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ObjectiveTo test the effect of proactive home visits by trained community health workers (CHWs) on child survival.MethodsWe conducted a two arm, parallel, unmasked cluster-randomized trial in 137 village-clusters in rural Mali. From February 2017 to January 2020, 31 761 children enrolled at the trial start or at birth. Village-clusters received either primary care services by CHWs providing regular home visits (intervention) or by CHWs providing care at a fixed site (control). In both arms, user fees were removed and primary health centres received staffing and infrastructure improvements before trial start. Using lifetime birth histories from women aged 15-49 years surveyed annually, we estimated incidence rate ratios (IRR) for intention-to-treat and per-protocol effects on under-five mortality using Poisson regression models.FindingsOver three years, we observed 52 970 person-years (27 332 in intervention arm; 25 638 in control arm). During the trial, 909 children in the intervention arm and 827 children in the control arm died. The under-five mortality rate declined from 142.8 (95% CI: 133.3-152.9) to 56.7 (95% CI: 48.5-66.4) deaths per 1000 live births in the intervention arm; and from 154.3 (95% CI: 144.3-164.9) to 54.9 (95% CI: 45.2-64.5) deaths per 1000 live births in the control arm. Intention-to-treat (IRR: 1.02; 95% CI: 0.88-1.19) and per-protocol estimates (IRR: 1.01; 95% CI: 0.87-1.18) showed no difference between study arms.ConclusionThough proactive home visits did not reduce under-five mortality, system-strengthening measures may have contributed to the decline in under-five mortality in both arms.

BackgroundChinese students are extremely vulnerable to developing mental illness. The stigma associated with mental illness presents a barrier to seeking help for their mental health. ObjectiveThe Linking Hearts—Linking Youth and ‘Xin’ (hearts) project is an implementation science project that seeks to reduce mental illness stigma and promote the mental health of university students in Jinan, China. The Linking Hearts project consists of 3 components. In this paper, we outline the protocol for the first component, that is, the contextual assessment and analysis of the mental health needs of university students as the first step to inform the adaptation of an evidence-based intervention to be implemented in Jinan, China. MethodsSix local universities will participate in the Linking Hearts project. A total of 100 students from each university (n=600) will engage in the contextual assessment through self-report surveys on depression, anxiety, stress, mental health knowledge, and mental health stigma. Quantitative data will be analyzed using several descriptive and inferential analyses via SPSS. A small number of participants (144 students and 144 service providers) will also be engaged in focus groups to assess the socio-environmental contexts of university students’ health and availability of mental health resources. Qualitative data will be transcribed verbatim and NVivo will be used for data management. Social network analysis will also be performed using EgoNet. ResultsLinking Hearts was funded in January 2018 for 5 years. The protocol of Linking Hearts and its 3 components was approved by the research ethics boards of all participating institutions in China in November 2018. Canadian institutions that gave approval were Ryerson University (REB2018-455) in January 2019, University of Alberta (Pro00089364), York University (e2019-162) in May 2019, and University of Toronto (RIS37724) in August 2019. Data collection took place upon ethics approval and was completed in January 2020. A total of 600 students were surveyed. An additional 147 students and 138 service providers took part in focus groups. Data analysis is ongoing. Results will be published in 2021. ConclusionsFindings from this contextual assessment and analysis will generate new knowledge on university students’ mental health status, mental health knowledge, and resources available for them. These findings will be used to adapt and refine the Acceptance and Commitment to Empowerment-Linking Youth N’ Xin intervention model. The results of this contextual assessment will be used to inform the adaptation and refinement of the mental health intervention to promote the mental health of Chinese university students in Jinan. International Registered Report Identifier (IRRID)RR1-10.2196/25009

The Proactive Community Case Management (ProCCM) trial in Mali reinforced the health system across both arms with user fee removal, professional Community Health Workers (CHWs), and upgraded primary health centres (PHCs)-and randomized village-clusters to receive proactive home visits by CHWs (intervention) or fixed site-based services by passive CHWs (control). Across both arms, sick children's 24-hour treatment and pregnant women's four or more antenatal visits doubled, and under-five mortality halved, over three years compared to baseline. In the intervention arm, proactive CHW home visits had modest effects on children's curative and women's antenatal care utilization, but no effect on under-five mortality, compared to the control arm. We aimed to explain these results by examining implementation, mechanisms, and context in both arms. We conducted a process evaluation with a mixed method convergent design that included 79 in-depth interviews with providers and participants over two time-points, surveys with 195 providers, and secondary analyses of clinical data. We embedded realist approaches in novel ways to test, refine, and consolidate theories about how ProCCM worked, generating three context-intervention-actor-mechanism-outcome nodes that unfolded in a cascade. First, removing user fees and deploying professional CHWs in every cluster enabled participants to seek health sector care promptly and created a context of facilitated access. Second, health systems support to all CHWs and PHCs enabled equitable, respectful, quality healthcare, which motivated increased, rapid utilization. Third, proactive CHW home visits facilitated CHWs and participants to deliver and seek care, and build relationships, trust, and expectations, but these mechanisms were also activated in both arms. Addressing multiple structural barriers to care, user fee removal, professional CHWs, and upgraded clinics interacted with providers' and patients' agency to achieve rapid care and child survival in both arms. Proactive home visits expedited or compounded mechanisms that were activated and changed the context across arms.

IntroductionAdverse sexual and reproductive health (SRH) outcomes, such as unplanned pregnancies and HIV infection, disproportionately affect adolescent girls and young women (AGYW; aged 15-24 years) in east Africa. Increasing uptake of preventive SRH services via innovative, youth-centred interventions is imperative to addressing disparities in SRH outcomes.Methods and analysisFrom 2018 to 2019, we used human-centred design to co-develop a theoretically driven HIV and pregnancy prevention intervention for AGYW at private drug shops called Accredited Drug Dispensing Outlets (ADDOs) in Tanzania. The result, Malkia Klabu (Queen Club), was a customer loyalty programme designed to strengthen ADDOs' role as SRH providers while encouraging uptake of critical SRH prevention products among AGYW. Malkia Klabu members had access to free contraceptives and oral HIV self-test (HIVST) kits and earned punches on a loyalty card for other shop purchases; punches were redeemable for small prizes. Our pilot among 40 shops showed that intervention ADDOs had higher AGYW patronage and distributed more HIVST kits and contraceptives to AGYW relative to business-as-usual (ie, client purchasing) comparison shops. We will conduct a cluster-randomised controlled trial (c-RCT) among 120-140 ADDOs in 40 health catchment areas in Shinyanga and Mwanza Regions (Lake Zone), Tanzania. ADDO shop recruitment includes a 1-month run-in with a tablet-based electronic inventory management system for tracking shop transactions, followed by enrolment, randomisation and a 24-month trial period. Our c-RCT evaluating the human-centred design-derived intervention will assess population impact on the primary outcomes of HIV diagnoses and antenatal care registrations, measured with routine health facility data. We will also assess secondary outcomes focusing on mechanisms of action, evaluate programme exposure and AGYW behaviour change in interviews with AGYW, and assess shop-level implementation strategies and fidelity.Ethics and disseminationEthical approval was granted from both the University of California, San Francisco and the Tanzanian National Institute for Medical Research. Study progress and final outcomes will be posted annually to the National Clinical Trials website; study dissemination will occur at conferences, peer-reviewed manuscripts and local convenings of stakeholders.Trial registration numberNCT05357144.

ObjectiveThe vast majority of the 300 000 pregnancy-related deaths every year occur in South Asia and sub-Saharan Africa. Increased access to quality antepartum and intrapartum care can reduce pregnancy-related morbidity and mortality worldwide. We used a population-based cross-sectional cohort design to: (1) examine the sociodemographic risk factors and structural barriers associated with pregnancy care-seeking and institutional delivery, and (2) investigate the influence of residential distance to the nearest primary health facility in a rural population in Mali.MethodsA baseline household survey of Malian women aged 15-49 years was conducted between December 2016 and January 2017, and those who delivereda baby in the 5 years preceding the survey were included. This study leverages the baseline survey data from a cluster-randomised controlled trial to conduct a secondary analysis. The outcomes were percentage of women who received any antenatal care (ANC) and institutional delivery; total number of ANC visits; four or more ANC visits; first ANC visit in the first trimester.ResultsOf the 8575 women in the study, two-thirds received any ANC in their last pregnancy, one in 10 had four or more ANC visits and among those that received any ANC, about one-quarter received it in the first trimester. For every kilometre increase in distance to the nearest facility, the likelihood of the outcomes reduced by 5 percentage points (0.95; 95% CI 0.91 to 0.98) for any ANC; 4 percentage points (0.96; 95% CI 0.94 to 0.98) for an additional ANC visit; 10 percentage points (0.90; 95% CI 0.86 to 0.95) for four or more ANC visits; 6 percentage points (0.94; 95% CI 0.94 to 0.98) for first ANC in the first trimester. In addition, there was a 35 percentage points (0.65; 95% CI 0.56 to 0.76) decrease in likelihood of institutional delivery if the residence was within 6.5 km to the nearest facility, beyond which there was no association with the place of delivery. We also found evidence of increase in likelihood of receiving any ANC care and its intensity increased with having some education or owning a business.ConclusionThe findings suggest that education, occupation and distance are important determinants of pregnancy and delivery care in a rural Malian context.Trial registration numberNCT02694055.

BackgroundAdolescent girls and young woman (AGYW) comprise a significant proportion of new HIV infections and unintended pregnancies in sub-Saharan Africa yet face many barriers to accessing family planning and reproductive health (FPRH) information and services. Developed via human-centered design, the Malkia Klabu ("Queen Club") program aimed to facilitate access to HIV self-testing (HIVST) and FPRH information and products at privately-owned drug shops. We sought to understand barriers and facilitators to program implementation in a 4-month pilot in Tanzania.MethodsForty semi-structured interviews were conducted with participants in a cluster randomized trial of the Malkia Klabu program from November 2019 through March 2020, including 11 with AGYW, 26 with drug shopkeepers, and three with counselors at health facilities to whom AGYW were referred. Interviews were audio-recorded, transcribed, coded, and analyzed to identify key themes. The Consolidated Framework for Implementation Research (CFIR) was used to assess barriers and facilitators to program implementation at multiple levels. CFIR considers the outer setting (e.g., culture and systemic conditions), the inner setting where the intervention is implemented (e.g., incentives, relationships, and available resources), the individuals involved, the innovation as it relates to stakeholder needs, and the implementation process.ResultsThe Malkia Klabu program reshaped and directed the role of drug shopkeepers as providers of information and resources rather than FPRH gatekeepers. Key implementation facilitators included the program's adaptability to a wide range of needs and stages of readiness among AGYW, ability to capitalize on AGYW social networks for driving membership, responsiveness to AGYW's need for privacy, and positive contributions to the income and community standing of drug shopkeepers. Components such as HIVST were highly acceptable to both AGYW and shopkeepers, and the introduction of the loyalty program and HIVST kits in shops opened doors to the provision of FPRH products and information, which was further facilitated by program tools such as videos, product displays, and symbol cards. Although some shopkeepers maintained beliefs that certain contraceptive methods were inappropriate for AGYW, most appeared to provide the products as part of the program.ConclusionsThe Malkia Klabu intervention's success was due in part to its ability to address key motivations of both AGYW and drug shopkeepers, such as maintaining privacy and increasing access to FPRH products for AGYW and increasing business for shops. Better understanding these implementation barriers and facilitators can inform the program's future adaptation and scale-up.Trial registrationclinicaltrials.gov #NCT04045912.

ObjectivesTo examine how sales of sexual and reproductive health (SRH) products varied among pharmacies in Kenya using administrative data, leveraging natural variation in the COVID-19 pandemic and accompanying policy restrictions between 2019 and 2021.Design and settingEcological study of pharmacies in Kenya.Participants761 pharmacies using the Maisha Meds product inventory management system (capturing 572 916 products sold).OutcomesSales quantity, price and revenue of SRH products sold per pharmacy per week.ResultsCOVID-19 deaths were associated with a -2.97% (95% CI -3.82%, -2.11%) decrease in sales quantity, a 1.09% (95% CI 0.44%, 1.72%) increase in sales price and a -1.89% (-1.00%, -2.79%) decrease in revenues per pharmacy per week. Results were similar when considering new COVID-19 cases (per 1000) and the Average Policy Stringency Index. Results differed substantially between individual SRH products-a large decrease in sales quantity in pregnancy tests, injectables and emergency contraception, a modest decrease in condoms and no change in oral contraception. Sales price increases were similarly varied; four of the five most sold products were revenue neutral.ConclusionsWe found a robust negative association between SRH sales at pharmacies in Kenya and COVID-19 reported cases, deaths and policy restriction. Although our data cannot definitively point to reduced access, existing evidence from Kenya regarding unchanged fertility intentions, increases in unintended pregnancies and reported reasons for non-use of contraceptives during COVID-19 suggests a prominent role of reduced access. While policymakers may have a role in sustaining access, their role may be limited by broader macroeconomic problems, such as global supply chain disruptions and inflation, during supply shocks.

Adolescent girls and young women (AGYW; ages 15-24) in sub-Saharan Africa face many barriers to accessing preventive sexual and reproductive health (SRH) services. We drew upon the strengths of two complementary approaches, human-centered design and behavioral economics, to craft a holistic, highly-tailored, and empathetic intervention to motivate AGYW to seek contraception and HIV self-test kits at community drug shops. To encourage engagement, we embedded "nudge" strategies at different opportunity points (uncovered during our design research) along the care-seeking and service delivery journey. Our Malkia Klabu intervention is a loyalty program designed to enhance drug shops' role as SRH providers through which AGYW earned punches for shop purchases redeemable for small prizes; free SRH products could be requested at any time. From our 4-month pilot in Shinyanga, Tanzania, we assess the extent to which different behavioral nudge strategies motivated behaviors as predicted by synthesizing findings from (1) in-depth interviews with AGYW and shopkeepers, (2) shop program records, (3) shop observations, and (4) customer exit surveys. Overall, we find that AGYW and shopkeepers were motivated by many intervention features as intended and consistent with hypothesized mechanisms. We found strong evidence of social norms for helping to spread awareness of Malkia Klabu among peers, prize incentives for drawing AGYW back to shops, and the opt-out default membership gift of an HIV self-test kit for encouraging testing uptake and exploration of contraceptives. Shopkeepers in both arms noted increased community status from distributing HIV self-testing kits (ego). Malkia Klabu shopkeepers experienced increased customer traffic and business revenues (incentives), which reduced shopkeepers' gatekeeping tendencies and earned them additional recognition as champions of AGYW well-being. Integrating human-centered design and behavioral economics was effective for developing an innovative and effective intervention that simultaneously met the different needs of economic actors in support of public health priorities.

Equating contraceptive use with programmatic success is fundamentally flawed in failing to account for whether individuals desire contraceptive use; this is problematic because nonuse can reflect empowered decision-making and use may reflect an individual's inability to refuse or discontinue a method. A rights-based approach demands respect for individuals' freedom to weigh options and choose how their desire for pregnancy prevention can be accommodated by available methods and within the context of their own personal, social, and material constraints. We offer an alternative construct, preference-aligned fertility management (PFM), that provides a more holistic indicator of whether one's contraceptive needs are met. PFM is more person-centered and informative for programming than status quo measures of unmet need, demand satisfied, and contraceptive use which define a positive outcome in relation to pregnancy risk rather than one's stated preferences. The PFM approach goes beyond other recent proposals for modifying the concept of unmet need by refraining from judgment of legitimate reasons for nonuse of contraception and offers a straightforward way to capture whether people act in line with their preferences. We conclude with discussion of how we plan to measure PFM in the Innovations for Choice and Autonomy (ICAN) study in Nigeria and Uganda.

IntroductionThough community health workers (CHWs) have improved access to antenatal care (ANC) and institutional delivery in different settings, it is unclear what package and delivery strategy maximises impact.MethodsThis study reports a secondary aim of the Proactive Community Case Management cluster randomised trial, conducted between December 2016 and April 2020 in Mali. It evaluated whether proactive home visits can improve ANC access at a population level compared with passive site-based care. 137 unique village clusters, covering the entire study area, were stratified by health catchment area and distance to the nearest primary health centre. Within each stratum, clusters were randomly assigned to intervention or control arm. CHWs in intervention clusters proactively visited all homes to provide care. In the control clusters, CHWs provided the same services at their fixed community health post to care-seeking patients. Pregnant women 15-49 years old were enrolled in a series of community-based and facility-based visits. We analysed individual-level annual survey data from baseline and 24-month and 36-month follow-up for the secondary outcomes of ANC and institutional delivery, complemented with CHW monitoring data during the trial period. We compared outcomes between: (1) the intervention and control arms, and (2) the intervention period and baseline.ResultsWith 2576 and 2536 pregnancies from 66 and 65 clusters in the intervention and control arms, respectively, the estimated risk ratios for receiving any ANC was 1.05 (95% CI 1.02 to 1.07), four or more ANC visits was 1.25 (95% CI 1.08 to 1.43) and ANC initiated in the first trimester was 1.11 (95% CI 1.02 to 1.19), relative to the controls; no differences in institutional delivery were found. However, both arms achieved large improvements in institutional delivery, compared with baseline. Monitoring data show that 19% and 2% of registered pregnancies received at least eight ANC contacts in the intervention and control arms, respectively. Six clusters, three from each arm had to be dropped in the last 2 years of the trial.ConclusionsProactive home visits increased ANC and the number of antenatal contacts at the clinic and community levels. ANC and institutional delivery can be increased when provided without fees from professional CHWs in upgraded primary care clinics.Trial registration numberNCT02694055.

BackgroundGlobally, HIV, TB and malaria account for an estimated three million deaths annually. The Global Fund partnered with the World Health Organization to assist countries with health workforce planning in these areas through the development of an integrated health workforce investment impact tool. Our study illustrates the development of a user-friendly tool (with two MS Excel calculator subcomponents) that computes associations between human resources for health (HRH) investment inputs and reduced morbidity and mortality from HIV, TB, and malaria via increased coverage of effective treatment services.MethodsWe retrieved from the peer-reviewed literature quantitative estimates of the relation among HRH inputs and HRH employment and productivity. We converted these values to additional full-time-equivalent doctors, nurses and midwives (DNMs). We used log-linear regression to estimate the relation between DNMs and treatment service coverage outcomes for HIV, TB, and malaria. We then retrieved treatment effectiveness parameters from the literature to calculate lives saved due to expanded treatment coverage for HIV, TB, and malaria. After integrating these estimates into the tool, we piloted it in four countries.ResultsIn most countries with a considerable burden of HIV, TB, and malaria, the health workforce investments include a mix of pre-service education, full remuneration of new hires, various forms of incentives and in-service training. These investments were associated with elevated HIV, TB and malaria treatment service coverage and additional lives saved. The country case studies we developed in addition, indicate the feasibility and utility of the tool for a variety of international and local actors interested in HRH planning.ConclusionsThe modelled estimates developed for illustrative purposes and tested through country case studies suggest that HRH investments result in lives saved across HIV, TB, and malaria. Furthermore, findings show that attainment of high targets of specific treatment coverage indicators would require a substantially greater health workforce than what is currently available in most LMICs. The open access tool can assist with future HRH planning efforts, particularly in LMICs.

Lateral ventral neurons (LNvs) in the fly circadian neural circuit mediate behaviors other than clock resetting, including light-activated acute arousal. Converging sensory inputs often confer functional redundancy. The LNvs have three distinct light input pathways: (1) cell autonomously expressed cryptochrome (CRY), (2) rhodopsin 7 (Rh7), and (3) synaptic inputs from the eyes and other external photoreceptors that express opsins and CRY. We explored the relative photoelectrical and behavioral input contributions of these three photoreceptor systems to determine their functional impact in flies. Patch-clamp electrophysiology measuring light evoked firing frequency (FF) was performed on large LNvs (l-LNvs) in response to UV (365 nm), violet (405 nm), blue (450 nm), or red (635 nm) LED light stimulation, testing controls versus mutants that lack photoreceptor inputs gl60j, cry-null, rh7-null, and double mutant gl60j-cry-null flies. For UV, violet, and blue short wavelength light inputs, all photoreceptor mutants show significantly attenuated action potential FF responses measured in the l-LNv. In contrast, red light FF responses are only significantly attenuated in double mutant gl60j-cry-null flies. We used a light-pulse arousal assay to compare behavioral responses to UV, violet, blue and red light of control and light input mutants, measuring the awakening arousal response of flies during subjective nighttime at two different intensities to capture potential threshold differences (10 and 400 μW/cm2). The light arousal behavioral results are similar to the electrophysiological results, showing significant attenuation of behavioral light responses for mutants compared to control. These results show that the different LNv convergent photoreceptor systems are integrated and together confer functional redundancy for light evoked behavioral arousal.

PurposeWe hypothesized that an intervention designed to create girl-friendly drug shops would increase access to sexual and reproductive health products and services among adolescent girls and young women (AGYW) (ages 15-24 years) in Tanzania.MethodsWe conducted a four-month randomized trial at 20 drug shops in Shinyanga, Tanzania from August-December 2019 to determine if the Malkia Klabu ("Queen Club") intervention increased AGYW patronage and the provision of HIV self-testing (HIVST), contraception, and health facility referrals to AGYW (primary outcomes). Drug shops were randomized 1:1 to the intervention or comparison arm. All shops were provided with OraQuick HIVST kits to give to AGYW for free. Intervention shops implemented Malkia Klabu, a loyalty program for AGYW created using human-centered design through which AGYW could also access free contraception. We compared outcomes in intention-to-treat analyses using shop observations and shopkeeper records.ResultsBy endline, shops implementing Malkia Klabu had higher AGYW patronage than comparison shops (rate ratio: 4.4; 95% confidence interval: 2.0, 9.8). Intervention shops distributed more HIVST kits (median per shop: 130.5 vs. 58.5, P = .02) and contraceptives (325.5 vs. 7.0, P < .01) to AGYW and provided more referrals for HIV, family planning, or pregnancy services combined (3.5 vs. 0.5, P = .02) than comparison shops.DiscussionThe Malkia Klabu intervention increased AGYW patronage and the provision of HIVST kits, contraception, and referrals to AGYW at drug shops, despite HIVST kits being freely available at all participating shops. Enhancing drug shops with girl-friendly services may be an effective strategy to reach AGYW with sexual and reproductive health services.

BackgroundProfessional community health workers (CHWs) can help achieve universal health coverage, although evidence gaps remain on how to optimise CHW service delivery. We conducted an unblinded, parallel, cluster randomised trial in rural Mali to determine whether proactive CHW delivery reduced mortality and improved access to health care among children under five years, compared to passive delivery. Here we report the secondary access endpoints.MethodsBeginning from 26-28 February 2017, 137 village-clusters were offered care by CHWs embedded in communities who were trained, paid, supervised, and integrated into a reinforced public-sector health system that did not charge user fees. Clusters were randomised (stratified on primary health centre catchment and distance) to care during CHWs during door-to-door home visits (intervention) or based at a fixed village site (control). We measured outcomes at baseline, 12-, 24-, and 36-month time points with surveys administered to all resident women aged 15-49 years. We used logistic regression with cluster-level random effects to estimate intention-to-treat and per-protocol effects over time on prompt (24-hour) treatment within the health sector.ResultsFollow-up surveys between February 2018 and April 2020 generated 20 105 child-year observations. Across arms, prompt health sector treatment more than doubled compared to baseline. At 12 months, children in intervention clusters had 22% higher odds of receiving prompt health sector treatment than those in control (cluster-specific adjusted odds ratio (aOR) = 1.22; 95% confidence interval (CI) = 1.06, 1.41, P = 0.005), or 4.7 percentage points higher (adjusted risk difference (aRD) = 0.047; 95% CI = 0.014, 0.080). We found no evidence of an effect at 24 or 36 months.ConclusionsCHW-led health system redesign likely drove the 2-fold increase in rapid child access to care. In this context, proactive home visits further improved early access during the first year but waned afterwards.RegistrationClinicalTrials.gov NCT02694055.

ObjectiveThe COVID-19 pandemic has forced many human subjects research to halt in-person activities and pivot to virtual engagement, including Focus Groups (FGs). We highlight learnings from our experience of hosting virtual FGs from our BEhavioral EConomics for Oral health iNnovation (BEECON) study focusing on oral hygiene behaviors among low-income, predominantly Hispanic families, including practical tips and potential pitfalls to avoid for researchers considering virtual engagement.ResultsThere can be particular benefits to holding virtual sessions among minority parents of young children-to provide flexibility, comfort, and reduced logistical barriers for participation-while still facilitating friendly conversation with minimal distractions. However, extensive preparation is needed to ensure smooth execution and minimal distractions.

Cryptochrome (CRY) is a short-wavelength light-sensitive photoreceptor expressed in a subset of circadian neurons and eyes in Drosophila that regulates light-evoked circadian clock resetting. Acutely, light evokes rapid electrical excitation of the ventral lateral subset of circadian neurons and confers circadian-modulated avoidance behavioral responses to short-wavelength light. Recent work shows dramatically different avoidance versus attraction behavioral responses to short-wavelength light in day-active versus night-active mosquitoes and that these behavioral responses are attenuated by CRY protein degradation by constant light exposure in mosquitoes. To determine whether CRY1s mediate species-specific coding for behavioral and electrophysiological light responses, we used an empty neuron approach and transgenically expressed diurnal Aedes aegypti (AeCRY1) versus nocturnal Anopheles gambiae (AgCRY1) in a cry-null Drosophila background. AeCRY1 is much less light sensitive than either AgCRY1 or DmCRY as shown by partial behavioral rhythmicity following constant light exposure. Remarkably, expression of nocturnal AgCRY1 confers low survival to constant white light as does expression of AeCRY1 to a lesser extent. AgCRY1 mediates significantly stronger electrophysiological cell-autonomous responses to 365 nm ultraviolet (UV) light relative to AeCRY1. AgCRY1 expression mediates electrophysiological sensitivity to 635 nm red light, whereas AeCRY1 does not, consistent with species-specific mosquito red light responses. AgCRY1 and DmCRY mediate intensity-dependent avoidance behavior to UV light at different light intensity thresholds, whereas AeCRY1 does not, thus mimicking mosquito and fly behaviors. These findings highlight CRY as a key non-image-forming visual photoreceptor that mediates physiological and behavioral light responses in a species-specific fashion.

Nocturnal Anopheles mosquitoes exhibit strong behavioral avoidance to blue-light while diurnal Aedes mosquitoes are behaviorally attracted to blue-light and a wide range of other wavelengths of light. To determine the molecular mechanism of these effects, we expressed light-sensing Anopheles gambiae (AgCRY1) and Aedes aegypti (AeCRY1) Cryptochrome 1 (CRY) genes under a crypGAL4-24 driver line in a mutant Drosophila genetic background lacking native functional CRY, then tested behavioral and electrophysiological effects of mosquito CRY expression relative to positive and negative CRY control conditions. Neither mosquito CRY stops the circadian clock as shown by robust circadian behavioral rhythmicity in constant darkness in flies expressing either AgCRY1 or AeCRY1. AgCRY1 and AeCRY1 both mediate acute increases in large ventral lateral neuronal firing rate evoked by 450 nm blue-light, corresponding to CRY's peak absorbance in its base state, indicating that both mosquito CRYs are functional, however, AgCRY1 mediates significantly stronger sustained electrophysiological light-evoked depolarization in response to blue-light relative to AeCRY1. In contrast, neither AgCRY1 nor AeCRY1 expression mediates measurable increases in large ventral lateral neuronal firing rates in response to 405 nm violet-light, the peak of the Rhodopsin-7 photoreceptor that is co-expressed in the large lateral ventral neurons. These results are consistent with the known action spectra of type 1 CRYs and lack of response in cry-null controls. AgCRY1 and AeCRY1 expressing flies show behavioral attraction to low intensity blue-light, but AgCRY1 expressing flies show behavioral avoidance to higher intensity blue-light. These results show that nocturnal and diurnal mosquito Cryptochrome 1 proteins mediate differential physiological and behavioral responses to blue-light that are consistent with species-specific mosquito behavior.

BackgroundPersistent challenges in meeting reproductive health and family planning goals underscore the value in determining what factors can be leveraged to facilitate modern contraceptive use, especially in poor access settings. In Mali, where only 15% of reproductive-aged women use modern contraception, understanding how women's realities and health system design influence contraceptive use helps to inform strategies to achieve the nation's target of 30% by 2023.MethodsUsing household survey data from the baseline round of a cluster-randomized trial, including precise geolocation data from all households and public sector primary health facilities, we used a multilevel model to assess influences at the individual, household, community, and health system levels on women's modern contraceptive use. In a three-level, mixed-effects logistic regression, we included measures of women's decision-making and mobility, as well as socio-economic sources of empowerment (education, paid labor), intrahousehold influences in the form of a co-residing user, and structural factors related to the health system, including distance to facility.ResultsLess than 5% of the 14,032 women of reproductive age in our study used a modern method of contraception at the time of the survey. Women who played any role in decision-making, who had any formal education and participated in any paid labor, were more likely to use modern contraception. Women had three times the odds of using modern contraception if they lived in a household with another woman, typically a co-wife, who also used a modern method. Compared to women closest to a primary health center, those who lived between 2 and 5 km were half as likely to use modern contraception, and those between 5 and 10 were a third as likely.ConclusionsDespite chronically poor service availability across our entire study area, some women-even pairings of women in single households-transcended barriers to use modern contraception. When planning and implementing strategies to expand access to contraception, policymakers and practitioners should consider women's empowerment, social networks, and health system design. Accessible and effective health systems should reconsider the conventional approach to community-based service delivery, including distance as a barrier only beyond 5 km.

BackgroundRural parts of Mali carry a disproportionate burden of the country's high under-five mortality rate. A range of household factors are associated with poor under-five health in resource-limited settings. However, it is unknown which most influence the under-five mortality rate in rural Mali. We aimed to describe household factors associated with under-five mortality in Bankass, a remote region in central Mali.MethodsWe analysed baseline household survey data from a trial being conducted in Bankass. The survey was administered to households between December 2016 and January 2017. Under-five deaths in the five years prior to baseline were documented along with detailed information on household factors and women's birth histories. Factors associated with under-five mortality were analysed using Cox regression.ResultsOur study population comprised of 17,408 under-five children from 8322 households. In the five years prior to baseline, the under-five mortality rate was 152.6 per 1000 live births (158.8 and 146.0 per 1000 live births for males and females, respectively). Living a greater distance from a primary health center was associated with a higher probability of under-five mortality for both males (adjusted hazard ratio [aHR] 1.53 for ≥10 km versus

Adolescent and young adult women in sub-Saharan Africa experience barriers to sexual and reproductive health (SRH) services that elevate their risk of human immunodeficiency virus (HIV) acquisition and unintended pregnancy. Community drug shops may be effective distribution points to connect young women with SRH products. Thus, we used human-centred design (HCD) to create drug shops where young women could access HIV self-testing and contraception in Shinyanga, Tanzania. Enhancing the HCD process with behavioural science, we collected diverse data (i.e. 18 in-depth interviews, 9 'shadowing' interviews, 6 shop observations, 6 focus groups) to understand the latent needs and motivations of young women and drug shopkeepers, brainstormed creative solutions and iteratively refined and tested solutions for acceptability, feasibility and cultural fit. We found a widespread moral imperative to control young women's behaviour via misinformation about SRH, community gossip and financial control. Young women often engaged in mundane shopping at the behest of others. At drug shops, few SRH products were deemed appropriate for unmarried women, and many reactively sought SRH products only after engaging in higher risk behaviours. In response to these insights, we designed the 'Malkia Klabu' ('Queen Club') loyalty programme through which young women could earn mystery prizes by shopping at drug shops and discreetly request free SRH products, including HIV self-test kits, by pointing at symbols on loyalty cards. Our HCD approach increases the likelihood that the intervention will address the specific needs and preferences of both drug shopkeepers and young women. We will evaluate its effectiveness in a randomized trial.

Proactive community case management (ProCCM) has shown promise to advance goals of universal health coverage (UHC). ProCCM community health workers (CHWs) face operational challenges when pursuing their goal of visiting every household in their service area at least twice monthly to proactively find sick patients. We developed a software extension (UHC Mode) to an existing CHW mobile application featuring user interface design improvements to support CHWs in planning daily home visits. We evaluated the effect of UHC Mode on minimum expected home visit coverage. We conducted a parallel-group, two-arm randomised controlled trial of ProCCM CHWs in two separate regions in Mali. CHWs were randomly assigned to UHC Mode or the standard mobile application (control) with a 1:1 allocation. Randomisation was stratified by health catchment area. CHWs and other programme personnel were not masked to arm allocation. CHWs used their assigned intervention for 4 months. Using a difference-in-differences analysis, we estimated the mean change in minimum expected home visit coverage from preintervention to postintervention between arms. Enrolment occurred in January 2019. Of 199 eligible CHWs randomised to the intervention or control arm, 196 were enrolled and 195 were included in the analysis. Households whose CHW used UHC Mode had 2.41 times higher odds of minimum expected home visit coverage compared with households whose CHW used the control (95% CI 1.68 to 3.47; p

The coronavirus disease 2019 (COVID-19) pandemic revealed systemic weaknesses in health-care systems worldwide. The breadth of challenges left health workers overwhelmed and overstretched, reducing their professional efficacy and causing long-term [...]

BackgroundHealth workforce planning is critical for health systems to safeguard the ability to afford, train, recruit, and retain the appropriate number and mix of health workers. This balance is especially important when macroeconomic structures are also reforming. The Kingdom of Saudi Arabia is moving toward greater diversification, privatization, and resiliency; health sectorreform is a key pillar of this transition.MethodsWe used the Ministry of Health Yearbook data on the number of workers and health expenditures from 2007 to 2018 and projected health labor market supply and demand of workers through 2030, evaluated the potential shortages and surpluses, and simulated different policy scenarios to identify relevant interventions. We further focused on projections for health workers who are Saudi nationals and health worker demand within the public sector (versus the private sector) to inform national objectives of reducing dependency on foreign workers and better deploying public sector resources.ResultsWe projected the overall health labor market to demand 9.07 physicians and nurses per 1,000 population (356,514) in 2030; the public sector will account for approximately 67% of this overall demand. Compared to a projected supply of 10.16 physicians and nurses per 1,000 population (399,354), we estimated an overall modest surplus of about 42,840 physicians and nurses in 2030. However, only about 17% of these workers are estimated to be Saudi nationals, for whom there will be a demand shortage of 287,895 workers. Among policy scenarios considered, increasing work hours had the largest effect on reducing shortages of Saudi workers, followed by bridge programs for training more nurses. Government resources can also be redirected to supporting more Saudi nurses while still ensuring adequate numbers of physicians to meet service delivery goals in 2030.ConclusionDespite projected overall balance in the labor market for health workers in 2030, without policy interventions, severe gaps in the Saudi workforce will persist and limit progress toward health system resiliency in Saudi Arabia. Both supply- and demand-side policy interventions should be considered, prioritizing those that increase productivity among Saudi health workers, enhance training for nurses, and strategically redeploy financial resources toward employing these workers.

ObjectivesTo identify social and structural barriers to timely utilisation of qualified providers among children under five years in a high-mortality setting, rural Mali and to analyse how utilisation varies by symptom manifestation.MethodsUsing baseline household survey data from a cluster-randomised trial, we assessed symptom patterns and healthcare trajectories of 5117 children whose mothers reported fever, diarrhoea, bloody stools, cough and/or fast breathing in the preceding two weeks. We examine associations between socio-demographic factors, symptoms and utilisation outcomes in mixed-effect logistic regressions.ResultsAlmost half of recently ill children reported multiple symptoms (46.2%). Over half (55.9%) received any treatment, while less than one-quarter (21.7%) received care from a doctor, nurse, midwife, trained community health worker or pharmacist within 24 h of symptom onset. Distance to primary health facility, household wealth and maternal education were consistently associated with better utilisation outcomes. While children with potentially more severe symptoms such as fever and cough with fast breathing or diarrhoea with bloody stools were more likely to receive any care, they were no more likely than children with fever to receive timely care with a qualified provider.ConclusionsEven distances as short as 2-5 km significantly reduced children's likelihood of utilising healthcare relative to those within 2 km of a facility. While children with symptoms indicative of pneumonia and malaria were more likely to receive any care, suggesting mothers and caregivers recognised potentially severe illness, multiple barriers to care contributed to delays and low utilisation of qualified providers, illustrating the need for improved consideration of barriers.

BackgroundPublic health initiatives must look for ways to cost-effectively scale critical interventions to achieve high coverage. Private sector distribution channels, can potentially distribute preventive healthcare products to hard-to-reach populations, decongest public healthcare systems, and increase the sustainability of programs by getting customers to share costs. However, little is known about how sellers set prices for new products. By introducing a new product, HIV self-test kits, to local drug shops, we observed whether shops experimented with pricing, charged different buyers different prices, and whether prices converged within the local market over our study period.MethodsFrom August to December 2019, we provided free HIV self-test kits, a new product, to 26 drug shops in Shinyanga, Tanzania to sell to the local community. We measured sales volume, price, customer age and sex using shop records. Using a multiple linear regression model, we conducted F-tests to determine whether shop, age, sex, and time (week) respectively were associated with price. We measured willingness-to-pay to restock test kits at the end of the study.Results514 test kits were sold over 18 weeks; 69% of buyers were male, 40% were aged 25-34 and 32% aged 35-44. Purchase prices ranged from 1000 to 6000 Tsh (median 3000 Tsh; ~$1.30 USD). Within shops, prices were 11.3% higher for 25-34 and 12.7% higher for 45+ year olds relative to 15-19-year olds (p = 0.029) and 13.5% lower for men (p = 0.023) on average. Although prices varied between shops, prices varied little within shops over time, and did not converge over the study period or cluster geospatially. Mean maximum willingness-to-pay to restock was 2000 Tsh per kit.ConclusionsShopkeepers charged buyers different prices depending on buyers' age and sex. There was limited variation in prices within shops over time and low demand among shopkeepers to restock at the end of the study. Given the subsidized global wholesale price ($2 USD or ~ 4600 Tsh), further demand creation and/or cost-reduction is required before HIV self-test kits can become commercially viable in drug shops in this setting. Careful consideration is needed to align the motivations of retailers with public health priorities while meeting their private for-profit needs.

BackgroundThe Kingdom of Saudi Arabia (KSA), as part of its 2030 National Transformation Program, set a goal of transforming the healthcare sector to increase access to, and improve the quality and efficiency of, health services. To assist with the workforce planning component, we projected the needed number of physicians and nurses into 2030. We developed a new needs-based methodology since previous global benchmarks of health worker concentration may not apply to the KSA.MethodsWe constructed an epidemiologic "needs-based" model that takes into account the health needs of the KSA population, cost-effective treatment service delivery models, and worker productivity. This model relied heavily on up-to-date epidemiologic and workforce surveys in the KSA. We used demographic population projections to estimate the number of nurses and physicians needed to provide this core set of services into 2030. We also assessed several alternative scenarios and policy decisions related to scaling, task-shifting, and enhanced public health campaigns.ResultsWhen projected to 2030, the baseline needs-based estimate is approximately 75,000 workers (5788 physicians and 69,399 nurses). This workforce equates to 2.05 physicians and nurses per 1000 population. Alternative models based on different scenarios and policy decisions indicate that the actual needs for physicians and nurses may range from 1.64 to 3.05 per 1000 population in 2030.ConclusionsBased on our projections, the KSA will not face a needs-based health worker shortage in 2030. However, alternative model projections raise important policy and planning issues regarding various strategies the KSA may pursue in improving quality and efficiency of the existing workforce. More broadly, where country-level data are available, our needs-based strategy can serve as a useful step-by-step workforce planning tool to complement more economic demand-based workforce projections.

BackgroundHIV risk remains high among adolescent girls and young women (AGYW, ages 15-24) in Tanzania. Many AGYW experience stigma and provider bias at health facilities, deterring their use of HIV prevention services. Privately-owned drug shops, ubiquitous in many communities, may be an effective and accessible channel to deliver HIV prevention products to AGYW, including oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring.MethodsIn July-August 2019, we enrolled 26 drug shops in Shinyanga, Tanzania in an ongoing study to create "girl-friendly" drug shops where AGYW can access HIV self-testing and contraception. At baseline, all shop dispensers were given basic information about oral PrEP and the dapivirine ring and were asked about their interest in stocking each. During the next 3-5 months, we surveyed AGYW (n = 56) customers about their interest in oral PrEP and the ring.ResultsAmong dispensers, the median age was 42 years and 77% were female. Overall, 42% of dispensers had heard of a medication for HIV prevention. Almost all dispensers reported some interest in stocking oral PrEP (92%) and the dapivirine ring (96%). Most (85%) reported they would provide oral PrEP to AGYW who requested it. Among AGYW customers, the median age was 17 years; 29% of AGYW were married or had a steady partner and 18% had children. Only 20% of AGYW had heard of a medication to prevent HIV, yet 64% and 43% expressed some interest in using oral PrEP and the dapivirine ring, respectively, after receiving information about the products. PrEP interest was higher among AGYW who were partnered and had children.ConclusionsDespite low prior awareness of PrEP among shop dispensers and AGYW, we found high levels of interest in oral PrEP and the dapivirine ring in both groups. Community-based drug shops represent a promising strategy to make HIV prevention more accessible to AGYW.

Abstract Background: HIV risk remains high among adolescent girls and young women (AGYW, ages 15-24) in Tanzania. Many AGYW experience stigma and provider bias at health facilities, deterring their use of HIV prevention services. Privately-owned drug shops, ubiquitous in many communities, may be an effective and accessible channel to deliver HIV prevention products to AGYW, including oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring. Methods: In July-August 2019, we enrolled 26 drug shops in Shinyanga, Tanzania in an ongoing study to create “girl-friendly” drug shops where AGYW can access HIV self-testing and contraception. At baseline, all shop dispensers were given basic information about oral PrEP and the dapivirine ring and were asked about their interest in stocking each. During the next 3-5 months, we surveyed AGYW (n=56) customers about their interest in oral PrEP and the ring. Results: Among dispensers, the median age was 42 years and 77% were female. Overall, 42% of dispensers had heard of a medication for HIV prevention. Almost all dispensers reported some interest in stocking oral PrEP (92%) and the dapivirine ring (96%). Most (85%) reported they would provide oral PrEP to AGYW who requested it. Among AGYW customers, the median age was 17 years; 18% of AGYW were married and 7% had children. Only 20% of AGYW had heard of a medication to prevent HIV, yet 64% and 43% expressed some interest in using oral PrEP and the dapivirine ring, respectively, after receiving information about the products. PrEP interest was higher among AGYW who were partnered and had children.Conclusions: Despite low prior awareness of PrEP among shop dispensers and AGYW, we found high levels of interest in oral PrEP and the dapivirine ring in both groups. Community-based drug shops represent a promising strategy to make HIV prevention more accessible to AGYW.

BackgroundEffective prevention-focused, value-based strategies are needed to improve oral health. Despite evidence that monetary incentives can motivate healthy behavior, well-powered studies have yet to examine incentives for improving children's oral hygiene.AimDescribe the rationale and design of the BEhavioral EConomics for Oral health iNnovation (BEECON) trial, which tests lottery-based monetary incentives as a consumer-oriented, value-based care model for improving children's oral hygiene.DesignPhase II, stratified, permuted block randomized, controlled, two-arm, parallel groups, prevention trial.SettingStudy visits occur at three Los Angeles, CA health clinics.ParticipantsTwo hundred and forty-four parent-child dyads with a child aged 6-48 months.InterventionsEligible dyads were randomized in equal allocation to one of two groups: lottery incentive group or waitlist (delayed incentive) control group. Weekly lottery incentives were offered for 6 months based on Bluetooth-recorded toothbrushing frequency. Both groups received weekly text message feedback on toothbrushing performance.OutcomesThe primary outcome was toothbrushing performance from baseline to 6 months, measured as the mean number of qualifying half-day Bluetooth-recorded episodes per week when the child's teeth were brushed. Secondary outcomes included toothbrushing performance sustainability through 12 months and dental caries status.ConclusionsBEECON offers a consumer-oriented approach to promoting value-based oral health care. We hypothesize that lottery-based incentives can improve oral hygiene in young children. Study results will inform programming efforts to enhance oral disease prevention in young children.Trial registrationClinicalTrials.gov identifier NCT03576326.

Protests are one of the most common expressions of modern political conflict, and the wave of demonstrations that marked the onset of the Arab Spring contributed to a global increase in protest activity. Yet few studies have examined the effects of exposure to protests on population well-being even though such exposure may have profound and lasting effects, especially if experienced at critical stages of development over the life course. The aim of our study is to estimate the effects of exposure to political protests on the human capital accumulation and well-being of youth during the tumultuous political transition experienced in Egypt from 2011 to 2014. For a nationally representative panel of youth captured in the 2009 and 2013/2014 waves of the Survey of Young People in Egypt (SYPE), we exploit exogenous geospatial variation in the occurrence of political protests from the Armed Conflict Location & Event Data (ACLED) Project to estimate individual-level changes in social trust, uncertainty, education, and health outcomes for youth exposed to protests. In our panel, 31.1% of the sample lived in districts where riots or protests occurred. Exposure to protests increased overall perceptions of uncertainty about the future. Young men ever exposed to protests were slightly more likely to report good overall health, but experienced sizable worsening in mental health compared to young women ever exposed. Differences by own and family participation in protest events were found for perceptions of uncertainty and mental health. In the aftermath of the Arab Spring and other mass protest movements around the globe, these findings highlight the importance of examining the population-level impacts of different forms of political conflict, particularly as substantial numbers of youth in Middle East and North Africa and elsewhere progress to adulthood under conditions of political instability.