Stefania Mantarro

Use of Selective Serotonin Reuptake Inhibitors during Pregnancy and Risk of Major and Cardiovascular Malformations: An Update

Abstract General consensus exists about the need to avoid drug intake as much as possible during pregnancy due to the lack of thorough evidence about the safety of pharmacologic treatments during gestation for both mothers and fetuses. In this respect, the overall safety profile of selective serotonin reuptake inhibitors (SSRIs) in pregnancy remains unclear. This article reviews current evidence about the safety of each SSRI during pregnancy in order to describe their specific teratogenic potential, with a particular focus on major and cardiovascular malformations, and to verify whether such toxicity can be considered as a class effect. The literature review included controlled studies and meta-analyses (retrieved using PsychINFO, EMBASE, and Medline from January 1966 to May 2010) from which the risk of major and/or cardiovascular malformations associated with a specific SSRI (ie, fluoxetine, paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine) could be estimated. Although there is evidence to support the association between birth defects and first-trimester exposure to paroxetine, findings from the studies reviewed suggest a teratogenic potential of the whole SSRI class, consistent with preclinical evidence. These teratogenic effects are mainly in the heart region, and they are often described as septal defects. It may be suggested that the higher frequency of teratogenic effects reported for paroxetine might depend on specific pharmacologic features of this drug compared with other SSRIs, although it is difficult to test this hypothesis. It is noteworthy that current evidence on SSRI teratogenicity stems from studies affected by several methodological weaknesses (ie, lack of investigations using control groups of untreated depressed mothers, confounding by indication, and recall bias). Accordingly, we are not yet able to rule out the possibility that positive associations, as determined in some studies, result from analyses of poor quality.

Adverse reactions to oncologic drugs: spontaneous reporting and signal detection

Oncology is one of the areas of medicine with the most active research being conducted on new drugs. New pharmacological entities frequently enter the clinical arena, and therefore, the safety profile of anticancer products deserves continuous monitoring. However, only very severe and (unusual) suspected adverse drug reactions (ADRs) are usually reported, since cancer patients develop ADRs very frequently and some practical selectivity must be used. Notably, a recent study was able to identify 76 serious ADRs reported in updated drug labels of oncologic drugs and 50% of them (n = 38) were potentially fatal. Of these, 49 and 58%, respectively, were not described in initial drug labels. The aims of this article are to provide an overview about spontaneous reporting of ADRs of oncologic drugs and to discuss the available methods to analyze the safety of anticancer drugs using databases of spontaneous ADR reporting.

Allopurinol adherence among patients with gout: an Italian general practice database study

Allopurinol is used as long‐term therapy to reduce the occurrence of gout flares. This study estimated the impact of patient adherence to allopurinol on hyperuricaemia (serum uric acid levels, sUA > 6 mg/dl) and the identification of non‐adherence predictors.

Autoimmune Hemolytic Anemia following MF59-Adjuvanted Influenza Vaccine Administration: A Report of Two Cases

Objective To describe 2 cases of autoimmune hemolytic anemia (AIHA) following the administration of MF59-adjuvanted influenza vaccine. Case Summary: An 83-year-old white woman developed persistent hyperpyrexia, polyarthralgia, and lower limb hypostenia about 2 days after receiving influenza vaccine. Clinical signs and laboratory evaluations suggested AIHA. The patient was treated with high-dose corticosteroids and immunoglobulins, and her clinical condition improved. A 74-year-old white woman developed severe abdominal pain and asthenia 3 days after the administration of influenza vaccine. Clinical signs and laboratory evaluations disclosed AIHA. She was treated with corticosteroids, rehydration, and blood transfusion; however, she died about 48 hours after hospitalization. Discussion: AIHA has been rarely described following influenza vaccine administration. In the cases described here, the causal relationship between influenza vaccination and the occurrence of AIHA, assessed by means of World Health Organization criteria, was scored as probable. It has been proposed that the mechanism whereby vaccines induce autoimmune responses can be molecular mimicry, although a possible role of other vaccine constituents, with particular regard for adjuvants, such as MF59, can not be excluded. Squalene, a constituent of MF59, has been suggested as a causative agent of autoimmune reactions. However, it is not clear how and under what conditions squalene can cause immune responses. Conclusions: Influenza vaccination may rarely trigger severe AIHA, shortly after vaccine administration. A mechanism of molecular mimicry is probably involved in the development of these reactions, although the possible role of adjuvants can not be excluded. Patients should be instructed to report signs and symptoms of autoimmune disorders occurring in the first weeks after administration of influenza vaccine.

Telogen effluvium following bivalent human papillomavirus vaccine administration: a report of two cases.

We describe two cases of telogen effluvium occurring in two 11-year-old children following bivalent human papillomavirus (HPV) vaccine administration. The two children began to lose their hair following the second HPV vaccine dose. Alopecia worsened following the third vaccine dose and then resolved spontaneously within a few months. In both cases, laboratory analysis and psychiatric evaluation excluded causes other than anti-HPV vaccine. Social discomfort and isolation were associated with alopecia in the two children. The clinical presentation was consistent with a pattern of telogen effluvium. The identification of specific vaccine components responsible for triggering the adverse event remains difficult. In similar cases, suspension of immunization is not recommended, as it provides health benefits that overcome the possible adverse effect of transient telogen effluvium. Caregivers should ensure psychiatric support to their patients to manage the social and emotional distress that might be associated with hair loss.

Hepatitis C virus infection: opportunities for an earlier detection in primary care.

Background/aim In the era of direct-acting antiviral medications, which can cure the hepatitis C virus (HCV) infection, the actual epidemiology of this condition in the general population is still unclear. We therefore aimed to estimate the prevalence rate of HCV and assess the determinants for incident cases of HCV in primary care in Italy. Methods We identified outpatients aged at least 15 years registered in the Italian Health Search IMS Health Longitudinal Patient Database from 1 January 2002 to 30 June 2013. The annual trend of HCV prevalence was estimated. The candidate determinants for the risk of incident HCV infection included geographical area of residence, sex, age, infections by the HIV, hepatitis B virus (HBV), or other forms of hepatitis, and abuse of illicit substances or drugs. Results The eligible cohort included 826 300 patients (53.5% women, mean age 48.1±19.1 years). The prevalence rate of HCV increased over the 11-year study period, ranging from 0.24 to 0.50%, with a small increase in men versus women. Patients aged more than 24 years had a higher risk than those aged 14–24 years, with up to a five-fold increase among patients aged 65–74 years. Being resident of Southern/Islands Italy, concurrent diagnosis HBV or HIV, and drug or illicit substance abuse were significant determinants for HCV infection. Conclusion Our study shows that the prevalence of HCV in Italy has doubled over the last decade. Patients with certain demographics and clinical characteristics are more prone to be infected by HCV. In this scenario, general practitioners may play a crucial role in screening, early identification, and therapy of high-risk patients.

Expected and actual adverse drug-drug interactions in elderly patients accessing the emergency department: data from the ANCESTRAL-ED study

ABSTRACT Objective: This study was aimed at evaluating the frequency and describing the adverse drug-drug interactions (DDIs) recorded among elderly patients accessing the emergency department (ED). Methods: Patients aged ≥65 years, accessing the ED of Pisa University Hospital (Italy) from 1 January 2015 to 31 December 2015 within the ANCESTRAL-ED program, were included in this study. ‘Expected’ DDIs were assessed using Thomson Micromedex®. Each ED admission (discharge diagnosis) consistent with the signs and symptoms of an expected DDI for each patient was classified as an ‘actual’ DDI. Results: Throughout the study period, 3473 patients (3812 ED admissions, 58% females, mean age: 80.3) were recorded. The total number of expected DDIs was 12,578 (67 contraindicated; 3334 major; 8878 moderate; 299 minor) detected in 2147 (62%) patients. Overall 464 expected DDIs were found to be consistent with the ED admission in 194 patients (representing 9% of patients with expected DDIs). Conclusions: More than one half of elderly patients admitted to ED presented at least one expected DDI at the time of ED presentation. However, 9% of the expected DDIs were identified as actual DDIs, based on the consistency of the expected event with the ED discharge diagnosis.

Acute portal vein thrombosis precipitated by indomethacin in a HCV-positive elderly patient

BackgroundAn increased risk of venous thromboembolism has been reported in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We describe a case of acute portal vein thrombosis (PVT) in a hepatitis C virus (HCV)-positive elderly patient following administration of indomethacin.Case presentationA 79-year-old HCV-positive man was hospitalized for severe abdominal pain, nausea and vomiting, 15 days after starting indomethacin for back pain. Clinical signs and imaging evaluations disclosed a picture of PVT. Indomethacin was discontinued, and the patient was started on fondaparinux and antithrombin. He was discharged 15 days later due to improvement of his clinical conditions. Thirty days later, a follow-up ultrasound did not show appreciable signs of PVT. The time elapsing between the start of analgesic therapy and PVT onset suggests a role of indomethacin as the triggering agent. Indomethacin could have precipitated PVT by a combination of at least two detrimental mechanisms: 1) direct action on liver vascular endothelium by inhibition of prostacyclin biosynthesis; 2) damage to the intestinal mucosa, followed by inflammatory and pro-coagulant activation of portal endothelium upon exposure to bacterial endotoxins.ConclusionsThis case can be of interest to physicians, who should exert caution when prescribing NSAIDs for inflammatory pain in patients with background inflammatory dysfunctions of the portal vein endothelium.

Intensive monitoring programme of adverse drug reactions In emergency department (MEREAFaPS Study): the Tuscan experience

Objectives: Individual case safety reports (ICSRs) could be an important source in giving further information to characterize the risk situation and aid in the prevention, diagnosis, management and treatment of adverse drug reactions (ADRs). The aim was to determine whether and where on the ICSRs clinically useful information was specified for rare ADRs in the paediatric population. Methods: ICSR concerning rhabdomyolysis occurring during use of antipsychotic medicines for patients up to 17 years of age were retrieved from the WHO Global ICSR database, VigiBase. The original case reports were requested and received from the national pharmacovigilance centres. We focused on five areas of information specified in a recent guideline for publishing ADRs.[1] Results: Eighteen original cases with an age span from 5 to 17 years were reviewed with the following outcomes. Circumstances preceding the reaction: 9 reports included this information, consisting primarily of abdominal, muscle and back pain. In eight of these reports, the full account of the symptoms and sequence of events were only found in the narratives. Underlying risk factors for rhabdomyolysis: Recorded for four of five patients in the narrative: seizures (n = 1), strenuous physical activity (n = 2), diabetic ketoacidosis (n = 1), alcohol use (n = 1). Four patients had Neuroleptic Malignant Syndrome (NMS) co-reported. Physical examination and laboratory tests: All values for patient temperature and laboratory values were given in free text. Elevated creatine phosphokinase (CPK) or myoglobin values were recorded in 14 reports ranging from 1200 to 95 000 IU/L (CPK). Patient temperature was specified for 5 patients, of whom 3 patients were also reported to experience NMS. Drug-reaction time-to-onset: 13 reports included information on the duration from drug start to reaction onset, which ranged from 4 days to 1.5 years. 9 reports included dates in the structured data, so that time to onset could be calculated and in 4 reports the information was specified in the narratives. Treatment of the reaction: Apart from stopping the drug (n = 18) and hospitalization (n = 16), other actions of treatment, such as forced intravenous fluids or resolving spontaneously, was given for 5 cases in the narrative. Conclusions: This study showed that useful clinical information was available to characterize the risk situation for these patients in this subset of reports. This should be regarded in the context that ICSRs are generally considered to be of poor quality. However, access to the free text fields recorded by the reporter was crucial to capture this information. Reference 1. Kelly WN, Arellano FM, Barnes J, et al. Guidelines for submitting adverse event reports for publication. Drug Saf 2007; 30 (5): 367-73