Nutritional status of people who inject drugs in Coastal Kenya: a cross-sectional study.

INTRODUCTION: Despite documentation on injection drug use (IDU) in Kenya, the nutritional status of people who inject drugs (PWIDs) is under-explored. Elsewhere studies report under-nutrition among PWIDs which is attributed to food insecurity; competing priorities between drugs and food supply; chaotic lifestyle; reduced food intake; substance use induced malnutrition due to inflammation and comorbidities. METHODS: This was a cross-sectional study that sought to assess the nutritional status of PWIDs in Coastal Kenya. We recruited 752 participants of whom 371(49%) were on IDUs and 75 non-IDUs and 306 non-drug users using respondent driven sampling, traditional snowball, makeshift outreach and purposive sampling methods. RESULTS: More than one half of the participants (56%) had BMI classified as normal while 35% had BMI < 18.5. The proportion with BMI < 18.5 was higher among IDUs (46%) compared to the non-IDUs (33%) and non-drug users (23%) at P < 0.001. Using the mid upper arm circumference (MUAC), 17% were classified as underweight and the proportion was lowest (11%) among non- drugs users compared to 22% among IDUs (P < 0.001). However, the IDUs had lower proportion of overweight (8.1%) compared to 55% among the non- drug users. The proportion with low waist-for-hip ratio was highest among the IDUs (74%) while high waist-for-hip ratio was lowest in the same group of IDUs (11%) at P < 0.001. One half (50%), of the participants had no signs of anaemia, (47%) had mild/moderate anaemia while 21 (2.8%) had severe anaemia. However, IDUs were more likely to be overweight based on waist circumference as a parameter. The IDUs had the highest proportion (54%) of mild to moderate anaemia compared to non-IDUs (37%) and 40% non- drug users (P < 0.001). In the multivariable models, IDUs (aRRR 2.83 (95%CI 1.84‒4.35)) and non-IDUs (aRRR 1.42 (95%CI 1.07‒1.88)) compared to non- drug users were positively associated with BMI < 18.5. Being an IDU was positively associated with mild or moderate anaemia (aRRR 1.65 (95%CI 1.13‒2.41)) while non-IDUs were positively associated with severe anaemia (aRRR 1.69 (95%CI 1.16‒2.48)). CONCLUSION: A significant proportion of the participants were under-nourished with those injecting drugs bearing the heaviest brunt. Being an IDU was positively associated with the low BMI, MUAC, waist for hip ratio and mild or moderate anaemia but high waist circumference. People who inject drugs have high risk for under-nutrition and should be targeted with appropriate interventions.

8-Year Follow-up of a Maternal Education Trial in a Low-Resource Setting.

OBJECTIVES: Nutrition and stimulation interventions promote early childhood development, but little is known about their long-term benefits in low- and middle-income countries. We conducted a follow-up study of a cluster-randomized maternal education trial performed in children aged 6 to 8 months to assess the sustainability of developmental benefits after 8 years. METHODS: The education intervention lasted 6 months and consisted of nutrition, hygiene, sanitation, and child stimulation aspects. We assessed child processing and cognitive abilities using the Kaufman Assessment Battery for Children Second Edition (KABC-II) and attention and inhibitory control using the Test of Variables of Attention after 8 years. The original trial included 511 mother-child pairs (intervention, n = 263; control, n = 248), whereas in the current study, 361 (71%; intervention, n = 185; control, n = 176) pairs were available for analyses. RESULTS: The intervention group scored higher than the controls (all P < .001) on all 5 KABC-II subscales and on the KABC-II global score (mean difference: 14; 95% confidence interval, 12-16; P < .001). For all 5 Test of Variables of Attention variables, the intervention group scored higher than the controls on both the visual and auditory tasks (all P < .05). Because the intervention was delivered as a package, a limitation is that we cannot pinpoint the individual contribution of each component (nutrition, hygiene, and stimulation) to the developmental benefits. CONCLUSIONS: The intervention group consistently scored markedly higher on both neuropsychological tests. Thus, even 8 years after the original maternal education intervention, the developmental benefits that we observed at child age of 1, 2, and 3 years, were sustained.

Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.

General ward nurses detection and response to clinical deterioration in three hospitals at the Kenyan coast: a convergent parallel mixed methods study.

BACKGROUND: In low and middle-income countries like Kenya, critical care facilities are limited, meaning acutely ill patients are managed in the general wards. Nurses in these wards are expected to detect and respond to patient deterioration to prevent cardiac arrest or death. This study examined nurses' vital signs documentation practices during clinical deterioration and explored factors influencing their ability to detect and respond to deterioration. METHODS: This convergent parallel mixed methods study was conducted in the general medical and surgical wards of three hospitals in Kenya's coastal region. Quantitative data on the extent to which the nurses monitored and documented the vital signs 24 h before a cardiac arrest (death) occurred was retrieved from patients' medical records. In-depth, semi-structured interviews were conducted with twenty-four purposefully drawn registered nurses working in the three hospitals' adult medical and surgical wards. RESULTS: This study reviewed 405 patient records and found most of the documentation of the vital signs was done in the nursing notes and not the vital signs observation chart. During the 24 h prior to death, respiratory rate was documented the least in only 1.2% of the records. Only a very small percentage of patients had any vital event documented for all six-time points, i.e. four hourly. Thematic analysis of the interview data identified five broad themes related to detecting and responding promptly to deterioration. These were insufficient monitoring of vital signs linked to limited availability of equipment and supplies, staffing conditions and workload, lack of training and guidelines, and communication and teamwork constraints among healthcare workers. CONCLUSION: The study showed that nurses did not consistently monitor and record vital signs in the general wards. They also worked in suboptimal ward environments that do not support their ability to promptly detect and respond to clinical deterioration. The findings illustrate the importance of implementation of standardised systems for patient assessment and alert mechanisms for deterioration response. Furthermore, creating a supportive work environment is imperative in empowering nurses to identify and respond to patient deterioration. Addressing these issues is not only beneficial for the nurses but, more importantly, for the well-being of the patients they serve.

Prevalence and correlates of paediatric guideline non-adherence for initial empirical care in six low and middle-income settings: a hospital-based cross-sectional study.

OBJECTIVES: This study evaluated the prevalence and correlates of guideline non-adherence for common childhood illnesses in low-resource settings. DESIGN AND SETTING: We used secondary cross-sectional data from eight healthcare facilities in six Asian and African countries. PARTICIPANTS: A total of 2796 children aged 2-23 months hospitalised between November 2016 and January 2019 with pneumonia, diarrhoea or severe malnutrition (SM) and without HIV infection were included in this study. PRIMARY OUTCOME MEASURES: We identified children treated with full, partial or non-adherent initial inpatient care according to site-specific standard-of-care guidelines for pneumonia, diarrhoea and SM within the first 24 hours of admission. Correlates of guideline non-adherence were identified using generalised estimating equations. RESULTS: Fully adherent care was delivered to 32% of children admitted with diarrhoea, 34% of children with pneumonia and 28% of children with SM when a strict definition of adherence was applied. Non-adherence to recommendations was most common for oxygen and antibiotics for pneumonia; fluid, zinc and antibiotics for diarrhoea; and vitamin A and zinc for SM. Non-adherence varied by site. Pneumonia guideline non-adherence was more likely among patients with severe disease (OR 1.82; 95% CI 1.38, 2.34) compared with non-severe disease. Diarrhoea guideline non-adherence was more likely among lower asset quintile groups (OR 1.16; 95% CI 1.01, 1.35), older children (OR 1.10; 95% CI 1.06, 1.13) and children presenting with wasting (OR 6.44; 95% CI 4.33, 9.57) compared with those with higher assets, younger age and not wasted. CONCLUSIONS: Non-adherence to paediatric guidelines was common and associated with older age, disease severity, and comorbidities, and lower household economic status. These findings highlight opportunities to improve guidelines by adding clarity to specific recommendations.

Stunting in the first year of life: Pathway analysis of a birth cohort.

Malnutrition among infants aged below 6 months has been largely overlooked creating gaps in our understanding of factors underlying stunting in early infancy. Recent evidence suggests that pre-natal and early childhood factors may contribute more to driving childhood stunting than previously appreciated. The study was set up to examine pathways including parental and household characteristics, birth size and gestation, and illness in infancy with stunting at birth and months 3, 6 and 12 using an a priori hypothesized framework. It was a secondary analysis of a birth cohort of 1017 infants recruited from four health facilities in Burkina Faso and followed up for one year. Structural equation models (SEM) were generated to explore pathways to stunting at birth and months 3, 6 and 12. The prevalence of being stunted at birth and months 3, 6 and 12 was 7.4%, 23%, 20% and 18% respectively. The fractions of month 12 stunting attributable to being stunted at birth, months 3 and 6 were 11% (95%CI 5.0‒16%), 32% (95%CI 22‒41%) and 40% (95%CI 31‒49%) respectively. In the structural equation model, male sex and maternal characteristics had direct effects on stunting at birth and at 3 months, but not subsequently. Premature birth, twin birth and being stunted at a previous time point were directly associated with stunting at months 3, 6 and 12. Both maternal and paternal characteristics were directly associated with preterm birth. Non-exclusive breastfeeding had borderline positive direct effect on stunting at month 6 but not at month 12. The direct and indirect pathways identified in this study highlight the complex interlinks between child, maternal, paternal and household characteristics. Interventions tackling preterm birth, in utero growth, exclusive breastfeeding and maternal wellbeing may reduce stunting in the first year of life.

Long-term effects on depressive symptoms among Ugandan mothers - Findings from a follow-up of a cluster-randomized education trial in a rural low-resource setting.

INTRODUCTION: Depression is increasingly affecting mothers in poor countries such as Uganda. Various interventions have been implemented to tackle this problem, but their sustainability is under-researched. Here we present follow-up data on maternal depression six years after a cluster-randomized controlled maternal education trial in rural Uganda. METHODS: The intervention lasted six months and consisted of nutrition, hygiene, sanitation and child stimulation education, delivered to 511 mothers of 6 to 8 months' old children. Six years later we assessed maternal depressive symptoms using two psychometric tools; the Beck Depression Inventory II (BDI-II) and Center for Epidemiologic Studies Depression scale (CESD). RESULTS: For this follow-up study, data was available from 307/511 (60 %) mothers. Intention-to-treat analyses adjusting for clustering showed that the intervention mothers had non-significantly less depression symptoms (absolute score difference - 2; 95 % CI -5 to 0; p = 0.07) on BDI-II, and borderline significantly less depression symptoms (absolute score difference - 3; 95 % CI -5 to 0; p = 0.05) on CES-D compared to the controls. For categorized depression scores, the control mothers had significantly higher proportion of women classified in the worse depression categories for both BDI-II and CESD. We did not find any baseline characteristics associated with maternal depression. LIMITATIONS: The BDI-II and CES-D tools are both self-reported and we cannot rule out the possibility of social desirability bias in reporting of depression symptoms. CONCLUSION: Six years after the maternal education trial, some benefits on maternal mental health were sustained. More studies are warranted on sustainability and scale-up of such interventions.

New approaches and technical considerations in detecting outlier measurements and trajectories in longitudinal children growth data.

BACKGROUND: Growth studies rely on longitudinal measurements, typically represented as trajectories. However, anthropometry is prone to errors that can generate outliers. While various methods are available for detecting outlier measurements, a gold standard has yet to be identified, and there is no established method for outlying trajectories. Thus, outlier types and their effects on growth pattern detection still need to be investigated. This work aimed to assess the performance of six methods at detecting different types of outliers, propose two novel methods for outlier trajectory detection and evaluate how outliers affect growth pattern detection. METHODS: We included 393 healthy infants from The Applied Research Group for Kids (TARGet Kids!) cohort and 1651 children with severe malnutrition from the co-trimoxazole prophylaxis clinical trial. We injected outliers of three types and six intensities and applied four outlier detection methods for measurements (model-based and World Health Organization cut-offs-based) and two for trajectories. We also assessed growth pattern detection before and after outlier injection using time series clustering and latent class mixed models. Error type, intensity, and population affected method performance. RESULTS: Model-based outlier detection methods performed best for measurements with precision between 5.72-99.89%, especially for low and moderate error intensities. The clustering-based outlier trajectory method had high precision of 14.93-99.12%. Combining methods improved the detection rate to 21.82% in outlier measurements. Finally, when comparing growth groups with and without outliers, the outliers were shown to alter group membership by 57.9 -79.04%. CONCLUSIONS: World Health Organization cut-off-based techniques were shown to perform well in few very particular cases (extreme errors of high intensity), while model-based techniques performed well, especially for moderate errors of low intensity. Clustering-based outlier trajectory detection performed exceptionally well across all types and intensities of errors, indicating a potential strategic change in how outliers in growth data are viewed. Finally, the importance of detecting outliers was shown, given its impact on children growth studies, as demonstrated by comparing results of growth group detection.

Intestinal disturbances associated with mortality of children with complicated severe malnutrition.

BACKGROUND: Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality. METHODS: A case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP). RESULTS: The fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality. CONCLUSIONS: Intestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM.

Malnourished children are at a high risk of dying when exposed to an acute illness. They often have symptoms like diarrhea that indicate their gut is not working properly. It is unclear whether these gut problems contribute to their deaths. Feces contain numerous small molecules processed by the gut that reflect gut health. We compare these fecal molecules between malnourished children who died during hospitalization to those who survived, and relate them to signs of inflammation in the body. We show that the fecal molecules are different between children who died and those who survived. These differences reveal that poor gut health could increase risk of death, potentially by perturbing the body's defensive response to an acute illness. These findings underscore that treatment for ill severely malnourished children should focus on improving gut health.

Polydrug Use among Students in a Public University in a Lower Middle-Income Country.

Recreational drug use among students in tertiary institutions remains a public health concern. Despite documentation of drug use in Kenyan universities, most of the studies are based on self-reported history which is prone to social desirability bias. It is in this context that we sought to establish lifetime and current drug use among university students. The study investigated self-reported and confirmed drug use. Using proportionate to size and snowball sampling methods, 380 respondents were enrolled from three university campuses. Actual drug use was confirmed qualitatively using a 6 panel plus alcohol saliva test kit. The study participants' median (IQR) age was 22 (20-23) years, and 262 (69%) were male; 328 (86%) were degree-level students, while 127 (33%) were in their fourth year and above. A total of 221 (58%) students reported a lifetime ever use of drugs, while 193 (51%) tested positive for at least one drug. Alcohol, tobacco products (cotinine), marijuana, and amphetamine or khat were the most preferred drugs. The usage was either solely, concurrently, or simultaneously. Having multiple sexual partners compared to students with no sexual partner (adjusted risk ratio (aRR) of 2.33 (95% CI 1.45, 3.76)) and residing in Mishomoroni and Kisauni (aRR 1.50 (95% CI 1.08, 2.09)) were associated with risk of testing positive for any drug. Having one (aRR of 1.54 (95% CI 1.05, 2.26)) and multiple sexual partners (aRR 2.03 (95% CI 1.27, 3.25) and residing in Mishomoroni and Kisauni (aRR 1.48 (95% CI 1.05, 2.08)) were associated with self-reported drug use. One out of two students was currently using drugs. Irrespective of the method used to record data, alcohol, tobacco products, marijuana, and amphetamine or khat were the most preferred drugs. The usage was solely, concurrently, or simultaneously. Future interventions should focus on continuing students, students' residences, and those who are sexually active.

Derivation and external validation of a clinical prognostic model identifying children at risk of death following presentation for diarrheal care.

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build clinical prognostic models (CPMs) to predict death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived CPM. Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieved an area under the ROC curve (AUC) of 0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC = 0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.

Burden of HIV and treatment outcomes among TB patients in rural Kenya: a 9-year longitudinal study.

BACKGROUND: Although tuberculosis (TB) patients coinfected with HIV are at risk of poor treatment outcomes, there is paucity of data on changing trends of TB/HIV co-infection and their treatment outcomes. This study aims to estimate the burden of TB/HIV co-infection over time, describe the treatment available to TB/HIV patients and estimate the effect of TB/HIV co-infection on TB treatment outcomes. METHODS: This was a retrospective data analyses from TB surveillance in two counties in Kenya (Nyeri and Kilifi): 2012‒2020. All TB patients aged ≥ 18 years were included. The main exposure was HIV status categorised as infected, negative or unknown status. World Health Organization TB treatment outcomes were explored; cured, treatment complete, failed treatment, defaulted/lost-to-follow-up, died and transferred out. Time at risk was from date of starting TB treatment to six months later/date of the event and Cox proportion with shared frailties models were used to estimate effects of TB/HIV co-infection on TB treatment outcomes. RESULTS: The study includes 27,285 patients, median (IQR) 37 (29‒49) years old and 64% male. 23,986 (88%) were new TB cases and 91% were started on 2RHZE/4RH anti-TB regimen. Overall, 7879 (29%, 95% 28‒30%) were HIV infected. The proportion of HIV infected patient was 32% in 2012 and declined to 24% in 2020 (trend P-value = 0.01). Uptake of ARTs (95%) and cotrimoxazole prophylaxis (99%) was high. Overall, 84% patients completed six months TB treatment, 2084 (7.6%) died, 4.3% LTFU, 0.9% treatment failure and 2.8% transferred out. HIV status was associated with lower odds of completing TB treatment: infected Vs negative (aOR 0.56 (95%CI 0.52‒0.61) and unknown vs negative (aOR 0.57 (95%CI 0.44‒0.73). Both HIV infected and unknown status were associated with higher hazard of death: (aHR 2.40 (95%CI 2.18‒2.63) and 1.93 (95%CI 1.44‒2.56)) respectively and defaulting treatment/LTFU: aHR 1.16 (95%CI 1.01‒1.32) and 1.55 (95%CI 1.02‒2.35)) respectively. HIV status had no effect on hazard of transferring out and treatment failure. CONCLUSION: The overall burden of TB/HIV coinfection was within previous pooled estimate. Our findings support the need for systematic HIV testing as those with unknown status had similar TB treatment outcomes as the HIV infected.

Derivation and external validation of a clinical prognostic model identifying children at risk of death following presentation for diarrheal care.

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models for death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived clinical prognostic model (CPM). Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieve an AUC=0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC=0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.

Pupal productivity of larval habitats of Aedes aegypti in Msambweni, Kwale County, Kenya.

Aedes aegypti is an important vector of several arboviruses including dengue and chikungunya viruses. Accurate identification of larval habitats of Ae. aegypti is considered an essential step in targeted control. This study determined Ae. aegypti productivity in selected larval habitats in Msambweni, Kwale County, Kenya. Three sequential larval habitat surveys were conducted. The first survey was habitat census (baseline) through which 83 representative larval habitats were identified and selected. The second and third surveys involved estimating daily productivity of the 83 selected larval habitats for 30 consecutive days during a wet and a dry season, respectively. Of 664 larval habitats examined at baseline, 144 larval habitats (21.7%) were found to be infested with Ae. aegypti larvae. At baseline, majority (71%) of the pupae were collected from two (2/6) larval habitat types, tires and pots. Multivariate analysis identified habitat type and the habitat being movable as the predictors for pupal abundance. During the 30-day daily pupal production surveys, only a few of the habitats harbored pupae persistently. Pupae were found in 28% and 12% of the larval habitats during the wet and dry seasons, respectively. In the wet season, drums, tires, and pots were identified as the key habitat types accounting for 85% of all pupae sampled. Three habitats (all drums) accounted for 80% of all the pupae collected in the dry season. Predictors for pupal productivity in the wet season were habitat type, place (whether the habitat is located at the back or front of the house), habitat purpose (use of the water in the habitat), and source of water. Although the multivariate model for habitat type did not converge, habitat type and habitat size were the only significant predictors during the dry season. Drums, pots, and tires were sources of more than 85% of Ae. aegypti pupae, reinforcing the "key container concept." Targeting these three types of habitats makes epidemiological sense, especially during the dry season.

Trends in inpatient and post-discharge mortality among young infants admitted to Kilifi County Hospital, Kenya: a retrospective cohort study.

OBJECTIVES: To describe admission trends and estimate inpatient and post-discharge mortality and its associated exposures, among young infants (YI) admitted to a county hospital in Kenya. DESIGN: Retrospective cohort study. SETTING: Secondary level hospital. PARTICIPANTS: YI aged less than 60 days admitted to hospital from January 2009 to December 2019: 12 271 admissions in 11 877 individuals. YI who were resident within a Kilifi Health and Demographic Surveillance System (KHDSS): n=3625 with 4421 admissions were followed-up for 1 year after discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient and 1-year post-discharge mortality, the latter in KHDSS residents. RESULTS: Of 12 271 YI admissions, 4421 (36%) were KHDSS-resident. Neonatal sepsis, preterm complications and birth asphyxia accounted for 83% of the admissions. The proportion of YI among under-5s admissions increased from 19% in 2009 to 34% in 2019 (Ptrend=0.02). Inpatient case fatality was 16%, with 66% of the deaths occurring within 48 hours of admission. The introduction of free maternity care in 2013 was not associated with a change in admissions or inpatient mortality among YI. During 1-year post-discharge, 208/3625 (5.7%) YI died, 64.3 (95% CI 56.2 to 73.7) per 1000 infant-years. 49% of the post-discharge deaths occurred within 1 month of discharge, and 49% of post-discharge deaths occurred at home. Both inpatient and post-discharge deaths were associated with low admission weight. Inpatient mortality was associated with clinical signs of disease severity, while post-discharge mortality was associated with the length of hospitalisation, leaving against advice and referral to a specialised hospital. CONCLUSIONS: YIs accounted for an increasing proportion of paediatric admissions and their overall mortality remains high. Post-discharge mortality accounts for a lower proportion of deaths but mortality rate is higher than among children aged 2-59 months. Services to address post-discharge mortality are needed and should focus on infants at higher risk.

Machine learning for predicting neurodegenerative diseases in the general older population: a cohort study.

BACKGROUND: In the older general population, neurodegenerative diseases (NDs) are associated with increased disability, decreased physical and cognitive function. Detecting risk factors can help implement prevention measures. Using deep neural networks (DNNs), a machine-learning algorithm could be an alternative to Cox regression in tabular datasets with many predictive features. We aimed to compare the performance of different types of DNNs with regularized Cox proportional hazards models to predict NDs in the older general population. METHODS: We performed a longitudinal analysis with participants of the English Longitudinal Study of Ageing. We included men and women with no NDs at baseline, aged 60 years and older, assessed every 2 years from 2004 to 2005 (wave2) to 2016-2017 (wave 8). The features were a set of 91 epidemiological and clinical baseline variables. The outcome was new events of Parkinson's, Alzheimer or dementia. After applying multiple imputations, we trained three DNN algorithms: Feedforward, TabTransformer, and Dense Convolutional (Densenet). In addition, we trained two algorithms based on Cox models: Elastic Net regularization (CoxEn) and selected features (CoxSf). RESULTS: 5433 participants were included in wave 2. During follow-up, 12.7% participants developed NDs. Although the five models predicted NDs events, the discriminative ability was superior using TabTransformer (Uno's C-statistic (coefficient (95% confidence intervals)) 0.757 (0.702, 0.805). TabTransformer showed superior time-dependent balanced accuracy (0.834 (0.779, 0.889)) and specificity (0.855 (0.0.773, 0.909)) than the other models. With the CoxSf (hazard ratio (95% confidence intervals)), age (10.0 (6.9, 14.7)), poor hearing (1.3 (1.1, 1.5)) and weight loss 1.3 (1.1, 1.6)) were associated with a higher DNN risk. In contrast, executive function (0.3 (0.2, 0.6)), memory (0, 0, 0.1)), increased gait speed (0.2, (0.1, 0.4)), vigorous physical activity (0.7, 0.6, 0.9)) and higher BMI (0.4 (0.2, 0.8)) were associated with a lower DNN risk. CONCLUSION: TabTransformer is promising for prediction of NDs with heterogeneous tabular datasets with numerous features. Moreover, it can handle censored data. However, Cox models perform well and are easier to interpret than DNNs. Therefore, they are still a good choice for NDs.

The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia.

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.

Factors associated with poor outcomes among people living with HIV started on anti-retroviral therapy before and after implementation of "test and treat" program in Coastal Kenya.

OBJECTIVES: To determine the factors associated with poor outcomes among people living with HIV (PLHIV) started on anti- retroviral therapy before and after implementation of "Test and treat" program in 18 facilities in Coastal Kenya. METHODS: A retrospective cohort study design was used to study PLHIV aged > 15 years and started on ART in the periods of April to August 2016, and April to August 2017, then followed up for 24 months. Primary outcome was retention defined as being alive and on ARVs after 24 months. Death and loss to follow-up were considered as poor outcomes. Kaplan-Meier survival methods were used to describe time to primary outcome. Cox proportional regression analysis was used to determine factors associated with poor outcomes. RESULTS: 86 patients (470 before test and treat, and 316 after test and treat cohorts) were enrolled. Overall, the median [IQR] age was 39.3 [32.5-47.5] years and 539 (69%) were female. After 24 months, retention rates for the before (68%) and after (64%) test and start groups were similar (absolute difference: -4.0%, 95%CI: -11-3.1, P = 0.27). There were 240(31%, 95%CI 27 to 34%) PLHIV with poor outcomes, 102 (32%) and 138 (29%) occurred among the test and treat group, and delayed treatment patients respectively. In multivariable regression model, test and treat had no significant effect on risk of poor outcomes (aHR = 1.17, 95%CI 0.89-1.54). Increasing age (aHR = 0.98, 95%CI 0.97-0.99), formal employment (aHR = 0.42, 95%CI 0.23-0.76) and not being employed (aHR = 0.53, 95%CI 0.34-0.81) were negatively associated with poor outcomes. The risk of poor outcomes was higher among males compared to female patients (aHR = 1.37, 95%CI 1.03-1.82) and among divorced/separated patients compared to the married (aHR = 1.44, 95%CI 1.04-1.99). CONCLUSION: Retention patterns for the "test and treat" cohort were comparable to those who started ART before "test and treat". Patients who are males, young, divorced/separated, with poor socio-economic status had higher risks for poor clinical outcomes. Interventions targeting PLHIV who are young, male and economically disadvantaged provide an opportunity to improve the long-term outcomes.

Long-Term Effects of a Randomized Maternal Education Trial in Rural Uganda: Implications for Child Oral Health.

The aim was to examine oral health among 5-6-year-old children whose mothers participated in a 6 months' cluster-randomized education trial in rural Uganda starting when their children were 6-8 months old. The education focused on nutrition, oral hygiene, and child stimulation. In the current follow-up study, 357/511 (70%) children from the original trial were available for data collection (200 in the intervention and 157 in the control group). Molar caries was assessed on intraoral photographs. Children and/or caregivers answered a WHO health questionnaire for collection of oral data. Dental practices were compared between the intervention and control group using multilevel mixed effect logistic regression accounting for clustering. The children in the intervention group had less caries compared with the control group: 41% versus 60% (odds ratio [OR] 0.46; 95% confidence intervals [CI] 0.24-0.86, P = 0.02). The use of toothbrush to clean teeth was more frequent in the intervention than in the control group: 66% versus 38% (OR 3.39; 95% CI 1.54-7.45, P = 0.003), as was high teeth-cleaning frequency: 74% versus 62% (OR 1.72; 95% CI 1.09-2.69, P = 0.02). Self-reported problems such as toothache (10% versus 19%), difficulty biting (12% versus 24%) and chewing food (8.5% versus 18%) were significantly less frequent among children in the intervention compared with the control group. No significant differences were found in dietary habits. Our data shows that an educational intervention adjusted to a low-resource setting, provided in infancy, resulted in improved oral hygiene and reduced development of dental caries among children aged 5-6 years.