Immunol Allergy Clin North Am. 2022 May;42(2):307-322. doi: 10.1016/j.iac.2022.01.003. Epub 2022 Mar 31.

ABSTRACT

In evaluating adverse drug reactions (ADRs), patch tests (PTs), skin prick tests (SPTs), and intradermal tests (IDTs) are useful tools for identifying responsible drugs and finding safe alternatives. Their diagnostic value depends on the clinical features of the ADR and on the drug tested. PTs have a good sensitivity in assessing acute generalized exanthematous pustulosis and drug rash with eosinophilia and systemic symptoms. SPTs done with all drugs except opiates are used for immediate hypersensitivity reactions. IDTs seem sensitive for immediate hypersensitivity reactions to beta-lactam antibiotics, iodinated contrast media, heparins, general anesthetics, and platinum salts.

PMID:35469620 | DOI:10.1016/j.iac.2022.01.003

Biomed Res Int. 2022 Apr 16;2022:4284146. doi: 10.1155/2022/4284146. eCollection 2022.

ABSTRACT

BACKGROUND: It is of vital importance to determine the safety of drugs. Pregnant women, as a special group, need to evaluate the effects of drugs on pregnant women as well as the fetus. The use of drugs during pregnancy may be subject to fetal toxicity, thus affecting the development of the fetus or even leading to stillbirth. The U.S. Food and Drug Administration (FDA) issued a toxicity rating for drugs used during pregnancy in 1979. These toxicity ratings are denoted by the letters A, B, C, D, and X. However, the query of drug pregnancy category has yet to be well established as electronic service.

RESULTS: Here, we presented PregTox, a publicly accessible resource for pregnancy category information of 1114 drugs. The PregTox database also included chemical structures, important physico-chemical properties, protein targets, and relevant signaling pathways. An advantage of the database is multiple search options which allow systematic analyses. In a case study, we demonstrated that a set of chemical descriptors could effectively discriminate high-risk drugs from others (area under ROC curve reached 0.81).

CONCLUSIONS: PregTox can serve as a unique drug safety data source for drug development and pharmacological research.

PMID:35469349 | PMC:PMC9034948 | DOI:10.1155/2022/4284146

Klin Monbl Augenheilkd. 2022 Apr;239(4):575-581. doi: 10.1055/a-1766-6119. Epub 2022 Apr 26.

ABSTRACT

BACKGROUND: The recently introduced tumor therapies including immune checkpoint and BRAF/MEK inhibitors (ICI) have substantially contributed to survival and quality of life of the affected patients, but are associated with class-specific, non-toxic immune-related side effects including uveitis. This narrative review focusses to summarize the immune-related adverse event profile associated with the use of ICI.

METHODS: A literature search in PubMed, the publication database of the National Institute of Health in the USA (https://www.ncbi.nlm.nih.gov/pubmed) used the search terms "uveitis" AND "drug-induced" AND/OR "immune checkpoint inhibitor". All articles published in the last five years and the for the purpose of this review relevant cross references were evaluated.

RESULTS: A class-specific phenomenon of ICI and BRAF/MEK inhibitors is their capability to induce systemic and ocular autoimmunity. Ocular side effects are observed in up to 3% of patients and should be differentiated from toxic side effects, since this is not dose-dependent. Melanoma as underlying disease and Pembrolizumab as ICI significantly increase the risk. If timely recognized, systemic treatment with corticosteroids allows to preserve vision without cessation of the tumor treatment in more than 90% of these potentially life-threatening instances.

CONCLUSION: Given their impact onto the survival of cancer and namely melanoma patients, ICI and BRAF/MEK inhibitors are increasingly used alone and in combination, which enhances their inherent risk of developing drug-induced ocular autoimmunity. Favorable functional outcomes are closely linked to early recognition and aggressive treatment of these complications considering the fact that these immune-related adverse events affect multiple organ systems and have an untreated lethality of up to 3%.

PMID:35472809 | DOI:10.1055/a-1766-6119

Brief Bioinform. 2022 Apr 25:bbac126. doi: 10.1093/bib/bbac126. Online ahead of print.

ABSTRACT

MOTIVATION: Computerized methods for drug-related side effect identification can help reduce costs and speed up drug development. Multisource data about drug and side effects are widely used to predict potential drug-related side effects. Heterogeneous graphs are commonly used to associate multisourced data of drugs and side effects which can reflect similarities of the drugs from different perspectives. Effective integration and formulation of diverse similarities, however, are challenging. In addition, the specific topology of each heterogeneous graph and the common topology of multiple graphs are neglected.

RESULTS: We propose a drug-side effect association prediction model, GCRS, to encode and integrate specific topologies, common topologies and pairwise attributes of drugs and side effects. First, multiple drug-side effect heterogeneous graphs are constructed using various kinds of similarities and associations related to drugs and side effects. As each heterogeneous graph has its specific topology, we establish separate module based on graph convolutional autoencoder (GCA) to learn the particular topology representation of each drug node and each side effect node, respectively. Since multiple graphs reflect the complex relationships among the drug and side effect nodes and contain common topologies, we construct a module based on GCA with sharing parameters to learn the common topology representations of each node. Afterwards, we design an attention mechanism to obtain more informative topology representations at the representation level. Finally, multi-layer convolutional neural networks with attribute-level attention are constructed to deeply integrate the similarity and association attributes of a pair of drug-side effect nodes. Comprehensive experiments show that GCRS's prediction performance is superior to other comparing state-of-the-art methods for predicting drug-side effect associations. The recall rates in top-ranked candidates and case studies on five drugs further demonstrate GCRS's ability in discovering potential drug-related side effects.

CONTACT: zhang@hlju.edu.cn.

PMID:35470853 | DOI:10.1093/bib/bbac126

Drug Ther Bull. 2022 Apr 25:dtb-2022-000024. doi: 10.1136/dtb.2022.000024. Online ahead of print.

ABSTRACT

Overview of: Wang Z, Brauer R, Man KKC, et al Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: a systematic review and meta-analysis. Br J Clin Pharmacol 2021;87:4101-23.

PMID:35470153 | DOI:10.1136/dtb.2022.000024

Curr Drug Metab. 2022 Apr 25. doi: 10.2174/1389200223666220425111931. Online ahead of print.

ABSTRACT

BACKGROUND: Urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein-7 (IGFBP7) predict severe acute kidney injury (AKI) in critical illness. Earlier but subtle elevation of either biomarker from nephrotoxicity may predict drug-induced AKI.

METHODS: A prospective study involving serial urine collection in patients treated with vancomycin, aminoglycosides, amphotericin, foscarnet, or calcineurin inhibitors was performed. Urinary TIMP2 and IGFBP7, absolute levels, normalized with urine creatinine were examined in days leading to AKI onset by KDIGO criteria in cases, or at final day of nephrotoxic therapy in non-AKI controls who were matched for age, baseline kidney function and nephrotoxic exposure.

RESULTS: Urinary biomarker analyses were performed in 21 AKI patients and 28 non-AKI matched-controls; both groups had comparable baseline kidney function and duration of nephrotoxic drug therapy. Significantly higher absolute, normalized, and composite levels of TIMP2 and IGFBP7 were observed in AKI cases versus controls as early as 2-3 days before AKI onset (all P<0.05); >70% of patients with corresponding levels above 75th percentile developed AKI. Normalized TIMP2 at 2-3 days pre-AKI predicted AKI with the highest average AUROC of 0.81, followed by that of composite [TIMP2]x[IGFBP7] (0.78) after cross-validation. [TIMP2]x[IGFBP7] >0.01 (ng/mL)2 /1000 predicted AKI with a sensitivity of 79% and specificity of 60%.

CONCLUSION: Elevated urinary TIMP2 or IGFBP7 predicts drug-induced AKI with a lead-time of 2-3 days; an opportune time for interventions to reduce nephrotoxicity.

PMID:35469565 | DOI:10.2174/1389200223666220425111931

Pan Afr Med J. 2022 Feb 9;41:114. doi: 10.11604/pamj.2022.41.114.30767. eCollection 2022.

ABSTRACT

INTRODUCTION: COVID-19 vaccination has been rolled out in Nigeria, with low uptake often attributed to shortage of the vaccine. We set out to find out the current trend so far and to the best of our knowledge, our study is one of the early studies since the roll out in the region looking at the real situation on ground. This will guide multidisciplinary decision making at increasing uptake of the vaccine.

METHODS: this is a descriptive cross-sectional study in the 5 South-Eastern States in Nigeria. A structured questionnaire was given to the members of the public to answer themselves or via the help of an interviewer. Data was analysed in SPSS and associations between variables compared using Chi square.

RESULTS: there are 1283 respondents in this study. Of this number, only 105 (8.2%) have had at least one of the vaccine doses. Stated reasons for not having been vaccinated are side effects (n=370, 31.5%), access to a vaccination centre (n= 239, 20.4%) and belief in one's own immunity 186 (15.5). Having a health-related degree (p-value of 0.021), non-governmental employees (p-value of 0.003), private sector employees (p-value of 0.029) and public sector employees (p-value of 0.009) are associated with relatively higher vaccination rates.

CONCLUSION: vaccination rate in Nigeria is still very low. Fear of side effect which is enhanced by mystical thinking is the leading factor for low turnout not just shortages. All forms of employed jobs, age and higher qualification all have significant p-values (p<0.05) and associated with higher uptake of the vaccine.

PMID:35465378 | PMC:PMC8994467 | DOI:10.11604/pamj.2022.41.114.30767

J Healthc Eng. 2022 Apr 15;2022:5622482. doi: 10.1155/2022/5622482. eCollection 2022.

ABSTRACT

BACKGROUND: Despite the increasing number of skin adverse drug reactions caused by nadroparin calcium have been reported, mostly, little is known regarding of their details of clinical characteristics, especially for generalized skin adverse drug reactions. We sought to evaluate localized and generalized characteristics of the skin adverse drug reaction to nadroparin calcium injection in pregnant women.

METHODS: A retrospective study was conducted on 6 pregnant women, who experienced localized and generalized skin adverse drug reactions during long-term nadroparin calcium injection. The patients' clinical and imaging information were retrieved from medical records. The skin prick test, patch test, and intradermal test were performed after they stopped lactation. Causality assessment of suspected adverse drug reactions was performed on these cases.

RESULTS: The average total dose of nadroparin calcium injection in the 6 cases was 64.17 ± 22.66. Localized skin adverse drug reaction, manifested as erythema at the injection point, appeared after 47.5 ± 17.4 days of subcutaneous injection of nadroparin calcium. Generalized urticaria-like lesions, progressing from the injection site on the abdomen, appeared in 5.17 ± 3.60 days after the first appearance of localized reaction, while laboratory test results revealed essential peripheral blood eosinophilia. All rashes in the 6 cases subsided in 2-5 weeks after drug withdrawal. After delivery, 5 of 6 cases received complete skin tests to evaluate drug hypersensitivity. Results presented positive in the intradermal test within 7 days. Both the skin prick test and skin patch test were negative. Localized skin reactions and generalized urticaria-like adverse drug reactions were considered as definitely and probably caused by nadroparin calcium injection, respectively.

CONCLUSION: Subcutaneous injection of nadroparin calcium in pregnant women appears to be at risk of localized and generalized urticaria-like adverse drug reaction. It is important to follow up the pregnant woman during nadroparin calcium injection for evaluating adverse drug reactions. Timely detection of symptoms is pivotal in early diagnosis and treatment of adverse drug reactions.

PMID:35463677 | PMC:PMC9033372 | DOI:10.1155/2022/5622482

Pharmacopsychiatry. 2022 Apr 25. doi: 10.1055/a-1804-6211. Online ahead of print.

ABSTRACT

INTRODUCTION: Long-acting injectable (LAI) antipsychotics are prescribed to people with severe psychiatric disorders who show poor adherence to oral medication. The present paper examined factors potentially associated with medication adherence to LAI treatment.

METHODS: The STAR (Servizi Territoriali Associati per la Ricerca) Network Depot Study was a multicenter, observational, prospective study that enrolled 461 subjects initiating a LAI from 32 Italian centers. After 6 and 12 months of treatment, we evaluated differences between participants with high (≥5 points) and low (<5 points) medication adherence using Kemp's 7-point scale in sociodemographic, clinical, psychopathological, and drug-related variables. Factors that differed significantly between the two groups were entered for multivariate logistic regression.

RESULTS: Six months after enrollment, participants with high medication adherence were younger, living with other people, had lower Brief Psychiatric Rating Scale (BPRS) total scores, lower adverse events, and a more positive attitude toward medication than participants with low adherence. Multivariate regression confirmed lower BPRS resistance and activation scores, absence of adverse events, and positive attitude toward medication as factors significantly associated with good adherence. After 12 months, all BPRS subscales were significantly lower in the high adherence group, which also showed a more positive attitude toward medication. BPRS resistance and attitude toward medication were confirmed as factors associated with medication adherence.

DISCUSSION: Our findings suggest that adherence to LAI is principally related to attitude toward medication and traits of suspiciousness/hostility. Quality of patient-clinician relationship and tailored psychoeducational strategies may positively affect adherence in people undergoing psychopharmacological treatment, including LAI.

PMID:35468642 | DOI:10.1055/a-1804-6211

Muscle Nerve. 2022 Apr 24. doi: 10.1002/mus.27560. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: Neuronal hyperexcitability (manifested by cramps) plays a pathological role in amyotrophic lateral sclerosis (ALS), and drugs affecting it may help symptomatic management and slow disease progression. We aimed to determine safety and tolerability of two doses of ranolazine in patients with ALS and evaluate for preliminary evidence of drug-target engagement by assessing muscle cramp characteristics.

METHODS: We performed an open-label dose-ascending study of ranolazine in 14 individuals with ALS in 2 sequential cohorts: 500 mg (Cohort 1) and 1000 mg (Cohort 2) orally twice daily. Each had a 2-week run-in period, 4-week drug administration, and 6-week safety follow up. Primary outcome was safety and tolerability. Exploratory measures included cramp frequency and severity, fasciculation frequency, cramp potential duration, ALS Functional Rating Scale-revised, and forced vital capacity.

RESULTS: Six and eight participants were enrolled in cohorts 1 and 2 respectively. There were no serious adverse events. Two subjects in cohort 2 discontinued the drug due to constipation. The most frequent drug-related adverse event was gastrointestinal (40%). Cramp frequency decreased by 54.8% (95% CI 39 to 70.8%) and severity decreased by 46.3% (95% CI 29.5 to 63.3%), which appeared to be dose-dependent, with decreased awakening due to cramps. Other outcomes showed no change.

DISCUSSION: Ranolazine was well tolerated in ALS up to 2000 mg daily with gastrointestinal side effects being the most frequent. Ranolazine reduced cramp frequency and severity, supporting its investigation for muscle cramps in a future placebo-controlled trial. This article is protected by copyright. All rights reserved.

PMID:35466411 | DOI:10.1002/mus.27560

Clin Psychopharmacol Neurosci. 2022 May 31;20(2):394-397. doi: 10.9758/cpn.2022.20.2.394.

ABSTRACT

Antidepressant-induced hypomania/mania is a complex issue that can be seen in mood disorders but is not clarified. There are case reports in the literature regarding vortioxetine-induced mania and hypomania; however, there is insufficient data. Here, we aim to present a case of vortioxetine-induced hypomania in a major depressive disorder patient who previously used various antidepressants but did not experience hypomania or mania. Our case is expected to contribute to the literature.

PMID:35466110 | DOI:10.9758/cpn.2022.20.2.394

Expert Rev Clin Pharmacol. 2022 Apr 23. doi: 10.1080/17512433.2022.2070474. Online ahead of print.

ABSTRACT

INTRODUCTION: The use of medications with anticholinergic (ACh) properties is associated with numerous adverse effects especially in older adults. Emerging evidence suggests the presence of long-term effects with ACh use.

AREAS COVERED: Our article presents an overview of ACh effects and falls in older individuals including examination of emerging evidence on ACh use and cumulative exposure on short-term and long-term falls risk. The databases CINAHL, MEDLINE, EMBASE, and Web of Science were searched for articles published from January 2002 to December 2021.

EXPERT OPINION: Anticholinergic side effects include muscle weakness, blurred vision and mental confusion which are likely to lead to increased falls risk. Many commonly used medications such as beta-blockers, calcium-channel blockers and antihistamines are now known to have mild ACh properties. With polypharmacy now considered unavoidable in older patients, the cumulative effects of the use of multiple drugs with mild ACh properties may also lead to increased falls risk. The relationship between ACh drugs and falls may also be irreversible as ACh effects may extend beyond the period of drug use, due to cognitive and physical deconditioning following the initial exposure to ACh drugs. Future long-term studies with accurate quantification of cumulative ACh exposure and measurement of actual falls outcomes are urgently required.

PMID:35465815 | DOI:10.1080/17512433.2022.2070474

Curr Ther Res Clin Exp. 2022 Mar 29;96:100668. doi: 10.1016/j.curtheres.2022.100668. eCollection 2022.

ABSTRACT

BACKGROUND: Dasiglucagon is a novel glucagon analog that is stable in aqueous formulation and approved for use in severe hypoglycemia. Concentration QTc analyses are critical for assessing risk of drug-induced QTc prolongation and potential for fatal cardiac arrhythmias such as torsades de pointes.

OBJECTIVE: The aim of this study was to determine whether dasiglucagon treatment resulted in any clinically relevant effect on cardiac repolarization in healthy volunteers.

METHODS: This double-blind, placebo-controlled, dose-escalation Phase I trial was conducted at a single center in Germany between November 2018 and June 2019. Sixty healthy volunteers aged 18 to 45 years were randomized within dose cohorts to receive intravenous dasiglucagon, intravenous placebo, or subcutaneous dasiglucagon. In the intravenous administration cohorts, doses ranged from 0.03 mg to 1.5 mg. The subcutaneous administration cohort received the approved 0.6 mg dose. In the intravenous administration cohorts, serial electrocardiograms were extracted from continuous Holter monitors at prespecified time points beginning the day before dosing and through 24 hours postdose. Heart rate, PR interval, and QRS duration were evaluated. Concentration-QT analyses corrected by Fridericia's formula (QTcF) were performed using both a linear mixed-effects and a maximum estimated effect (Emax) model.

RESULTS: At the doses studied, dasiglucagon did not have any clinically relevant effect on heart rate, PR interval, or QRS duration. A minor prolongation of the QTcF interval was observed without any clear dose or concentration dependency. Both the linear and Emax models predicted mean and 90% CIs of placebo-corrected change in QTcF remained below 10 ms (the threshold of regulatory concern), although the linear model did not fit the data well at low dasiglucagon plasma concentrations. In the Emax model, the Emax of dasiglucagon was 3.6 ms (90% CI, 1.23-5.95 ms), and the amount to produce half the effect of Emax) was 426.0 pmol/L (90% CI, -48.8 to 900.71 pmol/L). The treatment effect-specific intercept was -0.44 ms (90% CI, -2.37 to 1.49 ms). The most frequently observed treatment-emergent adverse events reported in the trial were gastrointestinal disorders such as nausea and vomiting.

CONCLUSIONS: Dasiglucagon does not cause clinically relevant QTc prolongation in concentrations up to ≈30,000 pmol/L, a level 5-fold higher than the highest observed plasma concentrations in clinical trials investigating use of the approved 0.6 mg SC dose. ClinicalTrials.gov Identifier: NCT03735225; EudraCT identifier: 2018-002025-32. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

PMID:35464292 | PMC:PMC9026613 | DOI:10.1016/j.curtheres.2022.100668

Front Pharmacol. 2022 Apr 7;13:859563. doi: 10.3389/fphar.2022.859563. eCollection 2022.

ABSTRACT

Globally, millions of people suffer from various substance use disorders (SUD), including mono-and polydrug use of opioids and methamphetamine. Brain regions such as the cingulate cortex, infralimbic cortex, dorsal striatum, nucleus accumbens, basolateral and central amygdala have been shown to play important roles in addiction-related behavioral changes. Clinical and pre-clinical studies have characterized these brain regions and their corresponding neurochemical changes in numerous phases of drug dependence such as acute drug use, intoxication, craving, withdrawal, and relapse. At present, many studies have reported the individual effects of opioids and methamphetamine. However, little is known about their combined effects. Co-use of these drugs produces effects greater than either drug alone, where one decreases the side effects of the other, and the combination produces a prolonged intoxication period or a more desirable intoxication effect. An increasing number of studies have associated polydrug abuse with poorer treatment outcomes, drug-related deaths, and more severe psychopathologies. To date, the pharmacological treatment efficacy for polydrug abuse is vague, and still at the experimental stage. This present review discusses the human and animal behavioral, neuroanatomical, and neurochemical changes underlying both morphine and methamphetamine dependence separately, as well as its combination. This narrative review also delineates the recent advances in the pharmacotherapy of mono- and poly drug-use of opioids and methamphetamine at clinical and preclinical stages.

PMID:35462918 | PMC:PMC9021401 | DOI:10.3389/fphar.2022.859563

BMC Geriatr. 2022 Apr 23;22(1):359. doi: 10.1186/s12877-022-03003-9.

ABSTRACT

BACKGROUND: Globally, it is estimated that the number of older adults will become 2 billion by 2050. The identification of the predictors of adverse drug reaction (ADR) in hospitalized older patients is crucial to the development of prediction tools and preventive strategies to mitigate the burden of ADRs. This study aimed to determine the predictors of hospital-acquired ADR occurrence among hospitalized older adults in a low-income country.

METHODS: We conducted a prospective cohort of older adults admitted to medical, oncology, and surgery wards at Mbarara Regional Referral Hospital (MRRH) for a consecutive 6 months where each patient was followed up daily from admission to discharge. We used Edwards and Aronson's definition of ADR and the Naranjo ADR Causality Scale. We employed Beer's criteria and Lexicomp to determine potentially inappropriate medications, and drug interactions, respectively. We conducted univariate and multivariable logistic regression using Statistical Package for the Social Science (SPSS) Version 23.0.

RESULTS: Out of 523 participants with median (Inter Quartile Range) age of 67 (62-76) years, 256 (48.9%) experienced at least one ADR. Independent predictors of occurrence of hospital acquired ADRs included age of 60-75 (Adjusted odds ratio (AOR) = 1.97, 95% C.I: 1.14-3.41; p value = 0.015) compared to > 75 years, previous ADR in 1 year (AOR = 2.43, 95% C.I: 1.42-4.17; p value = 0.001), potentially inappropriate medication (AOR = 4.56, 95% C.I: 2.70-7.70; p value< 0.001), polypharmacy (AOR = 3.29, 95% C.I: 1.98-5.46; p value< 0.001)), having a Charlison Comorbidity Index (CCI) ≥ 6 (AOR = 8.47, 95% C.I: 4.85-14.99; p value< 0.001), having heart failure (AOR = 2.83, 95% C.I: 1.34-6.02; p value = 0.007) or kidney disease (AOR = 1.95, 95% C.I: 1.05-3.61; p value = 0.034) and a hospital stay > 10 days (AOR = 3.53, 95% C.I: 1.89-6.61; p value< 0.001) compared to < 5 days.

CONCLUSION: The current prevalence of ADR is higher than previously reported in high-income countries. Disease-related factors followed by medication-related factors were shown to be the most important predictors of hospital-acquired ADRs. CCI and PIM showed the strongest association with ADR. The predictors of ADRs identified in our study were generally comparable with those reported by previous studies.

PLAIN LANGUAGE TITLE: Conditions that predispose older patients to experience harmful effects from their medications while in hospital. Identifying the conditions that predispose older adults to incur harmful effects of their medications helps to plan on how best to predict, take precautions and closely follow up on them and thus, to prevent these undesirable outcomes. This study aimed to identify these conditions which determine which older adults are higher risk to incur these harmful undesirable effects of medicines. Everydayduring their hospital stay, we closely followed older patients who were 60 years and above from their entry to the hospital wards until they left the hospital. We interviewed the participants, reviewed their medication files and we also examined them physically to identify any unwanted and harmful outcome from their current medications. Out of 523 participants, almost half of them experienced at least one harmful or undesired effect related to their medicine. Conditions which predisposed them to experience a harmful effect from their medicines included being in age bracket of 60-75 years, having a history of experiencing harmful outcomes from medicines in the previous 1 year, taking a medication which was listed as potentially inappropriate for older adults, taking 5 or more medications concurrently, having a lower 10 years survival chance, having heart or kidney disease and a hospital stay > 10 days.

PMID:35461224 | DOI:10.1186/s12877-022-03003-9

Int J Environ Res Public Health. 2022 Apr 8;19(8):4509. doi: 10.3390/ijerph19084509.

ABSTRACT

OBJECTIVE: To investigate the occurrence of adverse effects of antiepileptic drugs (AEDs) in pediatric epileptic patients on mono- or polytherapy.

METHOD: We evaluated eighty consecutive patients that met the following inclusion criteria: aged ≤18 years; diagnosed with epilepsy for at least one year; a stable dose of AED for at least three months; verbal consent to participation in the study. Patients were asked if they had experienced any adverse drug reaction (ADR) related to the AED. Afterward, regardless of the answer, they were interviewed based on a detailed semi-structured questionnaire about the presence of ADRs associated with the AED. The data were analyzed regarding the use of monotherapy or polytherapy.

RESULTS: Ninety-seven percent of the patients reported having experienced ADRs related to AEDs. The greatest number of seizures affected the group of patients treated with monotherapy (both at baseline and at followup), but the greatest number of ADRs were observed among patients treated with polytherapy. In patients on monotherapy, the most frequent ADRs reported at baseline included fatigue and somnolence, and among patients with polytherapy, it was fatigue and hair loss.

CONCLUSION: Children on polytherapy were significantly more likely to develop ADRs compared to those on monotherapy, but a statistically significant improvement in seizure frequency was also observed in the group of patients on polytherapy. Pharmacovigilance is very important in children with AEDs, so that ADRs can be identified early and managed appropriately.

PMID:35457375 | PMC:PMC9028571 | DOI:10.3390/ijerph19084509

Int J Environ Res Public Health. 2022 Apr 7;19(8):4447. doi: 10.3390/ijerph19084447.

ABSTRACT

Patients are recognized as important players in the pharmacovigilance system. This study aims to describe and compare the characteristics of patient reporting systems, reporting forms, awareness raising-activities, and the statistics related to patient reporting in the selected countries. Fifteen countries (eight Western countries and seven Asian countries) were purposively selected. A questionnaire survey was distributed to national pharmacovigilance authorities in those countries. Nine countries (five Western countries and four Asian countries) returned the questionnaire. A review of the websites of national pharmacovigilance centres was conducted. The proportion of patient reports in the selected Western countries ranged from 57.83% to 14.37%, while it was accounted for less than 1% in the selected Asian countries. Currently, patients in all nine countries can report adverse drug reactions online via a website. The number of clicks from the national pharmacovigilance website to reach the online reporting form range from one to five clicks. Countries with higher patient reporting rates seemed to share the following characteristics; provision of feedback, engagement with patient organizations, and implementation of several activities to raise the awareness of the general public on the importance of pharmacovigilance. To increase the number of patient reports, the strengths of each country's system should be adopted.

PMID:35457318 | PMC:PMC9028008 | DOI:10.3390/ijerph19084447

Int J Mol Sci. 2022 Apr 9;23(8):4154. doi: 10.3390/ijms23084154.

ABSTRACT

Neuromyelitis optica spectrum disorders (NMOSD) are rare neurologic autoimmune diseases that have a poor prognosis if left untreated. For many years, generic oral immunosuppressants and repurposed monoclonal antibodies that target the interleukin-6 pathway or B cells were the mainstays of drug treatment. Recently, these drug treatments have been complemented by new biologics developed and approved specifically for NMOSD. In principle, all of these drugs are effective, but treatment recommendations that take this into account are still pending. Instead, the choice of a drug may depend on other criteria such as drug safety or tolerability. In this review, we summarise current knowledge on the adverse effects of azathioprine, mycophenolate mofetil, rituximab, tocilizumab, eculizumab, satralizumab, and inebilizumab in NMOSD. Infections, cytopenias, and infusion-related reactions are most common, but the data are as heterogeneous as the manifestations are diverse. Nevertheless, knowledge of safety issues may facilitate treatment choices for individual patients.

PMID:35456972 | PMC:PMC9029040 | DOI:10.3390/ijms23084154

Cancers (Basel). 2022 Apr 10;14(8):1913. doi: 10.3390/cancers14081913.

ABSTRACT

Drug-related hepatotoxicity is an emerging clinical challenge with the widening use of immunotherapeutic agents in the field of oncology. This is an important complication to consider as more immune oncological targets are being identified to show promising results in clinical trials. The application of these therapeutics may be complicated by the development of immune-related adverse events (irAEs), a serious limitation often requiring high-dose immunosuppression and discontinuation of cancer therapy. Hepatoxicity presents one of the most frequently encountered irAEs and a better understanding of the underlying mechanism is crucial for the development of alternative therapeutic interventions. As a novel drug side effect, the immunopathogenesis of the condition is not completely understood. In the liver, myeloid cells play a central role in the maintenance of homeostasis and promotion of inflammation. Recent research has identified myeloid cells to be associated with hepatic adverse events of various immune modulatory monoclonal antibodies. In this review article, we provide an overview of the role of myeloid cells in the immune pathogenesis during hepatoxicity related to cancer immunotherapies and highlight potential treatment options.

PMID:35454819 | DOI:10.3390/cancers14081913

Medicine (Baltimore). 2022 Mar 11;101(10):e28997. doi: 10.1097/MD.0000000000028997.

ABSTRACT

RATIONALE: The Chaga mushroom (Hymenochaetaceae, Inonotus obliquus) is a fungus belonging to the Hymenochaetaceae family. It is parasitic on birch and other tree species. Chaga mushrooms are rich in various vitamins, minerals, and nutrients. Some people consider these mushrooms medicinal as they have been reported to suppress cancer progression through anti-inflammatory and antioxidant effects. However, recent studies have reported that excessive ingestion of Chaga mushrooms can cause acute oxalate nephropathy.

PATIENT CONCERNS: A 69-year-old man who ingested Chaga mushroom powder (10-15 g per day) and vitamin C (500 mg per day) for the past 3 months developed acute kidney injury (AKI) with the clinical manifestations of nephrotic syndrome (NS).

DIAGNOSIS: Pathological findings showed focal acute tubular injury and the deposition of calcium oxalate crystals in the tubules. Light microscopy showed interstitial fibrosis and tubular atrophy, and electron microscopy showed the effacement of the foot processes in podocytes. Based on these results, the diagnosis was acute oxalate nephropathy accompanied by minimal change disease (MCD).

INTERVENTIONS: The patient's kidney function did not improve with supportive care, such as hydration and blood pressure control. Thus, we recommended hemodialysis and the administration of a high dose of steroids (intravenous hydrocortisone 500 mg twice a day for 3 days and oral prednisolone at 1 mg/kg).

OUTCOMES: The patient's kidney function recovered just 1 month after the start of treatment, and the MCD was completely remitted.

LESSONS: In cases of AKI with an unknown cause, it is important to closely observe the patient's medication history, and it is recommended to perform kidney biopsy. Furthermore, this study showed that active dialysis and high-dose steroid treatment can restore kidney function in patients with AKI caused by acute oxalate nephropathy with MCD.

PMID:35451393 | PMC:PMC8913114 | DOI:10.1097/MD.0000000000028997