Front Pharmacol. 2024 Apr 17;15:1322473. doi: 10.3389/fphar.2024.1322473. eCollection 2024.

ABSTRACT

CONTEXT: Cabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC).

OBJECTIVES: We performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC.

METHODS: We extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials.

RESULTS: A total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR in randomized controlled trials was [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p < 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p < 0.0001].

CONCLUSION: Cabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events.

SYSTEMATIC REVIEW REGISTRATION: identifier CRD42023455878.

PMID:38694912 | PMC:PMC11061414 | DOI:10.3389/fphar.2024.1322473

Ann Med Surg (Lond). 2024 Mar 4;86(5):3029-3035. doi: 10.1097/MS9.0000000000001878. eCollection 2024 May.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity.

CASE PRESENTATION: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up.

CLINICAL DISCUSSION: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur.

CONCLUSION: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

PMID:38694384 | PMC:PMC11060267 | DOI:10.1097/MS9.0000000000001878

Farm Hosp. 2024 Apr 30:S1130-6343(24)00041-2. doi: 10.1016/j.farma.2024.03.004. Online ahead of print.

ABSTRACT

INTRODUCTION: Intensive care units (ICUs) pose challenges in managing critically ill patients with polypharmacy, potentially leading to adverse drug reactions (ADRs), particularly in the elderly.

OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU.

METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. ADR screening was performed daily through the identification of ADR triggers.

RESULTS: 1295 triggers were identified (median 30 per patient, IQR=28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001).

CONCLUSIONS: These data suggest that employing the severity and clinical prognosis scores used in ICUs is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

PMID:38693001 | DOI:10.1016/j.farma.2024.03.004

Folia Med (Plovdiv). 2024 Apr 30;66(2):161-170. doi: 10.3897/folmed.66.e117783.

ABSTRACT

Inappropriate polypharmacy is a common occurrence in elderly patients, resulting in increased adverse drug reactions, nonadherence, and increased healthcare costs. Medication review and deprescribing are the primary strategies described in the literature for dealing with problematic polypharmacy. To effectively carry out the medication review, various tools have been developed. These tools can support medication review in a variety of ways. Some tools include a list of medications requiring detailed attention, while others guide medical professionals with principles and algorithms for reviewing and prescribing medicines. A third category of tools focuses on tracking and identifying symptoms that may be due to drug-related problems.

PMID:38690810 | DOI:10.3897/folmed.66.e117783

Cureus. 2024 Mar 31;16(3):e57341. doi: 10.7759/cureus.57341. eCollection 2024 Mar.

ABSTRACT

Clozapine is an effective medication for treatment-resistant schizophrenia, and it has been associated with well-documented side effects that limit its use. Clozapine-induced hepatotoxicity is a less-known complication of clozapine therapy. The literature is unclear about the psychopharmacologic options available following clozapine cessation on account of liver toxicity. We present a patient with clinical symptomatology in keeping with clozapine-induced hepatotoxicity who achieved full recovery following clozapine cessation and conservative medical management. Her psychiatric symptomatology was successfully managed with oral olanzapine augmented with haloperidol without recurrence of psychosis or liver toxicity.

PMID:38690462 | PMC:PMC11060696 | DOI:10.7759/cureus.57341

Natl J Maxillofac Surg. 2024 Jan-Apr;15(1):151-153. doi: 10.4103/njms.njms_128_22. Epub 2024 Mar 19.

ABSTRACT

While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the present study aimed to present a unique case in which photobiomodulation therapy (PBMT) was employed to manage bullous erythema multiforme lesions secondary to fluconazole intake. A 32-year-old female patient sought emergency dental care due to painful orofacial lesions that had developed two days after oral fluconazole use for recurrent vulvovaginal candidiasis. Given the acute clinical features, a diagnosis of bullous erythema multiforme secondary to fluconazole was established. Prednisone 20 mg was then prescribed for five days, and fluconazole intake was immediately discontinued. As the initial treatment strategies failed to show improvement in the clinical condition, three PBMT sessions were proposed every other day. Within seven days, almost complete wound healing was observed, and any pain complaints were no longer present. The resolution of orofacial lesions within a short period suggests that PBMT could be a promising tool for managing drug-induced bullous erythema multiforme. However, more studies are needed to confirm this statement.

PMID:38690232 | PMC:PMC11057598 | DOI:10.4103/njms.njms_128_22

Toxicol Appl Pharmacol. 2024 Apr 28:116945. doi: 10.1016/j.taap.2024.116945. Online ahead of print.

ABSTRACT

Cytochrome P450 enzymes (CYPs) play a crucial role in the metabolism and synthesis of various compound classes. While drug-metabolizing CYP enzymes are frequently investigated as anti-targets, the inhibition of CYP enzymes involved in adrenal steroidogenesis is not well studied. The steroidogenic enzyme CYP17A1 is a dual-function enzyme catalyzing hydroxylase and lyase reactions relevant for the biosynthesis of adrenal glucocorticoids and androgens. Inhibition of CYP17A1-hydroxylase leads to pseudohyperaldosteronism with subsequent excessive mineralocorticoid receptor activation, hypertension and hypokalemia. In contrast, specific inhibition of the lyase function might be beneficial for the treatment of prostate cancer by decreasing adrenal androgen levels. This study combined in silico and in vitro methods to identify drugs inhibiting CYP17A1. The most potent CYP17A1 inhibitors identified are serdemetan, mocetinostat, nolatrexed, liarozole, and talarozole. While some of these drugs are currently under investigation for the treatment of various cancers, their potential for the treatment of prostate cancer is yet to be explored. The DrugBank database was screened for CYP17A1 inhibitors, to increase the awareness for the risk of drug-induced pseudohyperaldosteronism and to highlight drugs so far unknown for their potential to cause side effects resulting from CYP17A1 inhibition.

PMID:38688424 | DOI:10.1016/j.taap.2024.116945

JCO Clin Cancer Inform. 2024 Apr;8:e2300151. doi: 10.1200/CCI.23.00151.

ABSTRACT

PURPOSE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in the real-world data setting is critical for characterizing the benefit/risk profile of ICI therapies beyond the clinical trial population. Diagnosis codes, such as International Classification of Diseases codes, do not comprehensively illustrate a patient's care journey and offer no insight into drug-irAE causality. This study aims to capture the relationship between ICIs and irAEs more accurately by using augmented curation (AC), a natural language processing-based innovation, on unstructured data in electronic health records.

METHODS: In a cohort of 9,290 patients treated with ICIs at Mayo Clinic from 2005 to 2021, we compared the prevalence of irAEs using diagnosis codes and AC models, which classify drug-irAE pairs in clinical notes with implied textual causality. Four illustrative irAEs with high patient impact-myocarditis, encephalitis, pneumonitis, and severe cutaneous adverse reactions, abbreviated as MEPS-were analyzed using corticosteroid administration and ICI discontinuation as proxies of severity.

RESULTS: For MEPS, only 70% (n = 118) of patients found by AC were also identified by diagnosis codes. Using AC models, patients with MEPS received corticosteroids for their respective irAE 82% of the time and permanently discontinued the ICI because of the irAE 35.9% (n = 115) of the time.

CONCLUSION: Overall, AC models enabled more accurate identification and assessment of patient impact of ICI-induced irAEs not found using diagnosis codes, demonstrating a novel and more efficient strategy to assess real-world clinical outcomes in patients treated with ICIs.

PMID:38687915 | DOI:10.1200/CCI.23.00151

Rev Med Chil. 2023 May;151(5):576-582. doi: 10.4067/s0034-98872023000500576.

ABSTRACT

OBJECTIVE: To study the prevalence of adverse drug events (ADE) in hospitalized patients in Chile. As part of our research, we also assessed the validity of the method used to identify the occurrence of an ADE based on the discharge diagnoses of the patient.

DESIGN: The study included 1,7 million patients hospitalized during 2019-2020. We analyzed the following variables for each patient: ICD-10 discharge diagnoses, sociodemographic information, and clinical outcome indicators, i.e., diagnosis-related group (DRG) weight, length of stay, and mortality. To validate the method for the identification of ADEs, first, we generated a random representative sample of patients, stratified by sex and medical specialty, hospitalized in a Chilean public hospital in 2019, and then we compared the outcome of the method with the opinion of a group of clinical experts that reviewed each patient's discharge summary retrospectively.

RESULTS: The prevalence of ADEs in hospitalized patients in Chile during 2019 and 2020 was 2,7% and 3,1%, respectively. The precision of the method used to identify ADEs was 83,3% or higher (CI 90%).

CONCLUSIONS: This paper uses nationwide data to describe the prevalence of ADEs and their correlation with different factors associated with the patient, the patient's disease, and the health service. These studies are essential to designing public health policies that effectively address healthcare quality and patient safety.

PMID:38687539 | DOI:10.4067/s0034-98872023000500576

JAMA Netw Open. 2024 Apr 1;7(4):e248732. doi: 10.1001/jamanetworkopen.2024.8732.

ABSTRACT

IMPORTANCE: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population.

OBJECTIVE: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients 60 years or older who were enrolled in Medicare Parts A, B, and D receiving in-center hemodialysis from January 1 to December 31, 2019. Analyses were conducted from October 20, 2022, to June 16, 2023.

EXPOSURES: New-user prescriptions for the 7 most frequently filled QT-prolonging medications characterized by the timing of the new prescription relative to acute care encounters, the type of prescribing clinician and pharmacy that dispensed the medication, and concomitant use of selected medications known to interact with the 7 most frequently filled QT-prolonging medications with known TdP risk.

MAIN OUTCOMES AND MEASURES: The main outcomes were the frequencies of the most commonly filled and new-use episodes of QT-prolonging medications; the timing of medication fills relative to acute care events; prescribers and dispensing pharmacy characteristics for new use of medications; and the frequency and types of new-use episodes with concurrent use of potentially interacting medications.

RESULTS: Of 20 761 individuals receiving hemodialysis in 2019 (mean [SD] age, 74 [7] years; 51.1% male), 10 992 (52.9%) filled a study drug prescription. Approximately 80% (from 78.6% for odansetron to 93.9% for escitalopram) of study drug new-use prescriptions occurred outside of an acute care event. Between 36.8% and 61.0% of individual prescriptions originated from general medicine clinicians. Between 16.4% and 26.2% of these prescriptions occurred with the use of another QT-prolonging medication. Most potentially interacting drugs were prescribed by different clinicians (46.3%-65.5%).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, QT-prolonging medications for individuals with dialysis-dependent kidney failure were commonly prescribed by nonnephrology clinicians and from nonacute settings. Prescriptions for potentially interacting medications often originated from different prescribers. Strategies aimed at minimizing high-risk medication-prescribing practices in the population undergoing dialysis are needed.

PMID:38687480 | DOI:10.1001/jamanetworkopen.2024.8732

Transpl Int. 2024 Apr 15;37:12071. doi: 10.3389/ti.2024.12071. eCollection 2024.

ABSTRACT

Kidney transplantation is the best treatment for kidney failure in older patients. However, little is known regarding changes in health-related quality of life (HRQoL) from before to after transplantation and determinants of HRQoL in older kidney transplant recipients (KTR). We studied both, using data of older (≥65 years) patients waitlisted for kidney transplantation and older KTR 1 year after transplantation from the TransplantLines Biobank and Cohort Study. HRQoL was assessed using the SF-36 questionnaire. We included 145 older waitlisted patients (68% male, age 70 ± 4 years) and 115 older KTR at 1 year after transplantation (73% male, age 70 ± 4 years). Both mental (48.5 ± 8.4 versus 51.2 ± 7.7, p = 0.009) and physical (47.4 ± 8.5 versus 52.1 ± 7.2, p < 0.001) HRQoL were higher among included KTR, compared to the waitlisted patients. In paired analyses among 46 patients with HRQoL-data both before and after transplantation, there was a trend towards increased mental HRQoL (49.1 ± 8.4 to 51.6 ± 7.5, p = 0.054), and significantly increased physical HRQoL (48.1 ± 8.0 to 52.4 ± 6.7, p = 0.001) after transplantation. Among all assessed factors, the number of patient-reported immunosuppressive drug-related side effects was most strongly negatively associated with both mental and physical HRQoL. In conclusion, HRQoL is significantly higher among older KTR after kidney transplantation compared to older waitlisted patients.

PMID:38686099 | PMC:PMC11057459 | DOI:10.3389/ti.2024.12071

Arch Iran Med. 2024 Mar 1;27(3):122-126. doi: 10.34172/aim.2024.19.

ABSTRACT

BACKGROUND: Tuberculosis (TB) is one of the oldest and most well-known diseases that has been associated with humans for many years and remains a global health challenge today. Timely diagnosis and proper treatment are crucial for controlling and preventing the spread of the disease. While anti-TB drugs offer many benefits, inadequate monitoring can lead to a range of side effects, including hepatotoxicity, which is a major concern and can cause treatment discontinuation. The aim of this study was to determine the approach to the hepatotoxicity of anti-TB drugs and to investigate potential relationships between demographic factors, underlying medical conditions, and successful retreatment outcomes for hepatotoxicity induced by anti-TB drugs.

METHODS: For this study, we reviewed the medical records of patients who experienced hepatotoxicity due to anti-TB treatment and were admitted to the infectious ward of Imam Khomeini Hospital between April 2015 and February 2019. The data were collected using a questionnaire.

RESULTS: The findings indicated that the female gender, weight loss at the beginning of hospitalization, hepatitis C virus, hepatitis B virus (HBV), heart disease, and high levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) at the beginning of hepatotoxicity are risk factors for failure to the retreatment of hepatotoxicity. There were two different approaches to the anti-TB retreatment regimen. The first approach involved gradually starting the drugs in full dose, while the second approach encompassed starting the drugs in the minimum dose and then increasing to the maximum dose. The results demonstrated no significant difference between the two approaches to managing hepatotoxicity induced by anti-TB drugs.

CONCLUSION: Drug-induced hepatotoxicity is a common occurrence that often results in treatment discontinuation. Understanding the prevalence of this complication and identifying appropriate methods of rechallenge treatment is crucial to reducing complications and mortality rates.

PMID:38685836 | DOI:10.34172/aim.2024.19

Sr Care Pharm. 2024 May 1;39(5):173-177. doi: 10.4140/TCP.n.2024.173.

ABSTRACT

Traditional definitions of polypharmacy may largely not account for the market proliferation of herbal and dietary supplements, cannabis products, or incorporate the new science of pharmacogenomics (PGx). Polypharmacy is encountered by most pharmacists providing patient care in many settings. The "polypharmacist" can assist patients and providers with solving medication-related problems (MRPs) in this new and challenging environment of supplements and cannabis products by utilizing traditional pharmacology and pharmacokinetic principles, including PGx, broadly across many medical disciplines. One may encounter polypharmacy more in the geriatric population, though in an age of supplements and cannabis proliferation, polypharmacy is increasingly being encountered at younger ages. Not only is polypharmacy training at best fragmented in pharmacy curricula, but it may also not account for the above-mentioned products that may use the same metabolic pathways to increase drug interactions and adverse drug reactions (ADRs) regarding prescription medications. Polypharmacy being more formally prioritized in pharmacist training may better prepare pharmacists for commonly encountered polypharmacy and can be a viable model of practice.

PMID:38685622 | DOI:10.4140/TCP.n.2024.173

Sr Care Pharm. 2024 May 1;39(5):193-201. doi: 10.4140/TCP.n.2024.193.

ABSTRACT

Background Patients older than 65 years of age with an anticipated life-expectancy of 12 months or less may have complex medication regimens and an increased risk of adverse drug reactions, and drug-drug interactions. Within the Department of Veterans Affairs, a commonly used medication optimization model is known as the VIONE methodology. Objective This project aimed to pilot implementation of board-certified clinical pharmacist practitioners utilizing the VIONE model within a patient-aligned care team targeting patients 65 years of age and older. Methods The population was identified through the VIONE dashboards. Veteran inclusion criteria included five or more medications, a VIONE risk score of 5 or greater, and CAN scores of greater than 90. The project team reached out via telephone to the patients for a medication regimen review and a 14-day follow-up call. Primary outcomes were quantity of medications discontinued per patient, classes of medications that were discontinued, number and encounter time spent, and cost avoidance over 1 year. Secondary outcomes were VIONE classification of medications, VIONE discontinuation reason, number of recommendations given and accepted by primary provider, and safety analysis. Results There were 53 patients who were successfully contacted via telephone. The top four most discontinued medication classes included 1) vitamins/supplements, 2) ophthalmology medications, 3) gastrointestinal medications, and 4) non-controlled analgesic medications. During the project period the potential cost avoidance over 1 year was $17,716. CONCLUSION: This project demonstrated that usage of VIONE methodology ensures medication optimization with minimal harm and provides significant cost savings in the ambulatory care setting.

PMID:38685620 | DOI:10.4140/TCP.n.2024.193

BMJ Open. 2024 Apr 29;14(4):e081990. doi: 10.1136/bmjopen-2023-081990.

ABSTRACT

OBJECTIVES: Pharmacovigilance databases play a critical role in monitoring drug safety. The duplication of reports in pharmacovigilance databases, however, undermines their data integrity. This scoping review sought to provide a comprehensive understanding of duplication in pharmacovigilance databases worldwide.

DESIGN: A scoping review.

DATA SOURCES: Reviewers comprehensively searched the literature in PubMed, Web of Science, Wiley Online Library, EBSCOhost, Google Scholar and other relevant websites.

ELIGIBILITY CRITERIA: Peer-reviewed publications and grey literature, without language restriction, describing duplication and/or methods relevant to duplication in pharmacovigilance databases from inception to 1 September 2023.

DATA EXTRACTION AND SYNTHESIS: We used the Joanna Briggs Institute guidelines for scoping reviews and conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Two reviewers independently screened titles, abstracts and full texts. One reviewer extracted the data and performed descriptive analysis, which the second reviewer assessed. Disagreements were resolved by discussion and consensus or in consultation with a third reviewer.

RESULTS: We screened 22 745 unique titles and 156 were eligible for full-text review. Of the 156 titles, 58 (47 peer-reviewed; 11 grey literature) fulfilled the inclusion criteria for the scoping review. Included titles addressed the extent (5 papers), prevention strategies (15 papers), causes (32 papers), detection methods (25 papers), management strategies (24 papers) and implications (14 papers) of duplication in pharmacovigilance databases. The papers overlapped, discussing more than one field. Advances in artificial intelligence, particularly natural language processing, hold promise in enhancing the efficiency and precision of deduplication of large and complex pharmacovigilance databases.

CONCLUSION: Duplication in pharmacovigilance databases compromises risk assessment and decision-making, potentially threatening patient safety. Therefore, efficient duplicate prevention, detection and management are essential for more reliable pharmacovigilance data. To minimise duplication, consistent use of worldwide unique identifiers as the key case identifiers is recommended alongside recent advances in artificial intelligence.

PMID:38684275 | DOI:10.1136/bmjopen-2023-081990

Crit Rev Oncog. 2024;29(3):83-90. doi: 10.1615/CritRevOncog.2024051588.

ABSTRACT

The current rapid development of more selective and effective drugs for the treatment of thyroid cancer has open a new era in the treatment of patients with this condition, in the past limited to the possibility of only radioactive iodine for well differentiated tumor and surgery for medullary thyroid carcinoma (MTC). The treatment of advanced medullary thyroid carcinoma has evolved in the last few years and options for patients with advanced disease are now available. Multikinase inhibitors (MKIs) with nonselective RET inhibition like Vandetanib and Cabozantinib were approved for the treatment of MTC, although the efficacy is limited due to the lack of specificity resulting in a higher rate of drug-related adverse events, leading to subsequent dose reductions, or discontinuation, and the development of a resistance mechanism like seen on the RET Val804 gatekeeper mutations. MTC is associated with mutations in the RET protooncogene, and new highly selective RET inhibitors have been developed including Selpercatinib and Pralsetinib, drugs that have demonstrate excellent results in clinical trials, and efficacy even in the presence of gatekeeper mutations. However, despite their efficacy and great tolerability, mechanisms of resistance have been described, such as the RET solvent front mutations. Due to this, the need of constant evolution and drug research is necessary to overcome the emergence of resistance mechanisms.

PMID:38683155 | DOI:10.1615/CritRevOncog.2024051588

Rev Alerg Mex. 2024 Feb 1;71(1):1-7. doi: 10.29262/ram.v71i1.1169.

ABSTRACT

OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients.

METHODS: Analytical, observational, case-control study of patients with ADE. For statistical analysis, the following were calculated: percentages, frequencies, averages; odds ratio, χ2 test and multiple binary logistic regression. Data analysis was carried out with the Statistical Package, for the Social Sciences 23 program.

RESULTS: A 132 patients were registered: 66 cases (26 EM and 40 RAM) and 66 controls; with average age of 35 years (SD 17.41). The prevalence of adverse drug events was 3.6%. The most frequently reported medications: antibiotics and anti-inflammatories. The frequency of adverse events by gender was: 39.3% men and 60.7% women. The services with the greatest patient care: emergencies, surgery; the most frequent route of administration: intravenous (32.3%). The main symptoms: skin. (32.3%) frequent symptoms: cutaneous. Associated symptoms RAM: type A pruritus (OR: 8.5; p = 0.001; IC95%: 0.035-0.393), type B pruritus (OR: 11; p = 0.001; CI95%: 0.021-0.368) urticaria (OR: 19; p = 0.005; IC95%: 0.007-0.412). Risk factors Associated EAM: female (OR: 2.6; p = 0.05; CI95%: 1.33-5.43), history of allergy (OR: 3.4; p = 0.033; CI95%: 1.04-8.40), prolonged hospital stays (OR: 5.4; p = 0.023; IC95%: 3.82-6.74).

CONCLUSIONS: Patient safety is a priority when prescribing any drug, which represents a key point in prevention.

PMID:38683062 | DOI:10.29262/ram.v71i1.1169

Cureus. 2024 Mar 27;16(3):e57030. doi: 10.7759/cureus.57030. eCollection 2024 Mar.

ABSTRACT

Valproic acid (VPA) is utilized in the management of a variety of seizure and mood disorders. A rare side effect of this medication is dose-dependent thrombocytopenia. In this case, we report a patient with a treatment-resistant epilepsy GABRB3 genetic variant phenotype who was admitted for sepsis and found to have significant thrombocytopenia with clinical manifestations of epistaxis and easy bruising, which was found to be due to VPA use rather than secondary to other clinical pathologies. The patient's clinical condition improved with supportive treatment including fluid rehydration. Platelet counts normalized after a transfusion and holding of her valproate. She experienced breakthrough seizures despite the initiation of diazepam. The decision was made to restart VPA per Neurology consult recommendations for better seizure control. She had no breakthrough seizures reported after restarting VPA in the hospital. This case highlights the importance of monitoring antiseizure medication side effects, especially in populations at higher risk due to treatment resistance.

PMID:38681313 | PMC:PMC11046339 | DOI:10.7759/cureus.57030

Indian J Nephrol. 2024 Mar-Apr;34(2):175-177. doi: 10.4103/ijn.ijn_325_22. Epub 2023 Aug 4.

ABSTRACT

Hydroxychloroquine (HCQ) has immunomodulatory and immunosuppressive properties and is used in many rheumatological conditions like systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It is usually a widely used and well-tolerated DMARD (Disease Modifying Anti Rheumatic Drugs). Its most feared toxicities include retinopathy and, rarely, cardiomyopathy. Among its other reported side effects is drug-induced phospholipidosis. Here, we report two cases of HCQ-induced phospholipidosis based on renal biopsy electron microscopy. HCQ-induced phospholipidosis, although uncommon, must be considered as one of the differentials in a patient with persistent proteinuria.

PMID:38681001 | PMC:PMC11044673 | DOI:10.4103/ijn.ijn_325_22

Pharmacoepidemiol Drug Saf. 2024 May;33(5):e5797. doi: 10.1002/pds.5797.

ABSTRACT

PURPOSE: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications.

METHODS: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best-fit trendline based on an exponential function.

RESULTS: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%).

CONCLUSION: A 23-year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance.

PMID:38680101 | DOI:10.1002/pds.5797