First Trimester Screening for Preeclampsia and Prevention with Aspirin Prophylaxis

Abstract Background: Preeclampsia is a hypertensive disorder of pregnancy affecting multiple organ systems complicating 2-8% of pregnancies. It is defined as new-onset hypertension and proteinuria, or hypertension and significant end-organ dysfunction, typically presenting after 20 weeks of gestation. It is caused by placental and maternal vascular dysfunction and resolves with delivery of the fetus. Maternal and fetal/placental factors have been studied for their ability to aid in the early detection of preeclampsia. Objectives: The purpose of this literature review was to determine if early screening and detection of preeclampsia would allow for appropriate clinical management and pharmacological prophylaxis interventions to be implemented, ultimately to reduce maternal and fetal complications and preterm delivery. Method: An integrative literature review was conducted undergoing an extensive search to identify maternal risk factors, biophysical measurements and biochemical markers for the development of an early screening test for the detection of preeclampsia. A total of 2 databases were used to acquire relevant sources: PubMed and CINHAL and a total of 12 articles were reviewed. Results: Combined maternal and fetal/placental factors have shown higher detection rates for preeclampsia than when tested individually. This review suggests combining maternal risk factors, uterine artery resistance Doppler analysis and PAPP-A and placental growth factor (PlGF) biomarkers to have the highest detection rates in their ability to be used as a first trimester screening test for preeclampsia. Conclusions: Specific combined factors could be useful in the early detection of preeclampsia allowing for the initiation of aspirin in high-risk women. However, more research is needed to determine whether these measurements could be clinically useful and improve patient outcomes. Keywords: preeclampsia, risk factors, biomarkers, aspiri

Lessons learned on the design and the conduct of Post-Authorization Safety Studies:review of 3 years of PRAC oversight

AIMS: To describe and characterize the first cohort of Post-Authorization Safety Study (PASS) protocols reviewed under the recent European pharmacovigilance legislation. METHODS: A systematic approach was used to compile all publicly available information on PASS protocols and assessments submitted from July 2012 to July 2015 from Pharmacovigilance Risk Assessment Committee (PRAC) minutes, European Medicines Agency (EMA) and European Network of Pharmacovigilance and Pharmacoepidemiology (ENCePP) webpages. RESULTS: During the study period, 189 different PASS protocols were submitted to the PRAC, half of which were entered in the ENCePP electronic register of post-authorization studies (EU-PAS) by July 2015. Those protocols were assessed during 353 PRAC reviews. The EMA published only 31% of the PRAC feedback, of which the main concerns were study design (37%) and feasibility (30%). Among the 189 PASS, slightly more involved primary data capture (58%). PASS assessing drug utilization mainly leveraged secondary data sources (58%). The majority of the PASS did not include a comparator (65%) and 35% of PASS also evaluated clinical effectiveness endpoints. CONCLUSIONS: To the best of our knowledge this is the first comprehensive review of three years of PASS protocols submitted under the new pharmacovigilance legislation. Our results show that both EMA and PASS sponsors could respectively increase the availability of protocol assessments and documents in the EU-PAS. Protocol content review and the high number of PRAC comments related to methodological issues and feasibility concerns should raise awareness among PASS stakeholders to design more thoughtful studies according to pharmacoepidemiological principles and existing guidelines

Lessons learned on the design and the conduct of Post-Authorization Safety Studies:: review of 3 years of PRAC oversight

AIMS: To describe and characterize the first cohort of Post-Authorization Safety Study (PASS) protocols reviewed under the recent European pharmacovigilance legislation. METHODS: A systematic approach was used to compile all publicly available information on PASS protocols and assessments submitted from July 2012 to July 2015 from Pharmacovigilance Risk Assessment Committee (PRAC) minutes, European Medicines Agency (EMA) and European Network of Pharmacovigilance and Pharmacoepidemiology (ENCePP) webpages. RESULTS: During the study period, 189 different PASS protocols were submitted to the PRAC, half of which were entered in the ENCePP electronic register of post-authorization studies (EU-PAS) by July 2015. Those protocols were assessed during 353 PRAC reviews. The EMA published only 31% of the PRAC feedback, of which the main concerns were study design (37%) and feasibility (30%). Among the 189 PASS, slightly more involved primary data capture (58%). PASS assessing drug utilization mainly leveraged secondary data sources (58%). The majority of the PASS did not include a comparator (65%) and 35% of PASS also evaluated clinical effectiveness endpoints. CONCLUSIONS: To the best of our knowledge this is the first comprehensive review of three years of PASS protocols submitted under the new pharmacovigilance legislation. Our results show that both EMA and PASS sponsors could respectively increase the availability of protocol assessments and documents in the EU-PAS. Protocol content review and the high number of PRAC comments related to methodological issues and feasibility concerns should raise awareness among PASS stakeholders to design more thoughtful studies according to pharmacoepidemiological principles and existing guidelines

Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry.

BACKGROUND: Influenza A(H5N1) continues to cause infections and possesses pandemic potential. METHODS: Data sources were primarily clinical records, published case series, and governmental agency reports. Cox proportional hazards regression was used to estimate the effect of treatment on survival, with adjustment using propensity scores (a composite measure of baseline variables predicting use of treatment). RESULTS: In total, 308 cases were identified from 12 countries: 41 from Azerbaijan, Hong Kong SAR, Nigeria, Pakistan, and Turkey (from clinical records); 175 from Egypt and Indonesia (from various sources); and 92 from Bangladesh, Cambodia, China, Thailand, and Vietnam (from various publications). Overall crude survival was 43.5%; 60% of patients who received ≥1 dose of oseltamivir alone (OS(+)) survived versus 24% of patients who had no evidence of anti-influenza antiviral treatment (OS(-)) (P <.001). Survival rates of OS(+) groups were significantly higher than those of OS(-) groups; benefit persisted with oseltamivir treatment initiation <or=6-8 days after symptom onset. Multivariate modeling showed 49% mortality reduction from oseltamivir treatment. CONCLUSIONS: H5N1 causes high mortality, especially when untreated. Oseltamivir significantly reduces mortality when started up to 6-8 days after symptom onset and appears to benefit all age groups. Prompt diagnosis and early therapeutic intervention should be considered for H5N1 disease