Drug-induced Adverse Events

Combined application of dupilumab and mite allergen-specific immunotherapy in children with moderate to severe atopic dermatitis

Tue, 2023-03-14 06:00

Allergol Immunopathol (Madr). 2023 Mar 1;51(2):184-190. doi: 10.15586/aei.v51i2.778. eCollection 2023.

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that manifests in skin dryness, severe itching, and eczema, and can significantly impact a patient's quality of life. Current treatment regimens do not prevent the recurrence of the disease and are associated with adverse effects. Here, we report two cases of moderate-to-severe AD in children that were treated with dupilumab, a dual inhibitor of IL-4 and IL-13 signaling, in combination with mite allergen-specific immunotherapy.

CASE SUMMARY: Both patients presented with the diagnosis of AD that was not adequately controlled by the conventional treatment regimen, including topical corticosteroids (TCS), topical calcineurin inhibitors, emollients, and the traditional Chinese medicine treatments. In both patients, AD-associated skin irritation impacted the quality of life, disturbed sleep patterns, and caused stress and anxiety.Patients received treatment with dupilumab and mite allergen-specific immunotherapy in addition to the baseline treatment regimen of external glucocorticoids (TCS) and oral antihistamines. Nine months after beginning of treatment, clinical symptoms, signs, medication scores, and evaluation scale scores of both children significantly improved, and the treatment was associated with an overall good tolerance.

CONCLUSION: A combination of dupilumab and mite allergen-specific immunotherapy in addition to the standard anti-AD treatment improves clinical symptoms and is not associated with increased incidence of adverse effects.

PMID:36916105 | DOI:10.15586/aei.v51i2.778

Categories: Literature Watch

Adverse drug reactions affecting treatment adherence in first-line treatment of asthma: An observational study

Tue, 2023-03-14 06:00

Allergol Immunopathol (Madr). 2023 Mar 1;51(2):11-16. doi: 10.15586/aei.v51i2.774. eCollection 2023.

ABSTRACT

BACKGROUND: Asthma is the most common chronic lung disease among children. International guidelines recommend inhaled corticosteroids (ICS) as the first-line daily controller therapy for children with asthma and leukotriene receptor antagonists (LTRA) as the second alternative therapy. Adherence to treatment is the most significant component to optimize the benefits of therapy in asthma.

OBJECTIVE: This study aims to investigate the frequency of drug discontinuation due to adverse drug reactions (ADRs) that affect adherence to treatment in children with asthma or asthma and allergic rhinitis using LTRA or ICS as monotherapy.

METHODS: The subjects aged 4-18 years with asthma or asthma and allergic rhinitis and using montelukast or ICS as monotherapy were included in the study. They were evaluated in terms of ADRs affecting adherence to treatment in the first and third months of treatment.

RESULTS: A total of 468 cases, 356 of whom received montelukast monotherapy and 112 of whom received ICS treatment, with a mean age of 9.10 ± 3.08 (4-17) years, were included in the study. Males constituted 65.6% of the total cases (n = 307). In the first month of follow-up of the cases, it was observed that 4.8% (n = 17) of the patients in the montelukast group could not continue the treatment due to ADR. It was determined that the drug discontinuation rate in the montelukast group in the first month was significantly higher than in the ICS group (P = 0.016), and the risk of drug discontinuation due to ADR in the montelukast group was 1.333 (95% CI, 1.26-1.40) times higher.

CONCLUSIONS: As a result, it was observed that the drug was discontinued due to ADR at a higher rate in children with asthma who received montelukast monotherapy compared to those who received ICS monotherapy.

PMID:36916083 | DOI:10.15586/aei.v51i2.774

Categories: Literature Watch

Immune Checkpoint Inhibitors in Breast Cancer: A Narrative Review

Tue, 2023-03-14 06:00

Oncol Ther. 2023 Mar 14. doi: 10.1007/s40487-023-00224-9. Online ahead of print.

ABSTRACT

Breast cancer is the most frequently diagnosed malignancy in patients worldwide and the main cause of cancer-related death. Though still incurable, metastatic breast cancer's prognosis has been considerably improved in the past 10 years due to the introduction of new targeted agents, such as immune checkpoint inhibitors (ICI). However, these medications are associated with unique side effects known as immune-mediated adverse events (irAE). In this paper, we review the clinical evidence for the use of ICIs in breast cancer, in both the metastatic as well as neoadjuvant/adjuvant setting, followed by a review of irAE most commonly seen, and the medications used to treat them. Our opinion is that any cancer specialist treating patients with breast cancer should be aware of these side effects for early detection and management, and oncologists should be the leaders of the multidisciplinary team that will take care of them.

PMID:36917399 | DOI:10.1007/s40487-023-00224-9

Categories: Literature Watch

Topical Ocular TRPV1 Antagonist SAF312 (Libvatrep) for Postoperative Pain After Photorefractive Keratectomy

Tue, 2023-03-14 06:00

Transl Vis Sci Technol. 2023 Mar 1;12(3):7. doi: 10.1167/tvst.12.3.7.

ABSTRACT

PURPOSE: Evaluation of safety and efficacy of topical ocular SAF312 (Libvatrep) in post-photorefractive keratectomy (PRK) pain.

METHODS: In this placebo (vehicle)-controlled, participant- and investigator-masked study, 40 participants were randomized (1:1) to two treatment sequences in a bilateral PRK crossover design (SAF312 2.5% followed by vehicle [or vice versa], one eye drop, four times daily for 72 hours after PRK). Primary endpoints were visual analog scale (VAS) pain scores at 6 hours after first drop of study drug and average VAS scores over 0 to 12 hours postoperatively. Secondary endpoints included postoperative oral rescue medication (ORM) use and adverse events (AEs).

RESULTS: All 40 participants completed the study. Both primary endpoints were met; mean difference in VAS pain scores between SAF312- and vehicle-treated eyes was -11.13 (P = 0.005, -25%) at 6 hours postoperatively and -8.56 (P = 0.017, -22%) over 0 to 12 hours. Mean VAS pain scores with SAF312 were consistently lower than with vehicle from 1 hour postoperatively up to 30 hours (P ≤ 0.10 observed in 8/11 time points). Less ORM was taken with SAF312 up to 0 to 72 hours postoperatively, with a trend of fewer participants taking ORM at 0 to 24 hours postoperatively with SAF312 versus vehicle. No serious AEs were reported. All ocular AEs were mild and transient, and none were drug related. SAF312-treated eyes showed no delay in wound healing and had a lower grade 4 conjunctival hyperemia 24 hours postoperatively versus vehicle-treated eyes.

CONCLUSIONS: SAF312 was well tolerated and effective in reducing ocular pain post-PRK.

TRANSLATIONAL RELEVANCE: Topical SAF312 presents a new therapeutic option for patients undergoing PRK.

PMID:36917119 | DOI:10.1167/tvst.12.3.7

Categories: Literature Watch

Therapeutics for treating mpox in humans

Tue, 2023-03-14 06:00

Cochrane Database Syst Rev. 2023 Mar 14;3:CD015769. doi: 10.1002/14651858.CD015769.

ABSTRACT

BACKGROUND: Mpox was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 23 July 2022, following the identification of thousands of cases in several non-endemic countries in previous months. There are currently no licenced therapeutics for treating mpox; however, some medications may be authorized for use in an outbreak. The efficacy and safety of possible therapeutic options has not been studied in humans with mpox. There is a need to investigate the evidence on safety and effectiveness of treatments for mpox in humans; should any therapeutic option be efficacious and safe, it may be approved for use around the world.

OBJECTIVES: There are two parts to this Cochrane Review: a review of evidence from randomized controlled trials (RCTs), and a narrative review of safety data from non-randomized studies. Randomized controlled trials review To systematically review the existing evidence on the effectiveness of therapeutics for mpox infection in humans compared to: a) another different therapeutic for mpox, or b) placebo, or c) supportive care, defined as the treatment of physical and psychological symptoms arising from the disease. Non-randomized studies review To assess the safety of therapeutics for mpox infection from non-randomized studies (NRS).

SEARCH METHODS: Randomized controlled trials review We searched the following databases up to 25 January 2023: MEDLINE (OVID), Embase (OVID), Biosis previews (Web of Science), CAB Abstracts (Web of science), and Cochrane CENTRAL (Issue 1 2023). We conducted a search of trial registries (Clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP)) on 25 January 2023. There were no date or language limits placed on the search. We undertook a call to experts in the field for relevant studies or ongoing trials to be considered for inclusion in the review. Non-randomized studies review We searched the following databases on 22 September 2022: Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9 of 12, 2022), published in the Cochrane Library; MEDLINE (Ovid); Embase (Ovid); and Scopus (Elsevier). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress.

SELECTION CRITERIA: For the RCT review and the narrative review, any therapeutic for the treatment of mpox in humans was eligible for inclusion, including tecovirimat, brincidofovir, cidofovir, NIOCH-14, immunomodulators, and vaccine immune globulin. Randomized controlled trials review Studies were eligible for the main review if they were of randomized controlled design and investigated the effectiveness or safety of therapeutics in human mpox infection. Non-randomized studies review Studies were eligible for inclusion in the review of non-randomized studies if they were of non-randomized design and contained data concerning the safety of any therapeutic in human mpox infection.

DATA COLLECTION AND ANALYSIS: Randomized controlled trials review Two review authors independently applied study inclusion criteria to identify eligible studies. If we had identified any eligible studies, we planned to assess the risk of bias, and report results with 95% confidence intervals (CI). The critical outcomes were serious adverse events, development of disease-related complications, admission to hospital for non-hospitalized participants, pain as judged by any visual or numerical pain scale, level of virus detected in clinical samples, time to healing of all skin lesions, and mortality. We planned to perform subgroup analysis to explore whether the effect of the therapeutic on the planned outcomes was modified by disease severity and days from symptom onset to therapeutic administration. We also intended to explore the following subgroups of absolute effects: immunosuppression, age, and pre-existing skin disease. Non-randomized studies review One review author applied study inclusion criteria to identify eligible studies and extracted data. Studies of a non-randomized design containing data on the safety of therapeutics could not be meta-analyzed due to the absence of a comparator; we summarized these data narratively in an appendix.

MAIN RESULTS: Randomized controlled trials review We did not identify any completed RCTs investigating the effectiveness of therapeutics for treating mpox for the main review. We identified five ongoing trials that plan to assess the effectiveness of one therapeutic option, tecovirimat, for treating mpox in adults and children. One of these ongoing trials intends to include populations with, or at greater risk of, severe disease, which will allow an assessment of safety in more vulnerable populations. Non-randomized studies review Three non-randomized studies met the inclusion criteria for the narrative review, concerning data on the safety of therapeutics in mpox. Very low-certainty evidence from non-randomized studies of small numbers of people indicates no serious safety signals emerging for the use of tecovirimat in people with mpox infection, but a possible safety signal for brincidofovir. All three participants who received brincidofovir had raised alanine aminotransferase (ALT), but not bilirubin, suggesting mild liver injury. No study reported severe drug-induced liver injury with brincidofovir.

AUTHORS' CONCLUSIONS: Randomized controlled trials review This review found no evidence from randomized controlled trials concerning the efficacy and safety of therapeutics in humans with mpox. Non-randomized studies review Very low-certainty evidence from non-randomized studies indicates no serious safety signals emerging for the use of tecovirimat in people with mpox infection. In contrast, very low-certainty evidence raises a safety signal that brincidofovir may cause liver injury. This is also suggested by indirect evidence from brincidofovir use in smallpox. This warrants further investigation and monitoring. This Cochrane Review will be updated as new evidence becomes available to assist policymakers, health professionals, and consumers in making appropriate decisions for the treatment of mpox.

PMID:36916727 | DOI:10.1002/14651858.CD015769

Categories: Literature Watch

CYP11B2 Inhibitor Dexfadrostat Phosphate Suppresses the Aldosterone-to-Renin Ratio, an Indicator of Sodium Retention, in Healthy Volunteers

Tue, 2023-03-14 06:00

Br J Clin Pharmacol. 2023 Mar 13. doi: 10.1111/bcp.15713. Online ahead of print.

ABSTRACT

AIM: High aldosterone is a key driver of hypertension and long-term negative sequelae. We evaluated the safety and efficacy of dexfadrostat phosphate (DP13), a novel aldosterone synthase (CYP11B2) inhibitor, in healthy participants.

METHODS: This randomized, double-blind, placebo-controlled study was conducted in two parts. In part A, a single-ascending dose escalation, 16 participants received oral DP13 1-16 mg. Part B was a multiple-ascending dose, sequential group study in which 32 participants received oral DP13 4 mg, 8 mg or 16 mg once daily for 8 days. Safety and tolerability were monitored throughout. An adrenocorticotropic hormone (ACTH)-stimulation test at maximal blood drug concentrations defined the dose range for multiple dosing.

RESULTS: DP13 was well tolerated at all doses, with no serious adverse events. In part B, all DP13 doses (4 mg, 8 mg, 16 mg) over 8 days effectively suppressed aldosterone production, increased the urinary sodium/potassium ratio, decreased plasma sodium and increased plasma potassium and renin levels compared with placebo, resulting in potent suppression of the aldosterone-to-renin ratio (ARR). Endocrine counter-regulation resulted in the 4 mg dose no longer sustaining 24-hour aldosterone suppression after 8 days of treatment, unlike the 8 mg and 16 mg doses. There was no evidence of drug-induced adrenal insufficiency (ACTH stress challenge).

CONCLUSIONS: In patients with excess aldosterone and ensuing sodium retention driving hypertension, managing sodium balance is critical. A CYP11B2 inhibitor like DP13, whose effectiveness can be monitored by a reduction in ARR, may prove valuable in managing aldosterone-dependent hypertension and primary aldosteronism.

PMID:36914591 | DOI:10.1111/bcp.15713

Categories: Literature Watch

Imaging assessment of toxicity related to immune checkpoint inhibitors

Mon, 2023-03-13 06:00

Front Immunol. 2023 Feb 23;14:1133207. doi: 10.3389/fimmu.2023.1133207. eCollection 2023.

ABSTRACT

In recent years, a wide range of cancer immunotherapies have been developed and have become increasingly important in cancer treatment across multiple oncologic diseases. In particular, immune checkpoint inhibitors (ICIs) offer promising options to improve patient outcomes. However, a major limitation of these treatments consists in the development of immune-related adverse events (irAEs) occurring in potentially any organ system and affecting up to 76% of the patients. The most frequent toxicities involve the skin, gastrointestinal tract, and endocrine system. Although mostly manageable, potentially life-threatening events, particularly due to neuro-, cardiac, and pulmonary toxicity, occur in up to 30% and 55% of the patients treated with ICI-monotherapy or -combination therapy, respectively. Imaging, in particular computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT), plays an important role in the detection and characterization of these irAEs. In some patients, irAEs can even be detected on imaging before the onset of clinical symptoms. In this context, it is particularly important to distinguish irAEs from true disease progression and specific immunotherapy related response patterns, such as pseudoprogression. In addition, there are irAEs which might be easily confused with other pathologies such as infection or metastasis. However, many imaging findings, such as in immune-related pneumonitis, are nonspecific. Thus, accurate diagnosis may be delayed underling the importance for adequate imaging features characterization in the appropriate clinical setting in order to provide timely and efficient patient management. 18F-FDG-PET/CT and radiomics have demonstrated to reliably detect these toxicities and potentially have predictive value for identifying patients at risk of developing irAEs. The purpose of this article is to provide a review of the main immunotherapy-related toxicities and discuss their characteristics on imaging.

PMID:36911692 | PMC:PMC9995973 | DOI:10.3389/fimmu.2023.1133207

Categories: Literature Watch

The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes

Mon, 2023-03-13 06:00

Front Endocrinol (Lausanne). 2023 Feb 23;14:1125187. doi: 10.3389/fendo.2023.1125187. eCollection 2023.

ABSTRACT

DISCLOSURE SUMMARY: Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose.

BACKGROUND: Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity.

OBJECTIVE: The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity.

METHODS: In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase.

RESULTS: Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m2), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo Proteobacteria, Enterobacteriaceae, and Enterobacteriales were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month.

CONCLUSION: Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT04209075.

PMID:36909343 | PMC:PMC9996666 | DOI:10.3389/fendo.2023.1125187

Categories: Literature Watch

Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis

Mon, 2023-03-13 06:00

J Intern Med. 2023 Mar 13. doi: 10.1111/joim.13627. Online ahead of print.

ABSTRACT

BACKGROUND: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI).

METHODS: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted.

RESULTS: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84-8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46-9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448-0.1212), and DILI was 0.0296 (95% CI 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported.

CONCLUSIONS: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.

PMID:36912195 | DOI:10.1111/joim.13627

Categories: Literature Watch

Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials

Mon, 2023-03-13 06:00

HIV Med. 2023 Mar;24(3):290-300. doi: 10.1111/hiv.13386. Epub 2022 Aug 17.

ABSTRACT

OBJECTIVES: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF.

METHODS: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks.

RESULTS: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment-emergent resistance. Drug-related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate-containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01).

CONCLUSIONS: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment-emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens.

CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107).

PMID:36912172 | DOI:10.1111/hiv.13386

Categories: Literature Watch

Neuropsychiatric adverse drug reactions and associated factors in a cohort of individuals starting dolutegravir-based or efavirenz-based antiretroviral therapy in Belo Horizonte, Brazil

Mon, 2023-03-13 06:00

Curr Med Res Opin. 2023 Mar 13:1-14. doi: 10.1080/03007995.2023.2189855. Online ahead of print.

ABSTRACT

OBJECTIVE: To measure the incidence of neuropsychiatric adverse drug reactions (ADRs) in individuals living with HIV who initiated antiretroviral therapy (ART) with first-line regimens containing dolutegravir (DTG) or efavirenz (EFV) and associated factors.

METHODS: Prospective cohort study with individuals living with HIV who started ART with DTG or EFV associated with tenofovir disoproxil and lamivudine in Belo Horizonte, Brazil. Sociodemographic, clinical, and laboratory data were collected from September/2015 to October/2018 in three specialized HIV care services through interviews, clinical records, and computerized systems. We analyzed the frequency of neuropsychiatric ADRs recorded in clinical records 12 months after starting antiretroviral use, and the associated factors were investigated using binary logistic regression.

RESULTS: A total of 152 (35.1%) of the 433 individuals included had neuropsychiatric ADRs. The incidence density was 35.3/100 person-years. The subjects mainly had sleep disorders and disturbances (21.3%), neurological disorders (13.9%), headaches (8.1%), and anxiety disorders and symptoms (3.0%), more frequently in individuals using EFV. A lower likelihood of neuropsychiatric ADRs was associated with using a DTG-based antiretroviral regimen (OR = 0.24; 95% CI = 0.14-0.40) and anxiety or depression signs and symptoms at the onset of treatment (OR = 0.57; 95% CI = 0.37-0.89).

CONCLUSION: The incidence of neuropsychiatric ADRs was high in individuals starting ART with a lower likelihood of using a DTG-based regimen. The DTG-based regimen had a better safety profile for neuropsychiatric ADRs than the EFV-based regimen.

PMID:36912019 | DOI:10.1080/03007995.2023.2189855

Categories: Literature Watch

Neurodegenerative disorders: Assessing the impact of natural vs drug-induced treatment options

Mon, 2023-03-13 06:00

Aging Med (Milton). 2023 Feb 22;6(1):82-97. doi: 10.1002/agm2.12243. eCollection 2023 Mar.

ABSTRACT

Neurodegenerative illnesses refer to the gradual, cumulative loss of neural activity. Neurological conditions are considered to be the second leading cause of mortality in the modern world and the two most prevalent ones are Parkinson's disease and Alzheimer's disease. The negative side effects of pharmaceutical use are a major global concern, despite the availability of many different treatments for therapy. We concentrated on different types of neurological problems and their influence on targets, in vitro, in vivo, and in silico methods toward neurological disorders, as well as the molecular approaches influencing the same, in the first half of the review. The bulk of the second half of the review focuses on the many categories of treatment possibilities, including natural and artificial. Nevertheless, herbal treatment solutions are piquing scholarly attention due to their anti-oxidative properties and accessibility. However, more quality investigations and innovations are undoubtedly needed to back up these conclusions.

PMID:36911087 | PMC:PMC10000287 | DOI:10.1002/agm2.12243

Categories: Literature Watch

Half-Life of Lipid Emulsions Used in Lipid Emulsion Treatment for Drug Toxicity

Sat, 2023-03-11 06:00

J Emerg Med. 2023 Feb;64(2):253-254. doi: 10.1016/j.jemermed.2022.12.032.

NO ABSTRACT

PMID:36906377 | DOI:10.1016/j.jemermed.2022.12.032

Categories: Literature Watch

Ibuprofen: Toxicology and Biodegradation of an Emerging Contaminant

Sat, 2023-03-11 06:00

Molecules. 2023 Feb 23;28(5):2097. doi: 10.3390/molecules28052097.

ABSTRACT

The anti-inflammatory drug ibuprofen is considered to be an emerging contaminant because of its presence in different environments (from water bodies to soils) at concentrations with adverse effects on aquatic organisms due to cytotoxic and genotoxic damage, high oxidative cell stress, and detrimental effects on growth, reproduction, and behavior. Because of its high human consumption rate and low environmental degradation rate, ibuprofen represents an emerging environmental problem. Ibuprofen enters the environment from different sources and accumulates in natural environmental matrices. The problem of drugs, particularly ibuprofen, as contaminants is complicated because few strategies consider them or apply successful technologies to remove them in a controlled and efficient manner. In several countries, ibuprofen's entry into the environment is an unattended contamination problem. It is a concern for our environmental health system that requires more attention. Due to its physicochemical characteristics, ibuprofen degradation is difficult in the environment or by microorganisms. There are experimental studies that are currently focused on the problem of drugs as potential environmental contaminants. However, these studies are insufficient to address this ecological issue worldwide. This review focuses on deepening and updating the information concerning ibuprofen as a potential emerging environmental contaminant and the potential for using bacteria for its biodegradation as an alternative technology.

PMID:36903343 | PMC:PMC10004696 | DOI:10.3390/molecules28052097

Categories: Literature Watch

Transcriptome Sequencing Reveals the Mechanism behind Chemically Induced Oral Mucositis in a 3D Cell Culture Model

Sat, 2023-03-11 06:00

Int J Mol Sci. 2023 Mar 6;24(5):5058. doi: 10.3390/ijms24055058.

ABSTRACT

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.

PMID:36902486 | PMC:PMC10003620 | DOI:10.3390/ijms24055058

Categories: Literature Watch

Effect of SARS-CoV-2 mRNA-Vaccine on the Induction of Myocarditis in Different Murine Animal Models

Sat, 2023-03-11 06:00

Int J Mol Sci. 2023 Mar 6;24(5):5011. doi: 10.3390/ijms24055011.

ABSTRACT

In the course of the SARS-CoV-2 pandemic, vaccination safety and risk factors of SARS-CoV-2 mRNA-vaccines were under consideration after case reports of vaccine-related side effects, such as myocarditis, which were mostly described in young men. However, there is almost no data on the risk and safety of vaccination, especially in patients who are already diagnosed with acute/chronic (autoimmune) myocarditis from other causes, such as viral infections, or as a side effect of medication and treatment. Thus, the risk and safety of these vaccines, in combination with other therapies that could induce myocarditis (e.g., immune checkpoint inhibitor (ICI) therapy), are still poorly assessable. Therefore, vaccine safety, with respect to worsening myocardial inflammation and myocardial function, was studied in an animal model of experimentally induced autoimmune myocarditis. Furthermore, it is known that ICI treatment (e.g., antibodies (abs) against PD-1, PD-L1, and CTLA-4, or a combination of those) plays an important role in the treatment of oncological patients. However, it is also known that treatment with ICIs can induce severe, life-threatening myocarditis in some patients. Genetically different A/J (most susceptible strain) and C57BL/6 (resistant strain) mice, with diverse susceptibilities for induction of experimental autoimmune myocarditis (EAM) at various age and gender, were vaccinated twice with SARS-CoV-2 mRNA-vaccine. In an additional A/J group, an autoimmune myocarditis was induced. In regard to ICIs, we tested the safety of SARS-CoV-2 vaccination in PD-1-/- mice alone, and in combination with CTLA-4 abs. Our results showed no adverse effects related to inflammation and heart function after mRNA-vaccination, independent of age, gender, and in different mouse strains susceptible for induction of experimental myocarditis. Moreover, there was no worsening effect on inflammation and cardiac function when EAM in susceptible mice was induced. However, in the experiments with vaccination and ICI treatment, we observed, in some mice, low elevation of cardiac troponins in sera, and low scores of myocardial inflammation. In sum, mRNA-vaccines are safe in a model of experimentally induced autoimmune myocarditis, but patients undergoing ICI therapy should be closely monitored when vaccinated.

PMID:36902442 | PMC:PMC10002951 | DOI:10.3390/ijms24055011

Categories: Literature Watch

Over the Counter Pain Medications Used by Adults: A Need for Pharmacist Intervention

Sat, 2023-03-11 06:00

Int J Environ Res Public Health. 2023 Mar 3;20(5):4505. doi: 10.3390/ijerph20054505.

ABSTRACT

The safety of pharmacotherapy for geriatric patients is an essential aspect of the demographic perspective in view of the increasing size of this population. Non-opioid analgesics (NOAs) are among the most popular and often overused over-the-counter medications (OTC). The reasons for drug abuse are common in the geriatric population: musculoskeletal disorders, colds, inflammation and pain of various origins. The popularity of self-medication and the ability to easily access OTC drugs outside the pharmacy creates the danger of their misuse and the incidence of adverse drug reactions (ADRs). The survey included 142 respondents aged 50-90 years. The relationship between the prevalence of ADRs and the NOAs used, age, presence of chronic diseases, and place of purchasing and obtaining information about the mentioned drugs were evaluated. The results of the observations were statistically analyzed using Statistica 13.3. The most commonly used NOAs among the elderly included paracetamol, acetylsalicylic acid (ASA) and ibuprofen. Patients consumed the medications for intractable headaches, toothaches, fevers, colds and joint disorders. Respondents indicated the pharmacy as the main location for purchasing medications, and the physician as the source of information for selecting the therapy. ADRs were reported most frequently to the physician, and less frequently to the pharmacist and nurse. More than one-third of respondents indicated that the physician during the consultation did not take a medical history and did not ask about concomitant diseases. It is necessary to extend pharmaceutical care to geriatric patients that includes advice on adverse drug reactions, especially drug interactions. Due to the popularity of self-medication, and the availability of NOAs, long-term measures should be taken to increase the role of pharmacists in providing effective, safe health care to seniors. We are targeting pharmacists with this survey to draw attention to the problem of the prevalence of selling NOAs to geriatric patients. Pharmacists should educate seniors about the possibility of ADRs and approach patients with polypragmasy and polypharmacy with caution. Pharmaceutical care is an essential aspect in the treatment of geriatric patients, which can contribute to better results in their existing treatment and increase the safety of medication intake. Therefore, it is important to improve the development of pharmaceutical care in Poland in order to enhance patient outcomes.

PMID:36901514 | PMC:PMC10001525 | DOI:10.3390/ijerph20054505

Categories: Literature Watch

Hemophagocytic Lymphohistiocytosis Associated with Immunological Checkpoint Inhibitors: A Pharmacovigilance Study

Sat, 2023-03-11 06:00

J Clin Med. 2023 Mar 2;12(5):1985. doi: 10.3390/jcm12051985.

ABSTRACT

BACKGROUND: Acquired hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal condition characterized by hyperactivation of macrophages and cytotoxic lymphocytes, combining a series of non-specific clinical symptoms and laboratory disorders. Etiologies are multiple: infectious (mainly viral) but also oncologic, autoimmune or drug-induced. Immune checkpoint inhibitors (ICI) are recent anti-tumor agents associated with a novel profile of adverse events triggered by immune system over-activation. Here, we sought to provide a comprehensive description and analysis of HLH cases reported with ICI since 2014.

METHODS: Disproportionality analyses were performed in order to further explore the association between ICI therapy and HLH. We selected 190 cases, 177 from the World Health Organization pharmacovigilance database and 13 from the literature. Detailed clinical characteristics were retrieved from the literature and from the French pharmacovigilance database.

RESULTS: The cases of HLH reported with ICI concerned men in 65% of cases with a median age of 64 years. HLH occurred in an average of 102 days after the initiation of ICI treatment and mostly concerned nivolumab, pembrolizumab and nivolumab/ipilimumab combination. All cases were considered serious. Most cases presented a favorable outcome (58.4%); however, death was reported for 15.3% of patients. Disproportionality analyses showed that HLH was seven times more frequently reported with ICI therapy than with other drugs and three times more than with other antineoplastic agents.

CONCLUSIONS: Clinicians should be aware of the potential risk of ICI-related HLH to improve the early diagnosis of this rare immune-related adverse event.

PMID:36902771 | DOI:10.3390/jcm12051985

Categories: Literature Watch

Post-marketing surveillance study of the safety of the HPV-16/18 vaccine in Korea (2017-2021)

Fri, 2023-03-10 06:00

Hum Vaccin Immunother. 2023 Dec 31;19(1):2184756. doi: 10.1080/21645515.2023.2184756. Epub 2023 Mar 10.

ABSTRACT

Human papillomavirus (HPV) infection is associated with the risk of developing certain cancers, including cancers of the cervix, vulva, vagina, penis, anus, rectum, and oropharynx. In 2016, the bivalent HPV-16/18 vaccine was included in the Korea National Immunization Program. This vaccine protects against HPV types 16 and 18 and other oncogenic HPV types predominant in cervical and anal cancers. This post-marketing surveillance (PMS) study assessed the safety of the HPV-16/18 vaccine in Korea. The study was conducted in males and females aged between 9 and 25 years, from 2017 to 2021. Safety was measured in terms of frequency and intensity of adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) after each vaccine dose. The safety analysis included all participants who were vaccinated as per prescribing information and who completed a 30-day follow-up after at least one dose. Data were collected using individual case report forms. The total safety cohort included 662 participants. A total of 220 AEs were reported in 144 subjects (21.75%), and there were 158 ADRs in 111 subjects (16.77%), with the most common being injection site pain in all cases. No SAEs or serious ADRs were reported. Most AEs were reported after the first dose and were injection site reactions with mild intensity that recovered. No individuals required hospitalization or an emergency department visit. Safety results showed that the HPV-16/18 vaccine was generally well tolerated in the Korean population, and no safety concerns were identified.ClinicalTrials.gov Identifier: NCT03671369.

PMID:36896702 | DOI:10.1080/21645515.2023.2184756

Categories: Literature Watch

Reactogenicity within the first week after Sinopharm, Sputnik V, AZD1222, and COVIran Barekat vaccines: findings from the Iranian active vaccine surveillance system

Fri, 2023-03-10 06:00

BMC Infect Dis. 2023 Mar 10;23(1):150. doi: 10.1186/s12879-023-08103-4.

ABSTRACT

BACKGROUND: This study aimed to evaluate the reactogenicity effects of COVID-19 vaccines, used in Iran.

METHODS: At least 1000 people were followed up with phone calls or self-report in a mobile application within 7 days after vaccination. Local and systemic reactogenicities were reported overall and by subgroups.

RESULTS: The presence of one or more local and systemic adverse effects after the first dose of vaccines was 58.9% [(95% Confidence Intervals): 57.5-60.3)] and 60.5% (59.1-61.9), respectively. These rates were reduced to 53.8% (51.2-55.0) and 50.8% (48.8-52.7) for the second dose. The most common local adverse effect reported for all vaccines was pain in the injection site. During the first week after the first dose of vaccines, the frequency of the pain for Sinopharm, AZD1222, Sputnik V, and Barekat was 35.5%, 86.0%, 77.6%, and 30.9%, respectively. The same rates after the second dose were 27.3%, 66.5%, 63.9%, and 49.0%. The most common systemic adverse effect was fatigue. In the first dose, it was 30.3% for Sinopharm, 67.4% for AZD1222, 47.6% for Sputnik V, and 17.1% for Barekat. These rates were reduced to 24.6%, 37.1%, 36.5%, and 19.5%, in the second dose of vaccines. AZD1222 had the highest local and systemic adverse effects rates. The odds ratio of local adverse effects of the AZD1222 vaccine compared to the Sinopharm vaccine were 8.73 (95% CI 6.93-10.99) in the first dose and 4.14 (95% CI 3.32-5.17) in the second dose. Barekat and Sinopharm had the lowest frequency of local and systemic adverse effects. Compared to Sinopharm, systemic adverse effects were lower after the first dose of Barekat (OR = 0.56; 95% CI 0.46-0.67). Reactogenicity events were higher in women and younger people. Prior COVID-19 infection increased the odds of adverse effects only after the first dose of vaccines.

CONCLUSIONS: Pain and fatigue were the most common reactogenicities of COVID-19 vaccination. Reactogenicities were less common after the second dose of the vaccines. The adverse effects of AZD1222 were greater than those of other vaccines.

PMID:36899326 | PMC:PMC10000357 | DOI:10.1186/s12879-023-08103-4

Categories: Literature Watch

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