Generic placeholder image

Reviews on Recent Clinical Trials

Editor-in-Chief

ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

Short Communication

Multisystem Inflammatory Syndrome in Children (MIS-C) in a Low-income Country: What Treatment Should be Adopted in Case of a Lack of Immunoglobulin?

Author(s): Babakhouya Abdeladim*, Bouhmidi Massilia, Elouali Aziza, Elhaddar Zohair, Ghanam Ayad and Rkain Maria

Volume 19, Issue 2, 2024

Published on: 26 December, 2023

Page: [150 - 157] Pages: 8

DOI: 10.2174/0115748871257131231204114803

Price: $65

conference banner
Abstract

Introduction: In multisystem inflammatory syndrome (MIS-C), children typically present high-grade fever, gastrointestinal symptoms, Kawasaki-like symptoms, and even a toxic shock-like syndrome days to weeks after recovering from SARS-CoV-2 infection. It is important to raise awareness of this condition in order to have early diagnosis and immediate treatment of patients. We have, herein, reported 44 cases of MIS-C with various risk factors and symptoms. Furthermore, we have emphasized the efficacy of experience in treating children with MIS-C with high-dose corticosteroids as an alternative to immunoglobulin in low-income countries.

Methods: We conducted a targeted survey of MIS-C from early May 2020 to October 2022 on 44 children and adolescents with characteristics of multisystem inflammatory syndrome admitted to the pediatric department of the university hospital center in Oujda, Morocco, to which patients diagnosed with MIS-C were referred. The case definition included six criteria: serious illness leading to hospitalization, age under 18 years, fever of at least 24 hours, laboratory evidence of inflammation, multi-organ involvement, biological inflammatory syndrome, and evidence of coronavirus infection based on polymerase chain reaction, antibody testing or exposure to people with COVID-19 in the past month. The criteria used to diagnose myocarditis were impaired left ventricular function, central mitral leak, and elevation of BNP or pro-BNP. Coronary involvement was assessed by the z-score and the criteria for its presence was a z-score equal to or greater than 2.5.

Results: Our study included 44 children and adolescents with MIS-C in our hospital, with male predominance (79%) and a median age of six years. Cardiovascular involvement was present in 91%, mucocutaneous in 78%, gastrointestinal in 70%, hematologic in 84%, and respiratory in 2% of patients. Coronary abnormalities (z-score ≥ 2.5) were documented in 21 cases (48%). Glucocorticoids were frequently used in comparison to immunoglobulin, which were uncommonly available and expensive.

Conclusion: The therapeutic protocol that was adopted was high doses of short-term prednisone (Cortancyl) at 4mg/kg/day for 4 days. Favorable outcome was noted in all patients over a 2-year period.

[1]
Pritzker JB. Multisystem inflammatory syndrome in children (MISC) associated with coronavirus Disease. 24 févr 2022.
[2]
Harwood R, Allin B, Jones CE, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health 2021; 5(2): 133-41.
[http://dx.doi.org/10.1016/S2352-4642(20)30304-7] [PMID: 32956615]
[3]
Viner RM, Whittaker E. Kawasaki-like disease: Emerging complication during the COVID-19 pandemic. Lancet 2020; 395(10239): 1741-3.
[http://dx.doi.org/10.1016/S0140-6736(20)31129-6] [PMID: 32410759]
[4]
Labé P, Ly A, Sin C, Nasser M, Chapelon‐Fromont E, Ben Saïd P,, et al. Erythema multiforme and Kawasaki disease associated with COVID‐19 infection in children. J Eur Acad Dermatol Venereol 2020; 34(10)
[5]
Kaushik A, Gupta S, Sood M, Sharma S, Verma S. A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 Infection. Pediatr Infect Dis J 2020; 39(11): e340-6.
[http://dx.doi.org/10.1097/INF.0000000000002888] [PMID: 32925547]
[6]
Waltuch T, Gill P, Zinns LE, et al. Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department. Am J Emerg Med 2020; 38(10): 2246.e3-6.
[http://dx.doi.org/10.1016/j.ajem.2020.05.058] [PMID: 32471782]
[7]
Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study. Lancet 2020; 395(10239): 1771-8.
[http://dx.doi.org/10.1016/S0140-6736(20)31103-X] [PMID: 32410760]
[8]
Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: Prospective observational study. BMJ 2020; 369: m2094.
[http://dx.doi.org/10.1136/bmj.m2094] [PMID: 32493739]
[9]
Lima-Setta F, Magalhães-Barbosa MC, Rodrigues-Santos G, et al. Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: A multicenter, prospective cohort study. J Pediatr 2021; 97(3): 354-61.
[http://dx.doi.org/10.1016/j.jped.2020.10.008] [PMID: 33186512]
[10]
Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York state. N Engl J Med 2020; 383(4): 347-58.
[http://dx.doi.org/10.1056/NEJMoa2021756] [PMID: 32598830]
[11]
Bhattacharjee S, Banerjee M, Pal R. COVID-19 associated hemophagocytic lymphohistiocytosis and coagulopathy: Targeting the duumvirate. Indian Pediatr 2020; 57(9): 827-33.
[http://dx.doi.org/10.1007/s13312-020-1962-z] [PMID: 32583809]
[12]
Chanchlani N, Chesshyre E, Hart JW. Syndrome inflammatoire multisystémique chez les enfants. CMAJ 2022; 194(40): E1389-90.
[http://dx.doi.org/10.1503/cmaj.220384-f]
[13]
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395(10237): 1607-8.
[http://dx.doi.org/10.1016/S0140-6736(20)31094-1] [PMID: 32386565]
[14]
Kaushik S, Aydin SI, Derespina KR, et al. Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection: A multiinstitutional study from New York City. J Pediatr 2020; 224: 24-9.
[http://dx.doi.org/10.1016/j.jpeds.2020.06.045] [PMID: 32553861]
[15]
Swann OV, Holden KA, Turtle L, et al. Clinical characteristics of children and young people hospitalised with covid-19 in the United Kingdom: Prospective multicentre observational cohort study. medRxiv 2020. Internet
[http://dx.doi.org/10.1101/2020.07.14.20153320]
[16]
Al-Aamri MA, Al-Khars FT, Alkhwaitem SJ, et al. A Saudi G6PD deficient girl died with pediatric multisystem inflammatory syndrome-COVID-19. medRxiv 2020; 07.08.2013749. Internet
[http://dx.doi.org/10.1101/2020.07.08.20137497]
[17]
Rivera-Figueroa EI, Santos R, Simpson S, Garg P. Incomplete Kawasaki disease in a child with Covid-19. Indian Pediatr 2020; 57(7): 680-1.
[http://dx.doi.org/10.1007/s13312-020-1900-0] [PMID: 32393680]
[18]
Dhanalakshmi K, Venkataraman A, Balasubramanian S, et al. Epidemiological and clinical profile of pediatric inflammatory multisystem syndrome - temporally associated with SARSCoV-2 (PIMS-TS) in Indian children. Indian Pediatr 2020; 57(11): 1010-4.
[http://dx.doi.org/10.1007/s13312-020-2025-1] [PMID: 32769230]
[19]
Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020; 383(4): 334-46.
[http://dx.doi.org/10.1056/NEJMoa2021680] [PMID: 32598831]
[20]
Amirfakhryan H. Kawasaki-like disease in children with COVID-19: A hypothesis. Med Hypotheses 2020; 143: 110117.
[http://dx.doi.org/10.1016/j.mehy.2020.110117] [PMID: 32721809]
[21]
Hameed S, Elbaaly H, Reid CEL, et al. Spectrum of imaging findings at chest radiography, US, CT, and MRI in multisystem inflammatory syndrome in children. In: Associated with COVID-19 Radiology. 2020; 298: pp. (1)1-10.
[http://dx.doi.org/10.1148/radiol.2020202543]
[22]
Rostad CA, Chahroudi A, Mantus G, et al. Serology in children with multisystem inflammatory syndrome (MIS-C) associated with COVID-19. medRxiv 2020; 07.10.20150755. Internet
[http://dx.doi.org/10.1101/2020.07.10.20150755]
[23]
Belhadjer Z, Méot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020; 142: 429-36.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048360]
[24]
Moraleda C, Serna-Pascual M, Soriano-Arandes A, et al. Multi-inflammatory syndrome in children related to SARS-CoV-2 in Spain. Clin Infect Dis 72(9): 397-401.
[http://dx.doi.org/10.1093/cid/ciaa1042]
[25]
Malviya A, Mishra A, Childhood MIS. Childhood multisystem inflammatory syndrome: An emerging disease with prominent cardiovascular involvement—a scoping review. SN Compr Clin Med 2021; 3(1): 48-59.
[http://dx.doi.org/10.1007/s42399-020-00650-0] [PMID: 33437929]
[26]
Koné-Paut I, Cimaz R. Is it Kawasaki shock syndrome, Kawasaki-like disease or pediatric inflammatory multisystem disease? The importance of semantic in the era of COVID-19 pandemic. RMD Open 2020; 6(2): e001333.
[http://dx.doi.org/10.1136/rmdopen-2020-001333] [PMID: 32611651]
[27]
Iio K, Uda K, Hataya H, et al. Kawasaki disease or Kawasaki‐like disease: Influence of SARS‐CoV‐2 infections in Japan. Acta Paediatr 2021; 110(2): 600-1.
[http://dx.doi.org/10.1111/apa.15535] [PMID: 32799392]
[28]
Falah NU, Hashmi S, Ahmed Z, Jaan A, Akhtar A, Khalid F, et al. Kawasaki Disease-Like Features in 10 Pediatric COVID-19 Cases: A Retrospective Study. Cureus. 2020. Available from: https://www.cureus.com/articles/42304-kawasaki-disease-like-features-in-10-pediatric-covid-19-cases-a-retrospective-study
[29]
Bernstein KS, Klein JD. Distrust, but use it anyway – adolescent online health-information searching behavior. J Pediatr 2020; 224: 179-83.
[http://dx.doi.org/10.1016/j.jpeds.2020.07.020] [PMID: 32826020]
[30]
Shaigany S, Gnirke M, Guttmann A, et al. An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. Lancet 2020; 396(10246): e8-e10.
[http://dx.doi.org/10.1016/S0140-6736(20)31526-9] [PMID: 32659211]
[31]
Chérif MY, de Filette JMK, André S, Kamgang P, Richert B, Clevenbergh P. Coronavirus disease 2019–related Kawasaki-like disease in an adult: A case report. JAAD Case Rep 2020; 6(8): 780-2.
[http://dx.doi.org/10.1016/j.jdcr.2020.06.023] [PMID: 32754629]
[32]
Othenin-Girard A, Regamey J, Lamoth F, et al. Multisystem inflammatory syndrome with refractory cardiogenic shock due to acute myocarditis and mononeuritis multiplex after SARS-CoV-2 infection in an adult. Swiss Med Wkly 2020; 150(4546): w20387.
[http://dx.doi.org/10.4414/smw.2020.20387] [PMID: 33181855]
[33]
Kumar Anil. Cardiac affection in a young girl with post covid-19 kawasaki like syndrome. Indian J Pediatr 2020; 88(3): 303-4.
[http://dx.doi.org/10.1007/s12098-020-03513-7]
[34]
Eléonore Blondiaux 1, Pauline Parisot 1, Alban Redheuil 1. Cardiac MRI of Children with Multisystem Inflammatory Syndrome (MIS-C) Associated with COVID-19: Case Series. PubMed Radiology 2020; 297(3): E283-8.
[35]
Burger M, Moore M, Wilburn J. Case report: Pediatric patient with COVID-19 and multisystem inflammatory syndrome in children. Clin Pract Cases Emerg Med 2020; 4(4): 513-6.
[http://dx.doi.org/10.5811/cpcem.2020.8.48376] [PMID: 33217259]
[36]
Markus Hufnagel Jakob Armann. . A comparison of pediatric inflammatory multisystem syndrome temporarily-associated with SARS-CoV-2 and Kawasaki disease. Nat Library Med 2023; 13(1): 1173.
[37]
Ahmed M, Advani S, Moreira A, et al. Multisystem inflammatory syndrome in children: A systematic review. EClinicalMedicine 2020; 26: 100527.
[http://dx.doi.org/10.1016/j.eclinm.2020.100527] [PMID: 32923992]
[38]
Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: A systematic review. Eur J Pediatr 2021; 180(7): 2019-34.
[http://dx.doi.org/10.1007/s00431-021-03993-5] [PMID: 33599835]
[39]
Greene AG, Saleh M, Roseman E, Sinert R. Toxic shock-like syndrome and COVID-19: Multisystem inflammatory syndrome in children (MIS-C). Am J Emerg Med 2020; 38(11): 2492.e5-6.
[http://dx.doi.org/10.1016/j.ajem.2020.05.117] [PMID: 32532619]
[40]
Joshi K, Kaplan D, Bakar A, et al. Cardiac dysfunction and shock in pediatric patients with COVID-19. JACC Case Rep 2020; 2(9): 1267-70.
[http://dx.doi.org/10.1016/j.jaccas.2020.05.082] [PMID: 32835268]
[41]
Grimaud M, Starck J, Levy M, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Ann Intensive Care 2020; 10(1): 69.
[http://dx.doi.org/10.1186/s13613-020-00690-8] [PMID: 32488505]
[42]
Pouletty M, Borocco C, Ouldali N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): A multicentre cohort. Ann Rheum Dis 2020; 79(8): 999-1006.
[http://dx.doi.org/10.1136/annrheumdis-2020-217960] [PMID: 32527868]
[43]
Riollano-Cruz M, Akkoyun E, Briceno-Brito E, et al. PanizMondolfi A. multisystem inflammatory syndrome in children (MIS-C) related to COVID-19: A New York City experience. J Med Virol 2020; 93: 424-33.
[http://dx.doi.org/10.1002/jmv.26224] [PMID: 32584487]
[44]
Rogo T, Mathur K, Purswani M. Systemic inflammation with cardiac involvement in pediatric patients with evidence of COVID-19 in a community hospital in the Bronx, NY. J Pediatric Infect Dis Soc 2020; 9(4): 502-3.
[http://dx.doi.org/10.1093/jpids/piaa087] [PMID: 32687574]
[45]
Ferrero P, Piazza I, Bonino C, Ciuffreda M. Patterns of myocardial involvement in children during COVID-19 pandemic: Early experience from northern Italy. Ann Pediatr Cardiol 2020; 13(3): 230-3.
[http://dx.doi.org/10.4103/apc.APC_77_20] [PMID: 32863659]
[46]
Kest H, Kaushik A, DeBruin W, Colletti M, Goldberg D. Multisystem inflammatory syndrome in children (MIS-C) associated with 2019 novel coronavirus (SARS-CoV-2) infection. Case Rep Pediatr 2020; 18: 8875987.
[http://dx.doi.org/10.1155/2020/8875987]
[47]
Wolfler A, Mannarino S, Giacomet V, Camporesi A, Zuccotti G. Acute myocardial injury: A novel clinical pattern in children with COVID-19. Lancet Child Adolesc Health 2020; 4(8): e26-7.
[http://dx.doi.org/10.1016/S2352-4642(20)30168-1] [PMID: 32497521]
[48]
Chiotos K, Bassiri H, Behrens EM, et al. Multisystem inflammatory syndrome in children during the COVID-19 pandemic: A case series. J Pediatric Infect Dis Soc 2020; 9(3): 393-8.
[http://dx.doi.org/10.1093/jpids/piaa069] [PMID: 32463092]
[49]
Cazzaniga M, Baselli LA, Cimaz R, Guez SS, Pinzani R, Dellepiane RM. SARS-COV-2 Infection and kawasaki disease: Case report of a hitherto unrecognized association. Front Pediatr 2020; 8: 398.
[http://dx.doi.org/10.3389/fped.2020.00398]
[50]
Kaya Ummusen. Selman Kesici2 • Yasemin ozsurekci3. kawasaki-like disease in children with covid-19. Rheumatol Int 2020; 40(12): 2105-15.
[http://dx.doi.org/10.1007/s00296-020-04701-6]
[51]
Almoosa ZA, Al Ameer HH, AlKadhem SM, Busaleh F, AlMuhanna FA, Kattih O. Multisystem Inflammatory Syndrome in Children, the Real Disease of COVID-19 in Pediatrics - A Multicenter Case Series From Al-Ahsa, Saudi Arabia. Cureus. 2020. Available from: https://www.cureus.com/articles/42230-multisystem-inflammatory-syndrome-in-children-the-real-disease-of-covid-19-in-pediatrics-a-multicenter-case-series-from-al-ahsa-saudi-arabia (Accessed on 13 sept 2023).
[52]
Jones VG, Mills M, Suarez D, et al. COVID19 and Kawasaki disease: Novel virus and novel case. Hosp Pediatr 2020; 10: 537-40.
[http://dx.doi.org/10.1542/hpeds.2020-0123]
[53]
Trogen B, Gonzalez FJ, Shust GF. Associated myocarditis in an adolescent. Pediatr Infect Dis J 2020; 39(8): 204-5.
[http://dx.doi.org/10.1097/INF.0000000000002788]
[54]
Abdel-Mannan O, Eyre M, Löbel U, et al. Neurologic and radiographic findings associated with COVID-19 infection in children. JAMA Neurol Disponible sur 2020; 2687
[55]
Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020; 26(7): 1017-32.
[http://dx.doi.org/10.1038/s41591-020-0968-3]
[56]
Acharyya BC, Acharyya S, Das D. Novel coronavirus mimicking Kawasaki disease in an infant. Indian Pediatr 2020; 57(8): 753-4.
[http://dx.doi.org/10.1007/s13312-020-1924-5] [PMID: 32441271]
[57]
Dallan C, Romano F, Siebert J, Politi S, Lacroix L, Sahyoun C. Septic shock presentation in adolescents with COVID-19. Lancet Child Adolesc Health 2020; 4(7): e21-3.
[http://dx.doi.org/10.1016/S2352-4642(20)30164-4] [PMID: 32442421]
[58]
Bajolle F. Multisystem inflammatory syndrome associated with SARS-CoV-2 in children: Diagnosis and management. National Library of Medicine 2021; 4(1): 10-6.
[59]
Bapst T, Romano F, Müller M, Rohr M. Special dermatological presentation of paediatric multisystem inflammatory syndrome related to COVID-19: Erythema multiforme. BMJ Case Rep 2020; 13(6): e236986.
[http://dx.doi.org/10.1136/bcr-2020-236986]
[60]
Vari D, Miller JM, Rellosa N, Srivastava S, Frizzola M, Thacker D. Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report. Prog Pediatr Cardiol 2020; 58: 101270.
[http://dx.doi.org/10.1016/j.ppedcard.2020.101270] [PMID: 32837148]
[61]
Cogan E, Foulon P, Cappeliez O, Dolle N, Vanfraechem G, De Backer D. Multisystem inflammatory syndrome with complete Kawasaki disease features associated with SARS-CoV-2 infection in a young adult. A Case Report. Front Med 2020; 7: 428.
[http://dx.doi.org/10.3389/fmed.2020.00428] [PMID: 32760733]
[62]
Balasubramanian S, Nagendran TM, Ramachandran B, Ramanan AV. Hyper-inflammatory syndrome in a child with COVID-19 treated successfully with intravenous immunoglobulin and tocilizumab. Indian Pediatr 2020; 57(7): 681-3.
[http://dx.doi.org/10.1007/s13312-020-1901-z] [PMID: 32393681]
[63]
Klocperk A, Parackova Z, Dissou J, et al. Case report: Systemic inflammatory response and fast recovery in a pediatric patient with COVID-19. Front Immunol 2020; 11: 1665.
[http://dx.doi.org/10.3389/fimmu.2020.01665] [PMID: 32719688]
[64]
Raut S, Roychowdhoury S, Bhakta S, Sarkar M, Nandi M. Incomplete kawasaki disease as presentation of COVID-19 infection in an infant: A case report J Trop Pediatr 2020; 67(3): 047.
[http://dx.doi.org/10.1093/tropej/fmaa047]
[65]
Gupta A, Gill A, Sharma M, Garg M. Multi-system inflammatory syndrome in a child mimicking Kawasaki disease. J Trop Pediatr 2020.
[PMID: 32778886]
[66]
Deza Leon MP, Redzepi A, McGrath E, et al. COVID-19 associated pediatric multi-system inflammatory syndrome. J Pediatric Infect Dis Soc 2020; 9(3): 407-8.
[http://dx.doi.org/10.1093/jpids/piaa061] [PMID: 32441749]
[67]
Yozgat CY, Uzuner S, Duramaz BB, et al. Dermatological manifestation of pediatrics multisystem inflammatory syndrome associated with COVID-19 in a 3-year-old girl. Dermatol Ther 2020; 33(4): 13770.
[http://dx.doi.org/10.1111/dth.13770]
[68]
Foong Ng K, Kothari T, Bandi S, et al. COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection. J Med Virol 2020; 92(11): 2880-6.
[http://dx.doi.org/10.1002/jmv.26206]
[69]
Licciardi F, Pruccoli G, Denina M, et al. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome: A novel COVID phenotype in children. Pediatrics 2020; 1711.
[70]
Nguyen DC, Haydar H, Pace ER, Zhang XS, Dobbs KR. Pediatric case of severe COVID-19 with shock and multisystem inflammation. Cureus 2020; 12: 8915.
[71]
Rauf A, Vijayan A, John ST, Krishnan R, Latheef A. Multisystem inflammatory syndrome with features of atypical kawasaki disease during COVID-19 Pandemic. Indian J Pediatr 2020; 87(9): 745-7.
[http://dx.doi.org/10.1007/s12098-020-03357-1]
[72]
Capone CA, Subramony A, Sweberg T, et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood associated with severe acute respiratory syndrome coronavirus. Infection J Pediatr 2020; 224: 141-5.
[http://dx.doi.org/10.1016/j.jpeds.2020.06.044]
[73]
Lee PY, Day-Lewis M, Henderson LA, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest 2020; 130(11): 5942-50.
[http://dx.doi.org/10.1172/JCI141113]
[74]
Vergnano S, Alders N, Armstrong C, et al. Severe refractory Kawasaki disease in seven infants in the COVID-19 era. Lancet Rheumatol 2020; 2(9): 520.
[http://dx.doi.org/10.1016/S2665-9913(20)30231-9]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy