Cross-sectional survey on prevalence of attention deficit hyperactivity disorder symptoms at a tertiary care health facility in Nairobi

Background:Attention deficit hyperactivity disorder is the most common childhood neurobehavioral disorder with well documented adverse consequences in adolescence and adulthood, yet 60-80% of cases go undiagnosed. Routine screening is not practiced in most pediatric outpatient services and little information exists on factors associated with the condition in developing countries. Methods:This was a questionnaire based cross-sectional survey whose primary objective was to determine prevalence of attention deficit hyperactivity disorder (ADHD) symptoms in children aged 6-12 years attending a tertiary care hospital Accidents and Emergency unit. Secondary objectives were to: (i) ascertain if physical injury and poor academic performance were associated with ADHD, (ii) compare diagnostic utility of parent-filled Vanderbilt Assessment Scale (VAS) against Statistical Manual of Mental Disorders-IV (DSM-IV) as the gold reference and (iii) establish if there exists an association between ADHD symptoms cluster and co-morbid conditions. Results:Prevalence of cluster of symptoms consistent with ADHD was 6.3% (95% CI; 3.72-10.33) in 240 children studied. Those affected were more likely to repeat classes than the asymptomatic (OR 20.2; 95% CI 4.02-100.43). Additionally, 67% of the symptomatic had previously experienced burns and 37% post-traumatic open wounds. The odds of having an injury in the symptomatic was 2.9 (95% CI; 1.01-8.42) compared to the asymptomatic. Using DSM-IV as reference, VAS had a sensitivity of 66.7% (95%; CI 39.03-87.12) and specificity of 99.0% (95% CI; 96.1-99.2). Positive predictive value was 83.0% (95% CI; 50.4-97.3) and negative predictive value 98.0% (CI 95.1-99.1). Oppositional defiant disorder symptoms, anxiety, depression and conduct problems were not significantly associated with ADHD cluster of symptoms. Conclusion:The study found a relatively high prevalence of symptoms associated with ADHD. Symptomatic children experienced poor school performance. These findings support introduction of a policy on routine screening for ADHD in pediatric outpatient service. Positive history of injury and poor academic performance should trigger further evaluation for ADHD. Vanderbilt assessment scale is easier to administer than DSM-IV but has low sensitivity and high specificity that make it inappropriate for screening. It however provides a suitable alternative confirmatory test to determine who among clinically symptomatic patients requires referral to a psychiatrist

Mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in Kenya (M-SIMU): a cluster randomised controlled trial

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with logbinomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%

Differentiated type II pneumocytes can be reprogrammed by ectopic Sox2 expression

The adult lung contains several distinct stem cells, although their properties and full potential are still being sorted out. We previously showed that ectopic Sox2 expression in the developing lung manipulated the fate of differentiating cells. Here, we addressed the question whether fully differentiated cells could be redirected towards another cell type. Therefore, we used transgenic mice to express an inducible Sox2 construct in type II pneumocytes, which are situated in the distal, respiratory areas of the lung. Within three days after the induction of the transgene, the type II cells start to proliferate and form clusters of cuboidal cells. Prolonged Sox2 expression resulted in the reversal of the type II cell towards a more embryonic, precursor-like cell, being positive for the stem cell markers Sca1 and Ssea1. Moreover, the cells started to co-express Spc and Cc10, characteristics of bronchioalveolar stem cells. We demonstrated that Sox2 directly regulates the expression of Sca1. Subsequently, these cells expressed Trp63, a marker for basal cells of the trachea. So, we show that the expression of one transcription factor in fully differentiated, distal lung cells changes their fate towards proximal cells through intermediate cell types. This may have implications for regenerative medicine, and repair of diseased and damaged lungs

Hypoxia Inducible Factor 3α Plays a Critical Role in Alveolarization and Distal Epithelial Cell Differentiation during Mouse Lung Development

Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF). HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIFα, and a constitutively expressed subunit, HIF1β. HIF1α and HIF2α, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIFα gene, HIF3α, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3α, NEPAS and IPAS. HIF3α gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS) or weak transcriptional activators (HIF3α/NEPAS). Previously, we and others have shown the importance of the Hif1α and Hif2α factors in lung development, and here we investigated the role of Hif3α during pulmonary development. Therefore, HIF3α was conditionally expressed in airway epithelial cells during gestation and although HIF3α transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3α expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3α expression, the level of Hif2α was reduced, but that of Hif1α was not affected. Two regulatory genes, Rarβ, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3α expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3α binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3α affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel function of Hif3α beyond the hypoxia response

Improved Land Management in the Lake Victoria Basin: Annual Technical Report, July 2000 to June 2001

ICRAF and the Kenyan Ministry of Agriculture and Rural Development (MOARD) are implementing a project on “Improved Land Management in the Lake Victoria Basin.” The project began in 1999 – 2000 with a one-year startup year of activities under the Sida-sponsored National Soil and Water Conservation Programme (NSWCP). The collaborative project of ICRAF and MOARD has now been continued for another three years under the National Agriculture and Livestock Extension Programme (NALEP). This paper summarizes achievements and findings for the project for the year 2000 / 2001. The Swedish International Development Agency (SIDA) supports “Improved Land Management in the Lake Victoria Basin” through NALEP. Additional financial support for the activities reported herein was also provided by the Rockefeller Foundation, ICRAF core funds, Danida, the University of Florida and the USAID. Research conducted during 2000 / 2001 addressed a range of issues across a large tract of Western Kenya. A coarse resolution assessment of soil erosion risk conducted for the entire Lake Victoria Basin identified the Nzoia / Yala and Kagera river basins as those with the greatest percentage of land at risk. Biophysical research on land management problem domains has quantified the widespread spatial extent of soil physical and chemical degradation in the Nyando river basin and illustrated four contrasting biophysical problem domains within the basin. District-level data on population density, poverty and agricultural production available from secondary sources have been complemented with baseline household and community survey data collected in 9 villages around the Nyando river basin. The overall picture that is emerging is that while much of the Nyando river basin has experienced some physical and chemical land degradation, there are pockets of severe poverty, severe environmental degradation and extremely low agricultural production. Different approaches to extension, investment and policy may be needed to address poverty – environment – agricultural problems in different parts of the river basin. Reversing trends in environmental deterioration will require interventions on farmers fields and in the many areas between farms that publicly-used, although usually privately-owned. Farmers have demonstrated their willingness to adopt recommended conservation practices on their individual family fields, but the intensity of adoption depends upon the potential returns to investments, their cultural grouping, and the approach that extension providers take to the provision of information and mobilization of community participation. Adoption of improved practices and investments on publicly-used areas between farms requires the mobilization of collective action among small, medium and large groups. Collective action in the Nyando River basin is most likely to be effective where it harnesses local institutional arrangements (e.g. sub-clan affiliations among the Luo) and advances common interests in the provision of high quality water and the generation of additional cash income. Among other opportunities, there appears to be good prospects for market-oriented agroforestry for production of fruit, fuelwood and timber. Changes in local and national policies would help to ensure good returns for smallholder farmers. This report begins with a presentation of a number of major findings, implications of those findings for extension and investment and implications for policy. A summary of progress by activity is then presented, followed by lists of personnel involved, presentations and publications. An annex presents detailed accomplishments by activity

Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance

IntroductionDespite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way to improve response to ICB therapy.ResultsOur results show that combination anti-PD-1/CTLA-4 produces an initial antitumor effect with evidence of an activated immune response. Upon extended treatment with anti-PD-1/CTLA-4 acquired resistance developed with an increase of the immunosuppressive populations, including T-regulatory cells, neutrophils and monocytes. Addition of anti-Ly6C blocking antibody to anti-PD-1/CTLA-4 was capable of completely reversing treatment resistance and restoring CD8 T cell activity in multiple KP lung cancer models and in the autochthonous lung cancer KrasLSL-G12D/p53fl/fl model. We found that there were higher classical Ly6C+ monocytes in anti-PD-1/CTLA-4 combination resistant tumors. B7 blockade illustrated the importance of dendritic cells for treatment efficacy of anti-Ly6C/PD-1/CTLA-4. We further determined that classical Ly6C+ monocytes in anti-PD-1/CTLA-4 resistant tumors are trafficked into the tumor via IFN-γ and the CCL2-CCR2 axis. Mechanistically we found that classical monocytes from ICB resistant tumors were unable to differentiate into antigen presenting cells and instead differentiated into immunosuppressive M2 macrophages or myeloid-derived suppressor cells (MDSC). Classical Ly6C+ monocytes from ICB resistant tumors had a decrease in both Flt3 and PU.1 expression that prevented differentiation into dendritic cells/macrophages.ConclusionsTherapeutically we found that addition of anti-Ly6C to the combination of anti-PD-1/CTLA-4 was capable of complete tumor eradication. Classical Ly6C+ monocytes differentiate into immunosuppressive cells, while blockade of classical monocytes drives dendritic cell differentiation/maturation to reinvigorate the anti-tumor T cell response. These findings support that immunotherapy resistance is associated with infiltrating monocytes and that controlling the differentiation process of monocytes can enhance the therapeutic potential of ICB

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Myelomatous Pleural Effusion: A Rare Occurrence in Multiple Myeloma.

Various factors can cause pleural effusion in multiple myeloma patients. Myelomatous pleural effusion (MPE) is an uncommon but potentially life-threatening complication of multiple myeloma with a poor prognosis. After ruling out all other probable causes, the present case reports MPE in a patient with IgG kappa multiple myeloma

Adoption of Improved Mungbean Production Technologies in Selected East African Countries

This study analyzes the factors that influence the probability and extent of the adoption of mungbean production technologies in Tanzania, Kenya and Uganda, using multivariate probit and Poisson regression models. The results show that the probability and extent of the adoption of mungbean production technologies are influenced by gender of the household, household size, farm size, livestock size, household assets, access to extension services and access to credit. The study suggests that policy interventions that aimed at targeting women farmers, increasing household asset and information dissemination, such as field demonstrations and training programs, are crucial in enhancing technology adoption among smallholder farmers