Evaluation of the safety profile of rotavirus vaccines: a pharmacovigilance analysis on American and European data

Rotaviruses (RVs) are the most common cause of severe diarrheal disease. To date two rotavirus oral vaccines are licensed: Rotarix and Rotateq. Our aim was to contribute to the post-marketing evaluation of these vaccines safety profile. We collected all RV vaccines-related reports of Adverse Events Following Immunization (AEFI) in US Vaccine Adverse Events Reporting System (VAERS) and VigiBase between January 2007 and December 2017. A disproportionality analysis using Reporting Odds Ratio (ROR) was performed. A total of 17,750 reports in VAERS and 6,358 in VigiBase were retrieved. In VAERS, 86.2% of the reports concerned RotaTeq, whereas in VigiBase 67.7% of them involved Rotarix. Across the databases, diarrhea (1,672 events in VAERS, 1,961 in VigiBase) and vomiting (1,746 in VAERS, 1,508 in VigiBase) were the most reported AEFIs. Noteworthy, the RV vaccines-intussusception pair showed a ROR greater than 20 in both databases. Some new potential safety signals emerged such as fontanelle bulging, hypotonic-hyporesponsive episode, livedo reticularis, and opisthotonus. Overall, our data show that most of the reported AEFIs are listed in the Summary of Product Characteristics (SPCs). However, there remains the need to investigate the potential safety signals arose from this analysis, in order to complete the description of the AEFIs

National survey on prescription of cardiovascular drugs among outpatients with coronary artery disease in Switzerland.

Secondary prevention of coronary artery disease markedly reduces cardiovascular mortality and non-fatal endpoints. Outpatient care of subjects with coronary artery disease has been assessed in several European countries, but no current data is available for Switzerland. A random sample of office-based physicians across Switzerland recorded current drug prescription of outpatients with coronary artery disease in the years 2000/2001 by means of a mail questionnaire. We assessed treatment frequencies according to different patient characteristics. 565 patients were included (mean age 68 +/- 11 years, 75% male). There was no evidence for differences in drug utilisation among the regions. Drug prescription rates for antithrombotic agents, beta-blockers, ACE-inhibitors/angiotensin receptor blockers and lipid lowering drugs were 91%, 58%, 50% and 63% respectively. Lower treatment rates were observed among patients >70 years and in those without a history of myocardial infarction or coronary revascularisation. Forty-nine percent of the patients had a blood pressure >140/>90, and 60% had lipid readings above the intervention cut-off according to the Swiss recommendations. Among those without a history of myocardial infarction or coronary revascularisation, the respective figures were 60% and 80%. Compared to former surveys evidence based drug prescription has improved in Switzerland. Despite this, therapeutic goals for cholesterol levels and blood pressure are not being reached in a large proportion of patients. A high risk group for under use of evidence based drugs are patients without a history of myocardial infarction or coronary revascularisation

Supramolecular assemblies of Al3+ complexes with vitamin D3 (cholecalciferol) and phenothiazine. Encapsulation and complexation studies in β-cyclodextrin

Ternary assemblies of β-cyclodextrin with cholecalciferol (or vitamin D3) or phenothiazine and Al3+ ions were studied. The stability constants of aluminium binary complexes with cholecalciferol or phenothiazine and of ternary assemblies (β-cyclodextrin, cholecalciferol or phenothiazine and Al3+) were determined using potentiometric titrations at 25 °C (I = 0.100 M). The 13C NMR spectra of the supramolecular structures in the solid state showed that ternary supramolecular structures associating β-cyclodextrin, cholecalciferol or phenothiazine and aluminium(III) ions were obtained. Finally, X-ray powder diffraction patterns showed that the ternary assemblies with phenothiazine are channel type inclusion complexes

The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance

The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement

Background and aim: Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts. Methods: We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting. Results: Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts. Conclusions: The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence