ABSTRACT
BACKGROUND: Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. METHODS: This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. DISCUSSION: NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.
Subject(s)
Cognitive Dysfunction , Niemann-Pick Disease, Type C , Humans , Adult , Niemann-Pick Disease, Type C/drug therapy , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiologyABSTRACT
AIM: Vaccination against SARS-CoV2 has been proposed as a fundamental element for the control of the pandemic. This study aimed to describe the suspected adverse reactions (ADR) reported by vaccinated hospital workers. METHODS: A descriptive study of suspected ADR was conducted between January and March 2021. The suspected ADR were identified using a specifically designed electronic form and spontaneous reporting. Data were also collected regarding the characteristics of the professionals, vaccine administered, severity, and outcome of ADR. RESULTS: 8169 professionals received 2 doses of SARS-CoV2 vaccine (6672 Comirnaty® and 1497 Spikevax®) and 894 reports of suspected ADR were reported (762 for Comirnaty® and 132 for Spikevax®), resulting in a cumulative ADR incidence of 10.94% (95%CI: 10.27-11.62). The majority of ADR were reported only after the second dose, 497 (56.2%), while 211 (23.6%) were reported only after the first dose and 186 (21%) after both doses. The symptoms were mostly mild, did not require medical assistance, and disappeared within approximately 3 days. One hundred and seventeen professionals had a history of COVID-19 infection. These studies reported, statistically significant, more suspected ADR after the first dose (42.7%) than those with no history of COVID-19 (20.7%). Among professionals, more ADR occurred after the first dose with the Spikevax® vaccine (41.6%) than with the Comirnaty® vaccine (20.5%). CONCLUSION: The majority of suspected ADR reported were described in the summary of product characteristics (SmPC). Professionals with a history of COVID-19 reported more suspected ADR after the first dose than did those without a history.
Subject(s)
COVID-19 , Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , Hospitals, University , Humans , Immunization , RNA, Viral , SARS-CoV-2 , VaccinationABSTRACT
No disponible
Subject(s)
Humans , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Stroke/prevention & control , /statistics & numerical data , Thrombin/antagonists & inhibitors , Factor Xa/antagonists & inhibitorsSubject(s)
Information Dissemination , Practice Patterns, Physicians' , Drug Industry , Humans , Marketing , Publication BiasSubject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Isoenzymes/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cardiovascular Diseases/chemically induced , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Humans , Kidney Diseases/chemically induced , Membrane Proteins , Prostaglandin-Endoperoxide Synthases , Skin Diseases/chemically inducedABSTRACT
No disponible
