{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:36:31Z","timestamp":1790357791254,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: Case reports are usually excluded from systematic reviews. Patients with rare diseases are more dependent on novel individualized strategies than patients with common diseases. We reviewed and summarized the novelties reported by case reports in mucopolysaccharidosis type II (MPS-II) patients treated with enzyme replacement therapy (ERT). Methods: We selected the case reports included in a previous meta-analysis of patients with MPS-II treated with ERT. Later clinical studies evaluating the same topic of those case reports were reported. Our primary aim was to summarize novelties reported in previous case reports. Secondary objectives analyzed the number of novelties evaluated in subsequent clinical studies and the time elapsed between the publication of the case report to the publication of the clinical study. Results: We identified 11 innovative proposals in case reports that had not been previously considered in clinical studies. Only two (18.2%) were analyzed in subsequent nonrandomized cohort studies. The other nine novelties (81.8%) were analyzed in later case reports (five) or were not included in ulterior studies (four) after more than five years from their first publication. Conclusions: Case reports should be included in systematic reviews of rare disease to obtain a comprehensive summary of the state of research and offer valuable information for healthcare practitioners.<\/jats:p>","DOI":"10.3390\/ijerph17186590","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:10:09Z","timestamp":1599729009000},"page":"6590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II)"],"prefix":"10.3390","volume":"17","author":[{"given":"Miguel","family":"Sampayo-Cordero","sequence":"first","affiliation":[{"name":"Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ 07450, USA"},{"name":"Medica Scientia Innovation Research (MedSIR), 08018 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernat","family":"Miguel-Huguet","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital de Bellvitge, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Malfettone","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ 07450, USA"},{"name":"Medica Scientia Innovation Research (MedSIR), 08018 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"P\u00e9rez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ 07450, USA"},{"name":"Medica Scientia Innovation Research (MedSIR), 08018 Barcelona, Spain"},{"name":"Institute of Breast Cancer, Quiron Group, 08023 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Llombart-Cussac","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ 07450, USA"},{"name":"Medica Scientia Innovation Research (MedSIR), 08018 Barcelona, Spain"},{"name":"Hospital Arnau de Vilanova, Universidad Cat\u00f3lica de Valencia \u201cSan Vicente M\u00e1rtir\u201d, 46015 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ 07450, USA"},{"name":"Medica Scientia Innovation Research (MedSIR), 08018 Barcelona, Spain"},{"name":"Institute of Breast Cancer, Quiron Group, 08023 Barcelona, Spain"},{"name":"Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Pardo","sequence":"additional","affiliation":[{"name":"Albiotech Consultores y Redacci\u00f3n Cient\u00edfica S.L., 28035 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"P\u00e9rez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13023-018-0762-1","article-title":"Characteristics of drugs for ultra-rare diseases versus drugs for other rare diseases in HTA submissions made to the CADTH CDR","volume":"13","author":"Richter","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s13023-019-1202-6","article-title":"Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases","volume":"14","author":"Malfettone","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/1750-1172-6-72","article-title":"Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease","volume":"6","author":"Scarpa","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-017-0635-z","article-title":"Ten years of the Hunter Outcome Survey (HOS): Insights, achievements, and lessons learned from a global patient registry","volume":"12","author":"Muenzer","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-017-0712-3","article-title":"Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS)","volume":"12","author":"Muenzer","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1056\/NEJMra1614394","article-title":"Evidence for Health Decision Making\u2014Beyond Randomized, Controlled Trials","volume":"377","author":"Frieden","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-020-01382-z","article-title":"Critical clinical situations in adult patients with Mucopolysaccharidoses (MPS)","volume":"15","author":"Stepien","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ymgme.2019.06.008","article-title":"Enzyme replacement therapy initiated in adulthood: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program","volume":"127","author":"Lampe","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nissen, T., and Wynn, R. (2014). The clinical case report: A review of its merits and limitations. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-264"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/ccr3.58","article-title":"Aggregating case reports: A way for the future of evidence-based health care?","volume":"2","author":"Jackson","year":"2014","journal-title":"Clin. Case Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"608","DOI":"10.12998\/wjcc.v2.i11.608","article-title":"Important of case-reports\/series, in rare diseases: Using neuroendocrine tumors as an example","volume":"2","author":"Nakamura","year":"2014","journal-title":"World J. Clin. Cases"},{"key":"ref_12","unstructured":"(2018, February 04). Cochrane Handbook for Systematic Reviews of Interventions|Cochrane Training. Available online: http:\/\/training.cochrane.org\/handbook."},{"key":"ref_13","first-page":"138","article-title":"Agreement between the results of meta-analyses from case reports and from clinical studies regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age: An example of case reports meta-analyses as an useful tool for evidence-based medicine in rare diseases","volume":"121","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ymgme.2017.04.004","article-title":"Efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age. A systematic review and meta-analysis","volume":"121","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ymgme.2018.04.013","article-title":"Efficacy of Idursulfase therapy in patients with Mucopolysaccharidosis type II who initiated enzyme replacement therapy in adult age. A systematic review of the literature","volume":"124","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/01.gim.0000232477.37660.fb","article-title":"A phase II\/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)","volume":"8","author":"Muenzer","year":"2006","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/GIM.0b013e3181fea459","article-title":"Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/sj.bmt.1705934","article-title":"Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome","volume":"41","author":"Tolar","year":"2008","journal-title":"Bone Marrow Transpl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.jpeds.2008.11.005","article-title":"Improved Metabolic Correction in Patients with Lysosomal Storage Disease Treated with Hematopoietic Stem Cell Transplant Compared with Enzyme Replacement Therapy","volume":"154","author":"Wynn","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.jpeds.2012.07.052","article-title":"Enzyme Replacement is Associated with Better Cognitive Outcomes after Transplant in Hurler Syndrome","volume":"162","author":"Eisengart","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group","volume":"283","author":"Stroup","year":"2000","journal-title":"JAMA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ymgme.2017.06.001","article-title":"Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report","volume":"122","author":"Kim","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/all.12721","article-title":"Case of infusion reaction to idursulafase and successful re-administration with desensitization. Poster Session Group III\u2014Green TPS 39","volume":"70","author":"Gkavogiannakis","year":"2015","journal-title":"Allergy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s10719-013-9471-0","article-title":"Plasmatic kinetics of dermatan sulfate during enzyme replacement therapy with iduronate-2-sulfatase in a mucopolysaccharidosis II Patient","volume":"30","author":"Volpi","year":"2013","journal-title":"Glycoconj. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1111\/ijd.12206","article-title":"Characteristic \u201cpebbling\u201d skin eruption as a presenting sign of Hunter syndrome","volume":"53","author":"Noh","year":"2014","journal-title":"Int. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1525-1470.2011.01418.x","article-title":"Hunter Syndrome: Resolution of Extensive Typical Skin Lesions After 9 Months of Enzyme Replacement Therapy with Idursulfase","volume":"29","year":"2012","journal-title":"Pediatr. Dermatol."},{"key":"ref_28","first-page":"bcr2012007644","article-title":"Hunter syndrome follow-up after 1 year of enzyme-replacement therapy","volume":"2013","author":"Puiu","year":"2013","journal-title":"Case Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ymgme.2009.07.015","article-title":"Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II","volume":"98","author":"Wang","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kinoshita, M., Furujo, M., and Kubo, T. (2014, January 22). EEG Evaluation of Mucopolysaccharidosis Type II After Enzyme Replacement Therapy. Proceedings of the 55th Annual Meeting of the Japanese Society of Neurology, Fukuoka, Japan.","DOI":"10.1016\/S1388-2457(14)50564-0"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/j.1469-8749.2012.04228.x","article-title":"Non-convulsive status epilepticus of frontal origin in mucopolysaccharidosis type II successfully treated with ethosuximide: Case Report","volume":"54","author":"Bonanni","year":"2012","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sanchez, J.I., Ascaso, F.J., Perez, I., Almenara, C., Esteban, O., Martinez, M., Idoate, A., and Torralba, M.A. (2015). Role of SD-OCT in the follow-up of a patient with macular edema associated with mucopoysaccharidosis type II (Hunter syndrome) undergoing idursulfase enzyme replacement therapy. Acta Ophthalmol., 93.","DOI":"10.1111\/j.1755-3768.2015.0381"},{"key":"ref_33","first-page":"S69","article-title":"Multiple mechanisms of ophthalmologic involvement in attenuated Hunter syndrome: A case report","volume":"114","author":"Lau","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","first-page":"S21","article-title":"2015 ASPHO Abstracts. Autoimmune thrombocytopenia in a patient with hunter syndrome: Should iduronate-2-sulfatase replacement therapy still be considered?","volume":"62","author":"Fisher","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00277-011-1248-6","article-title":"Hunter syndrome and new onset idiopathic thrombocytopenic purpura in a young patient","volume":"91","author":"Uz","year":"2012","journal-title":"Ann. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1177\/0883073812438100","article-title":"Botulinum Toxin Type A for the Treatment of Equinus Deformity in Patients with Mucopolysaccharidosis Type II","volume":"27","author":"Nava","year":"2012","journal-title":"J. Child. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1002\/mds.22145","article-title":"A novel mutation in the iduronate 2 sulfatase gene resulting in mucopolysaccharidosis type II and chorea: Case report of two siblings","volume":"23","author":"Farooq","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_38","first-page":"253","article-title":"Long-term enzyme replacement therapy in a severe case of mucopolysaccharidosis type II (Hunter syndrome)","volume":"15","author":"Papadia","year":"2011","journal-title":"Eur. Rev. Med. Pharm. Sci"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-3-662-43748-3","article-title":"Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age","volume":"Volume 14","author":"Zschocke","year":"2014","journal-title":"JIMD Reports"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.ymgme.2013.12.042","article-title":"Mucopolysaccharidosis type II (MPS II): Case report of three affected siblings","volume":"111","author":"Bivina","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cca.2013.04.022","article-title":"Idursulfase enzyme replacement therapy in an adult patient with severe Hunter syndrome having a novel mutation of iduronate-2-sulfatase gene","volume":"423","author":"Christianto","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1007\/s00246-013-0653-0","article-title":"Massive Accumulation of Glycosaminoglycans in the Aortic Valve of a Patient with Hunter Syndrome During Enzyme Replacement Therapy","volume":"34","author":"Sato","year":"2013","journal-title":"Pediatr. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ymgme.2012.12.010","article-title":"Effects of idursulfase enzyme replacement therapy for Mucopolysaccharidosis type II when started in early infancy: Comparison in two siblings","volume":"108","author":"Tajima","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.pediatrneurol.2011.05.010","article-title":"Hunter Disease Before and During Enzyme Replacement Therapy","volume":"45","author":"Hoffmann","year":"2011","journal-title":"Pediatr. Neurol."},{"key":"ref_45","first-page":"e42","article-title":"Enzyme replacement therapy for mucopolysaccharidosis II from 3 months of age: A 3-year follow-up: Enzyme replacement therapy for mucopolysaccharidosis II","volume":"101","author":"Jurecka","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1016\/j.rce.2011.01.014","article-title":"Respuesta precoz a idursulfasa en un paciente de 31 a\u00f1os de edad con s\u00edndrome de Hunter","volume":"211","year":"2011","journal-title":"Rev. Cl\u00edn. Espa\u00f1ola"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"SSIEM (2011). Three Adult Siblings with Mucopolysaccharidosis Type II (Hunter Syndrome): A Report on Clinical Heterogeneity and 12 Months of Therapy with Idursulfase. JIMD Reports\u2014Case and Research Reports, 2011\/1, Springer. JIMD Reports.","DOI":"10.1007\/978-3-642-17708-8"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ejmg.2008.02.005","article-title":"Early response to idursulfase treatment in a 3 year-old boy affected of Hunter syndrome","volume":"51","year":"2008","journal-title":"Eur. J. Med Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"SSIEM (2011). Successful Noninvasive Ventilation and Enzyme Replacement Therapy in an Adult Patient with Morbus Hunter. JIMD Reports\u2014Case and Research Reports, 2012\/2, Springer. JIMD Reports.","DOI":"10.1007\/978-3-642-17708-8"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.3389\/fimmu.2020.01000","article-title":"Immune Modulation for Enzyme Replacement Therapy in A Female Patient with Hunter Syndrome","volume":"11","author":"Julien","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4103\/2229-5178.198772","article-title":"Pebbling of skin: Cutaneous marker of Hunter syndrome","volume":"8","author":"Srinivas","year":"2017","journal-title":"Indian Dermatol. Online J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s00247-017-3935-5","article-title":"Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis","volume":"47","author":"Matsubara","year":"2017","journal-title":"Pediatr. Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10545-011-9317-5","article-title":"Brain and spine MRI features of Hunter disease: Frequency, natural evolution and response to therapy","volume":"34","author":"Manara","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ymgme.2014.12.299","article-title":"Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II","volume":"114","author":"Yund","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/02643294.2017.1401530","article-title":"Cognitive and behaviour profiles of children with mucopolysaccharidosis Type II","volume":"34","author":"Crowe","year":"2017","journal-title":"Cogn. Neuropsychol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ymgme.2012.09.004","article-title":"Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: A nationwide survey in Japan","volume":"107","author":"Tanaka","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ymgme.2017.10.006","article-title":"Epilepsy in mucopolysaccharidosis disorders","volume":"122","author":"Scarpa","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.braindev.2013.12.002","article-title":"Nocturnal frontal lobe epilepsy in mucopolysaccharidosis","volume":"36","author":"Bonanni","year":"2014","journal-title":"Brain Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000500804","article-title":"Recovery of Vision following Enzyme Replacement Therapy in a Patient with Mucopolysaccharidosis Type II, Hunter Syndrome","volume":"10","author":"Yamanishi","year":"2019","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/cge.12738","article-title":"Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome: Mutational spectrum in a sample of Mexican MPSII patients","volume":"89","author":"Berumen","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1258\/shorts.2012.012046","article-title":"The recent history of the clinical case report: A narrative review","volume":"3","author":"Nissen","year":"2012","journal-title":"JRSM Short Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/gim.2017.30","article-title":"Treatment of mucopolysaccharidosis type II (Hunter syndrome): Results from a systematic evidence review","volume":"19","author":"Bradley","year":"2017","journal-title":"Genet. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"s45","DOI":"10.1590\/0102-311X00017613","article-title":"Efic\u00e1cia e seguran\u00e7a da terapia com idursulfase em pacientes com mucopolissacaridose tipo II, com e sem compara\u00e7\u00e3o com placebo: Revis\u00e3o sistem\u00e1tica e metan\u00e1lise","volume":"29","author":"Alegra","year":"2013","journal-title":"Cad. Sa\u00fade P\u00fablica"},{"key":"ref_64","first-page":"1465","article-title":"Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome)","volume":"2","author":"Strufaldi","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_65","unstructured":"Almeida, P.H.R.F., Lemos, L.L.P.D., Alvares, J., Godman, B., Bennie, M., Acurcio, F.D.A., and Junior, A.A.G. (2018). Safety of Enzyme Replacement Therapy for Mucopolysaccharidosis II. Pharmacoepidemiology and Drug Safety, Wiley."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1136\/bmjebm-2017-110853","article-title":"Methodological quality and synthesis of case series and case reports","volume":"23","author":"Murad","year":"2018","journal-title":"BMJ Evid. Based Med."},{"key":"ref_67","first-page":"bcr2013201554","article-title":"The CARE guidelines: Consensus-based clinical case reporting guideline development","volume":"2013","author":"Gagnier","year":"2013","journal-title":"Case Rep."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Luo, M., Cohen, A.M., Addepalli, S., and Smalheiser, N.R. (2020). Identifying main finding sentences in clinical case reports. Database, 2020.","DOI":"10.1093\/database\/baaa041"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s13643-019-1167-5","article-title":"A comparison between two recommendations to conduct and report systematic reviews on drug\u2019s safety","volume":"8","author":"Penedones","year":"2019","journal-title":"Syst. Rev."},{"key":"ref_70","first-page":"809","article-title":"Google Search as an Additional Source in Systematic Reviews","volume":"24","author":"Piasecki","year":"2017","journal-title":"Sci. Eng. Ethics"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lakhani, H.V., Pillai, S.S., Zehra, M., Sharma, I., and Sodhi, K. (2020). Systematic Review of Clinical Insights into Novel Coronavirus (CoVID-19) Pandemic: Persisting Challenges in U.S. Rural Population. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17124279"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1038\/cti.2015.15","article-title":"Medical case reports in the age of genomic medicine","volume":"4","author":"Cook","year":"2015","journal-title":"Clin. Transl. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Parini, R., and Deodato, F. (2020). Intravenous enzyme replacement therapy in mucopolysaccharidoses: clinical effectiveness and limitations. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082975"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s10038-019-0662-9","article-title":"Enzyme replacement therapy for mucopolysaccharidoses; past, present, and future","volume":"64","author":"Chen","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s40265-019-01147-4","article-title":"Therapeutic options for mucopolysaccharidoses: current and emerging treatments","volume":"79","author":"Sawamoto","year":"2019","journal-title":"Drugs"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"MPS Consensus Programme Steering Committee, MPS Consensus Programme Co-Chairs, Akyol, M.U., Alden, T.D., Amartino, H., Ashworth, J., Belani, K., Berger, K.I., Borgo, A., and Braunlin, E. (2019). Recommendations for the management of MPS IVA: Systematic evidence- and consensus-based guidance. Orphanet J. Rare Dis., 14.","DOI":"10.1186\/s13023-019-1074-9"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e163","DOI":"10.1055\/s-0038-1667350","article-title":"Innovative Treatments for Mucopolysaccharidoses","volume":"8","author":"Lagler","year":"2018","journal-title":"J. Child Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/164_2019_263","article-title":"Current and Emerging Therapies for Mucopolysaccharidoses","volume":"Volume 261","author":"Kiess","year":"2019","journal-title":"Pediatric Pharmacotherapy"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1055\/s-0039-3402070","article-title":"Spectrum of lysosomal storage disorders at tertiary centre: Retrospective case-record analysis","volume":"9","author":"Singh","year":"2020","journal-title":"J. Ped. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kubaski, F., de Oliveira Poswar, F., Michelin-Tirelli, K., Burin, M.G., Rojas-M\u00e1laga, D., Brusius-Facchin, A.C., Leistner-Segal, S., and Giugliani, R. (2020). Diagnosis of mucopolysaccharidoses. Diagnostics, 10.","DOI":"10.3390\/diagnostics10030172"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1053\/j.semdp.2018.12.001","article-title":"Hamartomas of skin and soft tissue","volume":"36","author":"Tjarks","year":"2019","journal-title":"Semin. Diag. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Almassi, G.H., and Algahim, M. (2013). Current and emerging management options for patients with Morquio A syndrome. Ther. Clin. Risk Manag., 45.","DOI":"10.2147\/TCRM.S24771"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"v49","DOI":"10.1093\/rheumatology\/ker396","article-title":"Therapy for the mucopolysaccharidoses","volume":"50","author":"Valayannopoulos","year":"2011","journal-title":"Rheumatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s00431-011-1644-x","article-title":"Diagnosis and treatment trends in mucopolysaccharidosis I: Findings from the MPS I Registry","volume":"171","author":"Underhill","year":"2012","journal-title":"Eur. J. Ped."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3174\/ajnr.A2832","article-title":"Brain and Spinal MR imaging findings in mucopolysaccharidoses: A review","volume":"34","author":"Zafeiriou","year":"2013","journal-title":"Am. J. Neuroradiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.ymgme.2012.09.024","article-title":"Heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III","volume":"107","author":"Wagemans","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/1750-1172-8-147","article-title":"A pilot newborn screening program for Mucopolysaccharidosis type I in Taiwan","volume":"8","author":"Lin","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ymgme.2013.03.005","article-title":"Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice","volume":"109","author":"Baldo","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ymgme.2012.05.005","article-title":"Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II","volume":"107","author":"Higuchi","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"946","DOI":"10.2174\/138920111795542642","article-title":"Intrathecal enzyme replacement therapy for mucopolysaccharidosis I: Translating success in animal models to patients","volume":"12","author":"Dickson","year":"2011","journal-title":"Current Pharm. Biotechnol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1148\/rg.2016150168","article-title":"Neuroimaging findings in patients with mucopolysaccharidosis: What you really need to know","volume":"36","author":"Reichert","year":"2016","journal-title":"Radiographics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.rcl.2013.11.008","article-title":"Imaging nanifestations of the leukodystrophies, inherited disorders of white matter","volume":"52","author":"Yang","year":"2014","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.nrleng.2011.10.005","article-title":"Neuroimaging findings in patient series with mucopolysaccharidosis","volume":"27","year":"2012","journal-title":"Neurolog\u00eda (English Edition)"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/glycob\/cwq088","article-title":"Effect of 6 years of enzyme replacement therapy on plasma and urine glycosaminoglycans in attenuated MPS I patients","volume":"20","author":"Coppa","year":"2010","journal-title":"Glycobiology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10545-012-9530-x","article-title":"Retroviral-vector-mediated gene therapy to mucopolysaccharidosis I mice improves sensorimotor impairments and other behavioral deficits","volume":"36","author":"Baldo","year":"2013","journal-title":"J. Inherited Metab. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"051","DOI":"10.1055\/s-0032-1306386","article-title":"Lysosomal Disorders associated with leukoencephalopathy","volume":"32","author":"Renaud","year":"2012","journal-title":"Sem. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.mehy.2014.01.029","article-title":"Lysosomal enzymes may cross the blood\u2013brain-barrier by pinocytosis: Implications for Enzyme Replacement Therapy","volume":"82","author":"Baldo","year":"2014","journal-title":"Med. Hypotheses"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/gim.2016.223","article-title":"Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1","volume":"19","author":"Grosse","year":"2017","journal-title":"Genet. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jfms.2010.09.001","article-title":"Fucosidosis in a domestic shorthair cat","volume":"13","author":"Arrol","year":"2011","journal-title":"J. Feline Med. Surg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/jhg.2013.92","article-title":"High-dose enzyme replacement therapy attenuates cerebroventriculomegaly in a mouse model of mucopolysaccharidosis type II","volume":"58","author":"Ahn","year":"2013","journal-title":"J. Hum. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Jelin, A.C., O\u2019Hare, E., Blakemore, K., Jelin, E.B., Valle, D., and Hoover-Fong, J. (2017). Skeletal Dysplasias: Growing Therapy for Growing Bones. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00079"},{"key":"ref_102","first-page":"453.e1","article-title":"Gu\u00eda de pr\u00e1ctica cl\u00ednica para el tratamiento del s\u00edndrome de Hunter","volume":"141","author":"Blasco","year":"2013","journal-title":"Med. Cl\u00edn."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"14068","DOI":"10.1038\/mtm.2014.68","article-title":"A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I","volume":"2","author":"Mendez","year":"2015","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s00247-018-4139-3","article-title":"Mucopolysaccharidoses: Overview of neuroimaging manifestations","volume":"48","author":"AlSayed","year":"2018","journal-title":"Ped. Radiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3171\/2015.9.PEDS15477","article-title":"Regression of ventriculomegaly following medical management of a patient with Hurler syndrome","volume":"17","author":"Liang","year":"2016","journal-title":"J. Neurosurg. Ped."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Levin, A.V., and Enzenauer, R.W. (2017). Ocular Manifestations of Inborn Errors of Metabolism. The Eye in Pediatric Systemic Disease, Springer International Publishing.","DOI":"10.1007\/978-3-319-18389-3"},{"key":"ref_107","unstructured":"Gera, K. (2020, September 10). Characterization of a Mucopolysaccharidosis Type I and GalNAc Transferase Deficiency Double Knockout Mouse 2018. Available online: https:\/\/lib.dr.iastate.edu\/cgi\/viewcontent.cgi?article=7589&context=etd."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-94-017-9214-1_7","article-title":"Enzyme replacement therapy in lysosomal storage diseases","volume":"Volume 6","year":"2015","journal-title":"Rare Diseases"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kubaski, F., de Oliveira Poswar, F., Michelin-Tirelli, K., da Matte, U.S., Horovitz, D.D., Barth, A.L., Baldo, G., Vairo, F., and Giugliani, R. (2020). Mucopolysaccharidosis Type I. Diagnostics, 10.","DOI":"10.3390\/diagnostics10030161"},{"key":"ref_110","unstructured":"Kubaski, F. (2020, July 27). Diagnosis and Therapies for Mucopolysaccharidoses. Doctoral Dissertation. Available online: https:\/\/udspace.udel.edu\/bitstream\/handle\/19716\/21745\/Kubaski_udel_0060D_12805.pdf?sequence=1&isAllowed=y."},{"key":"ref_111","first-page":"885","article-title":"Quantitative determination of urinary mucopolysaccharide and its clinical application","volume":"11","author":"Zhao","year":"2010","journal-title":"Chin. J. Children\u2019s Health"},{"key":"ref_112","unstructured":"Zheng, M., Tan, J., Pan, L., and Cai, R. (2013). Analysis of clinical features of mucopolysaccharidosis type II. Chinese J. Eugenics Genet., 110\u2013111. Available online: http:\/\/www.cqvip.com\/qk\/98444x\/201301\/44774375.html."},{"key":"ref_113","unstructured":"Wang, L., and Sun, J. (2013). The role of prenatal fetal heart monitoring in reducing fetal and neonatal injury. Chinese J. Eugenics Genet., 62\u201363. Available online: http:\/\/www.cqvip.com\/qk\/98444x\/201301\/44774346.html."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ymgme.2017.05.004","article-title":"Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure","volume":"121","author":"Morton","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ymgme.2017.05.005","article-title":"Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature","volume":"121","author":"Janzen","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.eplepsyres.2016.11.012","article-title":"The \u2018Photosensitivity Model\u2019 is ( also) a model for focal (partial) seizures","volume":"133","author":"Genton","year":"2017","journal-title":"Epilepsy Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.eplepsyres.2016.11.014","article-title":"Rebuttal to the manuscript by R.J. Porter","volume":"133","year":"2017","journal-title":"Epilepsy Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s10309-013-0353-z","article-title":"Ethosuximid bei strukturellen und l\u00e4sionellen Epilepsien","volume":"27","author":"Brandl","year":"2014","journal-title":"Z. Epileptol."},{"key":"ref_119","unstructured":"Scarpa, M., and Cinzia, B. (2020, September 10). Coinvolgimento neurologico nelle MPS. La Rivista delle Malattie Rare, Available online: https:\/\/malattierare.aou.udine.it\/news\/articoli\/coinvolgimento-neurologico-nelle-mps."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.eplepsyres.2016.11.015","article-title":"The photosensitivity model is not a model for partial (focal) seizures\u2014REBUTTAL","volume":"133","author":"Porter","year":"2017","journal-title":"Epilepsy Res."},{"key":"ref_121","first-page":"777","article-title":"Clinical analysis of status epilepticus secondary to acute cerebral hemorrhage","volume":"5","author":"Huang","year":"2013","journal-title":"J. Guangxi Med. Univ."},{"key":"ref_122","unstructured":"Luo, Q., Li, X., Tang, Y., and Gu, Y. (2018). Segmentation of diabetic macular edema for retinal OCT images. Proceedings of the Optics in Health Care and Biomedical Optics VIII, SPIE."},{"key":"ref_123","unstructured":"Emel, N. (2020). Evaluation of hematologic findings in mucopolysaccharidosis cases. Acta Med. Medit., 797\u2013800."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e226518","DOI":"10.1136\/bcr-2018-226518","article-title":"Hunter syndrome with persistent thrombocytopenia","volume":"12","author":"Panigrahi","year":"2019","journal-title":"BMJ Case Rep."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Kuzenkova, L., Namazova-Baranova, L., Gevorkyan, A., Vashakmadze, N., Podkletnova, T., Studenikin, V., and Lazurenko, S. (2012). The modern view of mucopolysaccharidosis type II in children: a multidisciplinary approach to the problem. Effect. Pharmacother. Pediatrics, Available online: https:\/\/umedp.ru\/articles\/sovremennyy_vzglyad_na_mukopolisakharidoz_ii_tipa_u_detey_multidistsiplinarnyy_podkhod_k_probleme.html.","DOI":"10.1016\/j.ymgme.2012.11.137"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/bmjspcare-2019-001943","article-title":"(Hal) Scoping review of symptoms in children with rare, progressive, life-threatening disorders","volume":"10","author":"Pawliuk","year":"2020","journal-title":"BMJ Support. Palliat. Care"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3724\/SP.J.1005.2009.01101","article-title":"Identification of a novel mutation of IDS gene from a Chinese pedigree with MPS II","volume":"31","author":"Guo","year":"2009","journal-title":"Hereditas (Beijing)"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/471325","article-title":"Glycosaminoglycan storage disorders: A review","volume":"2012","author":"Coutinho","year":"2012","journal-title":"Biochem. Res. Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/jcpt.12136","article-title":"Current and potential therapeutic strategies for mucopolysaccharidoses","volume":"39","author":"Noh","year":"2014","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ymgme.2018.07.013","article-title":"Evaluation of cerebrospinal fluid heparan sulfate as a biomarker of neuropathology in a murine model of mucopolysaccharidosis type II using high-sensitivity LC\/MS\/MS","volume":"125","author":"Tanaka","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000371658","article-title":"Cervical Spine MRI Findings in Patients with Mucopolysaccharidosis Type II","volume":"50","author":"Zuber","year":"2015","journal-title":"Pediatr. Neurosurg."},{"key":"ref_132","unstructured":"Rout-Pitt, N.B. (2015). The Effects of Undegraded Glycosaminoglycans from Mucopolysaccharidoses on Osteoblast Differentiation and Mineralisation In Vitro, University of Adelaide, School of Medicine."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/18\/6590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:48Z","timestamp":1760177328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/18\/6590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,10]]},"references-count":132,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijerph17186590"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17186590","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,10]]}}}