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1.
BMJ Glob Health ; 8(5)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37257937

RESUMO

BACKGROUND: The COVID-19 pandemic required science to provide answers rapidly to combat the outbreak. Hence, the reproducibility and quality of conducting research may have been threatened, particularly regarding privacy and data protection, in varying ways around the globe. The objective was to investigate aspects of reporting informed consent and data handling as proxies for study quality conduct. METHODS: A systematic scoping review was performed by searching PubMed and Embase. The search was performed on November 8th, 2020. Studies with hospitalised patients diagnosed with COVID-19 over 18 years old were eligible for inclusion. With a focus on informed consent, data were extracted on the study design, prestudy protocol registration, ethical approval, data anonymisation, data sharing and data transfer as proxies for study quality. For reasons of comparison, data regarding country income level, study location and journal impact factor were also collected. RESULTS: 972 studies were included. 21.3% of studies reported informed consent, 42.6% reported waivers of consent, 31.4% did not report consent information and 4.7% mentioned other types of consent. Informed consent reporting was highest in clinical trials (94.6%) and lowest in retrospective cohort studies (15.0%). The reporting of consent versus no consent did not differ significantly by journal impact factor (p=0.159). 16.8% of studies reported a prestudy protocol registration or design. Ethical approval was described in 90.9% of studies. Information on anonymisation was provided in 17.0% of studies. In 257 multicentre studies, 1.2% reported on data sharing agreements, and none reported on Findable, Accessible, Interoperable and Reusable data principles. 1.2% reported on open data. Consent was most often reported in the Middle East (42.4%) and least often in North America (4.7%). Only one report originated from a low-income country. DISCUSSION: Informed consent and aspects of data handling and sharing were under-reported in publications concerning COVID-19 and differed between countries, which strains study quality conduct when in dire need of answers.


Assuntos
COVID-19 , Pandemias , Humanos , Adolescente , Estudos Retrospectivos , Reprodutibilidade dos Testes , Consentimento Livre e Esclarecido
2.
J Inherit Metab Dis ; 34(3): 605-19, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21445610

RESUMO

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, recently developed chemical tools allowing specific visualization of enzymatically active lysosomal glucocerebrosidase are described. Such probes, coined inhibodies, offer entirely new possibilities for more sophisticated molecular diagnosis, enzyme replacement therapy monitoring, and fundamental research.


Assuntos
Anticorpos , Biomarcadores/análise , Lipídeos/análise , Doenças por Armazenamento dos Lisossomos/diagnóstico , Proteínas/análise , Animais , Biomarcadores/metabolismo , Terapia de Reposição de Enzimas , Doença de Fabry/diagnóstico , Doença de Fabry/metabolismo , Doença de Fabry/patologia , Doença de Fabry/terapia , Doença de Gaucher/diagnóstico , Doença de Gaucher/metabolismo , Doença de Gaucher/patologia , Doença de Gaucher/terapia , Humanos , Doenças por Armazenamento dos Lisossomos/metabolismo , Doenças por Armazenamento dos Lisossomos/patologia , Doenças por Armazenamento dos Lisossomos/terapia , Modelos Moleculares , Proteínas/metabolismo
3.
Ultrastruct Pathol ; 34(3): 126-32, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20455661

RESUMO

In mucopolysaccharidosis type I (MPS I; alpha-L-iduronidase deficiency), glycosaminoglycans (GAGs) accumulate in different cell types, causing characteristic vacuolization. Hematopoietic cell transplantation (HCT) and enzyme replacement therapy (ERT) both aim to restore tissue morphology by delivering alpha-L-iduronidase to the deficient cells. The authors investigated the efficacy of both therapies on dermal fibroblast morphology in 12 patients by electron microscopy of repeated skin biopsies before and during 2 years of ERT as well as before and 6 months after HCT. Cell vacuolization was rated according to a semi-quantitative scoring system. At baseline all patients showed an increased vacuolization score as compared to controls. In addition the vacuolization score was significantly higher in patients with the severe phenotype of the disease (n = 7) compared to patients with attenuated phenotypes (n = 5) (p = .009). After initiation of ERT a significant decrease in cell vacuolization was observed (p = .012). However, the response rate varied among patients, as the vacuolization score remained high during the first year of ERT in 3 patients with the severe phenotype. In all patients who received a successful HCT (n = 3) only minimal disturbances in cell morphology were observed afterward. In conclusion, both ERT and HCT are capable of restoring, at least partially, dermal fibroblast morphology in MPS I.


Assuntos
Derme/ultraestrutura , Terapia de Reposição de Enzimas , Fibroblastos/ultraestrutura , Transplante de Células-Tronco Hematopoéticas , Mucopolissacaridose I/terapia , Adolescente , Adulto , Biópsia , Criança , Terapia Combinada , Derme/metabolismo , Fibroblastos/metabolismo , Glicosaminoglicanos/urina , Humanos , Lactente , Mucopolissacaridose I/patologia , Mucopolissacaridose I/urina , Vacúolos/ultraestrutura
4.
Proc Natl Acad Sci U S A ; 105(8): 2812-7, 2008 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-18287059

RESUMO

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A that affects males and shows disease expression in heterozygotes. The characteristic progressive renal insufficiency, cardiac involvement, and neuropathology usually are ascribed to globotriaosylceramide accumulation in the endothelium. However, no direct correlation exists between lipid storage and clinical manifestations, and treatment of patients with recombinant enzymes does not reverse several key signs despite clearance of lipid from the endothelium. We therefore investigated the possibility that globotriaosylceramide metabolites are a missing link in the pathogenesis. We report that deacylated globotriaosylceramide, globotriaosylsphingosine, and a minor additional metabolite are dramatically increased in plasma of classically affected male Fabry patients and plasma and tissues of Fabry mice. Plasma globotriaosylceramide levels are reduced by therapy. We show that globotriaosylsphingosine is an inhibitor of alpha-galactosidase A activity. Furthermore, exposure of smooth muscle cells, but not fibroblasts, to globotriaosylsphingosine at concentrations observed in plasma of patients promotes proliferation. The increased intima-media thickness in Fabry patients therefore may be related to the presence of this metabolite. Our findings suggest that measurement of circulating globotriaosylsphingosine will be useful to monitor Fabry disease and may contribute to a better understanding of the disorder.


Assuntos
Doença de Fabry/sangue , Glicolipídeos/sangue , Esfingolipídeos/sangue , Adolescente , Adulto , Animais , Proliferação de Células/efeitos dos fármacos , Criança , Glicolipídeos/farmacologia , Humanos , Masculino , Camundongos , Miócitos de Músculo Liso/citologia , Países Baixos , Linhagem , Esfingolipídeos/farmacologia , alfa-Galactosidase/antagonistas & inibidores
5.
Mol Genet Metab ; 93(3): 331-40, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18023222

RESUMO

Fabry disease is a complex, multisystemic and clinically heterogeneous disease, in which the urinary excretion of globotriaosylceramide (Gb3), the principal substrate of the deficient enzyme, alpha-galactosidase A, is more prominent than the increased concentrations of the lipid in the plasma of affected hemizygotes and heterozygotes. We have developed and validated a simultaneous analysis of Gb3 and creatinine in a 2.6-min run using filter paper discs saturated with urine and analyzed by LC-MS/MS. Using this method, we studied the relationship between urinary levels of total Gb3/creatinine excretion and four types of mutations in the GLA gene (missense, nonsense, frameshift, and splice-site defects) in 32 children and 78 adult patients with Fabry disease. Forty-one patients were treated by enzyme replacement therapy and 69 were untreated. Our results show that the mean recoveries of Gb3 and creatinine from the urine filter paper standards were 91% and 97%, respectively, with precision, reproducibility, and linearity within acceptable ranges. Statistical analysis using the independent variables of sex, age, types of mutations and treatment showed that the mutation factor has a statistically significant impact on urinary Gb3 excretion (p = 0.0007). This means that the levels of urinary excretion of Gb3/creatinine in children and adults with Fabry disease are directly related to the types of mutations. The same correlation was found for the sex (p < 0.0001) and treatment (p = 0.0011). In conclusion, we studied 35 mutations in 110 children and adults with Fabry disease and found a significant correlation between the types of mutations and total Gb3 excretion in Fabry patients.


Assuntos
Doença de Fabry/enzimologia , Triexosilceramidas/urina , alfa-Galactosidase/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cromatografia Líquida , Creatinina/urina , Doença de Fabry/tratamento farmacológico , Doença de Fabry/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Espectrometria de Massas em Tandem , alfa-Galactosidase/genética , alfa-Galactosidase/uso terapêutico
6.
Eur J Hum Genet ; 15(5): 535-42, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17327876

RESUMO

Facial dysmorphology is an important feature in several lysosomal storage disorders. Although in Fabry disease facial dysmorphism is not a prominent sign, minor facial abnormalities have been previously reported. By analysing three-dimensional images of faces, we quantified facial dysmorphology in a cohort of both male and female Fabry patients. Morphometric analysis of different regions of the face revealed significant differences in face shape in male patients and to a lesser extent in female patients. In male patients, the most prominent abnormalities were located in the peri-orbital region. Pattern recognition techniques achieved a discrimination accuracy of up to 85% for male patients compared with healthy controls. The discrimination accuracy in female patients achieved only 67%. This objective method for facial dysmorphology assessment provided evidence for significant differences in face shape in both male and female Fabry patients compared with controls. However, because discrimination from healthy controls is too low, no key role in the diagnostic process can be expected.


Assuntos
Doença de Fabry/diagnóstico , Face/anormalidades , Fácies , Imageamento Tridimensional/métodos , Adulto , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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