs.To do so, we conducted a nationwide Twitter experiment in Indonesia with 46 high-profile celebrities and organizations, with a total of 7 .8 million followers, who agreed to let us randomly tweet or retweet content promoting immunization from their accounts.Our design exploits the structure of what information is passed on along a retweet chain on Twitter to parse reach versus endorsement effects.Endorsements matter: tweets that users can identify as being originated by a celebrity are far more likely to be liked or retweeted by users than similar tweets seen by the same users but without the celebrities' imprimatur.By contrast, explicitly citing sources in the tweets actually reduces diffusion.By randomizing which celebrities tweeted when, we find suggestive evidence that overall exposure to the campaign may influence beliefs about vaccination and knowledge of immunization-seeking behavior by one's network.Taken together, the findings suggest an important role for celebrity endorsement.

Estimating the impact of child health investments on adult living standards entails multiple methodological challenges, including the lack of experimental variation in health status, an inability to track individuals over time, and accurately measuring living standards and productivity in low-income settings. This study exploits a randomized school health intervention that provided deworming treatment to Kenyan children, and uses longitudinal data to estimate impacts on economic outcomes up to 20 y later. The effective respondent tracking rate was 84%. Individuals who received two to three additional years of childhood deworming experienced a 14% gain in consumption expenditures and 13% increase in hourly earnings. There are also shifts in sectors of residence and employment: treatment group individuals are 9% more likely to live in urban areas, and experience a 9% increase in nonagricultural work hours. Most effects are concentrated among males and older individuals. The observed consumption and earnings benefits, together with deworming's low cost when distributed at scale, imply that a conservative estimate of its annualized social internal rate of return is 37%, a high return by any standard.

Recent research has pointed to large gaps in labor productivity between the agricultural and nonagricultural sectors in low-income countries, as well as between workers in rural and urban areas. Most estimates are based on national accounts or repeated cross-sections of micro-survey data, and as a result typically struggle to account for individual selection between sectors. This paper uses long-run individual-level panel data from two low-income countries (Indonesia and Kenya). Accounting for individual fixed effects leads to much smaller estimated productivity gains from moving into the nonagricultural sector (or urban areas), reducing estimated gaps by over 80%. Per capita consumption gaps are also small once individual fixed effects are included. Estimated productivity gaps do not emerge up to five years after a move between sectors. We evaluate whether these findings imply a re-assessment of the conventional wisdom regarding sectoral gaps, discuss how to reconcile them with existing cross-sectional estimates, and consider implications for the desirability of sectoral reallocation of labor.

Empirical research on the relationship between economic inequality and crime has focussed on income inequality, despite the fact that income is not easily observed by potential criminals. We extend this literature by shifting the focus from income to its visible manifestation—conspicuous consumption. Using variation within US states over time, we document a robust association between the distribution of conspicuous consumption and violent crime. Our results link violent crime to inequality in visible expenditure, but not to inequality in total expenditure, suggesting that information plays a key role in the determination of crime. Furthermore, focussing on conspicuous expenditure allows for new tests of competing theories of crime. Our findings are consistent with social theories that link crime with relative deprivation, but provide little support for traditional economic theory.

INTRODUCTION: Given rising rates of breast cancer in parts of Asia, immigrant Asian American women in the United States may have higher rates of breast cancer than previously anticipated. This study examined breast cancer risk among Asian American women by nativity and percentage of life lived in the United States, accounting for established breast cancer risk factors. METHODS: We analyzed a breast cancer case-control data set of Asian American women living in the San Francisco Bay Area; this data set included 132 cases of women with breast cancer selected from a Surveillance, Epidemiology, and End Results cancer registry and 438 Asian American women without diagnosed breast cancer matched to cases by age and country of origin. We used logistic regression to compare 3 Asian American groups: US-born, immigrants who lived 50% or more of their life in the United States, and immigrants who lived less than 50% of their life in the United States. RESULTS: In the minimally adjusted and fully adjusted models, both groups of immigrant Asian American women had higher risk of breast cancer than US-born Asian American women. In the fully adjusted model, compared with US-born Asian American women, immigrant Asian American women who lived more than 50% of their life in United States were on average 3 times as likely (odds ratio = 3.00; 95% confidence interval, 1.56-5.75) and immigrants who lived less than 50% of their life in United States were on average 2.46 times as likely (odds ratio = 2.46; 95% confidence interval, 1.21-4.99) to have breast cancer. We found no difference in fully adjusted odds ratios of having breast cancer between the 2 immigrant groups. CONCLUSION: This study provides preliminary evidence that breast cancer risk among immigrant Asian American women may be higher than among their US-born counterparts.

This paper analyzes a randomized experiment that uses novel strategies to promote handwashing with soap at critical points in time in Peru. It evaluates a large-scale comprehensive initiative that involved both community and school activities in addition to communication campaigns. The analysis indicates that the initiative was successful in reaching the target audience and in increasing the treated population's knowledge about appropriate handwashing behavior. These improvements translated into higher self-reported and observed handwashing with soap at critical junctures. However, no significant improvements in the health of children under the age of 5 years were observed. Copyright © 2015 John Wiley & Sons, Ltd.

Inefficient cookstoves contribute to deforestation and global climate change, require substantial time (usually of women and girls) collecting wood or money for fuel and lead to just under two million deaths a year. We examined the effect of solar ovens on fuel use, time spent collecting wood, carbon monoxide exposure, and respiratory illness symptoms. A phased randomised controlled trial was run among women interested in purchasing a solar oven in rural Senegal. Of the envisioned 1000 households, 465 treatments and 325 controls took part in the baseline survey. Households randomly allocated to the control group received their stoves 6 months after treatments. Eighty per cent of our respondents typically cook for more people than the capacity of the solar oven and thus even cooks using the solar oven continue using their traditional stove. In the sixth month of owning the stove, treatments used their solar oven 19 per cent of days measured and did not have statistically significantly lower fuel consumption, time spent collecting fuel or time spent next to the cook fire. However, treatments cooking for 7–12 persons did lower their wood consumption for cooking by 14 per cent (P < .01). There is no evidence solar ovens reduced exposure to carbon monoxide or self-reported respiratory symptoms such as coughs and sore throats. This evaluation was a policy success because its results halted the proposed nationwide rollout of the solar oven, thus avoiding mass distribution of a stove which cannot reduce indoor air pollution or generate a sizeable decrease in fuel use. The results from this randomised controlled trial show that the HotPot is a poor product choice for the population as a one-pot stove cannot replace the three-stone fire for the lunch meal due to complex cooking patterns with multiple stoves, cooks and burners. A key result from our programme is stove designers – both solar and other improved biomass cookstoves – should reassess the product design to produce stoves that are affordable, durable, locally appropriate, consistent with current cooking practices (i.e., containing two burners) and large enough to accommodate multi-generational and/or polygamous households with limited incomes and no electricity.

This study examines the medium-term effects of a two-year cash transfer program targeted to adolescent girls and young women. Significant declines in HIV prevalence, teen pregnancy, and early marriage among recipients of unconditional cash transfers (UCTs) during the program evaporated quickly two years after the cessation of transfers. However, children born to UCT beneficiaries during the program had significantly higher height-for-age z-scores at follow-up. On the other hand, conditional cash transfers (CCTs) offered to out-of-school females at baseline produced a large increase in educational attainment and a sustained reduction in the total number of births, but caused no gains in health, labor market outcomes, or empowerment. The findings point to both the promise and the limitations of cash transfer programs for sustained gains in welfare among young women.