ABSTRACT
BACKGROUND: Pulmonary toxicity has been associated with drug use. This is often not recognized in clinical practice, and underestimated. OBJECTIVE: We aimed to establish whether polymorphisms in certain genes corresponding with a metabolic pathway of drug(s) used are associated with pulmonary toxicity in patients with suspected drug-induced interstitial lung disease (DI-ILD). METHODS: This retrospective observational study explored genetic variations in three clinically relevant cytochrome P450 (CYP) iso-enzymes (i.e., CYP2D6, CYP2C9, and CYP2C19) in a group of patients with a fibroticinterstitial lung disease, either non-specific interstitial pneumonia (n = 211) or idiopathic pulmonary fibrosis (n = 256), with a suspected drug-induced origin. RESULTS: Of the 467 patients, 79.0% showed one or more polymorphisms in the tested genes accompanied by the use of drug(s) metabolized by a corresponding affected metabolic pathway (60.0% poor metabolizers and/or using two or more drugs [likely DI-ILD], 37.5% using three or more [highly likely DI-ILD]). Most commonly used drugs were statins (63.1%) with a predominance among men (69.4 vs 47.1%, p < 0.0001). Nitrofurantoin, not metabolized by the tested pathways, was prescribed more frequently among women (51.9 vs 4.5%, p < 0.00001). CONCLUSIONS: In our cohort with suspected DI-ILD, 79% carried one or more genetic variants accompanied by the use of drugs metabolized by a corresponding affected pathway. In 60%, the diagnosis of DI-ILD was likely, whereas in 37.5%, it was highly likely, based on CYP analyses. This study underlines the importance of considering both drug use and genetic make-up as a possible cause, or at least a contributing factor, in the development and/or progression of fibrotic lung diseases. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00267800, registered in 2005.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Male , Humans , Female , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/genetics , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/genetics , Cytochrome P-450 Enzyme System/genetics , Drug-Related Side Effects and Adverse Reactions/complications , Risk AssessmentABSTRACT
Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.
Subject(s)
Acute Kidney Injury , Drug-Related Side Effects and Adverse Reactions , Kidney Failure, Chronic , Humans , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Kidney , Biomarkers , Kidney Failure, Chronic/complications , Risk Factors , Drug-Related Side Effects and Adverse Reactions/complications , CreatinineABSTRACT
RATIONALE: Rhabdomyolysis is a serious complication of status epilepticus (SE) caused by muscle cell damage and can lead to a life-threatening acute kidney injury (AKI). PATIENT CONCERNS: A 35-year-old man with a history of seizures treated with 3 different antiepileptic drugs (carbamazepine, lamotrigine, and levetiracetam) presented with SE. The patient received 5 doses of diazepam to control the SE in another hospital and was transferred to our emergency due to AKI. DIAGNOSES: Laboratory tests corresponded with rhabdomyolysis-induced AKI and disseminated intravascular coagulation. Thereafter, the decrease in renal excretion of both drugs (diazepam and carbamazepine) caused acute liver injury and neurotoxicity. The carbamazepine concentration was 16.39 mcg/mL, which considered in toxic level, despite using the usual dose. INTERVENTIONS: The patient was treated with hydration and sodium bicarbonate, however; severe AKI mandated a hemodialysis session. OUTCOMES: The diuresis started to increase, kidney and liver functions improved, and altered mental status reversed. LESSONS: This case alerts physicians to consider the synergistic drug side effects and interactions, especially when patients present with impaired liver or kidney functions. The reduction in metabolism or excretion of drugs can cause an increase in serum concentrations and induce toxicity, even when the drug intake at the usual dose.
Subject(s)
Acute Kidney Injury , Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Rhabdomyolysis , Status Epilepticus , Male , Humans , Adult , Diazepam/therapeutic use , Anticonvulsants/adverse effects , Status Epilepticus/chemically induced , Status Epilepticus/drug therapy , Status Epilepticus/complications , Carbamazepine/therapeutic use , Rhabdomyolysis/complications , Drug-Related Side Effects and Adverse Reactions/complications , Acute Kidney Injury/etiology , Chemical and Drug Induced Liver Injury/complicationsABSTRACT
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treatments. As experience in the use of immunotherapy increases, more is known about its safety profile and immune-mediated adverse effects. Among them is diabetic ketoacidosis (DKA), a rare but serious fatal complication of treatment. In this paper we describe the cases of three patients who presented with episodes of DKA during treatment with ICIs, two of which manifested with fulminant forms, leading to an acute course with initially normal glycosylated hemoglobin values. In addition, we conducted a review of the literature on DKA associated with ICIs in order to highlight the importance of noticing these potentially fatal complications and promptly establishing appropriate therapy.
Los inhibidores de puntos de control inmune (ICIs) son anticuerpos monoclonales cada vez más utilizados en tratamientos oncológicos. A medida que aumenta la experiencia en el uso de inmunoterapia, se conoce cada vez más su perfil de seguridad y los efectos adversos inmunomediados. Entre ellos se encuentra la cetoacidosis diabética (CAD), complicación infrecuente, grave y potencialmente mortal. En este trabajo describimos los casos de tres pacientes que se presentaron con episodios de CAD durante el tratamiento con ICIs, dos de los cuales manifestaron con formas fulminantes, llevando un curso agudo con valores de hemoglobina glicosilada inicialmente normales. Asimismo, realizamos una revisión de la literatura sobre la CAD asociada a ICIs a fines de resaltar la importancia de advertir estas complicaciones potencialmente fatales e instaurar rápidamente la terapéutica apropiada.
Subject(s)
Diabetes Mellitus , Diabetic Ketoacidosis , Drug-Related Side Effects and Adverse Reactions , Humans , Diabetic Ketoacidosis/chemically induced , Diabetic Ketoacidosis/therapy , Antibodies, Monoclonal , Immunotherapy/adverse effects , Drug-Related Side Effects and Adverse Reactions/complicationsABSTRACT
As a common cause of shoulder pain, rotator cuff tears (RCTs) are difficult to treat clinically because of their unsatisfactory prognosis due to the fatty infiltration caused by muscle-derived stem cells (MDSCs). Previous studies have found that rapamycin (RAPA) can inhibit fatty infiltration. However, systemic administration of RAPA may cause complications such as infection and nausea, while local administration of RAPA may lead to the cytotoxicity of tendon cells, affecting the healing of rotator cuffs. In this study, biocompatible and clinically approved polycaprolactone-polyethylene glycol (PCL-PEG) is formulated into an injectable nanoparticle for the sustained release of RAPA. The results indicate that the RAPA/PCL-PEG nanoparticles (NPs) can efficiently prolong the release of RAPA and significantly reduce the cytotoxicity of tendon cells caused by RAPA. The study of the fatty infiltration model in rats with delayed rotator cuff repair shows that weekly intraarticular injection of RAPA/PCL-PEG NPs can more effectively reduce the fatty infiltration and muscle atrophy of rat rotator cuffs and leads to better mechanical properties and gait improvements than a daily intraarticular injection of RAPA. These findings imply that local injection of RAPA/PCL-PEG NPs in the shoulder joints can be a potential clinical option for RCTs patients with fatty infiltration.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Rotator Cuff Injuries , Humans , Rats , Animals , Rotator Cuff Injuries/drug therapy , Rotator Cuff Injuries/complications , Rotator Cuff Injuries/pathology , Rotator Cuff/pathology , Tendons , Muscular Atrophy/complications , Muscular Atrophy/pathology , Drug-Related Side Effects and Adverse Reactions/complications , Drug-Related Side Effects and Adverse Reactions/pathology , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: The objective of this study was to review the available literature for dexmedetomidine sublingual film use in the treatment of acute agitation associated with schizophrenia and bipolar disorders. DATA SOURCES: A literature search of PubMed (January 2017-March 2023) and EMBASE (January 2017-March 2023) was performed using the terms: Igalmi, dexmedetomidine, schizophrenia, bipolar disorder, and agitation. Additional information sources include ClinicalTrials.gov, scientific posters, and articles identified through review of references from clinical trials publications. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language articles conducted in humans were considered, with a preference for phase 3 clinical trials. Trial analyses and articles discussing pharmacology, pharmacokinetics, efficacy, and safety were also evaluated. DATA SYNTHESIS: Dexmedetomidine sublingual film was evaluated for use in schizophrenia in the SERENITY 1 pivotal trial and for bipolar disorders in the SERENITY 2 pivotal trial. Both studies found treatment of mild to moderate agitation with dexmedetomidine sublingual film 180 and 120 µg to be superior to placebo in reducing the severity of agitation. Treatment effect was seen as early as 20 minutes. Somnolence was the most common adverse effect in both studies. Cardiovascular adverse effects were mild and transient in most cases. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Dexmedetomidine sublingual film is a new and novel treatment for agitation and gives clinicians an alternative to antipsychotic and benzodiazepine use. It has advantageous properties including its noninvasive route of administration, fast absorption, and rapid onset of effect. Cost may limit its use. CONCLUSION: Dexmedetomidine sublingual film provides an alternative approach to treatment of acute agitation in adults with schizophrenia and bipolar disorders based on both mechanism of action and route of administration.
Subject(s)
Antipsychotic Agents , Bipolar Disorder , Dexmedetomidine , Drug-Related Side Effects and Adverse Reactions , Schizophrenia , Adult , Humans , Schizophrenia/complications , Schizophrenia/drug therapy , Bipolar Disorder/complications , Bipolar Disorder/drug therapy , Bipolar Disorder/chemically induced , Dexmedetomidine/adverse effects , Psychomotor Agitation/drug therapy , Psychomotor Agitation/etiology , Antipsychotic Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions/complicationsABSTRACT
Tubulointerstitial nephritis is a common cause of acute renal failure, in two thirds of cases it is associated with drugs (mostly antimicrobials and NSAIDs), in 5-10% of cases it is associated with infections (bacterial/viral/parasitic), in 5-10% of cases it is idiopathic (this is the case of the TINU syndrome characterized by interstitial nephritis and bilateral uveitis, and the anti-glomerular basal membrane antibody syndrome), and finally in 10% of cases it is associated with systemic diseases (sarcoidosis, by Sjogren, LES). The pathogenesis is based on a cell-mediated immune response and in most cases removing the causative agent is the gold standard of therapy. However, a percentage of patients, in a variable range from 30% to 70% of cases, do not fully recover renal function, due to the rapid transformation of the interstitial cell infiltrate into vast areas of fibrosis. Clozapine is a second generation atypical antipsycothic usually used for the treatment of schizophrenia resistant to other types of treatment; it can cause severe adverse effects among which the best known is a severe and potentially fatal neutropenia, furthermore a series of uncommon adverse events are recognized including hepatitis, pancreatitis, vasculitis. Cases of acute interstitial tubular nephritis associated with the use of clozapine have been described in the literature, although this complication is rare. Medical personnel using this drug need to be aware of this potential and serious side effect. We describe the case of a 48-year-old man who developed acute renal failure after initiation of clozapine.
Subject(s)
Acute Kidney Injury , Clozapine , Drug-Related Side Effects and Adverse Reactions , Nephritis, Interstitial , Uveitis , Male , Humans , Middle Aged , Clozapine/adverse effects , Uveitis/chemically induced , Uveitis/complications , Uveitis/drug therapy , Nephritis, Interstitial/chemically induced , Nephritis, Interstitial/complications , Nephritis, Interstitial/pathology , Drug-Related Side Effects and Adverse Reactions/complications , Acute Kidney Injury/etiologyABSTRACT
Neuroleptic malignant syndrome (NMS) is a rare but serious and sometimes fatal complication in patients taking antipsychotic drugs, and its underlying mechanism still remains unclear. The pharmacotherapy for psychotic disorders is complicated and often involves a combination of two or more drugs, including drugs other than antipsychotics. In the present study, we used the Japanese Adverse Drug Event Report (JADER) database to broadly investigate the drugs associated with NMS, following their related pathways, as well as the drug-drug interactions (DDIs) in NMS. All analyses were performed using data from the JADER database from April 2004 to May 2022. Single-drug signals were evaluated using the reporting odds ratio (ROR) and proportional reporting ratio (PRR), and drug pathways were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG). DDIs were evaluated using the Ω shrinkage measure and Chi-square statistics models. All drugs associated with 20 or more NMS cases in the JADER database exhibited signals for NMS, including non-antipsychotics. Pathways associated with the drugs included the dopaminergic or serotonergic synapses related to antipsychotics. DDIs leading to NMS were confirmed for several drug combinations exhibiting single-drug signals. This study confirmed the significant association of various drugs, including non-psychotics, with NMS and suggested that various pathways related to these drugs may be involved in the progression of NMS. In addition, several combinations of these drugs were found to interact (DDI), increasing the risk of NMS, which suggests that appropriate caution should be taken when administering these drugs.
Subject(s)
Antipsychotic Agents , Drug-Related Side Effects and Adverse Reactions , Neuroleptic Malignant Syndrome , Psychotic Disorders , Humans , Antipsychotic Agents/adverse effects , Neuroleptic Malignant Syndrome/etiology , Neuroleptic Malignant Syndrome/drug therapy , Psychotic Disorders/drug therapy , Drug-Related Side Effects and Adverse Reactions/complications , Drug InteractionsABSTRACT
INTRODUCTION: Immune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs). AREAS COVERED: This review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism. EXPERT OPINION: There is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.
Subject(s)
Antineoplastic Agents, Immunological , Drug-Related Side Effects and Adverse Reactions , Endocrine System Diseases , Humans , Immune Checkpoint Inhibitors/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Immunotherapy/adverse effects , Endocrine System , Endocrine System Diseases/chemically induced , Drug-Related Side Effects and Adverse Reactions/complications , Drug-Related Side Effects and Adverse Reactions/drug therapyABSTRACT
In order to replenish iron stores and bring hemoglobin (Hb) levels back to normal, oral iron is the primary treatment option for women with iron deficiency anemia (IDA). This study investigated the efficacy and side effects of daily versus alternate-day, given single doses versus double doses oral iron supplementation for treating IDA. A retrospective cohort study was performed between 2021 and 2022, including 120 patients. Study group were divided into 4 age-sex-matched groups; Group I (nâ =â 30) and Group II (nâ =â 30) which were received ferrous sulphate tablets daily in single or double doses, respectively, containing 60 mg of elemental iron each. Groups III (nâ =â 30) and IV (nâ =â 30) were received a single and double dose on alternate days, respectively. The primary outcome was the mean difference in Hb from baseline at week 4. Gastrointestinal (GI) side effects were accepted as a secondary outcome. The daily single dose and alternate day double dose groups had median Hb changes of 2.3 (2.1) and 2.6 (1.8) g/dL. The differences in Hb between Groups I and II, I and III, and Groups IV and II, IV and III were significant (Pâ <â .001, Pâ =â .001, Pâ <â .001, and Pâ <â .001, respectively). There is no significant difference between groups regarding improving iron parameters such as serum iron, total iron binding capacity, transferrin saturation, and ferritin. The incidence of GI side effects were greater in double doses than in single doses of daily or alternate-day therapies (43.3% and 30% vs 10% and 3.3%). Daily or alternate-day double dose resulted in more side effects but less therapeutic efficacy in women with IDA. To find the best supplementation method, randomized controlled trials with a larger sample of participants, longer study lengths, and various iron doses may be helpful.
Subject(s)
Anemia, Iron-Deficiency , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Iron , Anemia, Iron-Deficiency/etiology , Retrospective Studies , Ferritins , Administration, Oral , Drug-Related Side Effects and Adverse Reactions/complications , Hemoglobins/metabolismABSTRACT
INTRODUCTION: Nephrotoxic medication (NTM) is one of the common causes of acute kidney injury (AKI) in critically ill infants. Current knowledge about the long-term effects of NTM exposure and associated AKI during the neonatal period and early infancy is limited. Hence, we aimed to explore the risk of chronic kidney disease (CKD) after NTM-AKI in this age group. METHODS: We performed a cross-sectional study including children 2-7 years of age, who had a history of high NTM exposure during NICU hospitalization. Cases and controls were defined as children who developed AKI and who did not develop AKI after NTM exposure, respectively. The primary outcome of interest was to explore the prevalence of composite CKD. In addition, we explored differences in urinary biomarker kidney injury molecule-1 (KIM-1) between the groups. RESULTS: We enrolled 48 children, 18 cases and 30 controls in which 25/48 (52%) had at least one finding of CKD. The composite CKD outcome tended to be higher in cases vs controls (61.1% vs. 46.6%, odds ratio = 1.79 (95% confidence interval 0.54-5.8)); however, this was not statistically significant. Median urinary KIM-1 value trended higher in controls, 0.367(0.23-0.59) vs. 0.20 (IQR 0.11-0.47), which was not statistically significant. CONCLUSION: In this study, 52% of children exposed to NTM had at least one marker of CKD at a median age of 5 years. Multicenter, large prospective studies are needed to improve our understanding of the natural course of NTM-AKI and to determine risk factors and strategies to reduce CKD in this high-risk population.
Subject(s)
Acute Kidney Injury , Drug-Related Side Effects and Adverse Reactions , Renal Insufficiency, Chronic , Infant, Newborn , Humans , Infant , Child , Child, Preschool , Cross-Sectional Studies , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Acute Kidney Injury/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/complications , Kidney , Prospective Studies , Risk Factors , Drug-Related Side Effects and Adverse Reactions/complications , Retrospective StudiesABSTRACT
INTRODUCTION: Rasagiline is indicated for treating idiopathic Parkinson's disease (PD) as monotherapy and adjunct therapy to levodopa in patients. OBJECTIVES: To assess the post-marketing safety and tolerability of rasagiline in Chinese PD patients, as well as its effectiveness in improving motor symptoms. METHODS: This prospective, non-interventional, multicenter, cohort study included PD patients administered rasagiline monotherapy or adjunct therapy to levodopa. The primary outcome was the incidence of adverse drug reactions (ADRs) according to MedDRA® (version 22.0), and the secondary outcomes were the Parkinson's Disease Unified Rating Scale (UPDRS) part III, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Global-Improvement (CGI-I), assessed at Weeks 4, 12, and 24. RESULTS: In total, 734 patients, 95 in the monotherapy subgroup and 639 in the adjunct therapy subgroup, were included in the safety population. The incidence rates of all ADRs were comparable between the monotherapy (15.8%) and adjunct therapy (13.6%) subgroups. The most common ADRs by system organ class were nervous system disorders (5.6%), gastrointestinal disorders (3.3%), psychiatric disorders (1.8%), vascular disorders (1.2%), and general disorders and administration site conditions (1.1%). Five (0.7%) participants experienced 5 serious ADRs. Improvements in UPDRS part III, CGI-S and CGI-I at Weeks 4, 12 and 24 from baseline were observed. CONCLUSIONS: Safety data in this study indicated no extra safety concerns. Rasagiline is generally safe and well tolerated in Chinese PD patients. The safety profile and tolerability were in line with the established safety profile. Moreover, rasagiline reduced the severity of PD motor symptoms, confirming findings by previous clinical trials.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Parkinson Disease , Humans , Parkinson Disease/drug therapy , Levodopa/adverse effects , Cohort Studies , East Asian People , Prospective Studies , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/complications , Treatment OutcomeABSTRACT
Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Graves Ophthalmopathy , Leg Dermatoses , Myxedema , Ototoxicity , Male , Humans , Aged , Leg Dermatoses/complications , Ototoxicity/complications , Graves Ophthalmopathy/complications , Drug-Related Side Effects and Adverse Reactions/complicationsABSTRACT
Background & objectives: The information available regarding delayed adverse donor reactions (D-ADRs) is limited. Proactive follow up of donors for delayed reactions is not done routinely. This study was undertaken to analyze frequency and type of D-ADRs in whole blood donors as also the contributory factors. Methods: In this prospective observational study, all eligible whole blood donors were contacted telephonically twice (24 h and 2 wks after donation) and asked about general health and ADR specific questions. The International Society of Blood Transfusion standard guidelines were used to categorize ADRs. Results: The ADR data of 3514 donors were analyzed in the study. D-ADRs were more common as compared to immediate delayed adverse donor reactions (I-ADRs) (13.7 vs. 2.9%, P<0.001). The most common D-ADRs were bruises (4.98%), fatigue or generalized weakness (4.24%) and sore arms (2.25%). D-ADRs were more common in first time donors as compared to the repeat blood donors (16.1 vs. 12.5%, P=0.002). Females were more prone to D-ADRs (17 vs. 13.6%). Localized D-ADRs were more frequent as compared to systemic D-ADRs (P<0.001). Repeat donors had a lower incidence of systemic D-ADRs (4.11% vs. 7.37%, P<0.001). Interpretation & conclusions: D-ADRs were more common than I-ADRs with a different profile. First time, female and young donors were more prone to D-ADRs. These categories need special care at the time of blood donation. Active follow up of blood donors should be done from time to time to strengthen donor safety.
Subject(s)
Blood Donors , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Watchful Waiting , Drug-Related Side Effects and Adverse Reactions/complications , Pain , Prospective StudiesABSTRACT
Oral mucositis is a common side effect of cancer treatment, and in particular of treatment with the mTORC1 inhibitor everolimus. Current treatment methods are not efficient enough and a better understanding of the causes and mechanisms behind oral mucositis is necessary to find potential therapeutic targets. Here, we treated an organotypic 3D oral mucosal tissue model consisting of human keratinocytes grown on top of human fibroblasts with a high or low dose of everolimus for 40 or 60 h and investigated (1) the effect of everolimus on microscopic sections of the 3D cell culture for evidence of morphologic changes and (2) changes in the transcriptome by high throughput RNA-Seq analysis. We show that the most affected pathways are cornification, cytokine expression, glycolysis, and cell proliferation and we provide further details. This study provides a good resource towards a better understanding of the development of oral mucositis. It gives a detailed overview of the different molecular pathways that are involved in mucositis. This in turn provides information about potential therapeutic targets, which is an important step towards preventing or managing this common side effect of cancer treatment.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Mucositis , Stomatitis , Humans , Everolimus/pharmacology , Transcriptome , Stomatitis/etiology , Mouth Mucosa , Mucositis/chemically induced , Drug-Related Side Effects and Adverse Reactions/complications , Cell Culture Techniques, Three DimensionalABSTRACT
Oral mucositis (OM) is a common side effect in patients undergoing chemotherapy (CT), especially in children due to their rapid epithelial mitotic rate. It has been associated with a significant reduction in life quality since it leads to pain, an inadequate intake of nutrients, an increased risk of opportunistic infections, and interruptions of CT. Photobiomodulation (PMB) with low-level laser therapy (LLLT) has shown faster healing, reduction in pain, and the reduced use of analgesic compared to placebo groups. The purpose of this review is to analyze and compare the existing clinical trials and identify their shortcomings in hope to make future research easier. Using MeSH terms and keywords, the Embase, Medline, and PubMed databases we searched for the period of the last 5 years. We identified a total of 15 clinical trials, with a total of 929 pediatric patients analyzed in this review. We compared different light sources and other laser technique characteristics used in clinical trials such as wavelength, energy and power density, spot size, irradiation time, PBM protocol, and OM evaluation. The main findings show inconsistent laser parameter quotations, differences in the PBM protocol along with a laser application technique, and a lack of clinical trials. Based on that, more studies with a high methodological quality should be conducted in order to provide a unified PBM protocol suitable for the pediatric population.
Subject(s)
Antineoplastic Agents , Drug-Related Side Effects and Adverse Reactions , Low-Level Light Therapy , Stomatitis , Humans , Child , Stomatitis/drug therapy , Drug-Related Side Effects and Adverse Reactions/complications , Low-Level Light Therapy/methods , Quality of Life , Antineoplastic Agents/adverse effectsABSTRACT
BACKGROUND AND OBJECTIVE: Evidence highlights the allergenic potential of PEGylated drugs because of the production of anti-polyethylene glycol immunoglobulins. We investigated the risk of hypersensitivity reactions of PEGylated drugs using the Italian spontaneous adverse drug reaction reporting system database. METHODS: We selected adverse drug reaction reports attributed to medicinal products containing PEGylated active substances and/or PEGylated liposomes from the Italian Spontaneous Reporting System in the period between its inception and March 2021. As comparators, we extracted adverse drug reaction reports of medicinal products containing the same non-PEGylated active substances and/or non-PEGylated liposomes (or compounds belonging to the same mechanistic class). A descriptive analysis of reports of hypersensitivity reactions was performed. Reporting rates and time to onset of hypersensitivity reactions were also calculated in the period between January 2009 and March 2021. As a measure of disproportionality, we calculated the reporting odds ratio. RESULTS: Overall, 3865 adverse drug reaction reports were related to PEGylated medicinal products and 11,961 to their non-PEGylated comparators. Around two-thirds of patients were female and reports mostly concerned patients aged between 46 and 64 years. The frequency of hypersensitivity reactions reporting was higher among PEGylated versus non-PEGylated medicinal products (11.7% vs 9.4%, p < 0.0001). The hypersensitivity reaction reporting rates were higher for PEGylated medicinal products versus non-PEGylated medicinal products, with reporting rate ratios that ranged from 1.4 (95% confidence interval 0.8-2.5) for pegfilgrastim versus filgrastim to 20.0 (95% confidence interval 2.8-143.5) for peginterferon alpha-2a versus interferon alpha-2a. The median time to onset of hypersensitivity reactions was 10 days (interquartile range: 0-61) for PEGylated medicinal products, and 36 days (interquartile range: 3-216) for non-PEGylated comparators. Statistically significant reporting odds ratios were observed when comparing the reporting of hypersensitivity reactions for PEGylated versus non-PEGylated medicinal products (reporting odds ratio: 1.3; 95% confidence interval 1.1-1.4). However, when using all other drugs as comparators, the disproportionality analysis showed no association with hypersensitivity reactions for PEGylated nor non-PEGylated medicinal products, thus suggesting that many other triggers of drug-induced hypersensitivity reactions play a major role. CONCLUSIONS: The findings of this analysis of the Italian spontaneous adverse drug reaction database suggest a potential involvement for PEGylation in triggering drug-related hypersensitivity reactions, especially clinically relevant reactions. However, when comparing both PEGylated and non-PEGylated drugs under study to all other drugs no disproportionate reporting of hypersensitivity reactions was observed, probably due to a masking effect owing to the presence in the same database of other medicinal products increasing the threshold required to highlight a safety signal when the entire database is used as a reference.
Subject(s)
Drug Hypersensitivity , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Middle Aged , Male , Adverse Drug Reaction Reporting Systems , Liposomes , Drug Hypersensitivity/epidemiology , Drug Hypersensitivity/etiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/complications , Italy/epidemiology , Databases, FactualABSTRACT
Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2â¯mg (0.04â¯mg/kg body weight, BW) administered over 5â¯min. For serotonin syndrome an initial dose of 12â¯mg cyproheptadine followed by 2â¯mg every 2â¯h is recommended (maximum 32â¯mg/day or 0.5â¯mg/kgBW day-1) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120â¯mg dantrolene (1-2.5â¯mg/kgBW maximum 10â¯mg/kgBW day-1) is the recommended treatment.
Subject(s)
Anticholinergic Syndrome , Antipsychotic Agents , Drug-Related Side Effects and Adverse Reactions , Neuroleptic Malignant Syndrome , Serotonin Syndrome , Humans , Neuroleptic Malignant Syndrome/diagnosis , Antipsychotic Agents/adverse effects , Serotonin Syndrome/chemically induced , Diagnosis, Differential , Cholinergic Antagonists/adverse effects , Anticholinergic Syndrome/diagnosis , Consciousness , Drug-Related Side Effects and Adverse Reactions/complicationsABSTRACT
We aimed to determine whether knee OA is associated with CVD risk and all-cause death and to evaluate whether the association differs by exercise behavior. We used Korea National Health Insurance Service (KNHIS) database and included 201,466 participants (7572 subjects diagnosed with knee OA) who underwent health screening between 2009 and 2015. Those who had been diagnosed with knee OA or CVD before the index year were excluded. Cox proportional hazard models were used after adjusting for sociodemographic and CVD risk factors to evaluate the association between knee OA and CVD risk and all-cause death. Stratification analysis was further performed to determine the effect of exercise behavior on this relationship. During a median follow-up of 7.06 ± 2.24 years, 8743 CVD (2510 MI and 6553 stroke) cases developed. Individuals with knee OA had increased risks of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.15-1.38], myocardial infarction (MI) (HR 1.20, 95% CI 1.00-1.44), and stroke (HR 1.29, 95% CI 1.16-1.43) compared with those without knee OA. Those with knee OA who did not exercise had an increased risk of CVD (HR 1.25, 95% CI 1.11-1.40), whereas no significant increased CVD risk was observed in those with knee OA who exercised at least once a week (HR 1.11, 95% CI 0.96-1.28). There was no association between knee osteoarthritis and all-cause death. Knee OA was independently associated with an increased risk of CVD. Lack of exercise might have a synergistic adverse effect on the association between knee OA and CVD.
Subject(s)
Cardiovascular Diseases , Drug-Related Side Effects and Adverse Reactions , Myocardial Infarction , Osteoarthritis, Knee , Stroke , Humans , Cardiovascular Diseases/etiology , Cardiovascular Diseases/complications , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/epidemiology , Myocardial Infarction/etiology , Myocardial Infarction/complications , Risk Factors , Stroke/etiology , Stroke/complications , Drug-Related Side Effects and Adverse Reactions/complications , Iatrogenic DiseaseABSTRACT
BACKGROUND: Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI. METHODS: We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis). RESULTS: Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR<90 vs. eGFR≥90 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered. CONCLUSIONS: This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity.