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

Accounting for Individual Differences in Decision-Making Competence: Personality and Gender Differences

Emerging research has highlighted the utility of measuring individual differences in decision-making competence (DMC), showing that consistently following normatively rational principles is associated with positive psychosocial and health behaviors. From another level of analysis, functional theories of personality suggest that broad trait dimensions represent variation in underlying self-regulatory systems, providing a mechanistic account for robust associations between traits and similar life outcomes. Yet, the degree to which broad dispositional personality dimensions predict global tendencies to respond rationally is less understood. In a large online community sample (N = 804), we tested the associations between HEXACO personality dimensions, a 6-factor structural trait model, and a subset of DMC indicators (Applying Decision Rules, Resistance to Framing, Recognizing Social Norms, and Consistency in Risk Perception). Additionally, we examined gender differences across the DMC, first considering the potential for measurement non-invariance across groups for the DMC. We observed partial measurement invariance between men and women; only the Applying Decision Rules scale showed evidence of differential functioning across groups. Controlling for these differences, analyses revealed that higher Conscientiousness, Honesty/Humility, and Openness were associated with higher DMC scores. In contrast, Emotionality and Extraversion demonstrated gender-specific associations. Specifically, low Extraversion was associated with higher DMC scores for men, whereas higher Emotionality was associated with higher DMC scores for women. Our results suggest that traits related to self-regulatory functions of cognitive and behavioral control, and cognitive flexibility are associated with an increased tendency to engage in rational thought

Cross-cultural validation and measurement invariance of the Short Grit scale (Grit-S): preliminary results.

Preliminary results of a cross-cultural validation of the Grit -

Arzneimittelinteraktionen mit antiretroviralen Medikamenten

Zusammenfassung: Arzneimittelwechselwirkungen sind bei der Behandlung von HIV-Infizierten häufig, da die hochaktive antiretrovirale Therapie immer mehrere Wirkstoffe beinhaltet. Dazu kommen oft Medikamente gegen opportunistische Infektionen und Begleiterkrankungen. Alle Proteaseinhibitoren führen zu einer Inhibition von CYP3A, das im Metabolismus von rund 50% aller Arzneistoffe wichtig ist, beispielsweise Simvastatin, Atorvastatin, Sildenafil und Clarithromycin. Ritonavir ist von allen Proteaseinhibitoren der stärkste Hemmstoff der CYP3A-Aktivität. Dies wird auch genutzt, um die Bioverfügbarkeit anderer Proteaseinhibitoren zu erhöhen. Durch die nichtnukleosidischen Reverse-Transkriptase-Inhibitoren Efavirenz und Nevirapin wird die CYP3A-Aktivität in der Dauertherapie gesteigert. Um Interaktionen vorzubeugen, müssen zu Beginn und bei Therapieende die Dosierungen von CYP3A-Substraten angepasst werden. Interaktionen können auch durch die Beeinflussung von glukuronidierenden Enzymen oder Transportproteinen entstehen. So wird P-Glykoprotein durch Ritonavir gehemmt, was zu einer Erhöhung der Exposition gegenüber vielen Chemotherapeutika führ

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

Isotonitazene: Fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland.

The paper describes the first three deaths reported in Europe involved in isotonitazene consumption, a potent benzimidazole derivate opioid consumed in the recreational drug scene. Isotonitazene powder and purity determination was performed on the sample collected in the first death scene by NMR, HRMS, GC-FTIR, ATR-FTIR and GC-MS. Isotonitazene purity was determined by GC-MS analysis and proton NMR, and was defined to be above 95 % and 98 %, respectively. Quantification of isotonitazene in biological samples was performed using a targeted analysis based on SPE extraction and ultra-high performance liquid chromatography tandem mass spectrometry. The isotonitazene median concentration in femoral whole blood was 1.20ng/mL. Isotonitazene concentration in hair was similar or even lower compared to that seen in fentanyl abusers. Isotonitazene distribution in tissues converges in the brain, lungs and heart, respectively. Surprisingly, isotonitazene concentration in liver is the lowest measured for all tissues and fluids analyzed. Based on circumstantial evidence, autopsy findings and the results of the toxicological analysis, the medical examiner concluded that the cause of all three deaths was an acute intoxication with isotonitazene. Since isotonitazene toxic concentration levels are very low, the consumption of this new psychoactive drug is a real hazard for human health

Moderate toxic effects following acute zonisamide overdose

Zonisamide is an antiepileptic drug that acts on voltage-sensitive sodium and calcium channels, with a modulatory effect on GABA-mediated neuronal inhibition and an inhibitory effect on carbonic anhydrase. It is used mainly for the treatment of partial seizures, and is generally well tolerated at therapeutic doses. The most common reported adverse effects are somnolence, anorexia, dizziness, and headache. There are limited data on zonisamide overdose in the literature, and no case of zonisamide mono-intoxication has been published to date. We describe the first case of zonisamide mono-intoxication in a 25-year-old woman who ingested 12.6 g of this substance with suicidal intent. Despite a plasma zonisamide concentration of 182 mg/L on admission, the patient exhibited a benign clinical course with vomiting and central nervous system depression, requiring brief intubation. Somnolence persisted for 50 hours, and normal-anion-gap metabolic acidosis and polyuria for several days. Complete recovery may be expected with supportive care, even after ingestion of large zonisamide overdoses

Acute Thiopurine Overdose: Analysis of Reports to a National Poison Centre 1995-2013

Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995–2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion

Return to work after maternity leave: the role of support policies on work attitudes of women in management positions

Purpose. This study is intended to expand our knowledge on the processes through which work-family policies relate to work-family conflict as well as work-related attitudes among women in management positions returning to work after maternity leave. Design. Two-hundred and thirty-eight women in management positions who recently have returned to work after maternity leave completed a self-report questionnaire. Findings. Results show that the availability of policies was either directly or indirectly positively related to work attitudes among female managers. Also, findings show that work-family conflict partially mediates the relationship between the availability of communication and psychological support and flexible time management policies with work engagement, and policy availability moderates the relationship between work-family conflict and work engagement. Originality/value. Managers have a crucial role in conveying the value of work-family policies and in creating a culture supporting the management of work and family. By investigating the processes underlying the role of work-family policies in influencing work attitudes of women in managerial positions, this study sheds light on how the awareness of the available policies might be an important determinant of work-related well-being and organizational commitment