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

Medication incidents in primary care medicine: protocol of a study by the Swiss Federal Sentinel Reporting System.

BACKGROUND/RATIONALE: Patient safety is a major concern in healthcare systems worldwide. Although most safety research has been conducted in the inpatient setting, evidence indicates that medical errors and adverse events are a threat to patients in the primary care setting as well. Since information about the frequency and outcomes of safety incidents in primary care is required, the goals of this study are to describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents. Label="METHODS AND ANALYSIS" ="METHODS"/> <AbstractText STUDY DESIGN AND SETTING: We will conduct a prospective surveillance study to identify cases of medication incidents among primary care patients in Switzerland over the course of the year 2015. PARTICIPANTS: Patients undergoing drug treatment by 167 general practitioners or paediatricians reporting to the Swiss Federal Sentinel Reporting System. INCLUSION CRITERIA: Any erroneous event, as defined by the physician, related to the medication process and interfering with normal treatment course. EXCLUSION CRITERIA: Lack of treatment effect, adverse drug reactions or drug-drug or drug-disease interactions without detectable treatment error. PRIMARY OUTCOME: Medication incidents. RISK FACTORS: Age, gender, polymedication, morbidity, care dependency, hospitalisation. STATISTICAL ANALYSIS: Descriptive statistics to assess type, frequency, seasonal and regional distribution of medication incidents and logistic regression to assess their association with potential risk factors. Estimated sample size: 500 medication incidents. LIMITATIONS: We will take into account under-reporting and selective reporting among others as potential sources of bias or imprecision when interpreting the results. ETHICS AND DISSEMINATION: No formal request was necessary because of fully anonymised data. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT0229537

Chronic conditions and multimorbidity in a primary care population: a study in the Swiss Sentinel Surveillance Network (Sentinella).

To provide estimates of the prevalence of chronic conditions in Swiss primary care. In total, 175 general practitioners (GP) or pediatricians (PED) reporting to the Swiss Sentinel Surveillance Network collected morbidity data. In 26,853 patient contacts, mean (± SD) age was 55.8 ± 21.6 or 6.1 ± 5.7 years (in GPs vs. PEDs, respectively) and 47% were males. In GP patients, median Thurgau Morbidity Index was 2 (IQR 1-3). The median numbers of chronic conditions and permanently used prescribed drugs were 2 (0-5) and 2 (1-4), respectively; in PEDs medians were 0. Out of all patients, 16.7 and 7.0% of the PED patients were hospitalized during the previous year; patients cared by family/proxies or community nurses were hospitalized significantly more often than patients living in homes (50.1 vs. 35.4%, OR 1.41, p < 0.001). Out of patients over 80 years of age, 51.5% were care dependent and 45.5% of the patients over 90 years were living in homes for the elderly. In a representative sample of Swiss primary care patients, a substantial part shows multimorbidity with a high prevalence of chronic diseases, multiple drug treatment, and care dependency. These data may serve to be compared with other patient groups or other primary care systems. Trial registration www.clinicaltrials.gov NCT0229537, national study registry www.kofam.ch SNCTP000001207

Some Findings Concerning Requirements in Agile Methodologies

gile methods have appeared as an attractive alternative to conventional methodologies. These methods try to reduce the time to market and, indirectly, the cost of the product through flexible development and deep customer involvement. The processes related to requirements have been extensively studied in literature, in most cases in the frame of conventional methods. However, conclusions of conventional methodologies could not be necessarily valid for Agile; in some issues, conventional and Agile processes are radically different. As recent surveys report, inadequate project requirements is one of the most conflictive issues in agile approaches and better understanding about this is needed. This paper describes some findings concerning requirements activities in a project developed under an agile methodology. The project intended to evolve an existing product and, therefore, some background information was available. The major difficulties encountered were related to non-functional needs and management of requirements dependencies

Crop changes from the XVI century to the present in a hill/mountain area of eastern Liguria (Italy)

<p>Abstract</p> <p>Background</p> <p>Chronological information on the composition and structure of agrocenoses and detailed features of land cover referring to specific areas are uncommon in ethnobotanical studies, especially for periods before the XIX century. The aim of this study was to analyse the type of crop or the characteristics of soil cover from the XVI century to the present.</p> <p>Methods</p> <p>This diachronic analysis was accomplished through archival research on the inventories of the Parish of St. Mary and those of the Municipality of Pignone and from recent surveys conducted in an area of eastern Liguria (Italy).</p> <p>Results</p> <p>Archival data revealed that in study area the primary means of subsistence during the last five centuries, until the first half of the XX century, was chestnuts. In the XVIII and XIX centuries, crop diversification strongly increased in comparison with previous and subsequent periods. In more recent times, the abandonment of agricultural practices has favoured the re-colonisation of mixed woodland or cluster-pine woodland.</p> <p>Conclusion</p> <p>Ancient documents in the ecclesiastic or municipal inventories can be a very useful tool for enhancing the knowledge of agricultural practice, as well as of subsistence methods favoured by local populations during a particular time and for reconstructing land use change over time.</p

Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort

<p>Abstract</p> <p>Background</p> <p>Only a limited number of studies have performed comprehensive investigations of coding variation in relation to breast cancer risk. Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk.</p> <p>Methods</p> <p>We sequenced the coding exons of 17 genes (<it>EP300, CCND1, NME1, NCOA1, NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1, PPARBP </it>and <it>CREBBP</it>) suggested to influence transcriptional activation by steroid hormone receptors in a multiethnic panel of women with advanced breast cancer (n = 95): African Americans, Latinos, Japanese, Native Hawaiians and European Americans. Association testing of validated coding variants was conducted in a breast cancer case-control study (1,612 invasive cases and 1,961 controls) nested in the Multiethnic Cohort. We used logistic regression to estimate odds ratios for allelic effects in ethnic-pooled analyses as well as in subgroups defined by disease stage and steroid hormone receptor status. We also investigated effect modification by established breast cancer risk factors that are associated with steroid hormone exposure.</p> <p>Results</p> <p>We identified 45 coding variants with frequencies ≥ 1% in any one ethnic group (43 non-synonymous variants). We observed nominally significant positive associations with two coding variants in ethnic-pooled analyses (<it>NCOR2</it>: His52Arg, OR = 1.79; 95% CI, 1.05–3.05; <it>CALCOCO1</it>: Arg12His, OR = 2.29; 95% CI, 1.00–5.26). A small number of variants were associated with risk in disease subgroup analyses and we observed no strong evidence of effect modification by breast cancer risk factors. Based on the large number of statistical tests conducted in this study, the nominally significant associations that we observed may be due to chance, and will need to be confirmed in other studies.</p> <p>Conclusion</p> <p>Our findings suggest that common coding variation in these candidate genes do not make a substantial contribution to breast cancer risk in the general population. Cataloging and testing of coding variants in coactivator and corepressor genes should continue and may serve as a valuable resource for investigations of other hormone-related phenotypes, such as inter-individual response to hormonal therapies used for cancer treatment and prevention.</p

SNP-SNP interactions in breast cancer susceptibility

BACKGROUND: Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. METHODS: In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle. RESULTS: None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways. CONCLUSION: The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described. The strategy used here has the potential to identify complex biological links among breast cancer genes and processes. This will provide novel biological information, which will ultimately improve breast cancer risk management

H-infinity filter design for nonlinear systems with quantised measurements in finite frequency domain

International audienceThis paper deals with the problem of finite frequency (FF) H-infinity full-order fuzzy filter design for nonlinear discrete-time systems with quantised measurements, described by Takagi-Sugeno models. The measured signals are assumed to be quantised with a logarithmic quantiser. Using a fuzzy-basis-dependent Lyapunov function, the finite frequency l(2) gain definition, the generalised S-procedure, and Finsler's lemma, a set of sufficient conditions are established in terms of matrix inequalities, ensuring that the filtering error system is stable and the H-infinity attenuation level, from disturbance to the estimation error, is smaller than a given value over a prescribed finite frequency domain of the external disturbances. With the aid of Finsler's lemma, a large number of slack variables are introduced to the design conditions, which provides extra degrees of freedom in optimising the guaranteed H-infinity performance. This directly leads to performance improvement and reduction of conservatism. Finally, we give a simulation example to demonstrate the efficiency of the proposed design method, and we show that a lower H-infinity attenuation level can be obtained by our developed approach in comparison with another result in the literature

The career decision-making competence: a new construct for the career realm

Purpose \u2013 This paper aims to link fndings from laboratory-based decision-making research and decision-making competence (DMC) aspects that may be central for career-related decision-making processes. Past research has identifed individual differences in rational responses in decision situations, which the authors refer to as DMC. Although there is a robust literature on departures from rational responses focused on heuristics and biases (H&amp;B) in decision-making, such evidence is largely confned to group-level differences observed in psychology laboratories and has not been extended to the realm of career development and workforce behavior. Design/methodology/approach \u2013 By frst introducing the concept of DMC and contextualizing it within organizations and the work environment, the paper outlines a review on recent development concerning debiasing interventions in organizations and provides insights on how these may be effective with regard to organizational performance and individual career development. Findings \u2013 The contribution presents a perspective to improve knowledge about career decision-making competence (C-DMC) by presenting an approach linking decision-making research to interventions aiming at managing H&amp;B and systematic misperceptions in career processes. Originality/value \u2013 This contribution is one of the few linking decision-making research to the applied context of organizations and of career competences. Moreover, while some research has treated decision-making skills as traits, this contribution provides support to consider them developable as competencies