{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:45:28Z","timestamp":1785725128578,"version":"3.56.0"},"reference-count":46,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1182864"],"award-info":[{"award-number":["OPP1182864"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,1,13]]},"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diagnosis of infantile thiamine deficiency disorders (TDD) is challenging due to the non-specific, highly variable clinical presentation, often leading to misdiagnosis. Our primary objective is to develop a case definition for thiamine responsive disorders (TRD) to determine among hospitalised infants and young children, which clinical features and risk factors identify those who respond positively to thiamine administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This prospective study will enrol 662 children (aged 21 days to &lt;18 months) seeking treatment for TDD symptoms. Children will be treated with intravenous or intramuscular thiamine (100\u2009mg daily for a minimum of 3 days) alongside other interventions deemed appropriate. Baseline assessments, prior to thiamine administration, include a physical examination, echocardiogram and venous blood draw for the determination of thiamine biomarkers. Follow-up assessments include physical examinations (after 4, 8, 12, 24, 36, 48 and 72\u2009hours), echocardiogram (after 24 and 48\u2009hours) and one cranial ultrasound. During the hospital stay, maternal blood and breast-milk samples and diet, health, anthropometric and socio-demographic information will be collected for mother\u2013child pairs. Using these data, a panel of expert paediatricians will determine TRD status for use as the dependent variable in logistic regression models. Models identifying predictors of TRD will be developed and validated for various scenarios. Clinical prediction model performance will be quantified by empirical area under the receiver operating characteristic curve, using resampling cross validation. A frequency-matched community-based cohort of mother\u2013child pairs (n=265) will serve as comparison group for evaluation of potential risk factors for TRD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval has been obtained from The National Ethics Committee for Health Research, Ministry of Health, Lao PDR and the Institutional Review Board of the University of California Davis. The results will be disseminated via scientific articles, presentations and workshops with representatives of the Ministry of Health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03626337\">NCT03626337<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-036539","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T04:25:37Z","timestamp":1581654337000},"page":"e036539","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: protocol for a prospective cohort study"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct03626337","registry":"10.18810\/clinical-trials-gov","type":"preResults"},{"clinical-trial-number":"nct03626337","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-277X","authenticated-orcid":false,"given":"Sonja Y","family":"Hess","sequence":"first","affiliation":[{"name":"Department of Nutrition, Institute for Global Nutrition, University of California Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn J","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Institute for Global Nutrition, University of California Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R","family":"Fischer","sequence":"additional","affiliation":[{"name":"Pediatric and Adolescent Medicine, Mayo, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-6858","authenticated-orcid":false,"given":"Indi","family":"Trehan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Department of Global Health, University of Washington, Seattle, Washington, USA"},{"name":"Lao Friends Hospital for Children, Luang Prabang, Lao People\u2019s Democratic Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Hiffler","sequence":"additional","affiliation":[{"name":"Independent Pediatrician, Lagny sur Marne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-3172","authenticated-orcid":false,"given":"Charles D","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Institute for Global Nutrition, University of California Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalaphone","family":"Sitthideth","sequence":"additional","affiliation":[{"name":"Lao Tropical and Public Health Institute, Vientiane, Lao People\u2019s Democratic Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-7907","authenticated-orcid":false,"given":"Daniel J","family":"Tancredi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis Health System, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Schick","sequence":"additional","affiliation":[{"name":"Emergency Medicine, University of California Davis Health System, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Cardiology, University of California Davis Health System, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Stein-Wexler","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California Davis Health System, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine N","family":"McBeth","sequence":"additional","affiliation":[{"name":"Emergency Medicine, University of California Davis Health System, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Institute for Global Nutrition, University of California Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouyang","family":"Nhiacha","sequence":"additional","affiliation":[{"name":"Lao-Korea Children Hospital, Vientiane, Lao People\u2019s 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