Paracetamol orodispersible tablets: a risk for severe poisoning in children?

Purpose: Childhood paracetamol (acetaminophen) ingestion with subsequent risk of hepatotoxicity is a major medical problem. The aim of this study was to investigate the risk of high-dose ingestion of orodispersible, fast-disintegrating paracetamol tablets in children. Methods: A retrospective single-center case study of all accidental selfadministrations of solid or orodispersible 500-mg paracetamol tablets occurring in children ≤ 6 years, reported to the Swiss Toxicological Information Centre between June 2003 and August 2009. Results: We found 187 cases with ingestion of solid 500-mg paracetamol tablets and 16 cases with ingestion of orodispersible 500-mg tablets. The mean ingested dose in the orodispersible-tablet group was 59% higher than in the solid-tablet group (p = 0.085). Administration of activated charcoal and/or N-acetylcysteine because of ingestion of a potentially hepatotoxic paracetamol dose ( ≥ 150 mg/kg body weight) was recommended in 32 patients (17.1%) in the solid-tablet group and in five (31%) in the orodispersible-tablet group. Conclusions: Orodispersible paracetamol formulations may represent an important risk factor for severe paracetamol poisoning in children. Over-the-counter availability may contribute to increasing the use of this galenic formulation and eventually the number of poisonings in childre

Comparative evaluation of three clinical decision support systems: prospective screening for medication errors in 100 medical inpatients

Purpose: Clinical decision support systems (CDSS) are promoted as powerful screening tools to improve pharmacotherapy. The aim of our study was to evaluate the potential contribution of CDSS to patient management in clinical practice. Methods: We prospectively analyzed the pharmacotherapy of 100 medical inpatients through the parallel use of three CDSS, namely, Pharmavista, DrugReax, and TheraOpt. After expert discussion that also considered all patient-specific clinical information, we selected apparently relevant alerts, issued suitable recommendations to physicians, and recorded subsequent prescription changes. Results: For 100 patients with a median of eight concomitant drugs, Pharmavista, DrugReax, and TheraOpt generated a total of 53, 362, and 328 interaction alerts, respectively. Among those we identified and forwarded 33 clinically relevant alerts to the attending physician, resulting in 19 prescription changes. Four adverse drug events were associated with interactions. The proportion of clinically relevant alerts among all alerts (positive predictive value) was 5.7, 8.0, and 7.6%, and the sensitivity to detect all 33 relevant alerts was 9.1, 87.9, and 75.8% for Pharmavista, DrugReax and TheraOpt, respectively. TheraOpt recommended 31 dose adjustments, of which we considered 11 to be relevant; three of these were followed by dose reductions. Conclusions: CDSS are valuable screening tools for medication errors, but only a small fraction of their alerts appear relevant in individual patients. In order to avoid overalerting CDSS should use patient-specific information and management-oriented classifications. Comprehensive information should be displayed on-demand, whereas a limited number of computer-triggered alerts that have management implications in the majority of affected patients should be based on locally customized and supported algorithm

Modern Times of Living (Loving) and Working: What Has Happened to Them?

The article is intended to be a reflection on modern times of living and working in the age of the smartphone and new technologies in general. Is there still, today, a clear distinction between living time and working time? Or has the smartphone, which we take as the most common and widely used representative of new technologies, made the boundaries between what were once clearly distinct living and working times increasingly blurred and con-fused? Smartphones contain all kinds of apps, from those useful or even necessary for life and work, to those for playing games, having fun and meeting people; and it is with us morning, afternoon, evening and night; weekdays and holidays; when we are well and when we are ill; when we are alone and when we are with friends. Losing it (or not being connected) is unthinkable for us and generates what is called nomophobia (NO MObile PHone PhoBIA). Another well-known fear related to new technologies in general and the smartphone in particular goes by the name of FOMO, short for “Fear Of Missing Out”, which is a worried feeling that you may miss events (both offline and, more importantly, online) that other people seem to take part in and thus run the risk of being excluded, forgotten, left out and substituted. Can all this be without consequences of various kinds? In this article, we focus on the consequences this has on our modern times of living (loving) and working

The impact of opioid analgesics with concomitant antipsychotic use on pain modulation and management in internal medicine: a cross-sequential study protocol

BackgroundAcute and chronic pain represents an escalating public health concern, necessitating safer and more effective in-hospital management approaches, including mental health. New treatment combinations involving psycholeptics are rising, but real-world evidence is lacking.ObjectivesThe study's primary objective is to evaluate the impact of combined opioid analgesics and antipsychotics in-hospital medication on pain modulation. The secondary objective is to evaluate pain management.MethodsThe cross-sequential study designed by this protocol will analyze retrospective data on 5,000 hospital admissions over four years (2019–2023) gathered from Electronic Health Records (EHR) of a multisite hospital in southern Switzerland. Eligible patients are aged 18 or older and hospitalized in an Internal Medicine ward. All patients with documented pain intensity assessment through a Visual Analogue Scale (VAS ≥ 1) will be included. Cross-sectional data on demographic and clinical variables and type of medication (opioid analgesics, antipsychotics, and selected other drugs according to the Anatomical Therapeutic Chemical classification system) will be screened at hospital admission (T1) and discharge (T2). Pain modulation will be assessed by gravity (VAS mean), intensity (VAS peak/extreme value), and pain treatment effectiveness (ΔT2-T1 VAS). Hospitalization paths (short- and long-term readmissions and total length of hospital stays) will be scrutinized as additional longitudinal indices for pain management and excluded from the cross-sectional analysis. A mixed model approach will assess VAS changes from T1 to T2. Logistic regression and regression models for count data will be used for short- and long-term readmission, respectively. Propensity score matching will be used to mitigate selection bias.DiscussionThis methodological approach combines cross-sectional and longitudinal EHR data gathering in a cross-sequential design. This integration allows for a comprehensive examination of pain modulation and management among internal medicine recipients of concomitant opioids and antipsychotic treatment, spanning both hospitalization and post-discharge periods. By leveraging EHR data, the study protocol ensures reliability and standardization while minimizing missing information. Additionally, the protocol addresses the potential limitations of observational designs.ConclusionsThis method offers a comprehensive and rigorous approach to investigating pain modulation and management in internal medicine patients receiving combined opioid analgesics and antipsychotics, with potential implications for enhancing clinical practice and healthcare resource utilization

Safety profile of monoclonal antibodies targeting the calcitonin gene-related peptide system in pregnancy: Updated analysis in VigiBase®

Background: Safety data on the use of migraine preventive monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) system in pregnancy are limited. Methods: Updated pharmacovigilance assessment of the safety reports related to pregnancy associated with erenumab, galcanezumab, fremanezumab and eptinezumab, retrieved from VigiBase® as of 31 December 2021. As primary outcome, the whole group of monoclonal antibodies targeting the CGRP system was considered and sex and age subgroup disproportionality analyses using the reporting odds ratio (ROR) were conducted. Results: 286 safety reports were found: 116 (40.6%) on erenumab, 125 (43.7%) on galcanezumab, 39 (13.6%) on fremanezumab, 6 (2.1%) on eptinezumab. One hundred and forty-nine (52.1%) safety reports reported only drug exposure in relation to pregnancy while 137 (47.9%) also included ≥1 pregnancy outcomes: maternal outcomes (n = 64), spontaneous abortion (n = 63), foetal growth restriction (n = 1), prematurity (n = 8), neonatal outcomes (n = 13), and poor breastfeeding (n = 1). No specific patterns of maternal, foetal and neonatal toxicity were observed. Spontaneous abortion was not disproportionally more frequently reported with erenumab, galcanezumab, fremanezumab and eptinezumab compared with the entire database (ROR 1.1, 95% confidence interval, CI, 0.8–1.5), the entire database since 2018 (ROR 1.3, 95% CI 1.0–1.8), and triptans (ROR 1.2, 95% CI 0.8–1.9). Conclusions: This updated safety analysis on erenumab, galcanezumab, fremanezumab and eptinezumab in pregnancy showed no signals of foeto-maternal toxicity according to VigiBase® safety reports

Calcitonin gene-related peptide antagonists in pregnancy: a disproportionality analysis in VigiBase®

Background Current evidence on the safety of calcitonin gene–related peptide antagonists (CGRP-A) in pregnancy for the treatment of both episodic and chronic migraine is scarce and does not yet provide definitive information. By querying VigiBase$^{®}$, the World Health Organization global pharmacovigilance database, this study aimed to detect differences in the reporting frequency between CGRP-A and triptans in relation to pregnancy. Methods Disproportionality analyses on de-duplicated safety reports collected in VigiBase$^{®}$ as of 31.05.2023 reporting exposure to CGRP-A in pregnancy with or without pregnancy outcomes. A Reporting Odds Ratio (ROR) with a 95% confidence interval (CI) was used as a measure of disproportionality and the threshold for the detection of a signal of disproportionate reporting was set with a 95% CI lower limit > 1. Findings Four hundred sixty-seven safety reports reported exposure to CGRP-A in pregnancy, mostly originating from the United States of America (360/467, 77%), more frequently reported by patients (225/467, 48%), who were mainly females (431/467, 92%), and more frequently reported exposure to CGRP-A during pregnancy (400/467, 86%). Compared to triptans, no signals of disproportionate reporting were detected with CGRP-A either for the overall reporting of pregnancy-related safety reports (ROR 0.91, 95% CI 0.78–1.06), for the reporting of pregnancy outcomes (maternal and/or foetal/neonatal, ROR 0.54, 95% CI 0.45–0.66), or for the reporting of foetal/neonatal outcomes (ROR 0.53, 95% CI 0.41–0.68). Conclusions This study showed that, to date, there are no signals of increased reporting with CGRP-A compared to triptans in relation to pregnancy in VigiBase$^{®}$. Future pharmacovigilance studies are needed to confirm these findings

Immune Checkpoint Inhibitors and Pregnancy: Analysis of the VigiBase® Spontaneous Reporting System

: In pregnancy, immune checkpoint pathways are involved in the maintenance of fetomaternal immune tolerance. Preclinical studies have shown that immune checkpoint inhibitors (ICIs) increase the risk of fetal death. Despite the fact that using ICIs in pregnant women and women of childbearing potential is not recommended, some case reports of ICI exposure in pregnancy have been published showing favorable fetal outcomes. This study aimed to gain further insight into ICI safety in pregnancy by querying VigiBase®, the World Health Organization's spontaneous reporting system. We performed raw and subgroup disproportionality analyses using the reporting odds ratio and comparing ICIs with the entire database, other antineoplastic agents, and other antineoplastic agents gathered in VigiBase® since 2011. Across 103 safety reports referring to ICI exposure during the peri-pregnancy period, 56 reported pregnancy-related outcomes, of which 46 were without concomitant drugs as potential confounding factors. No signals of disproportionate reporting were found for spontaneous abortion, fetal growth restriction, and prematurity. In light of the expanding indications of ICIs, continuous surveillance by clinicians and pharmacovigilance experts is warranted, along with pharmacoepidemiological studies on other sources of real-world evidence, such as birth records, to precisely assess ICI exposure during the peri-pregnancy period and further characterize relevant outcomes

Immune Checkpoint Inhibitors and Pregnancy: Analysis of the VigiBase® Spontaneous Reporting System

In pregnancy, immune checkpoint pathways are involved in the maintenance of fetomaternal immune tolerance. Preclinical studies have shown that immune checkpoint inhibitors (ICIs) increase the risk of fetal death. Despite the fact that using ICIs in pregnant women and women of childbearing potential is not recommended, some case reports of ICI exposure in pregnancy have been published showing favorable fetal outcomes. This study aimed to gain further insight into ICI safety in pregnancy by querying VigiBase®, the World Health Organization’s spontaneous reporting system. We performed raw and subgroup disproportionality analyses using the reporting odds ratio and comparing ICIs with the entire database, other antineoplastic agents, and other antineoplastic agents gathered in VigiBase® since 2011. Across 103 safety reports referring to ICI exposure during the peri-pregnancy period, 56 reported pregnancy-related outcomes, of which 46 were without concomitant drugs as potential confounding factors. No signals of disproportionate reporting were found for spontaneous abortion, fetal growth restriction, and prematurity. In light of the expanding indications of ICIs, continuous surveillance by clinicians and pharmacovigilance experts is warranted, along with pharmacoepidemiological studies on other sources of real-world evidence, such as birth records, to precisely assess ICI exposure during the peri-pregnancy period and further characterize relevant outcomes

Antipsychotic, benzodiazepine and Z-drug prescriptions in a Swiss hospital network in the Choosing Wisely and COVID-19 eras: a longitudinal study

AIMS OF THE STUDY: Physicians frequently prescribe antipsychotics off-label to treat, among others, insomnia and anxiety. The Swiss “smarter medicine – Choosing Wisely” campaign has tried to raise awareness about the risks and to limit benzodiazepine and Z-drug prescriptions. In the Italian-speaking part of Switzerland, our network of public hospitals joined the campaign with the aim of avoiding unnecessary benzodiazepine and Z-drug treatments, with prescription monitoring, benchmarking and educational contributions. Considering the risks of a possible shift towards the prescription of antipsychotics, and aware of the potential role of the COVID-19 pandemic, we decided to analyse the prescription trends of antipsychotics and benzodiazepines/Z-drugs before, during (2016–2017) and after the intervention. METHODS: For this longitudinal study, we reactivated a continuous monitoring of inpatient benzodiazepine/Z-drug and antipsychotics prescriptions/deprescriptions, paused in 2018 after the end of the internal Choosing Wisely campaign, based on routinely collected observational health data. We screened all demographic, administrative and prescription data of patients admitted to the internal medicine department of the four teaching hospitals (H1-H4) belonging to the EOC (Ente Ospedaliero Cantonale) network, from the fourth quarter of 2014 to the second quarter of 2023. RESULTS: We analysed 74,659 hospital stays (14,645 / 16,083 / 24,285 / 19,646 at hospitals H1 / H2 / H3 / H4 respectively). The mean (± SD) case mix (a metric that reflects the diversity, complexity and severity of the treated patients) and patient age were 1.08 ± 0.14 and 73 ± 2 years. 10.6% and 12.1% of patients received antipsychotics prior to admission and at discharge respectively (new prescriptions 3.3 ± 0.7%; deprescriptions 13.3 ± 5.2%). New prescriptions showed an upward trend, with +0.20% per year (p <0.001). Patients admitted with ongoing antipsychotics therapy increased 0.36% per year (p <0.001). New benzodiazepine/Z-drug prescriptions showed a 0.20% per year decrease (p = 0.01). Patients admitted with ongoing benzodiazepine/Z-drug therapy decreased 0.32% per year (p <0.001). New antipsychotics prescriptions showed differences between hospitals, with H3 above and H2 below the average. CONCLUSIONS: The increase in antipsychotics quantitatively matched the decrease in benzodiazepine/Z-drug prescribing, suggesting a shift from one to the other sedative therapy. The same trend was visible in the ongoing prescriptions at admission revealing a similar out-of-hospital approach. This suggests a change in sedative prescribing strategy rather than the choice of alternative, non-pharmacological approaches. Furthermore, the variation between similar services of different hospitals points out the consequences of local prescribing cultures and the importance of continuously monitoring and benchmarking medication prescriptions