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Ajcn093294 1.13

AJCN. First published ahead of print February 25, 2015 as doi: 10.3945/ajcn.114.093294.
Community-based management of severe acute malnutrition in India:new evidence from Bihar1–3 Sakib Burza, Raman Mahajan, Elisa Marino, Temmy Sunyoto, Chandra Shandilya, Mohammad Tabrez, Kabita Kumari,Prince Mathew, Amar Jha, Nuria Salse, and Kripa Nath Mishra Background: An estimated one-third of the world's children who are According to the third Indian National Family Health Survey-3 wasted live in India. In Bihar state, of children ,5 y old, 27.1% are wasted conducted in 2005–2006, 19.8% of children ,5 y of age were and 8.3% have severe acute malnutrition (SAM). In 2009, Medecins Sans wasted and 6.4% suffered from severe acute malnutrition (SAM)4 in Frontieres (MSF) initiated a community-based management of acute mal- India. the situation appeared worse in the state of Bihar, where in nutrition (CMAM) program for children aged 6–59 mo with SAM.
children ,5 y of age, 27.1% were wasted and 8.3% suffered from Objective: In this report, we describe the characteristics and outcomes SAM (1). These findings suggest that, at any one point in time, an of 8274 children treated between February 2009 and September 2011.
average of 8 million children in India ,5 y of age suffer from Design: Between February 2009 and June 2010, the program admitted severe wasting, which is the most common form of SAM. This children with a weight-for-height z score (WHZ) ,23 SD and/or mid- number constitutes one-third of the global burden (2). The Indian upper arm circumference (MUAC) ,110 mm and discharged those government and a number of nongovernmental organizations who reached a WHZ .22 SDs and MUAC .110 mm. These variables (NGOs) are currently implementing various initiatives that address changed in July 2010 to admission on the basis of an MUAC ,115 mm SAM across the country. Although the principal strategy being and discharge at an MUAC $120 mm. Uncomplicated SAM cases were deployed remains inpatient care through Nutritional Rehabilitation treated as outpatients in the community by using a WHO-standard, Centers and Malnutrition Treatment Centers (3–6), there is a grow- ready-to-use, therapeutic lipid-based paste produced in India; compli- ing consensus within India that the adoption of community-based cated cases were treated as inpatients by using F75/F100 WHO-standard management of acute malnutrition (CMAM) is crucial to achieving milk until they could complete treatment in the community.
widespread, effective coverage and treatment of all children with Results: A total of 8274 children were admitted including 5149 girls SAM (7, 8). Furthermore, standardized inpatient management of (62.2%), 6613 children aged 6–23 mo (79.9%), and 87.3% children who SAM has been associated with worse outcomes than has manage- belonged to Scheduled Caste, Scheduled Tribe, or Other Backward Caste ment in the community, which is attributable partly to the risk of families or households. Of 3873 children admitted under the old criteria, children with SAM acquiring serious infections from other hospi- 41 children (1.1%) died, 2069 children (53.4%) were discharged as cured, talized patients and partly because of families' lack of acceptance of and 1485 children (38.3%) defaulted. Of 4401 children admitted under hospital-based care (9, 10).
the new criteria, 36 children (0.8%) died, 2526 children (57.4%) weredischarged as cured, and 1591 children (36.2%) defaulted. For children 1 From Medecins Sans Frontieres (MSF), New Delhi, India (SB, RM, EM, discharged as cured, the mean (6SD) weight gain and length of stay TS, CS, MT, KK, PM, and AJ); MSF, Barcelona, Spain (NS); and the De- were 4.7 6 3.1 and 5.1 6 3.7 g $ kg21 $ d21 and 8.7 6 6.1 and 7.3 6 partment of Pediatrics, Darbhangha Medical College Hospital, Darbhangha, 5.6 wk under the old and new criteria, respectively (P , 0.01). After India (KNM).
adjustment, significant risk factors for default were as follows: no com- All funding for the implementation of the program was received as munity referral for admission, more severe wasting on admission, youn- part of normal Medecins Sans Frontieres fundraising activities. This isa free access article, distributed under terms ( ger age, and a long commute for treatment.
publications/guidelines-and-policies/license/) that permit unrestricted Conclusions: To our knowledge, this is the first conventional CMAM noncommercial use, distribution, and reproduction in any medium, pro- program in India and has achieved low mortality and high cure rates vided the original work is properly cited.
in nondefaulting children. The new admission criteria lower the 3 Address correspondence to S Burza, C203 Defence Colony, New Delhi threshold for severity with the result that more children are included 1100204, India. E-mail: [email protected].
who are at lower risk of death and have a smaller WHZ deficit to 4 Abbreviations used: ANM, auxiliary nurse midwife; ASHA, accredited correct than do children identified by the old criteria. This study was social health activist; ATFC, Ambulatory Therapeutic Feeding Center; registered as a retrospective observational analysis of routine program CMAM, community-based management of acute malnutrition; GNM, gen-eral nurse midwife; IEC, information, education, and communication; LOS, data at as ISRCTN13980582.
length of stay; MSF, Medecins Sans Frontieres; MUAC, midupper arm cir- Clin Nutr doi: 10.3945/ajcn.114.093294.
cumference; NGO, nongovernmental organization; PHC, Primary HealthCenter; SAM, severe acute malnutrition; SC, Stabilization Center; WHZ, community-based management of acute malnutrition, weight-for-height z score.
India, severe acute malnutrition, severe wasting, mean upper arm cir- Received January 9, 2014. Accepted for publication February 4, 2015.
Am J Clin Nutr doi: 10.3945/ajcn.114.093294. Printed in USA. Ó 2015 American Society for Nutrition Copyright (C) 2015 by the American Society for Nutrition
After widespread flooding in Bihar, Medecins Sans Frontieres Center (PHC), and over the next 3 y, 5 ambulatory treatment (MSF) conducted a household-based survey in Darbhanga, which is centers [called Ambulatory Therapeutic Feeding Centers a district of 3.9 million people and one of the poorest in Bihar. The (ATFCs)] were established at different community settings survey showed that the prevalence of wasting and SAM in children within the block. Within the existing health infrastructure, age ,5 y was 19.4% and 4.8%, respectively (11). Consequently, government general nurse midwives (GNMs), auxiliary nurse under a memorandum of understanding with the district authorities midwives (ANMs), and accredited social health activists and, thereafter, consent from the Bihar State Health Society, in (ASHAs) were trained to use midupper arm circumference February 2009, MSF initiated a CMAM program in Biraul block, (MUAC) tapes (provided by MSF) to screen children aged 6–59 mo Darbhanga district. The CMAM model has been extensively used for SAM and refer identified cases to the CMAM program.
outside India, with .50 countries adopting this approach as their Within the CMAM program, MSF used GNMs and ANMs who first-line strategy for treating SAM (12). CMAM is based on prin- were also trained in the use of Salter scales (precision to 100 g) ciples that acknowledge both the need for prolonged treatment and and locally produced height boards (precision to 0.1 cm) to the small proportion of children with SAM who require inpatient record weight and height/length, respectively, and as a way of care for medical reasons and evidence that ambulatory management monitoring progress throughout treatment. Salter scales were in the community can be a cost-effective solution from both societal regularly calibrated and replaced as per manufacturer guidelines.
and health care provider perspectives (13–15). A standard CMAM Children admitted to the program were a mixture of those program consists of treatment sites close to the community where screened in the community and referred by ASHAs, those who the children with uncomplicated SAM, who constitute the majority self-presented for SAM screening, and those visiting the sites to of patients, can be seen weekly and an inpatient facility [Stabili- seek health care for other reasons. On admission, information on zation Center (SC)] that admits only children with SAM plus as- caste, which is a form of social stratification used in India, was sociated medical complications that require specialist medical also recorded by using the following categories and definitions: attention and keeping the children only until they recover enough to Scheduled Caste and Scheduled Tribe (terms used for 2 groups continue treatment as outpatients in the community.
of historically disadvantaged people recognized in India's However, a major obstacle to the widespread adoption of this Constitution), Other Backward Class (a collective term used by strategy in India is that the vast majority of evidence on the the Indian government for castes that are educationally and effectiveness of CMAM programs comes from African settings.
socially disadvantaged but not specifically mentioned in the Therefore, we conducted an observational, retrospective cohort Constitution), and General Category (not considered disadvan- study to assess key programmatic variables and clinical outcomes taged). The first 3 groups combined account for w60% of In- of India's first (and currently only to our knowledge) conven- dia's population.
tional setting CMAM program, which treated 8274 children Treatment centers were open on an average of 1 d/wk at each between February 2009 and September 2011. We also analyzed location, generally on the same day each week to provide con- the impact of adopting simpler admission and discharge criteria sistency for caregivers. Once a child was newly diagnosed with on the profile of admitted children and treatment outcomes.
SAM, his or her details were entered into a register, and healtheducation was provided to the caregiver while an ANM or GNMrepeated anthropometric measurements, took the child's vital signs, and performed a basic triage including a standardizedappetite test to determine the child's ability and willingness to Overview of the program eat (Table 1). The purpose of this test is to provide the child The CMAM program opened in Biraul block, which has with a small amount of food to see if a child with severe wasting a population of w286,000 people, in February 2009. The in- has the desire and strength to eat; if this is not the case, the child patient SC was established within the Biraul Primary Health is considered to have anorexia, and, therefore, be at higher risk TABLE 1Criteria for diagnosis of complicated severe acute malnutrition1 Description of symptom/circumstance Poor appetite or refusal or inability to eat test dose of ready-to-use lipid based paste Medical complications Intractable vomitingSevere dehydration (on the basis of history and clinical signs)Fever .398C or hypothermia ,368CLower respiratory tract infection (as per IMCI guidelines)Severe anemia (very pale; difficulty breathing)Profound weakness, apathy, unconsciousness, or convulsionsEdema ++/+++2 Offered the choice, caregiver refuses ambulatory care Transfer in from ATFC Medical complication (see above)Static weight or weight loss for 2 consecutive weeksNo recovery after 2 mo in ambulatory program 1ATFC, ambulatory therapeutic treatment center; IMCI, Integrated Management of Childhood Illness.
2Edema was graded on a scale from + to +++, reflecting mild to most severe, respectively. The mildest form (+) was treated in the community.
COMMUNITY-BASED MANAGEMENT OF SAM IN INDIA of complications, and thus is admitted directly for inpatient care MSF inpatient-treatment protocol for SAM, which is very similar in the SC. All children were examined by a physician for to the later published Indian Ministry of Health 2011 operational complications that might require either admission into the SC or guidelines for facility-based management (17). Both protocols additional medication beyond that provided during the system- divide the treatment of complicated cases into the following atic initial treatment. The initial treatment comprised albenda- phases as shown in Table 3: phase 1 is used to restore metabolic zole, amoxicillin, vitamin A (given once edema resolved in function and stabilize clinical status by using frequent feeds of affected children), folic acid, measles vaccination, and screening WHO-standard F75 milk (18); a transition phase of increased for malaria.
energy intake within the same volume of feed is used to restore Children were considered complicated cases if they required lost tissue and reduce risk of refeeding syndrome and fluid admission to the SC, either immediately on diagnosis of SAM or overload; and phase 2 is used to promote weight gain by in- at any point during the community treatment phase, on the basis creasing nutritional intake and re-integration into the social envi- of the exhibition of one or more symptoms listed in Table 1.
ronment before transfer to the ATFC by using F100-equivalentlipid-based paste augmented with local foods.
Treatment at community-level ATFCs Caregivers of children considered uncomplicated were Classification of exits counseled regarding the program and given a 1-wk supply of To be discharged as cured, children had to meet the discharge WHO-standard (16), prepackaged F100-equivalent (per kcal), criteria on 2 consecutive visits. Defaulters were defined as those lipid-based, ready-to-use therapeutic paste produced in India who failed to attend the AFTC for 2 consecutive weeks or who (Eezeepaste; Compact). The quantity provided depended on the left the SC and did not return for 2 consecutive days. Caregivers child's weight as detailed in Table 2. Caregivers were informed who refused consent for their children to be admitted into the SC that the paste was medicine, not food, and, therefore, should not or removed them from the SC prematurely but agreed to continue be shared with other family members. To guard against re- treatment in the ATFC were not considered defaulters. Death was feeding syndrome (a group of clinical symptoms caused by fluid defined as children who died while registered in the program.
and electrolyte imbalances resulting from too rapid a rate of Children were classified as nonresponders if their nutritional nutritional supplementation in severely malnourished patients), status did not improve over an extended period of time despite caregivers were also educated about dividing the daily ration their having good appetite and no identified underlying medical into frequent small feeds with approximate gaps of 3 h to aug- conditions or reason for the lack of weight gain. Children treated ment the therapy with local foods if children remained hungry in the community who either did not gain or lost weight over a and ensure that children had plenty of drinking water during and 2-wk period were offered elective admission to the SC so that after eating. Continued breastfeeding of children #24 mo old feeding practices could be observed and a more detailed medical was encouraged for those who were not yet fully weaned.
examination (including diagnostic tests) performed. If no causes Caregivers were asked to return to the ATFC at weekly in- for failure to thrive were shown, the child was classified as tervals, at which time anthropometric measurements were re- a nonrespondent. However, this elective admission to the SC was peated and children examined for complications. Caregivers were not widely accepted by caregivers, and therefore, a large pro- also advised to seek medical advice or attend the SC if a child portion of children classified as nonresponders were based only became unwell between scheduled visits.
on prolonged periods of unsupervised community treatment.
Treatment of children at the inpatient SC Community information, education, and communicationstrategies Admission into the 24-h SC unit could occur at the initial presentation or any point during the community-treatment phase.
A critical component of the CMAM program involved regular, All children who presented with one or more conditions listed in active engagement of dedicated teams with communities across Table 1 were admitted directly to the SC and provided 24-h Biraul block by using information, education, and communica- medical care and nutritional treatment until their clinical con- tion (IEC) tools to explain CMAM. This engagement included dition stabilized enough for transfer (or return) to an ATFC.
mobilizing community leaders to disseminate information re- Within the SC, children were treated according to the standard garding severe malnutrition and providing details on the avail-ability and schedule of ATFCs. A variety of messaging tools weredeveloped for the local context including plays, songs recorded in the local language by local artists, and a show by local artists Treatment schedule for ready-to-use lipid-based paste in the community featuring paintings related to local concepts of malnutrition (and ambulatory setting subsequently used for delivering IEC messages to the wider Ready-to-use lipid-based paste sachet community). Over the course of the program, the majority of (92-g sachet containing 500 kcal) ASHAs in the block were sensitized about the CMAM programand relayed messages about SAM to the community.
Admission and discharge criteria The program initially aimed to treat all children between 6 and 59 mo of age who presented with a weight-for-height z score (WHZ) ,23 and/or MUAC ,110 mm and/or bilateral edema.
TABLE 3Summary of inpatient treatment protocol used in Stabilization Centers 8 meals/d (every 3 h), F75 milk 100 kcal $ kg21 $ d21(135 mL F75 milk $ kg21 $ d21) 8 meals/d (every 3 h), F100 milk 135 kcal $ kg21 $ d21(135 mL F100 milk $ kg21 $ d21) Ready-to-use lipid-based paste plus one local meal .200 kcal $ kg21 $ d21 Children were discharged after maintaining a WHZ .22 and MUAC .110 mm with no edema for 1 wk and in good clinical A total of 8542 children were admitted into the program condition with a good appetite (referred to here as the old cri- between February 2009 and September 2011 (Figure 1) with teria).With the use of updated recommendations from WHO and admissions following a similar seasonal pattern each year.
UNICEF (19) and to allow for wider screening coverage and Figure 2 illustrates local seasonal activities relative to the simplicity, in July 2010 the admission criteria were changed to numbers of children admitted in the program. There are 2 main an MUAC ,115 mm and/or bilateral edema; discharge criteria agricultural seasons, one before the monsoon rains of March that were changed to maintaining an MUAC $120 mm with no lasts through to May and represents the worst food-security edema for 1 wk with good clinical condition and good appetite period and another at the end of the monsoon rains in October (new criteria). The MUAC has been implemented throughout the through November that marks the beginning of the best food- world as a simple, sensitive, and easy to use tool to screen and security period.
identify children most at risk of death from SAM (20).
Patient characteristics Data handling and statistical analysis Of children who met the inclusion criteria for the analysis, Dedicated and frequently trained data-entry operators entered 5149 children (62.2%) admitted into the program were girls, all data into a standard Microsoft Excel 2010 database; however, which was a proportion substantially higher than in the back- double data entry was not done. An epidemiologist ensured that ground population (47.12% girls) (21). The mean (6SD) age was the database was well maintained by performing regular audits on 16.4 6 9.4 mo (range: 6–60 mo); 79.9% of all admitted children the quality of data transfer and integrity of the database. Regular were 6–23 mo old, of whom 36.5% were ,12 mo old; 6793 database cleaning comprised checks for inconsistencies relative children (87.3%) belonged to Scheduled Caste, Scheduled Tribe, to source documents when necessary, and all patient files were or Other Backward Caste families/households. A total of 791 maintained securely throughout the program for this purpose.
(9.3%) children required admission to the SC, 126 (1.5%) of WHO Anthro software (v.3.2.2) was used to calculate the WHZ.
whom were admitted with complicated SAM at initial pre- A retrospective analysis of all routinely collected program data sentation and the remainder admitted at some point during were conducted with SPSS version 19 statistical software (IBM).
community treatment. Just under one-half the children (n = A multivariate logistic regression model was also developed to 3989; 48.2%) came from within Biraul block, whereas the re- determine risk factors significantly (P , 0.05) associated with mainder commuted from outside.
being a defaulter on the bivariate analysis. Variables that were Of the 5198 children who did not default from the program, justified a priori or associated with default in other studies were 88.4% of children were discharged as cured with a mean (6SD) also included and added stepwise in the multivariate analysis.
weight gain of 4.9 6 3.4 g $ kg21 $ d21 and length of stay Children admitted despite not meeting admission criteria were (LOS) of 7.9 6 5.9 wk; the median weight gain was 4.1 g $ kg21 excluded from the final analysis (Figure 1) as were children $ d21 (IQR: 2.6–6.3 g $ kg21 $ d21) and LOS was 6 wk (IQR: admitted into the program with edema because of to their very 4–10 wk). Weight and MUAC followed the same trend limited numbers (n = 71, 0.8%).
throughout recovery and was most rapid in the early stages ofadmission (Figure 3).
This analysis met the MSF Institutional Ethics Review Profile and outcomes of children admitted and discharged Committee criteria for a study involving routinely collected under the old criteria program data. The program used a widely recognized treatment Table 4 shows profiles and outcomes of the 3873 children model (CMAM) for SAM and was conducted under a memo- admitted between February 2009 and June 2010 with a WHZ randum of understanding with the district authorities and, ,23 and/or MUAC ,110 mm and/or bilateral edema. Children thereafter, with consent of the Bihar State Health Society, which were discharged as cured when they had attained a WHZ .22 is the usual procedure for NGOs operating in this context. All and MUAC .110 mm with no edema for 1 wk and were in good electronic data were analyzed anonymously.
clinical condition with a good appetite.

COMMUNITY-BASED MANAGEMENT OF SAM IN INDIA Flowchart of analysis. ATFC, Ambulatory Therapeutic Feeding Center; CMAM, community-based management of acute malnutrition; MUAC, midupper arm circumference; SC, Stabilization Center; WHZ, weight-for-height z score.
Profile and outcomes of children admitted and discharged Profile and outcomes of children admitted into the SC under the new criteria Of 8542 children admitted during the study period, 791 Table 5 shows profiles and outcomes of 4401 children ad- children (9.3%) required admission to the SC at some point mitted between July 2010 and September 2011 with an MUAC during treatment; of those admitted, 698 children met the in- ,115 mm and/or bilateral edema. Children were discharged clusion criteria for analysis. Profiles and outcomes of these as cured when they reached an MUAC $120 mm with no children are summarized in Table 6.
edema for 1 wk and were in good clinical condition with For children who required care in the SC at any stage during a good appetite. WHZ targets were not incorporated in the their treatment, the mean MUAC at time of admission into the new criteria.
program (104. 0 mm 6 12.6) was lower than that in children

Seasonal variations in admissions (top) and associated local socio-environmental factors (bottom) that may influence admission trends treated solely in the ATFC [107.9 6 7.5 mm; mean difference: LOS was 5.7 6 4.4 d. The mean MUAC increase during SC stay 3.9 mm (95% CI: 2.9, 4.8); P , 0.01]. The mean weight gain appeared to be higher in children with more-severe wasting.
during SC stay was 6.7 6 19.3 g $ kg21 $ d21, and the mean Default rates from the SC were low (n = 15; 2.1%) as was the Mean increase in weight and MUAC over time for children discharged as cured (n = 4595). MUAC, midupper arm circumference.
COMMUNITY-BASED MANAGEMENT OF SAM IN INDIA TABLE 4Admission characteristics and outcomes of children admitted under old criteria stratified by admission MUAC1 90 to ,100 mm 100 to ,110 mm 110 to ,115 mm Children admitted, n (%) Nutritional status at admission Admissions with ,23 WHZ, % Admitted to SC during ATFC Direct referral to SC at admission, n (%) Nutritional status at discharge of children discharged as cured Attained $15% of body weight, n (%) WHZ ,23 at discharge, n (%) Treatment-response indicators (cured) Mean weight gain, g $ kg21 $ d21 Mean length of stay, wk Length of stay, wk 12.0 (7.1–17.9) Height gain, cm/wk 1ATFC, Ambulatory Therapeutic Feeding Center; HAZ, height-for-age z score; LOS, length of stay; MUAC, midupper arm circumference; SC, Stabilization Center; WG, weight gain; WHZ, weight-for-height z score.
2Median; IQR in parentheses (all such values).
3Mean 6 SD (all such values).
overall mortality rate (n = 32; 4.6%). The mortality rate of children who defaulted improved as the LOS increased before children admitted directly to the SC at time of entry into the default. Of 1063 children who were in the program $6 wk program was 15% compared with 3.3% in children admitted to before defaulting, 43.5% of subjects had an MUAC $115 mm the SC during ATFC treatment.
on the last visit before default.
The adjusted odds (95% CI) of children aged ,12 mo for defaulting were 1.5 times (1.3, 1.7 times) those of children Analysis of defaulters aged $24 mo of age (P , 0.01), whereas the adjusted odds Of 8274 children who met the inclusion criteria during the (95% CI) of defaulting in children who presented with an MUAC study period, 3076 children (37.2%) defaulted. Of 3076 de- ,100 mm were 1.6 times (1.4, 1.9) times higher than in children ad- faulters, 542 children (17.6%) defaulted immediately after the mitted with an MUAC between 110 and ,115 mm (P , 0.01). On initial admission visit. For the remaining 2534 defaulters, the bivariate analysis, a younger age, admission WHZ ,23, lower ad- mean (6SD) time to default was 6.2 6 5.2 wk, and the median mission MUAC, residence outside Biraul block, nonreferral to the time was 5 wk (IQR: 2.3–8.4 wk). Just over one-third of children program by an ASHA, and admission under the old criteria were sig- (34.6%) defaulted $6 wk after admission. At the time of de- nificantly associated with default. Female sex (OR: 1.02; 95% CI: 0.9, fault, 67.8% of children had an MUAC ,115 mm (Figure 4), 1.1; P = 0.712) and lower caste did not appear to be associated with 25.1% of children had an MUAC .115–120 mm, and 7% of higher risk of default. All variables significant in the bivariate analysis children had an MUAC .120 mm. The nutritional status of remained significant after the multiple logistic regression analysis, BURZA ET AL.
TABLE 5Admission and outcome characteristics of children admitted under new criteria stratified by admission MUAC1 Children admitted, n (%) Nutritional status at admission WHZ ,23 at admission, % Admitted to SC during ATFC treatment, n (%) Direct referral to SC at admission, n (%) Nutritional status at discharge of children discharged as cured Attained $15% of body weight, n (%) WHZ ,23 at discharge, n (%) WHZ ,22 at discharge, n (%) Treatment-response indicators (cured) Weight gain, g $ kg21 $ d21 Length of stay, wk Length of stay, wk 13.3 (9.1–20.6) 11.0 (7.0–15.8) Height/length gain, cm/wk 1ATFC, Ambulatory Therapeutic Feeding Center; HAZ, height-for-age z score; LOS, length of stay; MUAC, midupper arm circumference; SC, Stabilization Center; WG, weight gain; WHZ, weight-for-height z score.
2Median; IQR in parentheses (all such values).
3Mean 6 SD (all such values).
although with the old admission criteria became slightly protective (OR: 0.8; 95% CI: 0.7, 0.9; P , 0.01) against default (Table 7).
As home to nearly one-third of the world's children with SAM, India's approach to treating SAM has relied almost ex-clusively on inpatient care, whereas the community-based ap- Impact of change of admission and discharge criteria proaches shown to be effective and feasible in African settings There was a higher proportion of girls admitted [66.8% have not been well tested, studied, or implemented in India. This compared with 57.0%; RR: 1.17 (95% CI: 1.1, 1.2); P , 0.01] article describes the clinical outcomes of 8274 children with and a shift toward admission of younger age groups [mean SAM treated in an MSF-implemented and -supported CMAM age: 15 compared with 18 mo; mean difference: 3.0 mo (95% program in a rural area of one of the poorest districts in Bihar CI: 2.6, 3.4 mo); P , 0.01] under the new criteria. The (22). This large observational study represents, to the authors' change had a substantial impact on decreasing the LOS and best knowledge, the only one from India to describe the out- increasing the mean weight gain in children discharged as comes of a conventional setting CMAM program by using WHO cured (Figure 5). The mean WHZ at discharge decreased standard ready-to-use therapeutic lipid-based paste produced in from 21.6 to 21.5, whereas the mean percentage increase in India. Our findings suggested that CMAM was an effective body weight fell from 22% to 19.4% under the new criteria strategy, which led to cures for 88.4% of children who com- pleted the treatment although hindered by substantial default COMMUNITY-BASED MANAGEMENT OF SAM IN INDIA TABLE 6Admission and outcome characteristics of children admitted into the Stabilization Center (n = 698)1 Children admitted, 9.1 (7.0–15.9)2 12.0 (8.6–18.4) 12.5 (9.5–18.1) 14.0 (10.7–19.0) 16.9 (11.9–25.1) 13.5 (9.9–19.4) Direct Admission to Nutritional status at time of admissionto SC OutcomeTransfer to ATFC Defaulted from SC Length of stay, d 1ATFC, Ambulatory Therapeutic Feeding Center; HAZ, height-for-age z score; LOS, length of stay; MUAC, midupper arm circumference; SC, Stabilization Center; WG, weight gain; WHZ, weight-for-height z score.
2Median; IQR in parentheses (all such values).
3Mean 6 SD (all such values).
rates. Because these results represent operational field outcomes suggests that active case-detection strategies may benefit achieved despite challenges that might also be present if other from focusing on this age group.
large-scale CMAM initiatives are undertaken in India, they The introduction of an MUAC ,115 mm and/or edema as sole suggest that CMAM has significant, under-exploited potential as admission criteria in July 2010 resulted in a change in the de- a strategy for scaling up.
mographic of patients admitted into the program. Notably, a higherproportion of girls and younger age groups were admitted after thenew criteria were implemented. Both phenomena were noted in other contexts (23) and also within India (3). The new admission Demographic data showed a disproportionate share of girls criteria lowered the threshold for severity with the result that more (62.2%) in children admitted to the program and reinforced children were included who are at lower risk of death and have the importance of social identity (caste) as a predisposing a smaller WHZ deficit to correct (WHZ: 3.1 compared with 3.5) factor for SAM. The data also confirmed observations in other than do children identified by the old criteria. Consequently, the published Indian studies that suggested a much higher burden mortality and time to recovery can be expected to be lower in of SAM in children ,2 y old (3, 4), which was consistent children identified by the new criteria.
with data from African settings (23). The severity of stunting Although 9.3% of children required admission to the SC at correlated directly with the severity of wasting on admission, some point during treatment, the proportion admitted immedi- with a mean (6SD) height-for-age z score of 23.9 6 1.5 for ately to the SC on entering the program (0.9%; n = 77) was far the overall cohort. That 79.9% of children admitted into the lower than the 10–20% reported in African settings (24). This program were ,2 y of age has major public health implica- result suggested that the morbidity associated with SAM may be tions for the prevention and reversal of stunting and also less severe in the Indian context. During their SC stay, average

Length of stay before defaulting and associated MUAC at time of default (n = 3076). MUAC, midupper arm circumference.
weight gain was lower and the LOS was higher in children with The overall in-program mortality was 0.9%, which was well more-severe wasting than in children with a higher MUAC on within the bounds of standards set out in both national (,5% admission to the SC, reflecting longer periods spent in phase 1 mortality) and international (,10% mortality) standards of care treatment (because of more-severe illness) when weight gain (17, 25). Although excluded from the analysis, the mortality rate was not expected.
was far higher (15.5%) in the 71 children admitted with edema TABLE 7Risk factors for default from CMAM program1 Adjusted OR (95% CI) Age group (n = 7671) (mo) Caste category (n = 7199) Other Backward Class WHO WHZ on admission (n = 7654) MUAC on admission (n = 7657) (mm) Child's residence (n = 7671) Admission criteria (n = 7671) Referred into the program by ASHA (n = 7656) 1Nonresponders were not included in this analysis. CMAM, community-based management of acute malnutrition; MUAC, midupper arm circumference; WHZ, weight-for-height z score.
2Included in regression model as borderline significance on univariate analysis (P = 0.08).

COMMUNITY-BASED MANAGEMENT OF SAM IN INDIA Mean weight gain and length of stay for children discharged as cured stratified by admission midupper arm circumference cutoff (n = 4595).
in keeping with other studies from the Indian context (4). In studies that the MUAC may be useful as a program-monitoring addition, the case fatality rate of children admitted directly into tool for recovery from SAM (23). Height gain correlated well the SC at the time of entry into the program (n = 11 of 77; 15%) with average weight gain and the mean MUAC gain across was substantially higher than in children admitted to the SC different severities of wasting, suggesting that it may be a useful after a period of treatment in the ATFC (n = 21 of 621; 3.3%), indicator of proportionate growth during recovery.
which could have reflected a need for better standard of care for However, a substantial number of children (37.2%) defaulted children who presented in a more-critical condition. As shown in from care, a figure that failed to meet national and international Figure 3, weight and MUAC followed the same trend throughout standards of care (,15%) but was consistent with outcomes recovery and was most rapid in the early stages of admission as from other inpatient SAM treatment programs in India (3, 4); for noted elsewhere (26). This result supports conclusions of other example, the Nutritional Rehabilitation Centers in Uttar Pradesh TABLE 8Comparison of outcomes of old compared with new criteria for admission and discharge1 Old criteria (n = 3873) New criteria (n = 4401) Combined (n = 8274) 0.92 (0.88, 0.98) Treatment response if cured WG, g $ kg21 $ d21 0.34 [0.15, 0.54]4 WG, g $ kg21 $ d21 21.5 [21.8, 21.2] 0.06 [0.05, 0.08] Children who gained $15% BW, % Percentage increase in BW Nutrition status at discharge 0.05 [0.003, 0.09] 0.30 [0.21, 0.39] 1BW, body weight; HAZ - height-for-age z score; LOS, length of stay; MUAC, midupper arm circumference; WG, weight gain; WHZ, weight-for-height 2RR; 95% CI in parentheses (all such values).
3Mean 6 SD (all such values).
4Mean difference; 95% CI in brackets (all such values).
5Median; IQR in parentheses (all such values).
reported a defaulter rate as high as 47.2% (5). Adjusted odds of Centers and discharged them to a community program in which defaulting were slightly higher for children commuting to Biraul Ministry of Health frontline workers monitored their progress and block for treatment than for those living within Biraul block, ensured that they benefited from the Integrated Child De- suggesting that the increased distance from ATFCs posed velopment Services Supplementary Nutrition Program. No pri- a barrier to completing treatment. This finding was consistent ority was given to admitting children with complicated SAM, and with the results of successive Semi-Quantitative Assessment of discharge was automatic after 60 d of community follow-up.
Access and Coverage surveys conducted by MSF in Biraul Overall, the program reported a 0.4% overall mortality rate with block, which identified caregiver time constraints along with a 32% default, 23.7% discharged-as-nonrecovered, and 43.9% poor perception of self-recovery and seasonal agricultural labor discharged-as-recovered rates. The mean weight gain was 2.7 g $ demands as important contributors to nonadherance with treat- kg21 $ d21, whereas the mean LOS was 75.8 d. The mean weight gain during the community-treatment phase was 1.6 g $ Risk factors for defaulting were similar to those shown in other kg21 body weight $ d21 (6).
studies that described the default from other inpatient nutritionalprograms in India (4), although in this study, identity as OtherBackward Class did not appear to be a risk factor for default.
Limitations and future direction Notably, seasonal trends showed an increase in defaulters during A major strength of this study was the data that were main- months when women's field work is in high demand (March tained throughout the program with relatively few missing data through June) and during the monsoon rains and yearly floods.
points for the final analysis. However, because the study was This period also includes the wedding season (May through a routine NGO-supported program rather than a clinical trial, June), which could have had an impact on the default rate be- there were a number of limitations in interpreting the data. Al- cause of the temporary migration of mothers (28). Children who though most children's admission anthropometric data were were identified and referred to the program by ASHAs had 10- measured by 3 individuals at the time of admission, only one fold lower odds of defaulting, which supported a central role for measurement was recorded, which meant that no interobserver these community workers in future CMAM initiatives in India.
and intra-observer reliability could be analyzed.
On the basis of this finding, the program put substantial effort Many children defaulted from the program and, therefore, into ASHA training and involvement in 2012 that, along with were lost to follow-up. Although data were used from defaulting improved community messaging and earlier identification of children to identify risk factors for default, not knowing the children at high risk of default, likely contributed to the sharp eventual outcome of this group of children could have created decline in default rates to ,20% seen in 2013 (MSF; un- a potential bias in presenting overall outcomes of the program published data).
(e.g., by underestimating mortality if children were defaultingbecause of death in the community). Although not systematicallyrecorded, very few children classed as defaulters were reported to Implications for SAM treatment strategies in India have died when traced by the IEC team to encourage them to Because of the high burden of SAM seen in India, the current return to the program. A longer-term follow-up of these patients strategy of inpatient treatment programs alone is unlikely to after exit from the program would be crucial to ascribe a more provide care for all of these SAM children at higher risk of death.
accurate survival status to this important cohort.
A 2012 study of 93 children treated in the state of Madhya However, the major challenge in interpretation was that these Pradesh concluded that, although the compulsory 14-d inpatient findings came from an externally supported program and may not stay succeeded in improving the condition of admitted children, have been achieved if the program was transferred to government the improvement was not sustained after discharge. Perhaps more facilities. In one comprehensive review of 33 studies of com- crucial was the supposition that even if all 175 dedicated inpatient munity-based nutritional rehabilitation programs over a 25-y nutritional facilities were running at full capacity, it would take period, none of the programs operating within routine health 15.5 y to provide this treatment method to the 1.3 million children systems and without external assistance were shown to be ade- in the state suffering from SAM (6).
quate (29). However, this result suggests that potential sustain- There are a limited number of other observational studies in the able solutions may be shown through private-public partnerships literature that described the outcomes of other models of inpatient between the government and local NGOs, which is a model that care elsewhere in India. A 2012 observational study that de- has already been adopted for the Nutritional Rehabilitation scribed the inpatient management of 3595 children with SAM in Centers in Bihar. In addition, this model assumes that governance Malnutrition Treatment Centers across the state of Jharkhand (leadership, resources, and accountability) for nutritional in- showed a mortality rate of 0.6%, default rate of 18.4%, mean in- terventions will remain low in the future, whereas already some program weight gain of 9.6 g $ kg21 $ d21, and mean LOS of state governments in India have been able to implement more- 16 d. No priority was given to the admission of children with complex programs such as Madhya Pradesh Newborn Care Units.
complicated SAM, and the main discharge criteria were the To this effect, the CMAM model has the capacity to be adopted good clinical condition of the child, toleration of feeds of 120– into an existing government capacity; for example, ANMs at the 130 kcal $ kg21 $ d21, and gain of 5 g $ kg21 body weight $ d21 PHC and additional PHC level can be trained and empowered to provide this service with appropriate training if adequate in- An additional 2013 study in Madhya Pradesh described the stitutional support is provided. Local ownership and community outcomes of 2740 children randomly sampled from the 44,017 understanding and acceptance of both messaging and treatment children treated for SAM in 2010. This program model admitted will likely also be critical in developing sustainable solutions all children for 14 d of inpatient care in Nutrition Rehabilitation (30). A cost-effectiveness analysis that compares routine CMAM COMMUNITY-BASED MANAGEMENT OF SAM IN INDIA projects with the current hospital-based model of care would be 10. Collins S, Dent N, Binns P, Bahwere P, Sadler K, Hallam A. Man- a useful next step in providing policy makers more evidence for agement of severe acute malnutrition in children. Lancet 2006;368:1992–2000.
future planning strategies.
11. Espie E, Pujol CR, Masferrer M, Saint-Sauveur JF, Urrutia PP, Grais In conclusion, the absence of Indian national guidelines re- RF. Acute malnutrition and under-5 mortality, northeastern part of garding CMAM makes the scale up of SAM treatment difficult.
India. J Trop Pediatr 2011;57:389–91.
The implementation of an effective public health approach for 12. Emergency Nutrition Network. Special focus on government experi- ences of CMAM scale up. Oxford (United Kingdom): Field Exchange; addressing SAM in India will require a significant investment 2012. p. 43.
by policymakers to develop state-specific sustainable, effective 13. Collins S, Sadler K, Dent N, Khara T, Guerrero S, Myatt M, Saboya M, models of care that provide sufficient coverage and capacity to Walsh A. Key issues in the success of community-based management treat the large burden of children with SAM that exist in the of severe malnutrition. Food Nutr Bull 2006;27:S49–82.
14. Wilford R, Golden K, Walker DG. Cost-effectiveness of community- country. More broadly, it will also require a holistic approach that based management of acute malnutrition in Malawi. Health Policy Plan incorporates preventive measures such as poverty reduction, hygiene promotion, clean water, prevention of prenatal macro- 15. Tekeste A, Wondafrash M, Azene G, Deribe K. Cost effectiveness of nutrient and micronutrient deficiencies, and the promotion of age- community-based and in-patient therapeutic feeding programs to treatsevere acute malnutrition in Ethiopia. Cost Eff Resour Alloc 2012 Mar appropriate foods and feeding practices for infants and young 19 (Epub ahead of print; DOI: 10.1186/1478-7547-10-4).
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at the Darbhangha Medical College Hospital and Dr. Amrendra Kumar Singh, 18. World Health Organization. Management of severe malnutrition: Medical Officer in Charge at Biraul Block PHC, who have all been pivotal in a manual for physicians and other senior health workers. Geneva assisting the work of MSF. We also thank and Patricia Kahn for editing (Switzerland): WHO; 1999.
19. World Health Organization, United Nations Children's Fund. WHO The authors' responsibilities were as follows—SB and RM: analyzed data child growth standards and the identification of severe acute malnu-trition in infants and children; a joint statement by the World Health and wrote the manuscript; SB, TS, EM, CS, MT, KK, PM, AJ, NS, and Organization and the United Nations Children's Fund. Geneva (Swit- KNM: were directly involved in the program design and implementation zerland): WHO; 2009. United Nations Children's Fund. Geneva and reviewed the manuscript; and all authors: read and approved the final (Switzerland): WHO; 2009.
manuscript No donor had any part in the study design or implementation.
20. Myatt M, Khara T, Collins S. A review of methods to detect cases of None of the authors reported a conflict of interest related to the study.
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21. International Institute for Population Sciences (IIPS) and Macro In- 1. International Institute for Population Sciences (IIPS) and Macro In- ternational. National Family Health Survey (NFHS-3), India, 2005-06: ternational. National Family Health Survey (NFHS-3), 2005-2006.
Bihar. Mumbai (India): IIPS; 2008.
Mumbai (India): IIPS; 2007.
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Microsoft word - 10. meeusen.doc

The Brain and Fatigue : New Opportunities for Nutritional Romain Meeusen1, Phil Watson2 , Jiri Dvorak3 1. Dept Human Physiology & Sportsmedicine - Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels , Belgium 2. School of Sport and Exercise Sciences, Loughborough University, Leicestershire, LE11 3TU, 3. Dept Neurology and F-MARC (FIFA Medical Assesment and Research Center) Schulthess

Microsoft word - 7thwribposterlist

7th Workshop on Recent Issues in Bioanalysis Poster List Tuesday April 9 Posters Poster T01: "Validation of a Dried Blood Spot Boanalytical Method for Perampanel Analysis in Pediatric Studies" Poster Presenter: Dr. Luca Matassa (Eisai, Woodcliff Lake, NJ, USA) Introduction: Perampanel is a first-in-class, orally administered, highly selective non-competitive AMPA-type glutamate receptor antagonist, developed by EISAI for epilepsy. A DBS-LC-MS/MS method has been developed and validated in order to analyse perampanel in heparinised blood samples from paediatric studies. Dried blood spots (DBS) have been shown to be a useful means of collecting, storing and shipping blood samples for quantitative drug analysis which provides advantages over conventional plasma collection. Moreover, due to low sample volume that DBS uses, it is a method of choice when it is comes to paediatric studies. Methods: A 20 uL dried blood spot on FTA DMPK A card is punched (6mm punch) and the subsample is solubilized by shaking in 150 uL of 90/10 methanol water containing internal standard (IS) stable label peramapanel. An aliquot of the solution is diluted with an equal volume of 50/50 methanol/water, centrifuged at 4C for 5 min prior to injecting 10uL on a reverse phase column (Chromolith RP18e 100x3mm) at 40C under gradient conditions. The detector was a Sciex API5500 Qtrap operated in positive ion ionspray mode. Quantitation was achieved monitoring precursor/product ions for analyte and IS (350/219 m/z perampanel; 356/219 IS) at retention time 2.5 minutes using 1/x2 linear weighted regression. Result: A full validation according to FDA and EMA guidance was conducted in human blood. Assay linearity was demonstrated over 7 validation runs with R-squared greater than 0.995. The intra-run accuracy and precision was between 95.2 -107.6% and 3.1-12.6%, respectively, at four concentration levels (LLQ, low QC, mid QC, high QC) demonstrating the repeatability of the analytical method from 1 to 500 ng/mL. The matrix factor in 6 lots of control blood was 1.0 for analyte and IS. Control blank matrix showed no interference at the LLQ. Punch tool carryover and autoinjector carryover were not found to impact assay performance. Analyte and IS recovery was 80% across all 3 QC levels with imprecision less than 5%. A 2-fold dilution factor was validated. The specificity of the method for perampanel at the LLOQ in presence of 10 other commonly used AEDs, individual y or pooled all together, (valproic acid, phenobarbital, lamotrigine, topiramate, oxcarbazepine, carbamazepine, levetiracetam, zonisamide, phenytoin, primidone) was demonstrated. A blood/plasma ratio of 0.88 was determined, allowing the correlation between blood and previous study plasma results. Short term autosample perampanel extract stability and perampanel stability in blood was demonstrated. Perampanel long term stability on DBS was demonstrated for 363 days at room temperature. Novel Aspect / Conclusion: The fully validated DBS-LC-MS/MS method was successfully applied to analysis of paediatric study clinical samples. Poster T02: "Unexpected Results for Sample Col ection and Handling Stability Assessment for Sumatriptan in Human Plasma" Poster Presenter: Ginny James (Celerion, Lincoln, Nebraska, USA) Introduction: Determination of sample col ection and handling stability (SCHS) is a requirement for validation of bioanalytical methods. SCHS of sumatriptan for 120 minutes did not meet pre-defined acceptance criteria. As sumatriptan was stable in plasma for 23 hours at ambient temperature, it was hypothesized that partitioning of sumatriptan between plasma and red blood cells was not immediate and was impacting the results of the early time points. Methods: Whole blood was fortified with sumatriptan at 0.150 and 100 ng/mL for target plasma concentrations of approximately 0.300 and 200 ng/mL. The samples were incubated in an ice-water bath, at ambient temperature, and at 37°C for multiple time points between 0 and 120 minutes. At each time point, samples were centrifuged, and the plasma layer was immediately frozen at -20°C. For samples in an ice-water bath for 30 minutes, the red cell fraction was also stored at -20°C for testing. The collected plasma samples were analyzed using a validated method for the quantitation of sumatriptan in human plasma. Red blood cel s were analyzed with the same chromatographic and instrument conditions after a protein crash of the cellular material.