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Introduction The expansion of telecommunication networks and smartphones in many African countries could be leveraged to deliver HIV prevention products directly to consumers. In collaboration with a private e‐commerce platform and online pharmacy in Kenya, MYDAWA, we piloted a new model of HIV pre‐ and post‐exposure prophylaxis (PrEP/PEP) delivery. Methods In the ePrEP Kenya pilot (NCT05377138), individuals living in Nairobi and Mombasa Counties could complete a free telehealth visit with a remote clinician to assess eligibility for online PrEP/PEP (i.e. ≥18 years; no medical contraindications). Eligible individuals could order HIV testing services—courier delivered to clients’ choice location—for a fee of 250 KES (∼ $2 USD) for self‐testing or 150 KES (∼$ 1 USD) for provider‐administered rapid diagnostic testing. Following confirmation of clients’ HIV‐negative status (via an uploaded test result image), free PrEP/PEP drugs from government supply were courier delivered with or separately from HIV testing services. Clients paid a delivery fee ≤149 KES (∼$1 USD) per courier visit. Results From October 2022 to December 2023, we screened 2257 individuals and enrolled 1915. Most PrEP/PEP clients were men (63%, 1428/1915), ≥25 years (72%, 1631/1915) and never married (80%, 1796/1915); few had ever used PrEP (3%, 48/1915) or PEP (14%, 263/1915). At enrolment, 227 (12%) were preliminarily eligible for PrEP and 1688 (88%) for PEP. Among PrEP‐eligible clients, 89% (203/227) completed HIV testing and 92% (208/227) received PrEP; among PEP‐eligible clients, 92% (1551/1688) completed HIV testing and 92% (1549/1688) received PEP. Most PrEP/PEP clients completed HIV testing within 6 hours of their telehealth visit (53%, 927/1757) and had drugs delivered with testing services (88%, 1546/1757). Among PrEP clients eligible for follow‐up, 47% (120/256) continued PrEP and 4% (10/256) initiated PEP following PrEP discontinuation. Among PEP clients eligible for follow‐up, 7% (99/1428) repeated PEP use and 6% (83/1428) transitioned from PEP to PrEP.). Conclusions Online PrEP/PEP delivery could expand access to prevention services by reaching individuals not engaged in existing delivery platforms. The uptake of online PEP was five times greater than PrEP, underscoring an unmet demand for PEP and highlighting the potential for online pharmacies to deliver time‐sensitive PEP services.

Background In malaria elimination settings, available metrics for malaria surveillance have been insufficient to measure the performance of passive case detection adequately. An indicator for malaria suspected cases with malaria test (MSCT) is proposed to measure the rate of testing on persons presenting to health facilities who satisfy the definition of a suspected malaria case. This metric does not rely on prior knowledge of fever prevalence, seasonality, or external denominators, and can be used to compare detection rates in suspected cases within and between countries, including across settings with different levels of transmission. Methods To compute the MSCT, an operational definition for suspected malaria cases was established, including clinical and epidemiological criteria. In general, suspected cases included: (1) persons with fever detected in areas with active malaria transmission; (2) persons with fever identified in areas with no active transmission and travel history to, or residence in areas with active transmission (either national or international); and (3) persons presenting with fever, chills and sweating from any area. Data was collected from 9 countries: Belize, Colombia (in areas with active transmission), Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, and Panama (September–March 2020). A sample of eligible medical records for 2018 was selected from a sample of health facilities in each country. An algorithm was constructed to assess if a malaria test was ordered or performed for cases that met the suspected case definition. Results A sample of 5873 suspected malaria cases was obtained from 239 health facilities. Except for Nicaragua and Colombia, malaria tests were requested in less than 10% of all cases. More cases were tested in areas with active transmission than areas without cases. Travel history was not systematically recorded in any country. Conclusions A statistically comparable, replicable, and standardized metric was proposed to measure suspected malaria cases with a test (microscopy or rapid diagnostic test) that enables assessing the performance of passive case detection. Cross-country findings have important implications for malaria and infectious disease surveillance, which should be promptly addressed as countries progress towards malaria elimination. Local and easy-to-implement tools could be implemented to assess and improve passive case detection.

Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020. We conducted a systematic review of data reporting the prevalence of major depressive disorder and anxiety disorders during the COVID-19 pandemic and published between Jan 1, 2020, and Jan 29, 2021. We searched PubMed, Google Scholar, preprint servers, grey literature sources, and consulted experts. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population during the COVID-19 pandemic and had a pre-pandemic baseline. We used the assembled data in a meta-regression to estimate change in the prevalence of major depressive disorder and anxiety disorders between pre-pandemic and mid-pandemic (using periods as defined by each study) via COVID-19 impact indicators (human mobility, daily SARS-CoV-2 infection rate, and daily excess mortality rate). We then used this model to estimate the change from pre-pandemic prevalence (estimated using Disease Modelling Meta-Regression version 2.1 [known as DisMod-MR 2.1]) by age, sex, and location. We used final prevalence estimates and disability weights to estimate years lived with disability and disability-adjusted life-years (DALYs) for major depressive disorder and anxiety disorders. We identified 5683 unique data sources, of which 48 met inclusion criteria (46 studies met criteria for major depressive disorder and 27 for anxiety disorders). Two COVID-19 impact indicators, specifically daily SARS-CoV-2 infection rates and reductions in human mobility, were associated with increased prevalence of major depressive disorder (regression coefficient [B] 0·9 [95% uncertainty interval 0·1 to 1·8; p=0·029] for human mobility, 18·1 [7·9 to 28·3; p=0·0005] for daily SARS-CoV-2 infection) and anxiety disorders (0·9 [0·1 to 1·7; p=0·022] and 13·8 [10·7 to 17·0; p<0·0001]. Females were affected more by the pandemic than males (B 0·1 [0·1 to 0·2; p=0·0001] for major depressive disorder, 0·1 [0·1 to 0·2; p=0·0001] for anxiety disorders) and younger age groups were more affected than older age groups (−0·007 [–0·009 to −0·006; p=0·0001] for major depressive disorder, −0·003 [–0·005 to −0·002; p=0·0001] for anxiety disorders). We estimated that the locations hit hardest by the pandemic in 2020, as measured with decreased human mobility and daily SARS-CoV-2 infection rate, had the greatest increases in prevalence of major depressive disorder and anxiety disorders. We estimated an additional 53·2 million (44·8 to 62·9) cases of major depressive disorder globally (an increase of 27·6% [25·1 to 30·3]) due to the COVID-19 pandemic, such that the total prevalence was 3152·9 cases (2722·5 to 3654·5) per 100 000 population. We also estimated an additional 76·2 million (64·3 to 90·6) cases of anxiety disorders globally (an increase of 25·6% [23·2 to 28·0]), such that the total prevalence was 4802·4 cases (4108·2 to 5588·6) per 100 000 population. Altogether, major depressive disorder caused 49·4 million (33·6 to 68·7) DALYs and anxiety disorders caused 44·5 million (30·2 to 62·5) DALYs globally in 2020. This pandemic has created an increased urgency to strengthen mental health systems in most countries. Mitigation strategies could incorporate ways to promote mental wellbeing and target determinants of poor mental health and interventions to treat those with a mental disorder. Taking no action to address the burden of major depressive disorder and anxiety disorders should not be an option. Queensland Health, National Health and Medical Research Council, and the Bill and Melinda Gates Foundation.

The discrimination of thatcherized faces from typical faces was explored in two simultaneous alternative forced choice tasks. Reaction times (RTs) and errors were measured in a behavioural task. Brain activation was measured in an equivalent fMRI task. In both tasks, participants were tested with upright and inverted faces. Participants were also tested on churches in the behavioural task. The behavioural task confirmed the face specificity of the illusion (by comparing inversion effects for faces against churches) but also demonstrated that the discrimination was primarily, although not exclusively, driven by attending to eyes. The fMRI task showed that, relative to inverted faces, upright grotesque faces are discriminated via activation of a network of emotion/social evaluation processing areas. On the other hand, discrimination of inverted thatcherized faces was associated with increased activation of brain areas that are typically involved in perceptual processing of faces.

National rates of COVID-19 infection and fatality have varied dramatically since the onset of the pandemic. Understanding the conditions associated with this cross-country variation is essential to guiding investment in more effective preparedness and response for future pandemics. Daily SARS-CoV-2 infections and COVID-19 deaths for 177 countries and territories and 181 subnational locations were extracted from the Institute for Health Metrics and Evaluation's modelling database. Cumulative infection rate and infection-fatality ratio (IFR) were estimated and standardised for environmental, demographic, biological, and economic factors. For infections, we included factors associated with environmental seasonality (measured as the relative risk of pneumonia), population density, gross domestic product (GDP) per capita, proportion of the population living below 100 m, and a proxy for previous exposure to other betacoronaviruses. For IFR, factors were age distribution of the population, mean body-mass index (BMI), exposure to air pollution, smoking rates, the proxy for previous exposure to other betacoronaviruses, population density, age-standardised prevalence of chronic obstructive pulmonary disease and cancer, and GDP per capita. These were standardised using indirect age standardisation and multivariate linear models. Standardised national cumulative infection rates and IFRs were tested for associations with 12 pandemic preparedness indices, seven health-care capacity indicators, and ten other demographic, social, and political conditions using linear regression. To investigate pathways by which important factors might affect infections with SARS-CoV-2, we also assessed the relationship between interpersonal and governmental trust and corruption and changes in mobility patterns and COVID-19 vaccination rates. The factors that explained the most variation in cumulative rates of SARS-CoV-2 infection between Jan 1, 2020, and Sept 30, 2021, included the proportion of the population living below 100 m (5·4% [4·0–7·9] of variation), GDP per capita (4·2% [1·8–6·6] of variation), and the proportion of infections attributable to seasonality (2·1% [95% uncertainty interval 1·7–2·7] of variation). Most cross-country variation in cumulative infection rates could not be explained. The factors that explained the most variation in COVID-19 IFR over the same period were the age profile of the country (46·7% [18·4–67·6] of variation), GDP per capita (3·1% [0·3–8·6] of variation), and national mean BMI (1·1% [0·2–2·6] of variation). 44·4% (29·2–61·7) of cross-national variation in IFR could not be explained. Pandemic-preparedness indices, which aim to measure health security capacity, were not meaningfully associated with standardised infection rates or IFRs. Measures of trust in the government and interpersonal trust, as well as less government corruption, had larger, statistically significant associations with lower standardised infection rates. High levels of government and interpersonal trust, as well as less government corruption, were also associated with higher COVID-19 vaccine coverage among middle-income and high-income countries where vaccine availability was more widespread, and lower corruption was associated with greater reductions in mobility. If these modelled associations were to be causal, an increase in trust of governments such that all countries had societies that attained at least the amount of trust in government or interpersonal trust measured in Denmark, which is in the 75th percentile across these spectrums, might have reduced global infections by 12·9% (5·7–17·8) for government trust and 40·3% (24·3–51·4) for interpersonal trust. Similarly, if all countries had a national BMI equal to or less than that of the 25th percentile, our analysis suggests global standardised IFR would be reduced by 11·1%. Efforts to improve pandemic preparedness and response for the next pandemic might benefit from greater investment in risk communication and community engagement strategies to boost the confidence that individuals have in public health guidance. Our results suggest that increasing health promotion for key modifiable risks is associated with a reduction of fatalities in such a scenario. Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01181-w

Although there is evidence of emotion perception deficits in autism spectrum disorder (ASD), research on this topic has been mostly confined to perception of emotions in faces. Using behavioral measures and 3T functional magnetic resonance imaging (fMRI), we examined whether such deficits extend to the perception of bodily expressed emotions. We found that individuals with ASD, in contrast to neurotypical (NT) individuals, did not exhibit a differential pattern of brain activation to bodies expressing fear as compared with emotionally neutral bodies. ASD and NT individuals showed similar patterns of activation in response to bodies engaged in emotionally neutral actions, with the exception of decreased activation in the inferior frontal cortex and the anterior insula in ASD. We discuss these findings in relation to possible abnormalities in a network of cortical and subcortical mechanisms involved in social orienting and emotion contagion. Our data suggest that emotion perception deficits in ASD may be due to compromised processing of the emotional component of observed actions.

Current study planning and practice relies heavily on the use of interactive web or voice response technology (or interactive response technology), also referred to as IWR or IRT. These tools are often integral to investigative site management of clinical supplies.1 At minimum, IRT systems help to reduce site burden and expedite reconciliation and return of unused investigational product (IP) at the end of a study.2 Published data indicate that IRT for clinical supply management will increasingly play a major role in managing global trials.3 Improved IRT systems could allow for better support overall for timing of supply and re-supply, mitigating issues such as limited storage space available at the sites and support proper labeling. IRT can also be used to manage patient compliance issues with the use of mobile patient visit and medication reminders.4 Seventeen percent of respondents rated IRT \"Poor\" and \"Fair\" with respect to design, and 13% gave a low rating to IRT ease of use. More than one-outof-four sites rated the number of IVR steps to get a drug dispensed as \"Poor\" to \"Fair.\" Respondents reported challenges in the area of temperature-monitored supplies specifically with temperature excursions and dealing with defective or complicated equipment. Our analyses revealed further differences by therapeutic area. Sites conducting trials in oncology, infectious disease, respi- ratory, or hematology therapeutic areas were more likely to report challenges with temperature excursions than those conducting trials in other areas. This difference was statistically significant (p c.Ol). This finding is not surprising given that sites participating in research with temperature monitored products (e.g., oncology and hematology) are likely to report challenges with temperature excursions. Clinical supply challenges were particularly evident in specific therapeutic areas: oncology, infectious disease, respiratory, and hematology. Increasingly, trials conducted in these therapeutic areas utilize temperature-controlled drugs and supplies and the costs involved in shipping and transporting clinical supplies are high and may require that current sponsor-site practices be re-assessed or evaluated. As more sites deal with temperature-controlled products and moving those through temperature and time zones as well as handling novel therapies, sites may require additional staff training, facilities, or technology. Given the industry's move toward more focused controls on shipping of various temperatures, sponsors' assessment of sites' practices could result in considerable cost savings for companies.

Social media presents new challenges to the biopharmaceutical industry for conducting pharmacovigilance activities. The authors reviewed worldwide regulatory guidance documents related to monitoring of adverse events posted on social media sites and identified gaps in current regulatory definitions for pharmacovigilance. Points to consider for addressing these gaps are made to offer standards for industry consideration and a potential framework for guidance from global health authorities.