The Safety Profile of General and Local Anaesthetic Agents: Data Collected during 20 Years of Spontaneous Reporting Activities in the Campania Region (Southern Italy)

Background: General and local anaesthetics are widely used during surgery. These drugs have peculiar safety profiles, being commonly associated with mild and reversible local adverse drug reactions (ADRs), but also with more severe and systemic ADRs, including respiratory and cardiovascular depression and anaphylaxis. Methods and Objectives: We carried out a descriptive analysis of Individual Case Safety Reports (ICSRs) sent to the Campania Regional Centre of Pharmacovigilance (Southern Italy) from 2001 to 2021 that reported general or local anaesthetics as suspected drugs, with the aim of describing their overall characteristics, focussing on the ADRs’ seriousness and distribution by System Organ Class (SOC) and Preferred Term (PT). Results: A total of 110 ICSRs documenting general or local anaesthetics were sent to the Italian pharmacovigilance database during 20 years of spontaneous reporting activities in the Campania region. ADRs mainly occurred in patients with a median age of 48 years and in a slightly higher percentage of men. ADRs were more commonly classified as not serious and had a favourable outcome. In terms of ADRs’ distribution by SOC and PT, both general and local anaesthetics were associated with general and cutaneous disorders, with common ADRs that included lack of efficacy, rash, and erythema. In addition, general anaesthetics were associated with the occurrence of respiratory ADRs, while local anaesthetics were associated with the occurrence of nervous ADRs. Conclusion: Even though a limited number of ICSRs documenting anaesthetics-induced ADRs were retrieved from the Italian spontaneous reporting database in the Campania region, we believe that the continuous monitoring of these drugs is highly recommended, especially among the frail population.

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Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvaa037 ◽

2020 ◽

Cited By ~ 3

Author(s):

Joachim Alexandre ◽

Joe-Elie Salem ◽

Javid Moslehi ◽

Marion Sassier ◽

Camille Ropert ◽

...

Keyword(s):

Atrial Fibrillation ◽

Anticancer Drugs ◽

Kinase Inhibitors ◽

Descriptive Analysis ◽

Individual Case ◽

World Health ◽

European Medicines Agency ◽

Individual Case Safety Report ◽

Pharmacovigilance Database ◽

Haematologic Malignancies

Abstract Aims The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF. Methods and results A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody. Conclusion Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.

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Applications and Limitations of Neuro-Monitoring in Paediatric Anaesthesia and Intravenous Anaesthesia: A Narrative Review

Journal of Clinical Medicine ◽

10.3390/jcm10122639 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2639

Author(s):

Chiara Grasso ◽

Vanessa Marchesini ◽

Nicola Disma

Keyword(s):

Hemodynamic Instability ◽

Favourable Outcome ◽

Neurotoxic Effect ◽

Brain Oxygenation ◽

High Quality ◽

Neurological Outcomes ◽

Anaesthetic Agents ◽

Haemodynamic Stability ◽

Safe Management ◽

International Initiative

Safe management of anaesthesia in children has been one of the top areas of research over the last decade. After the large volume of articles which focused on the putative neurotoxic effect of anaesthetic agents on the developing brain, the attention and research efforts shifted toward prevention and treatment of critical events and the importance of peri-anaesthetic haemodynamic stability to prevent negative neurological outcomes. Safetots.org is an international initiative aiming at raising the attention on the relevance of a high-quality anaesthesia in children undergoing surgical and non-surgical procedures to guarantee a favourable outcome. Children might experience hemodynamic instability for many reasons, and how the range of normality within brain autoregulation is maintained is still unknown. Neuro-monitoring can guide anaesthesia providers in delivering optimal anaesthetic drugs dosages and also correcting underling conditions that can negatively affect the neurological outcome. In particular, it is referred to EEG-based monitoring and monitoring for brain oxygenation.

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Coadministration of tizanidine and ciprofloxacin: a retrospective analysis of the WHO pharmacovigilance database

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-02981-2 ◽

2021 ◽

Author(s):

Annette Rudolph ◽

Hendrike Dahmke ◽

Hugo Kupferschmidt ◽

Andrea Burden ◽

Stefan Weiler

Keyword(s):

Real World ◽

Safety Issue ◽

Demographic Data ◽

Fatal Outcome ◽

Individual Case ◽

World Health ◽

Global Database ◽

The Usa ◽

Pharmacovigilance Database ◽

The Impact

Abstract Purpose Tizanidine, an alpha-adrenergic substance with antinociceptive and antihypertensive effects, is extensively metabolized via cytochrome P450 (CYP) 1A2. Therefore, coadministration with potent CYP1A2 inhibitors, such as ciprofloxacin, is contraindicated. However, both drugs are broadly utilized in various countries. Their concomitant use bears an inherent high risk for clinically significant symptoms, especially in multimorbid patients experiencing polypharmacy. This study aims to investigate the impact of coadministration of tizanidine and ciprofloxacin using real-world pharmacovigilance data and to raise awareness of this potentially underestimated safety issue. Methods We conducted a retrospective study including Individual Case Safety Reports (ICSR) registered until March 1, 2017, in the World Health Organization (WHO) global database. Demographic data, drug administration information, the course of the adverse drug reaction (ADR), its severity, and outcomes were analyzed for cases reporting ciprofloxacin comedication. Results In 91 (2.0%) of the identified 4192 worldwide ICSR on tizanidine, coadministration of ciprofloxacin was reported. Most of the patients were female (n = 59, 64.8%) with a median age of 54 years (range 13–85 years). The countries contributing most reports were the USA (n = 54, 59.3%) and Switzerland (n = 16, 17.6%). ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported. Conclusion Despite the existing formal contraindication, the concomitant use of tizanidine and ciprofloxacin can be observed in real-world clinical practice. Reactions mainly affected the central nervous and the cardiovascular system resulting in potentially severe adverse effects. The concomitant use of tizanidine and ciprofloxacin should absolutely be avoided.

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Abstract P088: Obesity, Hypertension and Insulin Resistance in a Primary Pediatric Setting in Southern Italy

Circulation ◽

10.1161/circ.129.suppl_1.p088 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Giampaolo De Filippo ◽

Domenico Rendina ◽

Domenico Viggiano ◽

Antonio Fasolino ◽

Paola Sabatini ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Weight ◽

Children And Adolescents ◽

Diagnostic Criteria ◽

Southern Italy ◽

Serum Insulin ◽

High Density Lipoproteins ◽

Obese Children ◽

Campania Region

Background: Obesity is the main risk factor for essential hypertension (EH) in childhood. The O.Si.Me. study (Obesity and Metabolic Syndrome in children and adolescents) evaluated the prevalence of metabolic syndrome (MetS) and its constitutive traits in a sample of obese children and adolescents living in Campania, southern Italy. Patients and methods: Four hundred and fifteen children and adolescents consecutively referred to the National Health Service participating Outpatient Clinics for minor health problems and found to have a Body Mass Index (BMI) Z-score > 2.0 were enrolled in the study. The entire sample was screened for MetS, which was defined as the presence of at least 2 of the following alterations in addition to obesity: fasting hyperglycemia, low levels of high-density lipoproteins cholesterol, hypertriglyceridemia, and EH. The present analysis evaluated the clinical characteristics of the O.Si.Me subgroup of EH participants (systolic and/or diastolic BP ≥ 95 th percentile for age, gender and height) as compared with normotensive participants. Results: The prevalence of EH in the O.Si.Me population was 23.6 % (98/415, 48M and 50F.) and two-thirds of the EH participants met the MetS diagnostic criteria. The EH participants featured serum insulin and HOMA-IR levels significantly higher compared with normotensive ones (11.6±0.6 vs. 9.5±0.4 μIU/ml, p = 0.014; 2.6±0.1 vs. 2.2±0.1, p = 0.028 for insulin and HOMA-IR, respectively). These differences were common to boys and girls and remained significant after correction for age, pubertal stage, body weight, length, BMI, gestational age at birth, duration of breastfeeding and anthropometric parental parameters. Accordingly, children and adolescents with EH had a a relative risk of being insulin resistant (defined as a HOMA-IR ≥2.5) significantly greater compared to those without. Moreover, they exhibited higher serum creatinine levels (53.8±7.1 vs. 35.4±6.8 μmol/l, p=0.025) accounting for gender and body weight. Conclusions: More than a quarter of obese children and adolescents meet the diagnostic criteria for EH in the Campania region in southern Italy. These obese boys and girls have an increased prevalence of insulin resistance and apparently an initial reduction in renal function compared with obese children and adolescents with normal BP.

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Debris-flow susceptibility assessment through cellular automata modeling: an example from 15–16 December 1999 disaster at Cervinara and San Martino Valle Caudina (Campania, southern Italy)

Natural Hazards and Earth System Science ◽

10.5194/nhess-3-457-2003 ◽

2003 ◽

Vol 3 (5) ◽

pp. 457-468 ◽

Cited By ~ 46

Author(s):

G. Iovine ◽

S. Di Gregorio ◽

V. Lupiano

Keyword(s):

Cellular Automata ◽

Debris Flow ◽

Urban Areas ◽

Debris Flows ◽

Soil Cover ◽

Southern Italy ◽

Landslide Risk ◽

Campania Region ◽

Optimal Values ◽

Debris Flow Susceptibility

Abstract. On 15–16 December 1999, heavy rainfall severely stroke Campania region (southern Italy), triggering numerous debris flows on the slopes of the San Martino Valle Caudina-Cervinara area. Soil slips originated within the weathered volcaniclastic mantle of soil cover overlying the carbonate skeleton of the massif. Debris slides turned into fast flowing mixtures of matrix and large blocks, downslope eroding the soil cover and increasing their original volume. At the base of the slopes, debris flows impacted on the urban areas, causing victims and severe destruction (Vittori et al., 2000). Starting from a recent study on landslide risk conditions in Campania, carried out by the Regional Authority (PAI –Hydrogeological setting plan, in press), an evaluation of the debris-flow susceptibility has been performed for selected areas of the above mentioned villages. According to that study, such zones would be in fact characterised by the highest risk levels within the administrative boundaries of the same villages ("HR-zones"). Our susceptibility analysis has been performed by applying SCIDDICA S3–hex – a hexagonal Cellular Automata model (von Neumann, 1966), specifically developed for simulating the spatial evolution of debris flows (Iovine et al., 2002). In order to apply the model to a given study area, detailed topographic data and a map of the erodable soil cover overlying the bedrock of the massif must be provided (as input matrices); moreover, extent and location of landslide source must also be given. Real landslides, selected among those triggered on winter 1999, have first been utilised for calibrating SCIDDICA S3–hex and for defining "optimal" values for parameters. Calibration has been carried out with a GIS tool, by quantitatively comparing simulations with actual cases: optimal values correspond to best simulations. Through geological evaluations, source locations of new phenomena have then been hypothesised within the HR-zones. Initial volume for these new cases has been estimated by considering the actual statistics of the 1999 landslides. Finally, by merging the results of simulations, a deterministic susceptibility zonation of the considered area has been obtained. In this paper, aiming at illustrating the potential for debris-flow hazard analyses of the model SCIDDICA S3–hex, a methodological example of susceptibility zonation of the Vallicelle HR-zone is presented.

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Mapping, cluster detection and evaluation of risk factors of ovine toxoplasmosis in Southern Italy

Geospatial health ◽

10.4081/gh.2016.432 ◽

2016 ◽

Vol 11 (2) ◽

Cited By ~ 5

Author(s):

Roberto Condoleo ◽

Vincenzo Musella ◽

Maria Paola Maurelli ◽

Antonio Bosco ◽

Giuseppe Cringoli ◽

...

Keyword(s):

Risk Factors ◽

Geographical Information Systems ◽

Southern Italy ◽

Geographical Information ◽

Economic Losses ◽

Common Source ◽

High Exposure ◽

Campania Region ◽

Source Of Infection ◽

Serological Data

Toxoplasmosis, an important cause of reproductive failure in sheep, is responsible for significant economic losses to the ovine industry worldwide. Moreover, ovine meat contaminated by the parasite Toxoplasma gondii is considered as a common source of infection for humans. The aim of this study was to develop point and risk profiling maps of T. gondii seroprevalence in sheep bred in Campania Region (Southern Italy) and analyse risk factors associated at the flock-level. We used serological data from a previous survey of 117 sheep flocks, while environmental and farm management information were obtained from an analysis based on geographical information systems and a questionnaire purveyance, respectively. An univariate Poisson regression model revealed that the type of farm production (milk and meat vs only meat) was the only independent variable associated with T. gondii positivity (P<0.02); the higher within-flock seroprevalence in milking herds suggests that milking practices might influence the spread of the infection on the farm. Neither environmental nor other management variables were significant. Since a majority of flocks were seasonally or permanently on pasture, the animals have a high exposure to infectious T. gondii oocysts, so the high within-flock seroprevalence might derive from this management factor. However, further studies are needed to better assess the actual epidemiological situation of toxoplasmosis in sheep and to clarify the factors that influence its presence and distribution.

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Temporal evolution of flow-like landslide hazard for a road infrastructure in the municipality of Nocera Inferiore (southern Italy) under the effect of climate change

Natural Hazards and Earth System Science ◽

10.5194/nhess-18-3019-2018 ◽

2018 ◽

Vol 18 (11) ◽

pp. 3019-3035 ◽

Cited By ~ 5

Author(s):

Marco Uzielli ◽

Guido Rianna ◽

Fabio Ciervo ◽

Paola Mercogliano ◽

Unni K. Eidsvig

Keyword(s):

Climate Change ◽

Southern Italy ◽

Spatial Location ◽

Temporal Variations ◽

Landslide Hazard ◽

Climate Projections ◽

Atmospheric Concentration ◽

Campania Region ◽

Event Occurrence

Abstract. In recent years, flow-like landslides have extensively affected pyroclastic covers in the Campania region in southern Italy, causing human suffering and conspicuous economic damages. Due to the high criticality of the area, a proper assessment of future variations in event occurrences due to expected climate changes is crucial. The study assesses the temporal variation in flow-like landslide hazard for a section of the A3 “Salerno–Napoli” motorway, which runs across the toe of the Monte Albino relief in the Nocera Inferiore municipality. Hazard is estimated spatially depending on (1) the likelihood of rainfall-induced event occurrence within the study area and (2) the probability that the any specific location in the study area will be affected during the runout. The probability of occurrence of an event is calculated through the application of Bayesian theory. Temporal variations due to climate change are estimated up to the year 2100 through an ensemble of high-resolution climate projections, accounting for current uncertainties in the characterization of variations in rainfall patterns. Reach probability, or defining the probability that a given spatial location is affected by flow-like landslides, is calculated spatially based on a distributed empirical model. The outputs of the study predict substantial increases in occurrence probability over time for two different scenarios of future socioeconomic growth and atmospheric concentration of greenhouse gases.

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