| 11. |
- Johnstone, Devon L., et al.
(författare)
-
Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature
- 2020
-
Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:6, s. 1321-1332
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.
|
|
| 12. |
- Saito, Makoto, et al.
(författare)
-
Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
- 2023
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 401:10371, s. 118-130
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. Methods: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. Findings: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49–1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47–1·17), stillbirth (aHR=0·71, 0·32–1·57), and major congenital anomalies (aHR=0·60, 0·13–2·87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92). Interpretation: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.
|
|
| 13. |
- Tabernero, Patricia, et al.
(författare)
-
Ethical challenges in designing and conducting medicine quality surveys
- 2016
-
Ingår i: Tropical medicine & international health. - : Wiley. - 1360-2276 .- 1365-3156. ; 21:6, s. 799-806
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesIn this paper we discuss the main ethical challenges related to the conduct of medicine quality surveys and make suggestions on how to address them. MethodMost evidence-based information regarding medicine quality derives from surveys. However, existing research ethical guidelines do not provide specific guidance for medicine quality surveys. Hence, those conducting surveys are often left wondering how to judge what counts as best practice. A list of the main ethical challenges in the design and conduct of surveys is presented. Results and conclusionsIt is vital that the design and conduct of medicine quality surveys uphold moral and ethical obligations and analyse the ethical implications and consequences of such work. These aspects include the impact on the local availability of and access to medicines; the confidentiality and privacy of the surveyors and the surveyed; questions as to whether outlet staff personnel should be told they are part of a survey; the need of ethical and regulatory approvals; and how the findings should be disseminated. Medicine quality surveys should ideally be conducted in partnership with the relevant national Medicine Regulatory Authorities. An international, but contextually sensitive, model of good ethical practice for such surveys is needed. ObjectifsIdentifier et discuter les principaux enjeux ethiques lies a la conduite des surveillances et formuler des suggestions sur la facon de les aborder. MethodeLa plupart des informations fondees sur des preuves en ce qui concerne la qualite des medicaments decoule des enquetes. Cependant, les directives ethiques de recherche existantes ne fournissent pas d'indications precises pour les enquetes sur la qualite de la medecine. Par consequent, ceux menant des enquetes sont souvent laisses a se demander comment juger ce qui compte comme la meilleure pratique. Une liste des principaux defis ethiques dans la conception et la conduite des enquetes est presentee. Resultats et conclusionsIl est essentiel que la conception et la conduite des enquetes sur la qualite de la medecine respectent les obligations morales et ethiques et analysent les implications ethiques et les consequences d'un tel travail. Celles-ci sont: l'impact sur la disponibilite locale et l'acces aux medicaments, la confidentialite et la protection de la vie privee des enqueteurs et des enquetes, des questions quant a savoir si les membres du personnel de sortie doivent etre informes quils font partie d'une enquete, la necessite d'approbations reglementaires et d'ethique et la facon dont les resultats devraient etre diffuses. Les enquetes sur la qualite de la medecine devraient idealement etre menees en partenariat avec les autorites relevantes de reglementation des medicaments nationaux. Un modele international, mais contextuellement sensible, de bonne pratique ethique pour ces enquetes est necessaire. ObjetivosIdentificar y discutir los principales retos eticos relacionados con la realizacion de encuestas y hacer sugerencias sobre la forma de abordarlas. MetodoLa mayor parte de la informacion basada en la evidencia en lo que respecta a la calidad de los medicamentos se obtiene a traves de encuestas. Sin embargo, las guias eticas de investigacion existentes no proveen una guia especifica para las encuestas de calidad de medicamentos. Por lo tanto, aquellos que llevan a cabo las encuestas a menudo no saben como definir lo que se considera como la mejor practica. Aqui se presenta una lista de los principales retos eticos en el diseno y en la realizacion de encuestas. Resultados y conclusionesEs vital que el diseno y el pase de encuestas de calidad de medicamentos apoyen obligaciones eticas y morales, asi como el analisis de las implicaciones y las consecuencias eticas de dicho trabajo. Estas son: el impacto sobre la disponibilidad local de y el acceso a las medicinas; la confidencialidad y la privacidad de los encuestados y encuestadores; preguntas sobre si los trabajadores del punto de entrega deberian ser avisados de que estan formando parte de un estudio; la necesidad de aprobaciones eticas y regulatorias; y como diseminar los hallazgos obtenidos. Las encuestas sobre la calidad de los medicamentos deberian idealmente realizarse junto con las autoridades nacionales relevantes en regulacion de medicamentos. Se requiere un modelo internacional, pero contextualmente sensible, de buenas practicas eticas.
|
|
