Do we need to reconsider the CMAM admission and discharge criteria?; an analysis of CMAM data in South Sudan

Background: Weight-for-height Z-score (WHZ) and Mid Upper Arm Circumference (MUAC) are both commonly used as acute malnutrition screening criteria. However, there exists disparity between the groups identified as malnourished by them. Thus, here we aim to investigate the clinical features and linkage with chronicity of the acute malnutrition cases identified by either WHZ or MUAC. Besides, there exists evidence indicating that fat restoration is disproportionately rapid compared to that of muscle gain in hospitalized malnourished children but related research at community level is lacking. In this study we suggest proxy measure to inspect body composition restoration responding to malnutrition management among the malnourished children. Methods: The data of this study is from World Vision South Sudan’s emergency nutrition program from 2006 to 2012 (4443 children) and the nutrition survey conducted in 2014 (3367 children). The study investigated clinical presentations of each type of severe acute malnutrition (SAM) by WHZ (SAM-WHZ) or MUAC (SAM-MUAC), and analysed correlation between each malnutrition and chronic malnutrition. Furthermore, we explored the pattern of body composition restoration during the recovery phase by comparing the relative velocity of MUAC3 with that of weight gain. Results: As acutely malnourished children identified by MUAC more often share clinical features related to chronic malnutrition and minimal overlapping with malnourished children by WHZ, Therefore, MUAC only screening in the nutrition program would result in delayed identification of the malnourished children. Conclusions: The relative velocity of MUAC3 gain was suggested as a proxy measure for volume increase, and it was more prominent than that of weight gain among the children with SAM by WHZ and MUAC over all the restoring period. Based on this we made a conjecture about dominant fat mass gain over the period of CMAM program. Also, considering initial weight gain could be ascribed to fat mass increase, the current discharge criteria would leave the malnourished children at risk of mortality even after treatment due to limited restoration of muscle mass. Given this, further research should be followed including assessment of body composition for evidence to recapitulate and reconsider the current admission and discharge criteria for CMAM program

Analysis of pharmacogenomic variants associated with population differentiation.

In the present study, we systematically investigated population differentiation of drug-related (DR) genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB) database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA) F-test, Fst, and Nearest Shrunken Centroid Method (NSCM). Fst showed high sensitivity with stable specificity among varying sample sizes; thus, we selected Fst for determining population differentiation. Second, we divided DR genes from PharmGKB into two groups based on the degree of population differentiation as assessed by Fst: genes with a high level of differentiation (HD gene group) and genes with a low level of differentiation (LD gene group). Last, we conducted a gene ontology (GO) analysis and pathway analysis. Using all genes in the human genome as the background, the GO analysis and pathway analysis of the HD genes identified terms related to cell communication. "Cell communication" and "cell-cell signaling" had the lowest Benjamini-Hochberg's q-values (0.0002 and 0.0006, respectively), and "drug binding" was highly enriched (16.51) despite its relatively high q-value (0.0142). Among the 17 genes related to cell communication identified in the HD gene group, five genes (STX4, PPARD, DCK, GRIK4, and DRD3) contained single nucleotide polymorphisms with Fst values greater than 0.5. Specifically, the Fst values for rs10871454, rs6922548, rs3775289, rs1954787, and rs167771 were 0.682, 0.620, 0.573, 0.531, and 0.510, respectively. In the analysis using DR genes as the background, the HD gene group contained six significant terms. Five were related to reproduction, and one was "Wnt signaling pathway," which has been implicated in cancer. Our analysis suggests that the HD gene group from PharmGKB is associated with cell communication and drug binding

Do we need to reconsider the CMAM admission and discharge criteria?; an analysis of CMAM data in South Sudan

Background: Weight-for-height Z-score (WHZ) and Mid Upper Arm Circumference (MUAC) are both commonly used as acute malnutrition screening criteria. However, there exists disparity between the groups identified as malnourished by them. Thus, here we aim to investigate the clinical features and linkage with chronicity of the acute malnutrition cases identified by either WHZ or MUAC. Besides, there exists evidence indicating that fat restoration is disproportionately rapid compared to that of muscle gain in hospitalized malnourished children but related research at community level is lacking. In this study we suggest proxy measure to inspect body composition restoration responding to malnutrition management among the malnourished children. Methods: The data of this study is from World Vision South Sudan’s emergency nutrition program from 2006 to 2012 (4443 children) and the nutrition survey conducted in 2014 (3367 children). The study investigated clinical presentations of each type of severe acute malnutrition (SAM) by WHZ (SAM-WHZ) or MUAC (SAM-MUAC), and analysed correlation between each malnutrition and chronic malnutrition. Furthermore, we explored the pattern of body composition restoration during the recovery phase by comparing the relative velocity of MUAC3 with that of weight gain. Results: As acutely malnourished children identified by MUAC more often share clinical features related to chronic malnutrition and minimal overlapping with malnourished children by WHZ, Therefore, MUAC only screening in the nutrition program would result in delayed identification of the malnourished children. Conclusions: The relative velocity of MUAC3 gain was suggested as a proxy measure for volume increase, and it was more prominent than that of weight gain among the children with SAM by WHZ and MUAC over all the restoring period. Based on this we made a conjecture about dominant fat mass gain over the period of CMAM program. Also, considering initial weight gain could be ascribed to fat mass increase, the current discharge criteria would leave the malnourished children at risk of mortality even after treatment due to limited restoration of muscle mass. Given this, further research should be followed including assessment of body composition for evidence to recapitulate and reconsider the current admission and discharge criteria for CMAM program.This article is published as Ahn, E., Ouma, C., Loha, M. et al. Do we need to reconsider the CMAM admission and discharge criteria?; an analysis of CMAM data in South Sudan. BMC Public Health 20, 511 (2020). doi: 10.1186/s12889-020-08657-x.</p

Sensitivities (%) of each measure from simulation data under H₀:<i>d</i> = 0.05,0.1…,0.3 due to an increase in sample size (Scenario I).

<p><b>A</b>. (<i>n</i>₁,<i>n</i>₂,<i>n</i>₃) = (100,100,100). <b>B</b>. (<i>n</i>₁,<i>n</i>₂,<i>n</i>₃) = (200,200,200). <b>C</b>. (<i>n</i>₁,<i>n</i>₂,<i>n</i>₃) = (100,100,100). Blue line: chi-square test; red line: F_st; black dotted line: ANOVA F-test; green dotted line: SS_d from NSCM.</p

Summary of each SNP group.

<p>Summary of each SNP group.</p

Boxplots representing four measures of simulation data with an increase in <i>d</i>.

<p><b>A.</b> Variation of distributions due to increase in sample sizes (Case I). <b>B.</b> Variation of distributions due to bias of sample sizes (Case II). For both cases, the <i>x</i>-axis denotes the distance <i>d</i>, and the <i>y</i>-axis and denotes the following measures: -log₁₀<i>Pvalue</i> for chi-square test and ANOVA F-test; Weir and Cockerham’s F_st estimates for F_st; </p><p></p><p></p><p></p><p></p><p><mo>∑</mo></p><mo>​</mo><p></p><p><mi>d</mi><mi>i</mi><mn>2</mn></p><p></p><p></p><p></p> for NSCM.<p></p

Q-values and fold enrichments of significant terms in HD group.

<p>FE: Fold enrichment</p><p>BH’s q: Benjamini-Hochberg’s q-value</p><p>Q-values and fold enrichments of significant terms in HD group.</p

Sensitivities (%) of each measure from simulation data under H₀:<i>d</i>=0.05,0.1…,0.3 due to bias in sample size (Scenario II).

<p>A. (<i>n</i>₁,<i>n</i>₂,<i>n</i>₃) = (200,100,100). <b>B</b>. (<i>n</i>₁,<i>n</i>₂,<i>n</i>₃) = (100,200,100). <b>C</b>. (<i>n</i>₁,<i>n</i>₂,<i>n</i>₃) = (100,100,200). Blue line: chi-square test; red line: F_st; black dotted line: ANOVA F-test; green dotted line: SS_d from NSCM.</p

Histogram of sample sizes from 654 drug-related SNPs.

<p><b>A</b>. Total sample sizes of SNPs. <b>B</b>. Sample size of each population of SNPs. CHB and JPT are plotted separately according to the format of the original HapMap Data. SNPs with larger sample sizes are included in Phase III, and SNPs with smaller sample sizes are included in Phase II.</p