Adverse Events and Outcomes of High-volume Plasma Exchange in 50 Acute Liver Failure Patients: A Monocentric Retrospective Real-world Study.

Background and aims: Acute liver failure (ALF) is a condition that mostly requires Intensive Care Unit (ICU) admission and sometimes necessitates emergency liver transplantation. High-volume plasma exchange (HVPE) may improve transplant-free survival (TFS) in ALF. Our study assessed complications of HVPE therapy and outcome in ALF patients. Methods: We conducted a single-center retrospective study of all patients admitted to the ICU for ALF and who underwent HVPE between June 2016 and June 2021. The plasmapheresis technique used was centrifugation, and the volume exchanged was calculated as 15% of the ideal body weight. Dedicated staff prospectively collected clinical adverse effects, while biological data were retrospectively collected. The primary outcome was the rate of severe adverse effects (SAE, defined as severe manifestations of hypotension, allergy, metabolic disturbances or other life-threatening event) that occurred during HVPE sessions. Factors influencing day-21 TFS were also studied. Results: One hundred twenty sessions were performed in 50 patients. The main etiology for ALF was paracetamol (52% of the patients). During the session, hemoglobin, platelet, transaminases, ammonia and bilirubin decreased, coagulation factors increased, and creatinine and lactate remained unchanged. At least one SAE was reported for 32 out of 120 sessions (26.7% [19%-35.5%], mostly severe alkalosis [24/117], hypotension [4/120] and hypocalcemia [4/119]). Arterial pH ≤ 7.43 following HVPE and paracetamol etiology were negatively and positively associated with day-21 TFS, respectively. Conclusion: Severe adverse effects were frequent during HVPE performed for ALF, mainly severe alkalosis, hypotension and hypocalcemia. Post-HVPE, pH and paracetamol etiology were prognosis markers.

Efficacy of Rituximab Versus Cyclophosphamide and Mycophenolate for the Treatment of Interstitial Lung Disease in Systemic Sclerosis: A Systematic Review.

Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc), contributing to significant morbidity and mortality in affected individuals. The optimal treatment approach for SSc-associated ILD remains uncertain, with rituximab, cyclophosphamide, and mycophenolate among potential therapeutic options. This systematic review aims to evaluate and synthesize the existing evidence on the efficacy of rituximab compared to cyclophosphamide and mycophenolate for the treatment of ILD in patients with systemic sclerosis. A comprehensive search of the following electronic databases, PubMed, Science Direct, Google Scholar, and Cochrane Library, has been conducted to identify relevant studies, including randomized controlled trials, systematic review and meta-analysis, prospective cohort studies, and retrospective cohort studies. Data on study characteristics, participant demographics, interventions, outcomes, and key findings have been extracted and synthesized. The risk of bias in the included studies has been assessed using appropriate tools such as the Cochrane Bias assessment tool for randomized controlled trials, the New Castle Ottawa tool for cohort studies, and the AMSTAR checklist for systematic reviews and meta-analysis. The research team ultimately selected 15 high-quality studies for review. Rituximab demonstrated similar efficacy to cyclophosphamide and mycophenolate in improving lung function (forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO)), with fewer severe adverse events. Cyclophosphamide, while effective, had higher toxicity, leading to more frequent adverse events such as leukopenia and infections. Mycophenolate showed comparable efficacy to cyclophosphamide but with fewer side effects, making it a well-tolerated alternative. The findings of this systematic review will provide valuable insights into the comparative efficacy of rituximab, cyclophosphamide, and mycophenolate in the management of ILD in systemic sclerosis, informing clinical decision-making and guiding future research in this area.

Psychometric characteristics of the Spanish version of the HIV Symptom Index.

BACKGROUND: The aim of this study was to determine the psychometric properties of the Spanish-language version of the HIV-Symptom Index (HIV-SI) questionnaire in Spanish patients undergoing antiretroviral therapy. METHODS: Between 2014 and 2016, an observational, multicenter, prospective cohort study was conducted in seventeen Spanish hospitals to validate HIV-SI questionnaire in terms of: construct validity (confirmatory factor analysis), internal consistency (Cronbach's alpha), convergent validity (Pearson's correlation coefficient) and Known-group validity. In addition, a sensitivity to change analysis was also performed. RESULTS: A total of 232 patients were included in the study. They had a mean age of 46.17 (SD9.82) and were 75% male. The median overall score for the HIV-SI was 10 (IQR 4- 19.5) and the most common symptoms reported were feelings of nervousness or anxiety, fatigue or energy loss, feeling sad or depressed, stomach pain or bloating, and difficulty sleeping. In the current study, the Spanish HIV-SI questionnaire showed a high internal consistency (α = 0.89) and adequate construct validity (CFI and TLI > 0.90). When contrasted with the MOS-HIV questionnaire, an inverse correlation was found. It showed a good association with the mental (r=-0.61; P < 0.0001) and physical score (r=-0.60; P < 0.0001). In a multivariate analysis, the age of the patient, female condition, hepatitis C coinfection, concomitant treatment and non-adherence resulted in a higher HIV-SI score. CONCLUSIONS: Our study has shown that the Spanish HIV-SI is a valid and reliable self-administered PROM for routine measurement of patient- reported symptoms among Spanish patients on antiretroviral treatment.

Respiratory adverse effects in patients treated with immune checkpoint inhibitors in combination with radiotherapy: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy. METHODS: We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio. RESULTS: Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1-5 cough, 0.176 (95%CI: 0.113-0.274, I2 = 92.36%); grades 1-5 pneumonitis, 0.118 (95%CI: 0.067-0.198, I2 = 88.64%); grades 1-5 upper respiratory tract infection, 0.064 (95%CI: 0.049-0.080, I2 = 0.98%); grades 3-5 cough, 0.050 (95%CI: 0.012-0.204, I2 = 8.90%); grades 3-5 pneumonitis, 0.052 (95%CI: 0.031-0.078, I2 = 83.86%); grades 3-5 upper respiratory tract infection, 0.040 (95%CI: 0.007-0.249, I2 = 45.31%). CONCLUSIONS: Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.

Use of the Abrysvo Vaccine in Pregnancy to Prevent Respiratory Syncytial Virus in Infants: A Review.

The FDA's approval of Pfizer's new respiratory syncytial virus (RSV) prefusion (preF) vaccine, Abrysvo, marks a critical milestone in infant health and well-being by preventing lower respiratory tract infections in the most vulnerable. The vaccine has been approved for administration to pregnant women at 32 to 36 weeks of gestation and elderly people over 60. This review explores the Abrysvo vaccine, detailing its mechanism, efficacy, safety, and adverse events. It aims to inform healthcare providers about this vital method for safeguarding infant respiratory health through maternal immunization.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

BACKGROUND: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. METHODS: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. RESULTS: The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

Tobacco and Nicotine Products Adverse Health Events: Findings From the FDA Safety Reporting Portal.

Introduction: The FDA oversees regulatory aspects of all U.S. tobacco products. Understanding the impact of emerging health trends and incidents associated with various tobacco and nicotine products is vital for public health. This study utilizes the FDA's Tobacco Product Problem Reports (TPPRs) to characterize and track adverse health events (AHEs) associated with tobacco and nicotine products over time, considering the impact of EVALI and the COVID-19 pandemic. Methods: FDA TPPRs from 2017-2022 provided information on AHEs related to various tobacco products. After data cleaning, 839 reports were categorized by two independent coders based on affected health category, frequency of AHEs reports, and proportion of AHEs per each health category. Additionally, variations in AHEs over time were assessed, considering major health events like EVALI and the COVID-19 pandemic. Results: Among the 839 reports, electronic cigarettes (e-cigarettes) were the primary product of concern, comprising 90.6% (n = 760) of all reports, surpassing traditional cigarettes (5.1%; n = 43) and other products. Notably, 45.6% of reports (n = 383) identified the neurological system as the most frequently mentioned health category, each reporting at least one AHE. This was followed by the respiratory (39.1%; n = 328) and digestive (10.7%; n = 90) systems. Among all reported AHEs, respiratory system issues were most frequent (25.9%; n = 512), closely followed by neurological (25.2%; n = 499) and digestive (6.6%; n = 131) concerns. Most reports occurred in 2019 (65.7%; n = 551), coinciding with the EVALI outbreak, with a subsequent decline post-Q3 2019, highlighting the potential impact of specific health crises on reporting trends. Conclusion: E-cigarettes dominated adverse health reports, particularly affecting the neurological and respiratory systems, with a peak in 2019. Our findings provide insights to regulatory entities and future research, enhancing understanding of AHEs in lesser-explored bodily systems, such as the neurological and digestive systems. This study emphasizes the need for ongoing and improved surveillance of emerging tobacco products to protect public health.

Trends in adverse effects of medical treatment in Paediatric populations in the United States: A global burden of disease study, 2000-2019.

BACKGROUND: Adverse effects of medical treatment (AEMT) pose significant risks to paediatric patients. However, the mortality trends associated with AEMT in this population have been unclear. OBJECTIVE: We aimed to clarify the trends in the incidence, disability-adjusted life years (DALYs) and mortality rates of AEMT for children in the US from 2000 to 2019. METHODS: Data were retrieved from the Global Burden of Disease study 2019. We estimated age-standardized incidence, DALYs and mortality rates of paediatric AEMT per 100,000 children in the US using a Bayesian meta-regression model. We also analysed incidence, DALYs and mortality in different age groups, and employed Joinpoint regression models to assess the age- and sex-specific trends. RESULTS: The number of deaths due to AEMT in children, the number of cases, and DALYs were 105.1, 551,076 and 145,555 in 2019, decreased by 37.5%, 6% and 28% from those in 2000, respectively. Age-standardized mortality rates decreased across all age groups, while the incidence increased across all age groups with an average annual percentage change (AAPC) of 2.2% in those children <1 year and 4.5% in 5-9 years of age. The increases in DALYs over time was higher in children aged 1-4 years (AAPC: 0.51, 95% CI: 0.47, 0.62) and 5-9 years (AAPC: 0.33, 95% CI: 0.15, 0.50), with the 1-4 year age group being the highest. CONCLUSION: The study reveals declining AEMT mortality but rising incidence and DALYs, emphasizing a disproportionate burden in <1, 1-4 and 5-9 years. To develop effective mitigation strategies, future research is warranted to identify the causes of increased AEMT in children, especially young males.

A review of the scientific literature on experimental toxicity studies of COVID-19 vaccines, with special attention to publications in toxicology journals.

Since the reports of the first cases of COVID-19, in less than 5 years, a huge number of documents regarding that disease and the coronavirus (SARS-CoV-2), responsible for the infection, have been published. The tremendous number of scientific documents covers many topics on different issues directly related to COVID-19/SARS-CoV-2. The number of articles-including reviews-reporting adverse/side effects of the approved COVID-19 vaccines is considerable. A wide range of adverse/side effects have been reported in humans after COVID-19 vaccination: thrombotic events/thrombocytopenia, myocarditis/pericarditis, cutaneous reactions, immune-mediated effects, psychiatric adverse events, systemic lupus erythematosus, reproductive toxicity, and other miscellaneous adverse effects. In contrast, information on nonclinical studies conducted to assess the potential toxicity/adverse effects of the COVID-19 vaccines in laboratory animals, is comparatively very scarce. The present review was aimed at revising the scientific literature regarding the studies in laboratory animals on the toxic/adverse effects of COVID-19 vaccines. In addition, the investigations reported in those specific toxicology journals with the highest impact factors have been examined one by one. The results of the present review indicate that most nonclinical/experimental studies on the adverse/toxic effects of the COVID-19 vaccines and/or potential candidates showed-in general terms-a good safety profile. Only in some animal studies were certain adverse effects found. However, a rather surprising result has been the limited number of available (in the databases PubMed and Scopus) nonclinical studies performed by the companies that have been the largest manufacturers of mRNA vaccines in the world. It is assumed that these studies have been conducted. However, they have not been published in scientific journals, which does not allow the judgment of the international scientific community, including toxicologists.

The direct targets of metformin in diabetes and beyond.

Metformin, an oral antihyperglycemic drug that has been in use for over 60 years, remains a first-line therapy for type 2 diabetes (T2D). Numerous studies have suggested that metformin promotes health benefits beyond T2D management, including weight loss, cancer prevention and treatment, and anti-aging, through several proposed mechanistic targets. Here we discuss the established effects of metformin and the progress made in identifying its direct targets. Additionally, we emphasize the importance of elucidating the structural bases of the drug and its direct targets. Ultimately, this review aims to highlight the current state of knowledge regarding metformin and its related emerging discoveries, while also outlining critical future research directions.

Comprehensive understanding of the adverse effects associated with temozolomide: a disproportionate analysis based on the FAERS database.

Background: Temozolomide, which is the standard drug for glioma treatment, has several Adverse events (AEs) in the treatment of gliomas and other tumors that are not yet fully understood. This is due to the pharmacological nature of the alkylating agent. A significant proportion of these effects have not been systematically documented or reported. Methods: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2023. Four algorithms were used for disproportionate analysis, with the objective of assessing the association between temozolomide and related adverse events. Results: In this study, 20,079,906 case reports were collected from the FAERS database, of which 15,152 adverse events related to temozolomide were reported. A total of 352 preferred terms (PTs) and 24 system organ classes (SOCs) that were significantly disproportionally related to the four algorithms were included. The SOCs included blood and lymphatic system disorders (χ2 = 18,220.09, n = 4,325); skin and subcutaneous tissue disorders (χ2 = 408.06, n = 1,347); investigations (χ2 = 639.44, n = 3,925); musculoskeletal and connective tissue disorders (χ2 = 1,317.29, n = 588); and psychiatric disorders (χ2 = 1,098.47, n = 877). PT levels were screened for adverse drug reaction signals consistent with drug inserts, such as anemia, thrombocytopenia, liver function abnormalities, nausea and vomiting, as well as rarely reported adverse drug reactions, such as aplastic anemia, myelodysplastic syndromes, electrolyte disorders, cerebral edema, and high-frequency mutations. Conclusion: The results of our investigation demonstrated both adverse effects that had been reported and a multitude of unreported adverse effects that were serious in nature and lacked a clear cause. These novel findings suggest that more attention should be given to the clinical conditions of patients after treatment to provide a more comprehensive perspective and understanding for further clarifying the safety of temozolomide.

Low LDL-C: Is It all Good News?

PURPOSE OF REVIEW: This review presents the risks and benefits of very low LDL cholesterol and the safety of using lipid-lowering therapy to achieve these levels. RECENT FINDINGS: A growing body of literature suggests that lower LDL cholesterol levels are associated with a reduced risk of cardiovascular disease. Further, achieving these levels with pharmaceuticals is remarkably safe. Although statins may slightly increase the risk of diabetes mellitus and hemorrhagic stroke, the benefits outweigh the risks. While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals.

Mostly harmless? Clinical practice guidelines need further consideration of psychotherapy adverse effects.

The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines on mood disorders recommend psychotherapy as foundational care for patients with acute depression with minimal discussion of any potential adverse effects. Randomised controlled trial evidence on psychotherapy adverse effects is limited. This is problematic because clinicians must balance the benefits of treatment against the harms, and clinical decisions become skewed without data on adverse effects. We suggest that clinical practice guidelines should be more guarded about recommending psychotherapy and add consensus statements on adverse effects for informed consent and clinical decision-making.

Parasomnias and sleep-related movement disorders induced by drugs in the adult population: a review about iatrogenic medication effects.

Parasomnias and sleep-related movement disorders (SRMD) are major causes of sleep disorders and may be drug induced. The objective of this study was to conduct a systematic review of the literature to examine the association between drug use and the occurrence of parasomnias and SRMD. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting systematic reviews, we searched PubMed databases between January 2020 and June 2023. The searches retrieved 937 records, of which 174 publications were selected for full-text screening and 73 drugs were identified. The most common drug-induced parasomnias were nightmares and rapid eye movement (REM) sleep behaviour disorders and sleepwalking. In terms of drug-induced SRMD, restless legs syndrome, periodic limb movement disorders (PLMD), and sleep-related bruxism were most frequent. Medications that inhibit noradrenergic, serotonergic, or orexin transmission could induce REM sleep (e.g., nightmares). Regarding sleepwalking, dysregulation of serotoninergic neurone activity is implicated. Antipsychotics are mentioned, as well as medications involved in the gamma-aminobutyric acid (GABA) pathway. A mechanism of desensitisation-autoregulation of GABA receptors on serotoninergic neurones is a hypothesis. SRMD and PLMD could involve medications disrupting the dopamine pathway (e.g., antipsychotics or opioids). Opioids would act on mu receptors and increase dopamine release. The role of adenosine and iron is also hypothesised. Regarding bruxism, the hypotheses raised involve dysregulation of mesocortical pathway or a downregulation of nigrostriatal pathway, related to medications involving dopamine or serotonin. Parasomnias are rarely identified in drug product labels, likely due to the recent classification of their diagnoses. An analysis of pharmacovigilance data could be valuable to supplement existing literature data.