JCO Glob Oncol. 2022 Mar;8:e2100275. doi: 10.1200/GO.21.00275.

ABSTRACT

PURPOSE: Nephrotoxicity is a major dose-limiting toxicity among patients with cancer who were treated with cisplatin. Although no standard approach is available to prevent cisplatin-induced nephrotoxicity, administering intravenous isotonic saline is recommended. Additionally, mannitol combined with hydration has been evaluated, but none of them have been established. Our study aimed to determine the efficacy of mannitol combined hydration to prevent cisplatin-induced nephrotoxicity.

PATIENTS AND METHODS: This study was a phase II, randomized, placebo-controlled design. All patients with solid cancers who were treated with cisplatin (n = 48) were randomly assigned to receive either placebo (n = 25) or 20 g of mannitol (n = 23) after completing 2 L of prehydration and receiving cisplatin. Serum creatinine, blood urea nitrogen, electrolyte, and glomerular filtration rate (GFR) were measured at baseline and days 2 and 7. Moreover, GFR was calculated based on the 24-hour urine creatinine clearance rate to assess renal function at baseline and 48 hours after receiving cisplatin. Severity of nausea and vomiting was evaluated using Common Terminology Criteria for Adverse Events.

RESULTS: No difference was found regarding baseline characteristics between the two groups. Seven of 23 patients (37.4%) in the mannitol group and 10 of 25 patients (40%) in the placebo group increased serum creatinine level ≥ 0.3 mg/dL at 48 hours after intervention (P value = .48). Patients receiving mannitol exhibited significantly lower incidence of 24-hour urine GFR below 60 mL/min/1.73 m than those in the placebo group (13.6% v 48.0% in the placebo group; P value = .012). Univariate analysis showed the greatest benefit for administering mannitol among patients receiving cisplatin > 80 mg/m2, or patients receiving concomitant radiation.

CONCLUSION: Mannitol combined with hydration significantly prevented cisplatin-induced nephrotoxicity. Additionally, mannitol should be particularly considered among patients with cancer, treated with cisplatin > 80 mg/m2, or patients receiving concomitant radiation.

PMID:35436142 | DOI:10.1200/GO.21.00275

Indian J Med Res. 2021 Apr;154(4):559-570. doi: 10.4103/ijmr.IJMR_313_19.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are a relatively newer class of drugs approved for the treatment of malignancies such as melanoma, renal, bladder and lung cancer. Immune-related adverse events (IrAEs) involving the endocrine system are a common side effect of these drugs. The spectrum of endocrine adverse events varies by the drug class. Cytotoxic T-lymphocyte-associated antigen-4 inhibitors commonly cause hypophysitis/hypopituitarism, whereas the incidence of thyroid disease is higher with programmed cell death (PD)-1/ ligand (PD-L) protein 1 inhibitors. The focus of this review is to describe the individual endocrinopathies with their possible mechanisms, signs and symptoms, clinical assessment and disease management. Multiple mechanisms of IrAEs have been described in literature including type II/IV hypersensitivity reactions and development of autoantibodies. Patients with pre-existing autoimmune endocrine diseases can have disease exacerbation following ICI therapy rather than de novo IrAEs. Most of the endocrinopathies are relatively mild, and timely hormone replacement therapy allows continuation of ICIs. However, involvement of the pituitary-adrenal axis could be life-threatening if not recognized. Corticosteroids are helpful when the pituitary-adrenal axis is involved. In cases of severe endocrine toxicity (grade 3/4), ICIs should be temporarily discontinued and can be restarted after adequate hormonal therapy. Endocrinologists and general internists need to be vigilant and maintain a high degree of awareness for these adverse events.

PMID:35435341 | DOI:10.4103/ijmr.IJMR_313_19

J Healthc Eng. 2022 Apr 7;2022:5054932. doi: 10.1155/2022/5054932. eCollection 2022.

ABSTRACT

In this paper, the safety of Tripterygium wilfordii polyglycoside (TW) preparation was evaluated by combining literature research and evidence-based evaluation research, so as to provide evidence-based safety information of Tripterygium wilfordii polyglycoside preparation (nephroptosis) for government decision making and clinical application. In this paper, we propose a network structure inspired by the LSTM gate mechanism. All the research methods of the included references are evaluated by internationally recognized evaluation tools or standards. Prevalence was analyzed according to the type of intervention (e.g., time of administration) and route of administration. The results of this experiment provide methods and suggestions for the evaluation of traditional Chinese medicine nephroptosis in the future.

PMID:35432821 | PMC:PMC9010145 | DOI:10.1155/2022/5054932

Ann Intern Med. 2022 Apr 19. doi: 10.7326/M21-3445. Online ahead of print.

ABSTRACT

BACKGROUND: Concomitant use of oral organic nitrates (nitrates) and phosphodiesterase type 5 (PDE5) inhibitors is contraindicated.

OBJECTIVE: To measure temporal trends in the coprescription of nitrates and PDE5 inhibitors and to measure the association between cardiovascular outcomes and the coprescription of nitrates with PDE5 inhibitors.

DESIGN: Case-crossover design.

SETTING: Nationwide study of Danish patients from 2000 to 2018.

PATIENTS: Male patients with International Classification of Diseases, 10th Revision (ICD-10) codes for ischemic heart disease (IHD), including those who had a continuing prescription for nitrates and a new, filled prescription for PDE5 inhibitors.

MEASUREMENTS: Two composite outcomes were measured: 1) cardiac arrest, shock, myocardial infarction, ischemic stroke, or acute coronary arteriography and 2) syncope, angina pectoris, or drug-related adverse event.

RESULTS: From 2000 to 2018, 249 541 male patients with IHD were identified. Of these, 42 073 patients had continuing prescriptions for nitrates. During this period, the prescription rate for PDE5 inhibitors in patients with IHD who were taking nitrates increased from an average of 0.9 prescriptions (95% CI, 0.5 to 1.2 prescriptions) per 100 persons per year in 2000 to 19.5 prescriptions (CI, 18.0 to 21.1 prescriptions) in 2018. No statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for either composite outcome (odds ratio [OR], 0.58 [CI, 0.28 to 1.13] for the first outcome and OR, 0.73 [CI, 0.40 to 1.32] for the second outcome).

LIMITATION: An assumption was made that concurrently filled prescriptions for nitrates and PDE5 inhibitors equaled concomitant use.

CONCLUSION: From 2000 to 2018, the use of PDE5 inhibitors increased 20-fold among Danish patients with IHD who were taking nitrates. A statistically significant association between concomitant use of these medications and cardiovascular adverse events could not be identified.

PRIMARY FUNDING SOURCE: Ib Mogens Kristiansens Almene Fond and Helsefonden.

PMID:35436155 | DOI:10.7326/M21-3445

Case Rep Oncol. 2022 Mar 14;15(1):225-230. doi: 10.1159/000520158. eCollection 2022 Jan-Apr.

ABSTRACT

The discovery of tyrosine kinase oncogenic driver mutations, including anaplastic lymphoma kinase (ALK), has changed the face of non-small cell lung cancer (NSCLC) treatment. Whilst the development of tyrosine kinase inhibitors has improved survival, with their increasing use, it is important to be aware of the risks of rare yet serious adverse events, such as drug-induced pulmonary toxicity. Whilst little is known in regard to drug-induced pneumonitis in the setting of ALK inhibitors, such reactions carry a high morbidity and mortality rate, impacting greatly upon options for further treatment and management. We describe the case of a 73-year-old female with metastatic ALK-positive NSCLC who developed subacute dyspnoea 3 weeks after commencing lorlatinib. She was diagnosed with drug-induced pneumonitis, from which she recovered clinically following the cessation of her targeted therapy. Pneumonitis related to lorlatinib is a rare pulmonary toxicity, and early recognition and intervention is critical to reduce the associated risks of respiratory failure and death.

PMID:35431862 | PMC:PMC8958573 | DOI:10.1159/000520158

Colomb Med (Cali). 2021 Sep 30;52(3):e2074569. doi: 10.25100/cm.v52i3.4569. eCollection 2021 Jul-Sep.

ABSTRACT

OBJECTIVE: This study aimed to correlate the genetic profile of the NUDT15 and TPMT genes with the side effects of the treatment of pediatric patients with acute lymphoid leukemia who were undergoing maintenance therapy at a tertiary care hospital in 2017.

METHODS: This was an analytical, longitudinal, observational study in which the genotypes of the genes of interest were determined by PCR allelic discrimination with TaqMan® probes in patients receiving chemotherapy during the maintenance phase in the Pediatric Hematology and Oncology Unit in 2017. Sociodemographic and clinical data corresponding to the first six months of their maintenance chemotherapy were collected, and the correlation between the genotypes obtained and the development of side effects during the maintenance phase of chemotherapy in these patients was evaluated.

RESULTS: Seventy pediatric patients were included in the study. Genetic analyses were carried out of these for NUDT15 and TPMT (rs1800462 and rs1800460) on 68 patients, while for the rs1142345 polymorphism, typing was achieved in 42 patients. 4/68 patients were heterozygous for NUDT15, and the same number of patients were heterozygous for rs1800462 and rs1142345, while for rs1800460, 6 heterozygous patients were identified. No statistically significant association was identified between the genetic variants and the outcomes of interest.

CONCLUSION: Studies with a larger population size are needed and the evaluation of other genetic variants that may influence the development of side effects during maintenance chemotherapy.

PMID:35431360 | PMC:PMC8973308 | DOI:10.25100/cm.v52i3.4569

Med Arch. 2022 Feb;76(1):72-74. doi: 10.5455/medarh.2022.76.72-74.

ABSTRACT

BACKGROUND: Erythema nodosum (EN) is a common form of panniculitis that could be triggered by numerous conditions including infectious and non-infectious conditions. So far, few cases of EN caused by COVID-19 vaccine had been reported.

CASE REPORT: We report a case of atypical presentation of EN mimicking cellulitis in a patient who received the first dose of the Pfizer-BioNTech COVID-19 vaccine. A 38-year-old healthy woman who developed painful swelling on the left leg one week after receiving the first dose of Pfizer-BioNTech COVID-19 vaccine. Skin biopsy was revealed septal panniculitis. Due to the temporal association and the absence of other identifiable causes, Pfizer-BioNTech COVID-19 vaccine-related EN would be the most likely explanation.

CONCLUSION: COVID-19 vaccines could be associated with rare side effects that should be reported for a better understanding of related outcomes of COVID-19 vaccination. This case was reported to keep in mind that EN can have atypical presentation as a rare side effect of COVID-19 vaccines.

PMID:35422564 | PMC:PMC8978813 | DOI:10.5455/medarh.2022.76.72-74

Front Immunol. 2022 Mar 28;13:865267. doi: 10.3389/fimmu.2022.865267. eCollection 2022.

ABSTRACT

Rheumatoid arthritis (RA), one of the most common immune system diseases, mainly affects middle-aged and elderly individuals and has a serious impact on the quality of life of patients. Pain and disability caused by RA are significant symptoms negatively affecting patients, and they are especially seen when inappropriate treatment is administered. Effective therapeutic strategies have evolved over the past few decades, with many new disease-modifying antirheumatic drugs (DMARDs) being used in the clinic. Owing to the breakthrough in the treatment of RA, the symptoms of patients who could not be treated effectively in the past few years have been relieved. However, some patients complain about symptoms that have not been reported, implying that there are still some limitations in the RA treatment and evaluation system. In recent years, biomarkers, an effective means of diagnosing and evaluating the condition of patients with RA, have gradually been used in clinical practice to evaluate the therapeutic effect of RA, which is constantly being improved for accurate application of treatment in patients with RA. In this article, we summarize a series of biomarkers that may be helpful in evaluating the therapeutic effect and improving the efficiency of clinical treatment for RA. These efforts may also encourage researchers to devote more time and resources to the study and application of biomarkers, resulting in a new evaluation system that will reduce the inappropriate use of DMARDs, as well as patients' physical pain and financial burden.

PMID:35418971 | PMC:PMC8995470 | DOI:10.3389/fimmu.2022.865267

J Allergy Clin Immunol. 2022 Apr 11:S0091-6749(22)00451-1. doi: 10.1016/j.jaci.2022.04.003. Online ahead of print.

ABSTRACT

Mast cell activation is a key event in allergic reactions, other inflammatory states, and mast cell activation syndromes. Mast cell-stabilizing agents, mediator-targeting drugs and drugs interfering with mediator effects are often prescribed in these patients. However, the clinical efficacy of these drugs varies, depending on the numbers of involved mast cells and the underlying pathology. One straightforward approach would be to eradicate the primary target cell. However, to date, no mast cell-eradicating treatment approach has been developed for patients suffering from mast cell activation disorders. Nevertheless, recent data suggest that long-term treatment with agents that effectively inhibit KIT-function results in the virtual eradication of tissue mast cells and a sustained decrease in serum tryptase levels. In many of these patients, mast cell depletion is associated with a substantial improvement in mediator-induced symptoms. In patients with an underlying KIT D816V+ mastocytosis, such mast cell eradication requires an effective inhibitor of KIT D816V, such as avapritinib. However, the use of KIT inhibitors must be balanced against potential side effects. We here discuss mast cell-eradicating strategies in various disease models, the feasibility of this approach, available clinical data, and future prospects for the use of KIT-targeting drugs in mast cell activation disorders.

PMID:35421448 | DOI:10.1016/j.jaci.2022.04.003

Transl Clin Pharmacol. 2022 Mar;30(1):49-56. doi: 10.12793/tcp.2022.30.e3. Epub 2022 Mar 7.

ABSTRACT

UI026 is an expectorant and antitussive agent which is a new combination of Pelargonium sidoides extract and Coptis extract. The bioactive compounds of Pelargonium sidoides and Coptis extracts were identified as epicatechin and berberine, respectively. This study evaluated the effect of food on the pharmacokinetics (PKs) and safety of UI026. A randomized, open-label, single-dose, 2-treatment, parallel study in 12 healthy male subjects was performed. Subjects received a single oral dose of UI026 (27 mL of syrup) under a fed or fasted condition according to their randomly assigned treatment. Blood samples for the PK analysis were obtained up to 24 hours post-dose for berberine and 12 hours post-dose for epicatechin. The PK parameters were calculated by non-compartmental analysis. In the fed condition, the mean maximum plasma concentration (Cmax) and mean area under the plasma concentration-time curve from time zero to the last observed time point (AUClast) for berberine were approximately 33% and 67% lower, respectively, compared with the fasted condition, both showing statistically significant difference. For epicatechin, the mean Cmax and mean AUClast were about 29% and 45% lower, respectively, compared to the fasting condition, neither of which showed a statistically significant difference. There were no drug-related adverse events. This finding suggests that food affects the systemic exposure and bioavailability of berberine and epicatechin.

TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003451.

PMID:35419311 | PMC:PMC8979756 | DOI:10.12793/tcp.2022.30.e3

Saudi Med J. 2022 Apr;43(4):386-393. doi: 10.15537/smj.2022.43.4.20210905.

ABSTRACT

OBJECTIVES: To measure and assess the side-effects of Pfizer/BioNTech and AstraZeneca vaccines on residents of Saudi Arabia, as well as provide a database that gives insight into the relative safety of these 2 COVID-19 vaccines.

METHODS: A community-based cross-sectional study was conducted to determine the side-effects of the two COVID-19 vaccines. The study was initiated on the 5th of June 2021 at Hail University, Hail, Saudi Arabia. The information was collected through an online survey designed on Google forms. The questionnaire was pre-tested for validity, with all information carefully reviewed.

RESULTS: The study included 2,530 participants from different regions of Saudi Arabia, with a mean age of 26.9 ± 12.4 years old. The most common vaccine among the study group was Pfizer, which 73.8% of the population were provided; the remaining 26.2% received the AstraZeneca vaccine. Regarding the Pfizer vaccine, the common systemic side-effects followed the first dose, included headaches, followed by muscle pain, fever, and joint pain. Those who had the AstraZeneca vaccine reported a few more side-effects. For example, during the first dose fever was reported as the most common side-effect, followed by headache, muscle pain and fatigue.

CONCLUSION: The present study confirmed that vaccine side-effects are more frequently reported by smokers and those who received the AstraZeneca vaccine. Further studies are needed to acquire a better understanding of the association between risk factors and the experiencing of post-vaccine side-effects.

PMID:35414617 | DOI:10.15537/smj.2022.43.4.20210905

Expert Opin Drug Saf. 2022 Apr 13. doi: 10.1080/14740338.2022.2066078. Online ahead of print.

NO ABSTRACT

PMID:35417282 | DOI:10.1080/14740338.2022.2066078

BMJ Open. 2022 Apr 12;12(4):e055454. doi: 10.1136/bmjopen-2021-055454.

ABSTRACT

OBJECTIVES: This study aims to determine the proportion of initial cardiometabolic assessment and its predicting factors in adults with schizophrenia, bipolar disorder or other related diagnoses for whom a second-generation antipsychotic was prescribed in the hospital setting.

DESIGN: Cross-sectional study.

SETTING: The psychiatry unit of a Canadian tertiary care teaching hospital in Montreal, Canada.

PARTICIPANTS: 402 patients with aforementioned disorders who initiated, restarted or switched to one of the following antipsychotics: clozapine, olanzapine, risperidone, paliperidone or quetiapine, between 2013 and 2016.

PRIMARY OUTCOME MEASURES: We assessed the proportion of cardiometabolic parameters monitored.

SECONDARY OUTCOME MEASURES: We identified predictors that influence the monitoring of cardiometabolic parameters and we assessed the proportion of adequate interventions following the screening of uncontrolled blood pressure and fasting glucose or glycated haemoglobin (HbA1c) results.

RESULTS: Only 37.3% of patients received monitoring for at least three cardiometabolic parameters. Blood pressure was assessed in 99.8% of patients; lipid profile in 24.4%; fasting glucose or HbA1c in 33.3% and weight or body mass index in 97.8% of patients while waist circumference was assessed in 4.5% of patients. For patients with abnormal blood pressure and glycaemic values, 42.3% and 41.2% subsequent interventions were done, respectively. The study highlighted the psychiatric diagnosis (substance induced disorder OR 0.06 95% CI 0.00 to 0.44), the presence of a court-ordered treatment (OR 0.79 95% CI 0.35 to 1.79) and the treating psychiatrist (up to OR 34.0 95% CI 16.2 to 140.7) as predictors of cardiometabolic monitoring.

CONCLUSIONS: This study reports suboptimal baseline cardiometabolic monitoring of patients taking an antipsychotic in a Canadian hospital. Optimising collaboration within a multidisciplinary team may increase cardiometabolic monitoring.

PMID:35414553 | DOI:10.1136/bmjopen-2021-055454

Int J Environ Res Public Health. 2022 Apr 4;19(7):4313. doi: 10.3390/ijerph19074313.

ABSTRACT

At present, 19.2% of the Spanish population is aged 65 or older. Polypharmacy is a frequent condition among the elderly, especially in those living in nursing homes, which is associated with adverse outcomes, such as adverse drug events or drug-drug interactions. This study aimed to assess the pattern of polypharmacy in a nursing home in Leon, one of Spain's most ageing regions, and its relationship with different drug-related problems. A descriptive, observational, and cross-sectional study design was used; 222 residents were involved in this study. Data on drug use were collected from medical charts. Information was screened with the software CheckTheMeds, BOT PLUS and Drug-Reax. Residents were on a median of 7 medicines. Polypharmacy and inappropriate medications were present in 78.8% and 96.8% of residents, respectively. Drug-related problems were present in almost all the populations evaluated. Drug-drug interactions were very common in participants (81.1%), being severe/moderate in 24.7%. A high prevalence of polypharmacy and drug-related problems in the nursing home population assessed has been observed. A significantly higher risk of suffering drug-drug interactions was revealed for increasing polypharmacy and anticholinergic risk. A regular evaluation of drug prescribing in nursing home residents is necessary to minimize drug-related problems risk.

PMID:35409994 | DOI:10.3390/ijerph19074313

Int J Environ Res Public Health. 2022 Mar 31;19(7):4169. doi: 10.3390/ijerph19074169.

ABSTRACT

OBJECTIVES: To compare neurologists' knowledge, practice, and barriers of pharmacovigilance (PV) process among patients with epilepsy in Poland and Egypt.

METHODS: It was an international study that used an online questionnaire e-mailed to neurologists registered to practice in Poland and Egypt.

RESULTS: Most of the neurologists were familiar with the definition of PV and adverse drug reactions (ADRs), but relatively few neurologists knew where to report ADRs, especially the Egyptian neurologists. Only 31.11% of the neurologists from Egypt and 39.90% neurologists from Poland declared that they had reported ADRs at least once during their professional practice, and few of them declared the regular reporting of such incidents. The main reason for the neurologists not reporting ADRs was the lack of time and a conviction that reporting ADRs would be an additional burden that would generate extra work.

CONCLUSION: The standards of pharmacovigilance process, safety control, and quality are not the same throughout the world. System-regulated PV stabilization in a country translates into the practice of maintaining PV. Monitoring the safety of pharmacotherapy and knowledge of risks associated with ADRs should be included in the academic curricula of physician courses.

PMID:35409851 | DOI:10.3390/ijerph19074169

Int J Environ Res Public Health. 2022 Mar 22;19(7):3754. doi: 10.3390/ijerph19073754.

ABSTRACT

Spontaneous reports (SRs) of adverse drug reactions (ADRs) remain the basis of pharmacovigilance systems. The main objective of this study was to evaluate the quality of SRs received by the Pharmacovigilance Unit of Beira Interior, in Central Portugal. The second objective was to identify factors associated with complete SRs. SRs received between 1 January 2017 and 31 October 2019 were analyzed. SR information was classified as "mandatory" or "recommended" criteria. SR were then grouped into three categories (well, slightly, and poorly documented). Association between "well documented" SR and confounding variables was estimated using a multiple logistic regression model. The results showed 22.4% of SRs are "well documented", and 41.2% are "poorly documented". Most of the complete SRs correspond to non-serious ADRs (55.8%), with a negative association between complete SRs and serious ADRs (OR = 0.595, [95% CI 0.362-0.977], p = 0.040). There is also a significant association between complete SRs and e-mail notification (OR = 1.876, [95% CI 1.060-3.321], p = 0.002). The results highlight the small amount of SR documentation sent to pharmacovigilance systems. There is an association between non-serious ADRs and complete SRs. These results reinforce the need for training for notification of ADRs and that these SRs include as much information as possible for an effective drug risk management.

PMID:35409436 | DOI:10.3390/ijerph19073754

Cells. 2022 Mar 24;11(7):1102. doi: 10.3390/cells11071102.

ABSTRACT

Preclinical toxicity screening is the first and most crucial test that assesses the safety of new candidate drugs before their consideration for further evaluation in clinical trials. In vitro drug screening using stem cells has lately arisen as a promising alternative to the "gold standard" of animal testing, but their suitability and performance characteristics in toxicological studies have so far not been comprehensively investigated. In this study, we focused on the evaluation of human mesenchymal stem cells isolated from the matrix (Wharton's jelly) of fetal umbilical cord (WJSCs), which bear enhanced in vitro applicability due to their unique biological characteristics. In order to determine their suitability for drug-related cytotoxicity assessment, we adopted a high-throughput methodology that evaluated their sensitivity to a selected panel of chemicals in different culture environments. Cytotoxicity was measured within 48 h by means of MTS and/or NRU viability assays, and was compared directly (in vitro) or indirectly (in silico) to adult human mesenchymal stem cells and to reference cell lines of human and murine origin. Our data clearly suggest that human WJSCs can serve as a robust in vitro alternative for acute drug toxicity screening by uniquely combining rapid and versatile assay setup with high-throughput analysis, good representation of human toxicology, high reproducibility, and low cost.

PMID:35406666 | DOI:10.3390/cells11071102

Eur J Hosp Pharm. 2022 Apr 11:ejhpharm-2021-003053. doi: 10.1136/ejhpharm-2021-003053. Online ahead of print.

ABSTRACT

OBJECTIVE: The standard treatment for epilepsy is based on the appropriate use of antiseizure medications (ASMs) to prevent the recurrence of seizures. For the newer ASMs, however, little information on their safety profile is available. This work sought to fill this gap by creating a database for ASM use in a paediatric hospital and the adverse drug reactions (ADRs) reported.

METHODS: This observational single-centre study was conducted from January 2018 to December 2020 and recorded the type of ASM treatment for paediatric epileptic patients cared for at the Neuropsychiatry Unit of the Salesi Paediatric Hospital in Ancona, Italy, as well as any ADRs.

RESULTS: In all, 519 patients were admitted to the ward with a diagnosis of epilepsy, 362 (69.7%) of whom were prescribed ASMs. Valproic acid was the most frequently prescribed drug (29.96%), followed by levetiracetam (13.97%) and carbamazepine (9.16%). We recorded 24 ADRs in 20 patients, half of which (n=12) occurred with polytherapy. Among the ADRs associated with monotherapy, 25% (n=6) were induced by carbamazepine; 12.5% (n=3) were associated with either valproic acid, clonazepam or lamotrigine; 8.3% (n=2) were associated with perampanel, clobazam or levetiracetam; while one patient experienced ADR due to vigabatrin, one due to ethosuximide and one due to cannabidiol. The median patient age was 7.5 years and most ADRs were not serious.

CONCLUSION: During the 3-year observation period, 6% of epileptic patients on ASMs showed one or more ADRs. Carbamazepine was responsible for about a quarter of these reactions, two of which were serious. Half of the ADRs occurred with polytherapy, which often included valproic acid and stiripentol. It is to be hoped that such active pharmacovigilance through the collaboration of hospital pharmacists and physicians will serve to improve the management of treatment.

PMID:35410875 | DOI:10.1136/ejhpharm-2021-003053

Am J Manag Care. 2022 Mar 1;28(3):e113-e120. doi: 10.37765/ajmc.2022.88844.

ABSTRACT

OBJECTIVES: To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF).

STUDY DESIGN: Systematic literature review.

METHODS: A systematic literature review was conducted in PubMed, Ovid MEDLINE, and Clinical Key covering January 1990 to December 2018. Key search terms were ADEs for β-blockers (BBs), ACE inhibitors (ACEis), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and/or angiotensin receptor-neprilysin inhibitors (ARNis) in adult patients (≥ 18 years) with HFrEF.

RESULTS: A total of 279 eligible articles were identified, of which 29 reported drug-related adverse effects and were included in this review. Of the 29 studies, 11 examined BBs; 9, MRAs; 6, ARNis; 2, ACEis; and 1, ARBs. The most common reported ADEs across these therapeutic classes included bradycardia, dizziness, hypotension, hyperkalemia, cough, and renal impairment. The incidence of BB-induced bradycardia was 1% to 52% based on 9 studies, and 6 studies described dizziness as a result of BBs and ARNis (15%-43%). Fourteen studies reported induced hypotension (1.4%-63%); 13 studies, hyperkalemia (0.6%-30.2%); 3 studies, cough (37%-50%); and 4 studies, renal impairment (0.6%-7.6%).

CONCLUSIONS: Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted.

PMID:35404555 | DOI:10.37765/ajmc.2022.88844

Comput Math Methods Med. 2022 Apr 1;2022:9547317. doi: 10.1155/2022/9547317. eCollection 2022.

ABSTRACT

Drugs can treat different diseases but also bring side effects. Undetected and unaccepted side effects for approved drugs can greatly harm the human body and bring huge risks for pharmaceutical companies. Traditional experimental methods used to determine the side effects have several drawbacks, such as low efficiency and high cost. One alternative to achieve this purpose is to design computational methods. Previous studies modeled a binary classification problem by pairing drugs and side effects; however, their classifiers can only extract one feature from each type of drug association. The present work proposed a novel multiple-feature sampling scheme that can extract several features from one type of drug association. Thirteen classification algorithms were employed to construct classifiers with features yielded by such scheme. Their performance was greatly improved compared with that of the classifiers that use the features yielded by the original scheme. Best performance was observed for the classifier based on random forest with MCC of 0.8661, AUROC of 0.969, and AUPR of 0.977. Finally, one key parameter in the multiple-feature sampling scheme was analyzed.

PMID:35401786 | PMC:PMC8993545 | DOI:10.1155/2022/9547317