Community health workers and health equity in low- and middle-income countries: systematic review and recommendations for policy and practice.

BACKGROUND: The deployment of Community Health Workers (CHWs) is widely promoted as a strategy for reducing health inequities in low- and middle-income countries (LMIC). Yet there is limited evidence on whether and how CHW programmes achieve this. This systematic review aimed to synthesise research findings on the following questions: (1) How effective are CHW interventions at reaching the most disadvantaged groups in LMIC contexts? and (2) What evidence exists on whether and how these programmes reduce health inequities in the populations they serve? METHODS: We searched six academic databases for recent (2014-2020) studies reporting on CHW programme access, utilisation, quality, and effects on health outcomes/behaviours in relation to potential stratifiers of health opportunities and outcomes (e.g., gender, socioeconomic status, place of residence). Quantitative data were extracted, tabulated, and subjected to meta-analysis where appropriate. Qualitative findings were synthesised using thematic analysis. RESULTS: One hundred sixty-seven studies met the search criteria, reporting on CHW interventions in 33 LMIC. Quantitative synthesis showed that CHW programmes successfully reach many (although not all) marginalized groups, but that health inequalities often persist in the populations they serve. Qualitative findings suggest that disadvantaged groups experienced barriers to taking up CHW health advice and referrals and point to a range of strategies for improving the reach and impact of CHW programmes in these groups. Ensuring fair working conditions for CHWs and expanding opportunities for advocacy were also revealed as being important for bridging health equity gaps. CONCLUSION: In order to optimise the equity impacts of CHW programmes, we need to move beyond seeing CHWs as a temporary sticking plaster, and instead build meaningful partnerships between CHWs, communities and policy-makers to confront and address the underlying structures of inequity. TRIAL REGISTRATION: PROSPERO registration number CRD42020177333 .

Clinical Significance of MicroRNA-29a and MicroRNA-100 Gene Expression in Pediatric Acute Myeloid Leukemia.

AIM: The aim of this study was to evaluate the diagnostic and prognostic performance of miRNA-29a and miRNA-100 in pediatric acute myeloid leukemia (AML). PATIENTS AND METHODS: In all, 73 children with diagnosed pediatric AML (based on standard morphologic, cytochemical, cytogenetic, immunologic, and molecular workup, and the French-American British classification) admitted to Children's Cancer Hospital Egypt (CCHE-57357), and 9 healthy age-matched and sex-matched controls were recruited for a case-control study. Gene expression levels of miRNA-29a and miRNA-100 were assessed using real-time quantitative RT-PCR. RESULTS: When diagnosed, patients had a significantly higher expression of miRNA-100 as against controls (median [range]: 12.99 [0.92-851.38] vs. 0.26 [0.03-2.67], P<0.001), with a significantly lower expression of miRNA-29a (2.08 [0.02-19.72] vs. 24.95 [15.48-42.54], P<0.001). Likewise, high-risk patients according to cytogenetic stratification had significantly higher miRNA-100 expression and lower miRNA-29a expression. Both miRNA-100 and miRNA-29a performed well as diagnostic markers of pediatric AML with an area under the curve of 0.977 (95% confidence interval [95% CI: 0.943-1.0]) and 0.994 (0.982-1.0) for miRNA-100 and miRNA-29a, respectively. Both miRNA-29a (odds ratio [95% CI]: 0.160 [0.054-0.474], P=0.001) and miRNA-100 (odds ratio [95% CI]: 1.997 [1.994-2.001], P=0.047) were identified as significant predictors of treatment response. CONCLUSION: The miRNA-29a and miRNA-100 expression may serve as diagnostic and prognostic markers in pediatric AML.

Temporal trends in childhood cancer survival in Egypt, 2007 to 2017: A large retrospective study of 14 808 children with cancer from the Children's Cancer Hospital Egypt.

Childhood cancer is a priority in Egypt due to large numbers of children with cancer, suboptimal care and insufficient resources. It is difficult to evaluate progress in survival because of paucity of data in National Cancer Registry. In this study, we studied survival rates and trends in survival of the largest available cohort of children with cancer (n = 15 779, aged 0-18 years) from Egypt between 2007 and 2017, treated at Children's Cancer Hospital Egypt-(CCHE), representing 40% to 50% of all childhood cancers across Egypt. We estimated 5-year overall survival (OS) for 14 808 eligible patients using Kaplan-Meier method, and determined survival trends using Cox regression by single year of diagnosis and by diagnosis periods. We compared age-standardized rates to international benchmarks in England and the United States, identified cancers with inferior survival and provided recommendations for improvement. Five-year OS was 72.1% (95% CI 71.3-72.9) for all cancers combined, and survival trends increased significantly by single year of diagnosis (P < .001) and by calendar periods from 69.6% to 74.2% (P < .0001) between 2007-2012 and 2013-2017. Survival trends improved significantly for leukemias, lymphomas, CNS tumors, neuroblastoma, hepatoblastoma and Ewing Sarcoma. Survival was significantly lower by 9% and 11.2% (P < .001) than England and the United States, respectively. Significantly inferior survival was observed for the majority of cancers. Although survival trends are improving for childhood cancers in Egypt/CCHE, survival is still inferior in high-income countries. We provide evidence-based recommendations to improve survival in Egypt by reflecting on current obstacles in care, with further implications on practice and policy.

Systematic review of infant and young child complementary feeding practices in South Asian families: the Pakistan perspective.

OBJECTIVE: Suboptimal nutrition among children remains a problem among South Asian (SA) families. Appropriate complementary feeding (CF) practices can greatly reduce this risk. Thus, we undertook a systematic review of studies assessing CF (timing, dietary diversity, meal frequency and influencing factors) in children aged <2 years in Pakistan. DESIGN: Searches between January 2000 and June 2016 in MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, CINAHL, Cochrane Library, BanglaJOL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research on CF practices in SA children aged 0-2 years and/or their families. Search terms: 'children', 'feeding' and 'Asians' with their derivatives. Two researchers undertook study selection, data extraction and quality appraisal (EPPI-Centre Weight of Evidence). RESULTS: From 45 712 results, seventeen studies were included. Despite adopting the WHO Infant and Young Child Feeding guidelines, suboptimal CF was found in all studies. Nine of fifteen studies assessing timing recorded CF introduced between 6 and 9 months. Five of nine observed dietary diversity across four of seven food groups; and two of four, minimum meal frequency in over 50 % of participants. Influencing factors included lack of CF knowledge, low maternal education, socio-economic status and cultural beliefs. CONCLUSIONS: This is the first systematic review to evaluate CF practices in Pakistan. Campaigns to change health and nutrition behaviour are needed to meet the substantial unmet needs of these children.

Systematic review of infant and young child complementary feeding practices in South Asian families: the India perspective.

OBJECTIVE: Suboptimal nutrition among children remains a problem among South Asian (SA) families. Appropriate complementary feeding (CF) practices can greatly reduce this risk. Thus, we undertook a systematic review of studies assessing CF (timing, dietary diversity, meal frequency and influencing factors) in children aged <2 years in India. DESIGN: Searches between January 2000 and June 2016 in MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, CINAHL, Cochrane Library, BanglaJOL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research on CF practices in SA children aged 0-2 years and/or their families. Search terms: 'children', 'feeding' and 'Asians' and derivatives. Two researchers undertook study selection, data extraction and quality appraisal (EPPI-Centre Weight of Evidence). RESULTS: From 45 712 abstracts screened, sixty-four cross-sectional, seven cohort, one qualitative and one case-control studies were included. Despite adopting the WHO Infant and Young Child Feeding guidelines, suboptimal CF practices were found in all studies. In twenty-nine of fifty-nine studies, CF was introduced between 6 and 9 months, with eight studies finding minimum dietary diversity was achieved in 6-33 %, and ten of seventeen studies noting minimum meal frequency in only 25-50 % of the study populations. Influencing factors included cultural influences, poor knowledge on appropriate CF practices and parental educational status. CONCLUSIONS: This is the first systematic review to evaluate CF practices in SA in India. Campaigns to change health and nutrition behaviour and revision of nationwide child health nutrition programmes are needed to meet the substantial unmet needs of these children.

Monitoring Activity for Recognition of Illness in Experimentally Infected Weaned Piglets Using Received Signal Strength Indication ZigBee-based Wireless Acceleration Sensor.

In this experiment, we proposed and implemented a disease forecasting system using a received signal strength indication ZigBee-based wireless network with a 3-axis acceleration sensor to detect illness at an early stage by monitoring movement of experimentally infected weaned piglets. Twenty seven piglets were divided into control, Salmonella enteritidis (SE) infection, and Escherichia coli (EC) infection group, and their movements were monitored for five days using wireless sensor nodes on their backs. Data generated showed the 3-axis movement of piglets (X-axis: left and right direction, Y-axis: anteroposterior direction, and Z-axis: up and down direction) at five different time periods. Piglets in both infected groups had lower weight gain and feed intake, as well as higher feed conversion ratios than the control group (p<0.05). Infection with SE and EC resulted in reduced body temperature of the piglets at day 2, 4, and 5 (p<0.05). The early morning X-axis movement did not differ between groups; however, the Y-axis movement was higher in the EC group (day 1 and 2), and the Z-axis movement was higher in the EC (day 1) and SE group (day 4) during different experimental periods (p<0.05). The morning X and Y-axis movement did not differ between treatment groups. However, the Z-axis movement was higher in both infected groups at day 1 and lower at day 4 compared to the control (p<0.05). The midday X-axis movement was significantly lower in both infected groups (day 4 and 5) compared to the control (p<0.05), whereas the Y-axis movement did not differ. The Z-axis movement was highest in the SE group at day 1 and 2 and lower at day 4 and 5 (p<0.05). Evening X-axis movement was highest in the control group throughout the experimental period. During day 1 and 2, the Z-axis movement was higher in both of the infected groups; whereas it was lower in the SE group during day 3 and 4 (p<0.05). During day 1 and 2, the night X-axis movement was lower and the Z-axis movement was higher in the infected piglets (p<0.05). Overall, the movement of infected piglets was altered, and the acceleration sensor could be successfully employed for monitoring pig activity.

Effects of Bacillus amyloliquefaciens as a probiotic strain on growth performance, cecal microflora, and fecal noxious gas emissions of broiler chickens.

This experiment was conducted to investigate the effects of Bacillus amyloliquefaciens probiotic (BAP) as a direct-fed microbial on growth performance, cecal microflora, serum immunoglobulin levels, and fecal noxious gas emissions of broiler chickens. A total of 400 one-day-old broiler chicks (Ross 308) were randomly assigned to 1 of 5 treatment diets formulated to supply 0, 1, 5, 10, and 20 g/kg of BAP and were fed for 35 d. Each treatment had 8 replicate pens with 10 birds per replicate. On completion of the growth trial, fecal samples were collected, and ammonia (NH3) and hydrogen sulfide (H2S) emissions were measured. Increasing concentration of BAP had positive linear effect on the ADG of broilers (P < 0.05) throughout the experimental period, with the highest values being observed in broilers offered 20 g/kg of BAP. The ADFI increased linearly (P < 0.02) with the inclusion of BAP during the overall experimental period (d 0 to 35). Providing BAP had a negative linear effect on FCR from d 0 to 21 and d 0 to 35 (P < 0.01). Supplementation with BAP did not affect cecal Lactobacillus and Bacillus content, but exerted negative linear effect on cecal Escherichia coli (P < 0.05) with increasing the level of BAP in broiler diets. Additionally, BAP modified immune response of broilers by linearly increasing serum IgG and IgA (P < 0.01). Dietary BAP resulted in decreased fecal NH3 emissions at 0 (linear, P < 0.001), 3, 6, 12, 24, and 48 h of incubation (linear, P < 0.05; quadratic, P < 0.01). Supplementation of BAP exerted negative linear and quadratic effects on fecal emissions of H2S (P < 0.001) throughout the incubation period except at 48 h, and the optimum effect was found when BAP was provided at 5 g/kg of diet. Based on these results, Bacillus amyloliquefaciens could be suggested as a potential feed additive of broiler diets.

Acute promyelocytic leukemia in children cancer hospital Egypt.

BACKGROUND: Pediatric acute promyelocytic leukemia (APL) accounts for 5 to 15% of all myelocytic leukemia. A retrospective analysis of pediatric patients diagnosed and treated with APL was conducted at CCHE from July 2012 to the end of December 2019, to report the prevalence, clinical characteristics, results, and risk factors associated with induction failure and early death. RESULT: Sixty-two patients were reported, with an age greater than ten, an initial poor coagulation profile, and a total leukocyte count (TLC) greater than 30 103/mm3 influencing 5-year overall (OS) and event-free survival (EFS), as well as a high promyelocyte count affecting 5-year EFS. Patients received a regimen based on the COG AAML0631 protocol. High-risk patients with an initial TLC > 10 × 103/mm3 and an initial promyelocytic count of 30% or more with a substantial P-value are prognostic markers for early death during induction. In females, wild FLT3 increases the risk of differentiation syndrome (DS). Receiving steroids with all-trans retinoic acid (ATRA) induction may reduce the occurrence of DS. Relapse alters the outcome. In the current study, 45 patients are alive in complete remission, with a 5-year OS of 72.5% and a 5-year EFS of 69.4%, respectively. CONCLUSION: Pediatric APL outcomes are influenced by age above 10, an initial poor coagulation profile, and a promyelocyte count of more than 10%. An initial leukocyte count of more than 10 × 103/mm and an initial promyelocytic count of more than 30% increase the risk of early death. Receiving steroids with ATRA may reduce the occurrence of DS.

Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.

Background: Molecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis. Methods: Quantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders. Results: At diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders' post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, p<0.001), event-free survival (EFS) (33.3% vs 82.6%, p<0.001), and higher CIR (66.6% vs 10.6%, p<0.001) at 24 months compared to good responders. Even after adjusting for potential confounders, it remained an independent adverse prognostic factor for OS (p=0.04) and EFS (p=0.008). High concordance rates between WT1-based MRD response and molecular MRD were observed in CBF patients. Furthermore, failure to achieve either a 3-log reduction by RT-PCR or a 2-log reduction by WT1 indicated a high risk of relapse. Combining MFC-based and WT1-based MRD results among the intermediate-risk group identified patients with unfavorable prognosis (positive predictive value [PPV] 100%, negative predictive value [NPV] 85%, and accuracy 87.5%). Conclusion: WT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.

Pediatric pulmonary multisystem langerhans cell histiocytosis: does lung lesion severity affect the outcome?

BACKGROUND: The pediatric pulmonary multisystem Langerhans cell histiocytosis (PPM LCH) is associated with either low risk or high risk organ(s). The nodulo-cystic lung lesions although pathognomonic, yet are very variable in severity and remain a source of controversy in certifying pulmonary LCH diagnosis. The study aimed to examine the prognostic value of clinical respiratory manifestations and radiological lung lesions severity. This is through associating a CT chest triad of bilateral, extensive and diffuse lesions. It is a retrospective study of 350 LCH patients who received systemic treatment at Children's Cancer Hospital Egypt during the period from 2007 to 2020. RESULTS: Sixty-seven patients (67/350-19.1%) had PPM LCH at presentation. Severe lung lesions were present in 24 of them. The median follow-up period was 61 months (IQR: 3.4-8.3). The 5-year overall survival (OS) and event free survival (EFS) was 89% and 56.6% respectively. The EFS, for severe radiological lesions triad was 38% ± 20.7 versus 66% ± 16.2 for non-severe lesions triad p 0.002, while for presence of chest X-ray changes 27% ± 22.344 versus absence of chest X ray changes 66% ± 14.7 p 0.001, for clinical respiratory manifestations 13% ± 13.9 versus none 62% ± 22.9 p < 0.001, for RO- with severe lung lesions 47% ± 30.4 versus RO- without severe lung lesions 69% ± 5.9 p 0.04. There was a tendency for the independent prognostic impact of severe lung involvement; aHR = 1.7 (95% CI 0.92-3.13, p = 0.09). CONCLUSION: Although the lung is a low -risk organ per se in LCH, our study demonstrates a non negligeable prognostic impact of severe lung involvement in the risk stratification of pediatric LCH. This warrants further study and external validation.

Cost-effectiveness of childhood cancer treatment in Egypt: Lessons to promote high-value care in a resource-limited setting based on real-world evidence.

Background: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status. Methods: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality. Findings: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers. Interpretation: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy. Funding: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC.

Systematic review of costs and cost-effectiveness of treatment for relapsed/refractory acute leukemia in children and young adults.

INTRODUCTION: Survival outcomes of children with relapsed/refractory (r/r) acute leukemia remain poor. Novel expensive treatments have been developed to improve their outcomes, yet, limited evidence exists about cost-effectiveness of alternative treatment strategies. AREAS COVERED: A systematic review was conducted to summarize health-economic evidence about costs/cost-effectiveness of treating r/r acute leukemia in children/young adults. We searched Medline, Embase, and Cochrane databases until August 13th, 2021. Eligible articles included peer-reviewed original studies addressing r/r pediatric/young-adult acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Quality assessment was conducted using Consolidated Health Economics Evaluation Reporting Standards (CHEERS) checklist. EXPERT OPINION: The majority of papers focused on CAR-T cell therapy, which is still a novel treatment for r/r ALL, and was found to be cost-effective, yet, there remain concerns over its long-term effectiveness, affordability, and equity in access. The next best treatment option is Blinatumomab, followed by Clofarabine therapy, whereas FLA-IDA salvage chemotherapy provides least value for money. The quality of evidence is moderate to high, with limited generalizability of findings due to high variability in outcomes obtained from modeling studies. Limited studies evaluated r/r AML. We provide recommendations to deliver cost-effective treatments in real-world contexts, with implications for healthcare policy and practice.

Characteristics, Treatment Complexity, and Outcome of Mixed-Phenotype Acute Leukemia in Children in a Low-Middle-Income Country.

Background: Mixed-phenotype acute leukemia (MPAL) in children is an uncommon subtype of acute leukemia that cannot be definitively assigned to a specific lineage. There is no consensus on the best approach to therapy. Management is more complex in low-middle-income countries (LMICs). Aim: To evaluate the clinicopathological characteristics and outcomes of patients with MPAL in a developing country. Patients and Methods: A retrospective descriptive study of 42 pediatric patients newly diagnosed with MPAL from July 2007 until December 2017. Results: The immunophenotyping was T/Myeloid in 24 patients (57.1%) and B/Myeloid in 16 (38.1%). Three subjects had MLL gene rearrangement, two had Philadelphia-positive chromosomes, and eight had FMS-like tyrosine kinase 3 (FLT3-ITD) internal tandem duplication (FLT3-ITD) with a ratio >0.4. Two subjects died before starting chemotherapy. Ten patients (25%) received acute lymphoblastic leukemia (ALL) induction, and all achieved complete remission (CR) with no induction deaths and no shift of therapy. Thirty patients (75%) started therapy with acute myeloid leukemia (AML) induction: five (16.6%) died during induction, 17 (56.7%) achieved CR, and 10 patients received maintenance ALL therapy after ending AML treatment. Four of the eight patients with induction failure were switched to ALL therapy. The 5-year event-free survival (EFS) and overall survival (OS) rates were 56.7% [standard error (SE): 8.1%] and 61% (SE: 8%), while the cumulative incidence of relapse was 21.7% (SE: 6.7%), with a median follow-up duration of 5.8 years. Patients treated with ALL-directed therapy had a 5-year EFS rate of 111 70% (SE: 14%) and OS rate of 78.8% (SE: 13%). Patients treated with ALL-directed therapy had a 5-year EFS rate of 70% (SE: 14.5%) and OS rate of 78.8% (SE: 13%). FLT3-ITD mutation showed a significantly lower 5-year EFS rate of 28.6% (SE: 17%) vs. 75% (SE: 9%) for the wild type, p = 0.032. Undernourished patients with a body mass index (BMI) z-score ≤-2 at presentation had a significantly lower 5-year EFS rate of 20% (SE: 17%) compared to 61.8% (SE: 8%) for patients with BMI z-score >-2, p = 0.015. Conclusion: This study supports ALL-directed therapy for pediatric MPAL in a setting of LMIC. Given the poor outcome of FLT3-ITD, the role of FLT3 inhibitor needs to be explored in this subset of cases.

miR-370 is better than miR-375 as a non-invasive diagnostic biomarker for pediatric acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by heterogeneity in phenotypic, genotypic, and clinical traits. miRNAs play an important role in pathogenesis and diagnosis of adult AML. Such information is not available about miRNA expression role in pediatric AML. OBJECTIVE: We aimed to investigate the expression of miR-370 and miR-375 as new diagnostic biomarkers to discriminate pediatric AML patients and to predict their roles in the disease molecular basis. METHODS: The expression of both miR-370 and miR-375 in peripheral blood (PB) of pediatric AML patients was assessed by QPCR; their impact for diagnosis was evaluated by ROC curve and their roles in pediatric AML development were predicted by bioinformatics analysis. RESULTS: The expression of miR-370 and miR-375 levels was significantly decreased in pediatric AML patients, suggesting them as tumor suppressor miRNAs as supported by bioinformatics analysis. miR-370 showed better potential and sensitivity toscreen pediatric AML patients and more significant correlation with AML risk than miR-375. This is the first study to report the positive correlation between both miR-370 and miR-375. CONCLUSION: miR-370 level in peripheral blood can serve as a potential non-invasive diagnostic biomarker and was significantly correlated with AML risk. We strongly recommend PB miRNAs as diagnostic biomarkers for pediatric AML.

Aetiology of nutritional rickets in rural Bangladeshi children.

OBJECTIVES: A high prevalence of rickets of unknown aetiology has been reported in Chakaria, Bangladesh. Classically, rickets is caused by vitamin D deficiency but increasing evidence from Africa and Asia points towards other nutritional deficiencies or excessive exposure to some metals. The aim of this study was to investigate the aetiology of rickets in rural Bangladeshi children. METHODS: 64 cases with rickets-like deformities were recruited at first presentation together with age-sex-village matched controls. Data and sample acquisition included anthropometry, radiographs, fasted plasma and urinary samples, 24 h weighed dietary intake together with a 24 h urine collection, and 13C-breath tests to detect Helicobacter (H.) pylori infection. RESULTS: One child had active rickets and frank hypovitaminosis D (F, n = 1) and one had deformities with radiological features of Blount disease (M, n = 1). The remaining cases were grouped into those with active rickets, defined as a radiographic Thacher score ≥1.5 (Group A, n = 24, 12M, 12F) and rickets-like bone deformities but not active rickets (Group B, n = 38, 28M, 10F). All children had a low dietary calcium intake, but this was lower in Group A than their controls (mean (SD): 156 (80) versus 323 (249) mg/day, p = 0.005). Plasma 25-hydroxyvitamin D (25OHD) was lower in Group A compared to controls; 63% of Group A and 8% of controls had a concentration <25 nmol/L (p ≤ 0.0001). There was, however, no evidence of differences in skin sunshine exposure. Group A had lower plasma calcium and phosphate and higher 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH). 88% of Group A and 0% of controls had undetectable plasma intact fibroblast growth factor (iFGF23), with c-terminal FGF23 (cFGF23) concentrations in the normal range. Urinary phosphate and daily outputs of environmental metals relative to creatinine were higher and tubular maximal phosphate reabsorption per unit glomerular filtration rate (TmP/GFR) was lower in Group A compared to controls. Although less pronounced than Group A, Group B had higher alkaline phosphatase, 1,25(OH)2D and PTH concentrations than controls but similar calcium intake, TmP/GFR, iFGF23 and cFGF23 concentrations. Mean 25OHD concentrations were also similar to controls and there was no significant difference in the percentage <25 nmol/L (Group B: 13%, controls: 5%, p = 0.2) No group differences were seen in prevalence of anaemia, iron deficiency or H. pylori infection. CONCLUSION: Nutritional rickets in this region is likely to be predominantly due to low calcium intake in the context of poor vitamin D status and exposure to environmental metals, but not H. pylori infection, anaemia or iron deficiency.

Effect of timing of pulmonary metastasis occurrence on the outcome of metastasectomy in osteosarcoma patients.

BACKGROUND: Complete metastasectomy is the best predictor of survival in patients with osteosarcoma pulmonary metastases. There has been some controversy in the literature regarding the prognostic significance of the timing of occurrence of lung metastasis. METHODS: We reviewed the clinical course of all osteosarcoma patients with pulmonary metastases treated by metastasectomy in our hospital from January 2008 through December 2016. Each patient who underwent metastasectomy was placed into one of three groups based on whether lung metastases were present at initial presentation (Group 1), developed during chemotherapy (Group 2), or appeared after completion of chemotherapy (Group 3). Data were obtained retrospectively and follow-up was obtained until the end of June 2017. RESULTS: We identified 170 patients with pulmonary nodules of whom 99 (58.2%) underwent at least one metastasectomy (149 thoracotomies). Eleven patients had benign pulmonary nodules and were excluded. The other 88 patients were classified as Group 1 (37), Group 2 (18) or Group 3 (33). The median follow-up was 35 months (range 8 to 99). Postmetastasis 5-year overall survival (OS) was 38.1 ±â€¯6.4%; event-free survival (EFS) was 25 ±â€¯5.3%. By group, postmetastasis 5-year OS and EFS were 34.3 ±â€¯13% and 18 ±â€¯9.3% in Group 1, 8 ±â€¯6.5% and 6.5 ±â€¯5% in Group 2, and 52 ±â€¯11.4% and 25 ±â€¯9% in Group 3 (P < 0.001). In univariate analysis, the only significant factors associated with survival were timing of occurrence of lung metastasis and the number of lung nodules found. CONCLUSION: The timing of occurrence of lung metastasis is an important prognostic factor among osteosarcoma patients eligible for metastasectomy. Patients whose metastases occurred during chemotherapy had the worst survival. LEVEL OF EVIDENCE: Level II.

Complementary Feeding Practices for South Asian Young Children Living in High-Income Countries: A Systematic Review.

Sub-optimal nutrition among South Asian (SA) children living in high-income countries is a significant problem. High rates of obesity have been observed in this population, and differential complementary feeding practices (CFP) have been highlighted as a key influence. Our aim was to undertake a systematic review of studies assessing CFP in children under two years of age from SA communities living in high-income countries, including dietary diversity, timing, frequency and promotors/barriers. Searches covered January 1990⁻July 2018 using MEDLINE, EMBASE, Global Health, Web of Science, BanglaJOL, OVID Maternity and Infant Care, CINAHL, Cochrane Library, POPLINE and World Health Organisation (WHO) Global Health Library. Eligible studies were primary research on CFP in SA children aged 0⁻2 years. Search terms were "children", "feeding" and "South Asian", and derivatives. Quality appraisal used the Evidence for Policy and Practice Information (EPPI) Weight of Evidence scoring. From 50,713 studies, 13 were extracted with ten from the UK, and one each from the USA, Canada and Singapore. Sub-optimal CFP were found in all studies. All ten studies investigating timing reported complementary feeding (CF) being commenced before six months. Promoters/barriers influencing CFP included income, lack of knowledge, and incorrect advice. This is the first systematic review to evaluate CFP in SA children living in high-income countries and these findings should inform the development of effective interventions for SA infants in these settings.

Effects of Dietary Punica granatum L. By-products on Performance, Immunity, Intestinal and Fecal Microbiology, and Odorous Gas Emissions from Excreta in Broilers.

The fruit Punica granatum L. has been used for years in traditional medicine owing to the presence of several phytobiotics with antimicrobial and immunomodulatory properties. This study investigated the effects of dietary supplementation with Punica granatum L. by-products (PGB) on performance, immunity, intestinal and excreta microflora, and odorous gas emissions from excreta of broiler chickens. Three experimental diets containing 0, 0.5 and 1.0% PGB were fed to 240 one-day-old broiler chicks until 35 days. Dietary PGB linearly reduced the average daily feed intake and feed conversion ratio of broilers. Supplementation with 1% PGB led to a linear increase in the relative weight of the spleen and bursa of Fabricius. The concentration of serum IgA and IgG increased linearly in response to dietary PGB. In the ileal digesta, the concentration of Saccharomyces cerevisiae increased linearly and quadratically in response to dietary PGB. Moreover, dietary PGB led to a linear decrease in Escherichia coli and Salmonella spp. alongside reducing the pH of the ileal digesta. In the cecal digesta, the concentration of Bacillus bacteria increased linearly in response to both levels of dietary PGB, while the concentrations of E. coli and Salmonella decreased when the diet was supplemented with 1% PGB, as did cecal pH. At 35 day, both levels of PGB increased the concentration of fecal Bacillus, whereas only 1% PGB increased the concentration of S. cerevisiae at 21 day. Increasing levels of PGB induce a linear reduction in fecal E. coli at 21 and 35 day, whereas Salmonella only at 21 day. Regarding the average of 48 h, dietary PGB effectively reduced the emissions of ammonia and methanethiol from broiler excreta. In conclusion, the results suggest that, dietary PGB improved immunity and the intestinal microbial ecosystem of broilers along with reduced odorous gas emissions from excreta.

A systematic review of complementary feeding practices in South Asian infants and young children: the Bangladesh perspective.

BACKGROUND: Sub-optimal nutrition among children remains a problem across South Asia (SA). Appropriate complementary feeding practices (CFP) can greatly reduce this risk. The primary objective of this systematic review (SR) of CF studies was to assess timing, dietary diversity, meal frequency and influencing factors in children under two in Bangladesh. METHODS: Searches included English-language research published between January 2000 and June 2016 within MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, BanglaJOL, Cochrane Library, CINAHL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research concerning the adequacy of complementary feeding practices in South Asian children aged 0-2 years and/or their families. We excluded interventional papers and those focusing exclusively on breast-feeding. In total 45,712 titles and abstracts were screened against inclusion criteria, 860 of which received independent full text review by two reviewers. 36 papers relevant to Bangladesh were identified. The 'EPPI-Centre Weight of Evidence Framework' was used to objectively assess each study's value in answering the review question. As per WHO Infant and Young Children Feeding Guidelines (IYCF), introduction of CF was assessed as the proportion of infants aged 6-8 months who received solid, semi-solid or soft foods. Search terms were: "children", "feeding" and "Asians" with their derivatives. Two researchers undertook study selection, data extraction and quality appraisal. RESULTS: Three cohort, 30 cross-sectional and 3 mixed methods studies were included. Despite adopting the WHO IYCF Guidelines, sub-optimal CF practices were found in many studies. Timely initiation of CF practices ranged from 24 to 83%. Achieved minimum dietary diversity ranged from 25% to 44% and minimum meal frequency from 33% to 81%. Influencing factors included maternal education, poor knowledge of CF practices and socioeconomic variables. CONCLUSIONS: This is the first systematic review to evaluate CF practices in Bangladesh. Despite adoption of the WHO IYCF guidelines, inadequate CFP remain in communities across Bangladesh. TRIAL REGISTRATION: PROSPERO Registration No: CRD42014014025.