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In this article, we unravel an extension of shifted version of Lindley distribution, termed as extended generalized shifted Lindley (EGSL) distribution. Stochastic ordering, moment generating function, reliability characteristics and other relevant properties are studied for this distribution. To estimate the parameters involved, method of maximum likelihood is performed. A detailed simulation study for several choices of parameters is executed as well. Finally, as a comparative exploration, possible fitting of the proposed distribution to a real data along with model fitting by other competent distributions is documented through the aid of a few model checking criteria.

Background: The prevalence of household violence in low- and middle-income countries (LMICs) is high, and exposure to violence has significant adverse effects on both mental health and child development across generations. Evidence-based services to improve parenting practices and reduce household violence in LMICs are scarce, particularly across rural regions of West Africa. This study explored the feasibility, acceptability, and potential benefits of an evidence-based home-visiting intervention to promote early childhood development and reduce household violence-the Family Strengthening Intervention for Early Childhood Development and Violence-Prevention (FSI-ECD + VP)-among vulnerable families in rural regions of Sierra Leone., Methods: Eighty dual-caregiver households in the Makeni region of Sierra Leone were included in the study (N = 160 caregivers; 73% female). Eligibility criteria included having at least one child aged 6-36 months and elevated scores (> 62.5) on the Difficulties in Emotion Regulation Scale (DERS). Community Health Workers (CHWs) employed in the Makeni region completed a 3-week FSI-ECD + VP training. Families were randomized to receive either the FSI-ECD + VP or treatment as usual (TAU). Research assistants blinded to treatment assignment assessed caregiver mental health, caregiver-child interactions, and household violence at baseline, post-intervention, and 3-month follow-up time points., Results: Triangulation of quantitative and qualitative data showed that caregivers, CHWs, and supervisors generally perceived the intervention as beneficial, feasible, and acceptable. Mixed effects models showed that caregivers who received the FSI-ECD + VP had significantly improved caregiver-child relationship outcomes compared to TAU as assessed by the Home Observation for Measurement of the Environment and the Observation of Caregiver-Child Interactions at post-intervention. Preliminary data also suggests that caregivers receiving the FSI-ECD + VP were less likely to have experienced intimate partner physical violence during the post-intervention period, and had lower symptoms of anxiety and depression at 3-month follow-up., Conclusions: FSI-ECD + VP delivery by CHWs in Sierra Leone may be feasible and acceptable; it may also help improve caregiver-child interactions and reduce the likelihood of household violence among vulnerable families with young children. Task-sharing approaches may help increase acceptability and access to evidence-based behavioral interventions that promote early childhood development and violence prevention among families in rural regions of Sierra Leone and other similar settings., Trial Registration: The study is registered in clinicaltrials.gov (NCT03045640; 07/22/2020). This study follows the Consort 2010 guidelines for reporting of clinical trials., Competing Interests: Declarations Ethics approval and consent to participate This study received ethical approval from the Boston College Institutional Review Board and the Sierra Leone Ethics and Scientific Review Committee. All participants will provide informed consent prior to their enrollment and participation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemisinin-based Combination Therapy (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that mRDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Trials registration: Clinical Trials Registration Number: NCT04428307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816435/ Correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476591/., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Visser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

ACTs are responsible for a substantial proportion of the global reduction in malaria mortality over the last ten years, made possible by publicly-funded subsidies making these drugs accessible and affordable in the private sector. However, inexpensive ACTs available in retail outlets have contributed substantially to overconsumption. We test an innovative, scalable strategy to target ACT-subsidies to clients with a confirmatory diagnosis. We supported malaria testing(mRDTs) in 39 medicine outlets in western Kenya, randomized to three study arms; control arm offering subsidized mRDT testing (0.4USD), client-directed intervention where all clients who received a positive RDT at the outlet were eligible for a free (fully-subsidized) ACT, and a combined client and provider directed intervention where clients with a positive RDT were eligible for free ACT and outlets received 0.1USD for every RDT performed. Our primary outcome was the proportion of ACT dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients tested at the outlet and adherence to diagnostic test results. 43% of clients chose to test at the outlet. Test results informed treatment decisions, resulting in targeting of ACTs to confirmed malaria cases- 25.3% of test-negative clients purchased an ACT compared to 75% of untested clients. Client-directed and client+provider-directed interventions did not offer further improvements, compared to the control arm, in testing rates(RD = 0.09, 95%CI:-0.08,0.26) or dispensing of ACTs to test-positive clients(RD = 0.01,95% CI:-0.14, 0.16). Clients were often unaware of the price they paid for the ACT leading to uncertainty in whether the ACT subsidy was passed on to the client. This uncertainty undermines our ability to definitively conclude that client-directed subsidies are not effective for improving testing and appropriate treatment. We conclude that mRDTs could reduce ACT overconsumption in the private retail sector, but incentive structures are difficult to scale and their value to private providers is uncertain. Trial registration: ClinicalTrials.gov NCT04428307., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Laktabai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is limited information regarding the intergenerational transmission of mental health among three generations (i.e., grandparents, parents, and children) of Black families. Given that intergenerational and kinship ties are integral in Black families, this study explores the context that might contribute to the generational transmission of mental health among Black families., Methods: The present study examined the retrospective family history of mental health among fathers and mothers, current reports of their depression, and their children's internalizing and depressive symptoms among a sample of 2530 Black families from the Future of Families and Child Wellbeing Study using waves 4 to 6. All analyses were conducted using STATA 15.1., Results: Focal children's maternal and paternal grandparents' history of mental health was associated with higher odds of depression in their mothers and fathers; in addition, child-internalizing symptoms were associated with a report of depression in maternal grandparents in waves 4 and 5. Children of mothers who were depressed had higher internalizing scores in waves 4, 5, and 6., Limitations: This descriptive study did not account for how parenting might also be protective against childhood internalizing behaviors. A retrospective account may not fully encapsulate a complete understanding of mental health patterns., Conclusions: In treating the mental and behavioral health of Black families, it is essential to focus on multiple generations of family health, given that family history is the strongest predictor of the youth's onset of depression. The utility of these findings in understanding psychological distress and strengths among Black families is discussed., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Guidelines recommend that all children and adolescents with hypertension undergo evaluation for secondary causes. Identifying clinical factors associated with secondary hypertension may decrease unnecessary testing for those with primary hypertension., Objective: To determine the utility of the clinical history, physical examination, and 24-hour ambulatory blood pressure monitoring for differentiating primary hypertension from secondary hypertension in children and adolescents (aged ≤21 years)., Data Sources and Study Selection: The databases of MEDLINE, PubMed Central, Embase, Web of Science, and Cochrane Library were searched from inception to January 2022 without language limits. Two authors identified studies describing clinical characteristics in children and adolescents with primary and secondary hypertension., Data Extraction and Synthesis: For each clinical finding in each study, a 2 × 2 table was created that included the number of patients with and without the finding who had primary vs secondary hypertension. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool., Main Outcomes and Measures: Random-effects modeling was used to calculate sensitivity, specificity, and likelihood ratios (LRs)., Results: Of 3254 unique titles and abstracts screened, 30 studies met inclusion criteria for the meta-analysis and 23 (N = 4210 children and adolescents) were used for pooling in the meta-analysis. In the 3 studies conducted at primary care clinics or school-based screening clinics, the prevalence of secondary hypertension was 9.0% (95% CI, 4.5%-15.0%). In the 20 studies conducted at subspecialty clinics, the prevalence of secondary hypertension was 44% (95% CI, 36%-53%). The demographic findings most strongly associated with secondary hypertension were family history of secondary hypertension (sensitivity, 0.46; specificity, 0.90; LR, 4.7 [95% CI, 2.9-7.6]), weight in the 10th percentile or lower for age and sex (sensitivity, 0.27; specificity, 0.94; LR, 4.5 [95% CI, 1.2-18]), history of prematurity (sensitivity range, 0.17-0.33; specificity range, 0.86-0.94; LR range, 2.3-2.8), and age of 6 years or younger (sensitivity range, 0.25-0.36; specificity range, 0.86-0.88; LR range, 2.2-2.6). Laboratory studies most associated with secondary hypertension were microalbuminuria (sensitivity, 0.13; specificity, 0.99; LR, 13 [95% CI, 3.1-53]) and serum uric acid concentration of 5.5 mg/dL or lower (sensitivity range, 0.70-0.73; specificity range, 0.65-0.89; LR range, 2.1-6.3). Increased daytime diastolic blood pressure load combined with increased nocturnal systolic blood pressure load on 24-hour ambulatory blood pressure monitoring was associated with secondary hypertension (sensitivity, 0.40; specificity, 0.82; LR, 4.8 [95% CI, 1.2-20]). Findings associated with a decreased likelihood of secondary hypertension were asymptomatic presentation (LR range, 0.19-0.36), obesity (LR, 0.34 [95% CI, 0.13-0.90]), and family history of any hypertension (LR, 0.42 [95% CI, 0.30-0.57]). Hypertension stage, headache, and left ventricular hypertrophy did not distinguish secondary from primary hypertension., Conclusions and Relevance: Family history of secondary hypertension, younger age, lower body weight, and increased blood pressure load using 24-hour ambulatory blood pressure monitoring were associated with a higher likelihood of secondary hypertension. No individual sign or symptom definitively differentiates secondary hypertension from primary hypertension.

Objectives: To examine how drug shop clients' expenditures are affected by subsidies for malaria diagnostic testing and for malaria treatment, and also to examine how expenditures vary by clients' malaria test result and by the number of medications they purchased., Design: Secondary cross-sectional analysis of survey responses from a randomised controlled trial., Setting: The study was conducted in twelve private drug shops in Western Kenya., Participants: We surveyed 836 clients who visited the drug shops between March 2018 and October 2019 for a malaria-like illness. This included children >1 year of age if they were physically present and accompanied by a parent or legal guardian., Interventions: Subsidies for malaria diagnostic testing and for malaria treatment (conditional on a positive malaria test result)., Primary and Secondary Outcome Measures: Expenditures at the drug shop in Kenya shillings (Ksh)., Results: Clients who were randomised to a 50% subsidy for malaria rapid diagnostic tests (RDTs) spent approximately Ksh23 less than those who were randomised to no RDT subsidy (95% CI (-34.6 to -10.7), p=0.002), which corresponds approximately to the value of the subsidy (Ksh20). However, clients randomised to receive free treatment (artemisinin combination therapies (ACTs)) if they tested positive for malaria had similar spending levels as those randomised to a 67% ACT subsidy conditional on a positive test. Expenditures were also similar by test result, however, those who tested positive for malaria bought more medications than those who tested negative for malaria while spending approximately Ksh15 less per medication (95% CI (-34.7 to 3.6), p=0.102)., Conclusions: Our results suggest that subsidies for diagnostic health products may result in larger household savings than subsidies on curative health products. A better understanding of how people adjust their behaviours and expenditures in response to subsidies could improve the design and implementation of subsidies for health products., Trial Registration Number: NCT03810014., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Low adoption of effective health technologies increases illness morbidity and mortality worldwide. In the case of malaria, effective tools such as malaria rapid diagnostic tests (RDTs) and artemisinin-combination therapies (ACTs) are both under-used and used inappropriately. Individuals' confidence in RDTs and ACTs likely affects the uptake of these tools., Methods: In a cohort of 36 households (280 individuals) in Western Kenya observed for 30 months starting in June 2017, we examined if experience with RDTs and ACTs changes people's beliefs about these technologies and how those beliefs affect treatment behavior. Household members requested a free RDT from the study team any time they suspected a malaria illness, and positive RDT results were treated with a free ACT. We conducted annual, monthly, and sick visit surveys to elicit beliefs about the accuracy of malaria RDT results and the effectiveness of ACTs. Beliefs were elicited on a 5-point Likert scale from "very unlikely" to "very likely.", Results: Over the study period, the percentage of survey respondents that said a hypothetical negative RDT result was "very likely" to be correct increased from approximately 55% to 75%. Controlling for initial beliefs, people who had been tested at least once with an RDT in the past year had 3.6 times higher odds (95% CI [1 1.718 7.679], P = 0.001) of saying a negative RDT was "very likely" to be correct. Confidence in testing was associated with treatment behavior: those who believed a negative RDT was "very likely" to be correct had 1.78 times higher odds (95% CI [1.079 2.934], P = 0.024) of adhering to a negative RDT result (by not taking ACTs) than those who were less certain about the accuracy of negative RDTs. Adherence to a negative test also affected subsequent beliefs: controlling for prior beliefs, those who had adhered to their previous test result had approximately twice the odds (OR = 2.19, 95% CI [1.661 2.904], P < 0.001) of saying that a hypothetical negative RDT was "very likely" to be correct compared to those who had not adhered., Conclusions: Our results suggest that greater experience with RDTs can not only increase people's confidence in their accuracy but also improve adherence to the test result., (© 2022. The Author(s).)

Objective: The objective was to describe the relationship between the location of care, the malaria test result, and the type of medicine consumed for the fever, and to determine whether community-based access to malaria testing reduced polypharmacy . Methods: This is a secondary analysis of a cluster-randomized trial of an intervention designed to increase diagnostic testing and targeting of Artemesinin Combined Therapies (ACTs). Data collected at baseline, 12, and 18 months were analyzed to determine the impact of diagnostic testing on drug consumption patterns among febrile individuals. Results: Of the 5,756 participants analyzed, 60.1% were female, 42% were aged 5-17 years, and 58.1% sought care for fever in a retail outlet. Consumption of both ACT and antibiotics was 22.1% ( n = 443/2008) at baseline. At endline, dual consumption had declined to 16.6%. There was reduced antibiotic consumption among those testing positive for malaria (39.5%-26.5%) and those testing negative (63.4%-55.1%), accompanied by a substantial decline in ACT use among malaria-negative participants. Conclusion: Diagnostic testing for malaria reduces dual consumption of ACTs and antibiotics, especially among those testing outside the formal healthcare sector., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laktabai, Platt, Turner, Saran, Kipkoech, Menya and O’Meara.)

Objective: To estimate the prevalence of secondary hypertension among otherwise healthy children with hypertension diagnosed in the outpatient setting., Study Design: The MEDLINE, PubMed Central, Embase, Web of Science, and Cochrane Library databases were systematically searched for observational studies reporting the prevalence of secondary hypertension in children who underwent evaluation for hypertension and had no known comorbidities associated with hypertension at the time of diagnosis. Two authors independently extracted the study-specific prevalence of secondary hypertension in children evaluated for hypertension. Prevalence estimates for secondary hypertension were pooled in a random-effects meta-analysis., Results: Nineteen prospective studies and 7 retrospective studies including 2575 children with hypertension were analyzed, with a median of 65 participants (range, 9-486) in each study. Studies conducted in primary care or school settings reported a lower prevalence of secondary hypertension (3.7%; 95% CI, 1.2%-7.2%) compared with studies conducted in referral clinics (20.1%; 95% CI, 11.5%-30.3%). When stratified by study setting, there were no significant subgroup differences according to study design, country, participant age range, hypertension definition, blood pressure device, or study quality. Although the studies applied different approaches to diagnosing secondary hypertension, diagnostic evaluations were at least as involved as the limited testing recommended by current guidelines., Conclusions: The low prevalence of secondary hypertension among children with a new diagnosis of hypertension identified on screening reinforces clinical practice guidelines to avoid extensive testing in the primary care setting for secondary causes in most children with hypertension., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Availability of long-acting reversible contraception (LARC) is an important indicator of high-quality women's health care. There are limited data on the impact of state-level Medicaid eligibility changes on LARC use., Study Design: We used All-Payers Claims Databases to examine LARC insertions among women enrolled in Medicaid in Massachusetts, which expanded Medicaid in 2014, and Maine, which restricted Medicaid eligibility in 2013. We used interrupted time series (ITS) analyses to determine the impact of Medicaid eligibility changes on level and trends in LARC insertions in these states., Results: In Massachusetts, graphical evidence demonstrates that after Medicaid expansion, there was an immediate increase in mean monthly LARC insertions and insertions per 1000 enrollees. In ITS regression adjusting for age, LARC insertions per enrollee increased immediately after Medicaid expansion by 32% (P<0.001). After expansion, as the number of enrollees continued to rise, mean monthly LARC insertions rose, but there was a slightly decreasing trend in insertions per enrollee by 1% per month (P<0.001). In Maine, graphical evidence shows that initial reductions in Medicaid eligibility were associated with an immediate drop in LARC insertion numbers and rates per 1000, with ITS regression demonstrating an immediate 17% drop in insertions per enrollee (P<0.001). As Maine's Medicaid enrollment declined from 2013 to 2015, the number of LARC insertions remained flat, leading to an increasing trend in insertions per enrollee, similar to pre-2013 trends (P=0.17)., Conclusions: Medicaid eligibility changes were associated with immediate changes in LARC uptake. Medicaid expansion may help ensure access to this effective contraceptive method., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: About 10% of children worldwide do not live with either of their biological parents, and although some of these children are orphans, many have living parents. While research shows that orphaned children in Sub-Saharan Africa tend to engage in more sexual risk behaviors than their peers, possibly due to decreased parental oversight and support, it is unclear if these effects also apply to children separated from their living parents. Exploring the question of whether living without parents, regardless of whether they are deceased, is linked to greater sexual risk-taking, this study is the first, to our knowledge, to examine correlates of parental care status in a multi-country, nationally-representative analysis., Methods: This study was a secondary analysis of the Centers for Disease Control and Prevention's Violence Against Children Surveys from Kenya, Malawi, Tanzania, Nigeria, and Zambia. We conducted logistic regressions on N = 6770 surveys of youth aged 13 to 17 years to determine if living with their biological parents predicted the odds of engaging in risky sexual behavior, controlling for demographic factors including orphanhood. Post-hoc regressions examined specific risk behaviors., Results: Compared to those living with both parents, youth not living with either parent had heightened odds of engaging in any sexual risk behavior, even when controlling for orphanhood (OR = 2.56, 95% CI: [1.96, 3.33]). Non-parental care predicted heightened odds of non-condom use (OR = 3.35, 95% CI: [2.38, 4.72]), early sexual debut (OR = 1.80, 95% CI: [1.31, 2.46]), and more sexual partners (β = .60, p < .001)., Conclusions: This study extends prior research linking orphanhood and sexual risk behavior, lending credence to the idea that it is not parental death, but rather parental absence, that leads to sexual risk in youth. Public health programming in Sub-Saharan Africa should consider targeting not only "orphaned youth," but all children separated from their parents., (© 2021. The Author(s).)

Background: Depression affects approximately 7.5 million parents in the United States each year. Parental depression has detrimental consequences for both the parent and the parent-child relationship. The purpose of this study was to: (1) understand the prevalence of parental depressive episodes longitudinally, (2) identify the risk and protective factors for parental depressive episodes, and (3) compare the risk and protective factors for depressive episodes among mothers and fathers., Methods: We used six waves of the Fragile Families and Child Wellbeing Study to descriptively examine parental depression over a period of 15 years. We used logistic and fixed effects regressions to assess the association between a number of demographic, health and parenting variables and maternal and paternal depression., Results: Our sample was primarily Black (48%) and Hispanic/Latino (27%). Fathers had a slightly lower prevalence of depression compared to mothers at all waves (approximately 13% averaged across waves for fathers, compared to 18% for mothers). Factors negatively correlated with depression among mothers and fathers included: social support, employment, and better-perceived health. Factors positively associated with depression for mothers and fathers were substance misuse and having a parent with a history of depression, anxiety, or drug misuse., Limitations: Our study was unable to identify causal relationships and the directionality of the relationship between depression and other variables of interest., Conclusions: We found that parental depression is prevalent in a sample of predominantly racially minoritized parents. Addressing comorbidities and increasing social support access may help manage parental depression and ensure a healthy child development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: F.P. Wilson reports consultancy agreements with Translational Catalyst, LLC; reports having an ownership interest in Efference, LLC; reports being a scientific advisor or member of the Editorial Board American Journal of Kidney Disease and CJASN; and reports other interests/relationships through the Board of Directors of Gaylord Health Care and Medical Commentator of Medscape. All remaining authors have nothing to disclose.

Background: A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria., Methods: This study comprises two linked four-arm 2 × 2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider-directed and client-directed interventions. The linked trials will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT-at a study-recommended price-to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client-directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets., Results: The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes, we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet., Conclusions: If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria., Trial Registration: ClinicalTrials.gov NCT04428307 , registered June 9, 2020, and NCT04428385 , registered June 9, 2020.

Rationale & Objective: Acute kidney injury (AKI) is diagnosed based on changes in serum creatinine concentration, a late marker of this syndrome. Algorithms that predict elevated risk for AKI are of great interest, but no studies have incorporated such an algorithm into the electronic health record to assist with clinical care. We describe the experience of implementing such an algorithm., Study Design: Prospective observational cohort study., Setting & Participants: 2,856 hospitalized adults in a single urban tertiary-care hospital with an algorithm-predicted risk for AKI in the next 24 hours>15%. Alerts were also used to target a convenience sample of 100 patients for measurement of 16 urine and 6 blood biomarkers., Exposure: Clinical characteristics at the time of pre-AKI alert., Outcome: AKI within 24 hours of pre-AKI alert (AKI 24 )., Analytical Approach: Descriptive statistics and univariable associations., Results: At enrollment, mean predicted probability of AKI 24 was 19.1%; 18.9% of patients went on to develop AKI 24 . Outcomes were generally poor among this population, with 29% inpatient mortality among those who developed AKI 24 and 14% among those who did not (P<0.001). Systolic blood pressure<100mm Hg (28% of patients with AKI 24 vs 18% without), heart rate>100 beats/min (32% of patients with AKI 24 vs 24% without), and oxygen saturation<92% (15% of patients with AKI 24 vs 6% without) were all more common among those who developed AKI 24 . Of all biomarkers measured, only hyaline casts on urine microscopy (72% of patients with AKI 24 vs 25% without) and fractional excretion of urea nitrogen (20% [IQR, 12%-36%] among patients with AKI 24 vs 34% [IQR, 25%-44%] without) differed between those who did and did not develop AKI 24 ., Limitations: Single-center study, reliance on serum creatinine level for AKI diagnosis, small number of patients undergoing biomarker evaluation., Conclusions: A real-time AKI risk model was successfully integrated into the EHR., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: In many malaria-endemic countries, the private retail sector is a major source of antimalarial drugs. However, the rarity of malaria diagnostic testing in the retail sector leads to overuse of the first-line class of antimalarial drugs known as artemisinin-combination therapies (ACTs). The goal of this study was to identify the combination of malaria rapid diagnostic test (RDT) and ACT subsidies that maximises the proportion of clients seeking care in a retail outlet that choose to purchase an RDT (RDT uptake) and use ACTs appropriately., Methods: 842 clients seeking care in 12 select retail outlets in western Kenya were recruited and randomised into 4 arms of different combinations of ACT and RDT subsidies, with ACT subsidies conditional on a positive RDT. The outcomes were RDT uptake (primary) and appropriate and targeted ACT use (secondary). Participants' familiarity with RDTs and their confidence in test results were also evaluated., Results: RDT uptake was high (over 96%) across the study arms. Testing uptake was 1.025 times higher (98% CI 1.002 to 1.049) in the RDT subsidised arms than in the unsubsidised groups. Over 98% of clients were aware of malaria testing, but only 35% had a previous experience with RDTs. Nonetheless, confidence in the accuracy of RDTs was high. We found high levels of appropriate use and targeting of ACTs, with 86% of RDT positives taking an ACT, and 93.4% of RDT negatives not taking an ACT. The conditional ACT subsidy did not affect the RDT test purchasing behaviour (risk ratio: 0.994; 98% CI 0.979 to 1.009)., Conclusion: Test dependent ACT subsidies may contribute to ACT targeting. However, in this context, high confidence in the accuracy of RDTs and reliable supplies of RDTs and ACTs likely played a greater role in testing uptake and adherence to test results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Appropriate clinical management of malaria in children is critical for preventing progression to severe disease and for reducing the continued high burden of malaria mortality. This study aimed to assess the quality of care provided to children under 5 diagnosed with malaria across 9 sub-Saharan African countries., Methods and Findings: We used data from the Service Provision Assessment (SPA) survey. SPAs are nationally representative facility surveys capturing quality of sick-child care, facility readiness, and provider and patient characteristics. The data set contained 24,756 direct clinical observations of outpatient sick-child visits across 9 countries, including Uganda (2007), Rwanda (2007), Namibia (2009), Kenya (2010), Malawi (2013), Senegal (2013-2017), Ethiopia (2014), Tanzania (2015), and Democratic Republic of the Congo (2018). We assessed the proportion of children with a malaria diagnosis who received a blood test diagnosis and an appropriate antimalarial. We used multilevel logistic regression to assess facility and provider and patient characteristics associated with these outcomes. Subgroup analyses with the 2013-2018 country surveys only were conducted for all outcomes. Children observed were on average 20.5 months old and were most commonly diagnosed with respiratory infection (47.7%), malaria (29.7%), and/or gastrointestinal infection (19.7%). Among the 7,340 children with a malaria diagnosis, 32.5% (95% CI: 30.3%-34.7%) received both a blood-test-based diagnosis and an appropriate antimalarial. The proportion of children with a blood test diagnosis and an appropriate antimalarial ranged from 3.4% to 57.1% across countries. In the more recent surveys (2013-2018), 40.7% (95% CI: 37.7%-43.6%) of children with a malaria diagnosis received both a blood test diagnosis and appropriate antimalarial. Roughly 20% of children diagnosed with malaria received no antimalarial at all, and nearly 10% received oral artemisinin monotherapy, which is not recommended because of concerns regarding parasite resistance. Receipt of a blood test diagnosis and appropriate antimalarial was positively correlated with being seen at a facility with diagnostic equipment in stock (adjusted OR 3.67; 95% CI: 2.72-4.95) and, in the 2013-2018 subsample, with being seen at a facility with Artemisinin Combination Therapies (ACTs) in stock (adjusted OR 1.60; 95% CI:1.04-2.46). However, even if all children diagnosed with malaria were seen by a trained provider at a facility with diagnostics and medicines in stock, only a predicted 37.2% (95% CI: 34.2%-40.1%) would have received a blood test and appropriate antimalarial (44.4% for the 2013-2018 subsample). Study limitations include the lack of confirmed malaria test results for most survey years, the inability to distinguish between a diagnosis of uncomplicated or severe malaria, the absence of other relevant indicators of quality of care including dosing and examinations, and that only 9 countries were studied., Conclusions: In this study, we found that a majority of children diagnosed with malaria across the 9 surveyed sub-Saharan African countries did not receive recommended care. Clinical management is positively correlated with the stocking of essential commodities and is somewhat improved in more recent years, but important quality gaps remain in the countries studied. Continued reductions in malaria mortality will require a bigger push toward quality improvements in clinical care., Competing Interests: The authors have declared that no competing interests exist.

Background: Timely prediction of AKI in children can allow for targeted interventions, but the wealth of data in the electronic health record poses unique modeling challenges., Methods: We retrospectively reviewed the electronic medical records of all children younger than 18 years old who had at least two creatinine values measured during a hospital admission from January 2014 through January 2018. We divided the study population into derivation, and internal and external validation cohorts, and used five feature selection techniques to select 10 of 720 potentially predictive variables from the electronic health records. Model performance was assessed by the area under the receiver operating characteristic curve in the validation cohorts. The primary outcome was development of AKI (per the Kidney Disease Improving Global Outcomes creatinine definition) within a moving 48-hour window. Secondary outcomes included severe AKI (stage 2 or 3), inpatient mortality, and length of stay., Results: Among 8473 encounters studied, AKI occurred in 516 (10.2%), 207 (9%), and 27 (2.5%) encounters in the derivation, and internal and external validation cohorts, respectively. The highest-performing model used a machine learning-based genetic algorithm, with an overall receiver operating characteristic curve in the internal validation cohort of 0.76 [95% confidence interval (CI), 0.72 to 0.79] for AKI, 0.79 (95% CI, 0.74 to 0.83) for severe AKI, and 0.81 (95% CI, 0.77 to 0.86) for neonatal AKI. To translate this prediction model into a clinical risk-stratification tool, we identified high- and low-risk threshold points., Conclusions: Using various machine learning algorithms, we identified and validated a time-updated prediction model of ten readily available electronic health record variables to accurately predict imminent AKI in hospitalized children., (Copyright © 2020 by the American Society of Nephrology.)

A major puzzle in malaria treatment remains the dual problem of underuse and overuse of malaria medications, which deplete scarce public resources used for subsidies and lead to drug resistance. One explanation is that health behaviour, especially in the context of incomplete information, could be driven by beliefs, pivotal to the success of health interventions. The objective of this study is to investigate how population beliefs change in response to an experimental intervention which was shown to improve access to rapid diagnostic testing (RDT) through community health workers (CHWs) and to increase appropriate use of anti-malaria medications. By collecting data on individuals' beliefs on malaria testing and treatment 12 and 18 months after the experimental intervention started, we find that the intervention increases the belief that a negative test result is correct, and the belief that the first-line anti-malaria drugs (artemisinin-based combination therapies or ACTs) are effective. Using mediation analysis, we also explore some possible mechanisms through which the changes happen. We find that the experience and knowledge about RDT and experience with CHWs explain 62.4% of the relationship between the intervention and the belief that a negative test result is correct. Similarly, the targeted use of ACTs and taking the correct dose-in addition to experience with RDT-explain 96.8% of the relationship between the intervention and the belief that the ACT taken is effective. As beliefs are important determinants of economic behaviour and might guide individuals' future decisions, understanding how they change after a health intervention has important implications for long-term changes in population behaviour., (© The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motivating community health workers (CHWs), many of whom are volunteers, is important for the sustainability of integrated community case management programs. Given the limited budgets of many of these programs, and the increasingly important role played by CHWs, it is crucial to not only identify important motivators driving their engagement, but also which incentives could have the greatest impact on CHW motivation in their role. In this study, we aimed to assess CHWs' relative preferences for material and non-material incentives. We conducted a discrete choice experiment (DCE) with 199 randomly selected CHWs, working in 32 communities in western Kenya, to measure the relative importance that CHWs place on different incentives. Each CHW completed a series of 10 choice tasks (8 random, 2 fixed), where they had to choose between two hypothetical positions that had varying levels of monthly mobile phone airtime, training, monthly transport bonus, community appreciation and health facility staff appreciation of their work. Data was analyzed using mixed logit models. CHWs' most preferred job characteristic was high levels of community appreciation for their work which was valued approximately equivalently to receiving a 2000 Kenya Shillings (~US $20) monthly transport allowance. These incentives were valued more than appreciation from health facility staff or trainings six times per year. This study demonstrates that investing in efforts to improve community members' knowledge and recognition of CHWs' contribution to community health may have a significant impact on CHWs' motivation and retention in their role., (Copyright © 2019. Published by Elsevier Ltd.)

While the importance of social networks for health behaviors is well-recognized, relatively little is known regarding the accuracy of anonymous online communication and its impact on health behavior. In 2012, we conducted a laboratory experiment in Boston, Massachusetts with 679 individuals to understand how anonymous online communication affects individual prevention decisions. Participants had to opt for or against investing in prevention over three sessions, each consisting of 15 experimental rounds. In the third session only, participants could share their experiences with a group of 1-3 other anonymous participants after each round. Groups exchanged an average of 16 messages over the 15 rounds of the third session. 70% of messages contained information about the subject's prevention decision and the resulting health outcome. Participants were more likely to communicate when they prevented than when they did not, with prevention failures resulting in the highest probability of sending a message. Nonetheless, receiving an additional message reporting prevention increased the odds a subject would prevent by 32 percent. We find that participants tend to adopt the prevention behavior reported by others, with less weight given to the reported outcomes of prevention, suggesting that social networks may influence behaviors through more than just information provision., Competing Interests: The authors have declared that no competing interests exist.

Despite substantial public and private costs of non-adherence to infectious disease treatments, patients often do not finish their medication. We explore adherence to medication for malaria, a major cause of morbidity and health system costs in Africa. We conducted a randomized trial in Uganda testing specialized packaging and messaging, designed to increase antimalarial adherence. We find that stickers with short, targeted messages on the packaging increase adherence by 9% and reduce untaken pills by 29%. However, the currently used method of boosting adherence through costly, specialized packaging with pictorial instructions had no significant impacts relative to the standard control package. We develop a theoretical framework of the adherence decision, highlighting the role of symptoms, beliefs about being cured, and beliefs about drug effectiveness to help interpret our results. Patients whose symptoms resolve sooner are substantially less likely to adhere, and the sticker interventions have the strongest impact among these patients.

Background: More than half of artemisinin combination therapies (ACTs) consumed globally are dispensed in the retail sector, where diagnostic testing is uncommon, leading to overconsumption and poor targeting. In many malaria-endemic countries, ACTs sold over the counter are available at heavily subsidized prices, further contributing to their misuse. Inappropriate use of ACTs can have serious implications for the spread of drug resistance and leads to poor outcomes for nonmalaria patients treated with incorrect drugs. We evaluated the public health impact of an innovative strategy that targets ACT subsidies to confirmed malaria cases by coupling free diagnostic testing with a diagnosis-dependent ACT subsidy., Methods and Findings: We conducted a cluster-randomized controlled trial in 32 community clusters in western Kenya (population approximately 160,000). Eligible clusters had retail outlets selling ACTs and existing community health worker (CHW) programs and were randomly assigned 1:1 to control and intervention arms. In intervention areas, CHWs were available in their villages to perform malaria rapid diagnostic tests (RDTs) on demand for any individual >1 year of age experiencing a malaria-like illness. Malaria RDT-positive individuals received a voucher for a discount on a quality-assured ACT, redeemable at a participating retail medicine outlet. In control areas, CHWs offered a standard package of health education, prevention, and referral services. We conducted 4 population-based surveys-at baseline, 6 months, 12 months, and 18 months-of a random sample of households with fever in the last 4 weeks to evaluate predefined, individual-level outcomes. The primary outcome was uptake of malaria diagnostic testing at 12 months. The main secondary outcome was rational ACT use, defined as the proportion of ACTs used by test-positive individuals. Analyses followed the intention-to-treat principle using generalized estimating equations (GEEs) to account for clustering with prespecified adjustment for gender, age, education, and wealth. All descriptive statistics and regressions were weighted to account for sampling design. Between July 2015 and May 2017, 32,404 participants were tested for malaria, and 10,870 vouchers were issued. A total of 7,416 randomly selected participants with recent fever from all 32 clusters were surveyed. The majority of recent fevers were in children under 18 years (62.9%, n = 4,653). The gender of enrolled participants was balanced in children (49.8%, n = 2,318 boys versus 50.2%, n = 2,335 girls), but more adult women were enrolled than men (78.0%, n = 2,139 versus 22.0%, n = 604). At baseline, 67.6% (n = 1,362) of participants took an ACT for their illness, and 40.3% (n = 810) of all participants took an ACT purchased from a retail outlet. At 12 months, 50.5% (n = 454) in the intervention arm and 43.4% (n = 389) in the control arm had a malaria diagnostic test for their recent fever (adjusted risk difference [RD] = 9 percentage points [pp]; 95% CI 2-15 pp; p = 0.015; adjusted risk ratio [RR] = 1.20; 95% CI 1.05-1.38; p = 0.015). By 18 months, the ARR had increased to 1.25 (95% CI 1.09-1.44; p = 0.005). Rational use of ACTs in the intervention area increased from 41.7% (n = 279) at baseline to 59.6% (n = 403) and was 40% higher in the intervention arm at 18 months (ARR 1.40; 95% CI 1.19-1.64; p < 0.001). While intervention effects increased between 12 and 18 months, we were not able to estimate longer-term impact of the intervention and could not independently evaluate the effects of the free testing and the voucher on uptake of testing., Conclusions: Diagnosis-dependent ACT subsidies and community-based interventions that include the private sector can have an important impact on diagnostic testing and population-wide rational use of ACTs. Targeting of the ACT subsidy itself to those with a positive malaria diagnostic test may also improve sustainability and reduce the cost of retail-sector ACT subsidies., Trial Registration: ClinicalTrials.gov NCT02461628., Competing Interests: The authors have declared that no competing interests exist.

India's rapidly ageing population raises concerns about the burden of health care payments among older individuals who may have both limited income and greater health care needs. Using a nationally representative household survey, we investigate the association between age and financial hardship due to health expenditures. We find that both the probability of experiencing health problems and mean total out-of-pocket health expenditures increase with age. Second, the probability of households experiencing catastrophic health expenditures increases with each additional member aged 60 and above-33% of households with one 60+ member and 38% of households with 2 or more 60+ members experienced catastrophic health expenditures, compared to only 20% in households with all members under the age of 60 years. Lastly, we show that individuals aged 60 and above had a much higher probability of becoming impoverished as a result of health expenditures-the probability of impoverishment for 60+ individuals was 3 percentage points higher than for individuals under the age of 60. Overall, around 4.8% of the older population, representing 4.1 million people, fell into poverty. The results suggest that there is an urgent need for public investments in financial protection programs for older people in India., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Although use of malaria diagnostic tests has increased in recent years, health workers often prescribe anti-malarial drugs to individuals who test negative for malaria. This study investigates how health worker adherence to malaria case management guidelines influences individuals' beliefs about whether their illness was malaria, and their confidence in the effectiveness of artemisinin-based combination therapy (ACT)., Methods: A survey was conducted with 2065 households in Western Kenya about a household member's treatment actions for a recent febrile illness. The survey also elicited the individual's (or their caregiver's) beliefs about the illness and about malaria testing and treatment. Logistic regressions were used to test the association between these beliefs and whether the health worker adhered to malaria testing and treatment guidelines., Results: Of the 1070 individuals who visited a formal health facility during their illness, 82% were tested for malaria. ACT rates for malaria-positive and negative individuals were 89 and 49%, respectively. Overall, 65% of individuals/caregivers believed that the illness was "very likely" malaria. Individuals/caregivers had higher odds of saying that the illness was "very likely" malaria when the individual was treated with ACT, and this was the case both among individuals not tested for malaria [adjusted odds ratio (AOR) 3.42, 95% confidence interval (CI) [1.65 7.10], P = 0.001] and among individuals tested for malaria, regardless of their test result. In addition, 72% of ACT-takers said the drug was "very likely" effective in treating malaria. However, malaria-negative individuals who were treated with ACT had lower odds of saying that the drugs were "very likely" effective than ACT-takers who were not tested or who tested positive for malaria (AOR 0.29, 95% CI [0.13 0.63], P = 0.002)., Conclusion: Individuals/caregivers were more likely to believe that the illness was malaria when the patient was treated with ACT, regardless of their test result. Moreover, malaria-negative individuals treated with ACT had lower confidence in the drug than other individuals who took ACT. These results suggest that ensuring health worker adherence to malaria case management guidelines will not only improve ACT targeting, but may also increase patient/caregivers' confidence in malaria testing and treatment.

Background: In Sub-Saharan Africa, both under-treatment and over-treatment of malaria are common since illnesses are often diagnosed and treated on the basis of symptoms. We investigate whether malaria treatment rates among febrile individuals correspond to observed patterns of malaria infection by age and by local prevalence., Methods and Findings: We use data on treatment of febrile illnesses from a household survey that was conducted between March and May 2012 in 92 villages in six districts in Eastern Uganda. All household members were also tested for malaria using a rapid diagnostic test. We show that both the age of the febrile individual and the village prevalence rate are strongly associated with the odds that a febrile patient was infected with malaria, but not with the odds of ACT treatment. Compared to individuals who were aged 15 or above, febrile individuals aged 5-14 had 3.21 times the odds of testing positive for malaria (95% CI: [2.36 4.37], P<0·001), and febrile individuals who were under age 5 had 2.66 times the odds of testing positive for malaria (95% CI: [1.99 3.56], P<0·001). However, ACT treatment rates for febrile illnesses were not significantly higher for either children ages 5-14 (Unadjusted OR: 1.19, 95% CI: [0.88 1.62], P = 0.255) or children under the age of 5 (Unadjusted OR: 1.24, 95% CI: [0.92 1.68], P = 0·154). A one standard deviation increase in the village malaria prevalence rate was associated with a 2.03 times higher odds that a febrile individual under the age of five tested positive for malaria (95% CI: [1.63 2.54], p<0·001), but was not significantly associated with the odds of ACT treatment (Un-adjusted OR: 0.83, 95% CI: [0.66 1.05], P = 0·113). We present some evidence that this discrepancy may be because caregivers do not suspect a higher likelihood of malaria infection, conditional on fever, in young children or in high-prevalence villages., Conclusion: Our findings suggest that households have significant mis-perceptions about malaria likelihood that may contribute to the under-treatment of malaria. Policies are needed to encourage caregivers to seek immediate diagnostic testing and treatment for febrile illnesses, particularly among young children.

Most patients with suspected malaria do not receive diagnostic confirmation before beginning antimalarial treatment. We investigated the extent to which uncertainty about malaria diagnosis contributes to patient nonadherence to artemether-lumefantrine (AL) treatment through a randomized controlled trial in central Uganda. Among 1,525 patients purchasing a course of AL at private drug shops, we randomly offered 37.6% a free malaria rapid diagnostic test (RDT) and then assessed adherence through home visits 3 days later. Of these subjects, 68.4% tested positive for malaria and 65.8% adhered overall. Patients who tested positive did not have significantly higher odds of adherence than those who were not offered the test (adjusted odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.734-1.57,P= 0.719). Patients who received a positive malaria test had 0.488 fewer pills remaining than those not offered the test (95% CI: -1.02 to 0.043,P= 0.072). We found that patients who felt relatively healthy by the second day of treatment had lower odds of completing treatment (adjusted OR: 0.532, 95% CI: 0.394-0.719,P< 0.001). Our results suggest that diagnostic testing may not improve artemisinin-based combination therapy adherence unless efforts are made to persuade patients to continue taking the full course of drugs even if symptoms have resolved., (© The American Society of Tropical Medicine and Hygiene.)

Actin polymerization in the cytosol and at the plasma membrane is locally regulated by actin nucleators. Several microbial pathogens exploit cellular actin polymerization to spread through tissue. The movement of the enteric pathogen Shigella flexneri, both within the cell body and from cell to cell, depends on actin polymerization. During intercellular spread, actin polymerization at the bacterial surface generates protrusions of the plasma membrane, which are engulfed by adjacent cells. In the cell body, polymerization of actin by Shigella spp. is dependent on N-WASP activation of the Arp2/Arp3 complex. Here we demonstrate that, in contrast, efficient protrusion formation and intercellular spread depend on actin polymerization that involves activation of the Diaphanous formin Dia. While the Shigella virulence protein IpgB2 can bind and activate Dia1 (N. M. Alto et al., Cell 124:133-145, 2006), its absence does not result in a detectable defect in Dia-dependent protrusion formation or spread. The dependence on the activation of Dia during S. flexneri infection contrasts with the inhibition of this pathway observed during vaccinia virus infection.