J Headache Pain. 2024 Oct 7;25(1):169. doi: 10.1186/s10194-024-01858-4.

ABSTRACT

PURPOSE: This study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings.

METHODS: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning the second quarter of 2020 through the first quarter of 2023 were retrospectively analyzed in this pharmacovigilance investigation. This study focuses on employing subgroup analysis to monitor rimegepant drug safety. Descriptive analysis was employed to examine clinical characteristics and concomitant medication of adverse event reports associated with rimegepant, including report season, reporter country, sex, age, weight, dose, and frequency, onset time, et al. Correlation analysis, including techniques such as violin plots, was utilized to explore relationships between clinical characteristics in greater detail. Additionally, four disproportionality analysis methods were applied to assess adverse event signals associated with rimegepant.

RESULTS: A total of 5,416,969 adverse event reports extracted from the FAERS database, 10, 194 adverse events were identified as the "primary suspect" (PS) drug attributed to rimegepant. Rimegepant-associated adverse events involved 27 System Organ Classes (SOCs), and the significant SOC meeting all four detection criteria was "general disorders and administration site conditions" (SOC: 10018065). Additionally, new significant adverse events were discovered, including "vomiting projectile" (PT: 10047708), "eructation" (PT: 10015137), "motion sickness" (PT: 10027990), "feeling drunk" (PT: 10016330), "reaction to food additive" (PT: 10037977), etc. Descriptive analysis indicated that the majority of reporters were consumers (88.1%), with most reports involving female patients. Significant differences were observed between female and male patients across age categories, and the concomitant use of rimegepant with other medications was complex.

CONCLUSION: This study has preliminarily identified potential new adverse events associated with rimegepant, such as those involving the gastrointestinal system, nervous system, and immune system, which warrant further research to determine their exact mechanisms and risk factors. Additionally, significant differences in rimegepant-related adverse events were observed across different age groups and sexes, and the complexity of concomitant medication use should be given special attention in clinical practice.

PMID:39375581 | PMC:PMC11460227 | DOI:10.1186/s10194-024-01858-4

BMJ Open. 2024 Oct 7;14(10):e087701. doi: 10.1136/bmjopen-2024-087701.

ABSTRACT

BACKGROUND: Adverse drug reaction (ADR) reporting systems are critical for monitoring and managing drug safety. However, various factors influence the willingness to use these systems. This study aimed to investigate the willingness to use ADR reporting systems through an integrated model of the Technology Acceptance Model (TAM) and Task-Technology Fit (TTF) theory, conducting a multicentre qualitative study from the user's perspective.

METHODS: This study used qualitative research methods, including in-depth interviews with clinicians, nurses, pharmacists and administrators who reported ADRs through the National Adverse Drug Reaction Monitoring System (NADRMS) and the China Hospital Pharmacovigilance System (CHPS). The interviews were audio-recorded, transcribed verbatim and analysed using QDA Miner software for data management and thematic analysis.

RESULTS: Eighteen healthcare workers from five healthcare organisations participated in the study. They found the ease of use and usefulness of the current NADRMS and CHPS to be acceptable. The essential technical requirements identified included accuracy, standardisation, timeliness and confidentiality. However, challenges such as inaccurate information capture, unstable interfacing with medical record systems, low reporting efficiency and lack of data sharing were highlighted. Overall, front-line healthcare workers exhibited a generally negative attitude towards using NADRMS and CHPS, driven more by necessity than preference. Factors influencing their willingness to use these systems included ease of use, practicality, risk perception and social impact, with varying attitudes and requirements observed between user groups.

CONCLUSION: This study provides practical recommendations that can be readily implemented to enhance the effectiveness and sustainability of ADR reporting systems. While front-line users in China acknowledged the systems' ease of use and usefulness, they also noted significant gaps in technological adaptation. They expressed the need for improvements in data openness and sharing, accessibility and system intelligence.

PMID:39375182 | PMC:PMC11459300 | DOI:10.1136/bmjopen-2024-087701

Diabetes Obes Metab. 2024 Oct 7. doi: 10.1111/dom.15984. Online ahead of print.

ABSTRACT

AIMS: Pharmacotherapeutic options for obesity treatment include glucagon-like peptide-1 receptor (GLP-1R) agonists, for example, liraglutide. However, an unmet need remains, particularly in patients with a high body mass index (BMI), as GLP-1R agonists are associated with gastrointestinal adverse events (AEs) and some patients do not respond to treatment. Neuropeptide Y (NPY) and peptide YY bind G-protein-coupled Y receptors and represent attractive targets for modulating bodyweight.

MATERIALS AND METHODS: This first-in-human, three-part, partially blinded phase I study (NCT04903509) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of the peptidic NPY2R agonist BI 1820237, with/without low-dose liraglutide: part 1 (participants randomized to receive BI 1820237: 0.075-2.4 mg or placebo), part 2 (BI 1820237: 1.2 mg or placebo) and part 3 (BI 1820237: 0.025-1.2 mg + liraglutide 0.6 mg or placebo + liraglutide 0.6 mg). Primary endpoint is the proportion of participants with drug-related AEs. Secondary endpoints are tolerability, PK and PD.

RESULTS: In total, 95 otherwise healthy men with increased BMI (25.0-34.9 kg/m2) were randomized. Drug-related AEs, mainly gastrointestinal events, were reported by 39.0% of participants (n = 23) in parts 1 + 2 and 30.6% of participants (n = 11) in part 3; one drug-related AE (11.1%, part 3) was reported in a participant receiving placebo with liraglutide. Post-dose paracetamol PK suggested that BI 1820237 and low-dose liraglutide exhibited additive effects on gastric emptying.

CONCLUSIONS: BI 1820237 treatment was associated with transient nausea and vomiting at higher doses. No differences in tolerability were observed when combined with liraglutide; effects on gastric emptying appeared additive.

PMID:39373311 | DOI:10.1111/dom.15984

Hippokratia. 2023 Oct-Dec;27(4):155-157.

ABSTRACT

BACKGROUND: Statin regimens are essential for managing lipids and preventing cardiovascular diseases, both in primary and secondary prevention, alongside lifestyle changes. There are, however, some side-effects associated with statin intake, such as an elevation of (CK) and myopathy.

CASE DESCRIPTION: This case describes a coronary patient with high low-density lipoprotein cholesterol (LDL-C) who was undertreated due to elevated creatine kinase (CK) levels and myopathy initially linked to statin use. A proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) replaced statin therapy; however, the existence of persisting/recurrent symptoms or CK elevation posed the need for further investigation. A neurological examination, an electromyography (EMG), and a nerve conduction study (NCV) revealed an underlying sensorimotor polyneuropathy, probably Charcot-Marie-Tooth disease.

CONCLUSIONS: Persistent muscle symptoms in patients receiving statins should not be always attributed solely to statin intake. Further neurological evaluation could reveal underlying hereditary sensorimotor polyneuropathies. PCSK9i could serve as the therapy of choice in such cases, as additional drug-induced myopathy could pose severe problems for those patients. HIPPOKRATIA 2023, 27 (4):155-157.

PMID:39372326 | PMC:PMC11451505

Cureus. 2024 Sep 5;16(9):e68700. doi: 10.7759/cureus.68700. eCollection 2024 Sep.

ABSTRACT

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination of two antibiotics used to treat various bacterial infections, generally well-tolerated but can rarely cause neuropsychological adverse effects, including psychosis. This case report describes a 69-year-old immunocompetent female who developed acute visual and auditory hallucinations three days after starting TMP-SMX for a urinary tract infection (UTI). The patient had a history of depression, successfully treated with mirtazapine a decade ago, and no other psychiatric or medical conditions. Laboratory tests and imaging were unremarkable. Symptoms resolved completely within two days of discontinuing TMP-SMX, suggesting a causal relationship. This case highlights the need for vigilance regarding the neuropsychiatric side effects of TMP-SMX, even in immunocompetent individuals, and underscores the importance of considering medication-induced psychosis in differential diagnoses. Further research is warranted to elucidate the mechanisms underlying this adverse drug reaction.

PMID:39371790 | PMC:PMC11453036 | DOI:10.7759/cureus.68700

Regul Toxicol Pharmacol. 2024 Nov;153:105715. doi: 10.1016/j.yrtph.2024.105715. Epub 2024 Oct 5.

ABSTRACT

Drug impurities are undesirable but unavoidable chemicals which can occur throughout the drug life cycle. The safety implications of drug impurities can be significant given that they can impact safety, quality, and efficacy of drug products and that certain drug impurities are mutagenic, carcinogenic, or teratogenic. The characteristics of drug impurities could be specific to drug modalities (e.g., small molecules vs. biologics). The commonly encountered drug impurities include elemental impurity, residual solvent, organic impurity, host cell protein and DNA, residual viral vector, extractable and leachable, and particle. They can cause various adverse effects such as immunogenicity, infection, genotoxicity, and carcinogenicity upon significant exposure. Therefore, the effective control of these drug impurities is central for patient safety. Regulations and guidelines are available for drug developers to manage them. Their qualification is obtained based on authoritative qualification thresholds or safety assessment following the classic toxicological risk assessment. The current review focuses on the safety assessment science and methodology used for diverse types of drug impurities. Due to the different nature of diverse drug impurities, their safety assessment represents a significant challenge for drug developers.

PMID:39369763 | DOI:10.1016/j.yrtph.2024.105715

Biol Pharm Bull. 2024;47(10):1631-1636. doi: 10.1248/bpb.b24-00437.

ABSTRACT

The elderly Japanese population is growing rapidly due to increasing longevity and declining birth rates. These findings have implications for drug development and safety in elderly patients; however, the Japanese stakeholders have been slow to adapt. This study aimed at examining methods for providing sufficient information on safe use of pharmaceuticals in elderly patients in Japan. For new drugs recently approved in Japan for diseases with a high prevalence among the elderly, we investigated the state of safety information provision for elderly patients through the package insert and also safety data evaluation in elderly patients in clinical studies. Of the 64 targeted drugs, only 14 provided geriatric use information based on clinical study data or indication, 38 had general cautionary descriptions, and 12 did not have geriatric use information. Most drugs met the recommendation of enrolling >100 elderly patients in the clinical development program. However, a discrepancy was observed in the proportion of elderly patients in clinical trials compared to that in real-world clinical setting. Twenty-nine drugs compared the incidence of key adverse events (AEs) in elderly and younger patients, whereas 25 only reported the overall incidence of AEs. To improve healthcare outcomes, healthcare professionals need access to sufficient safety information through package inserts containing data from clinical trials. Marketing authorization holders and regulatory authorities must work together to ensure that such safety information based on sufficient data is included in package inserts.

PMID:39370267 | DOI:10.1248/bpb.b24-00437

Front Pharmacol. 2024 Sep 19;15:1441147. doi: 10.3389/fphar.2024.1441147. eCollection 2024.

ABSTRACT

Despite the extraordinary anti-tubercular activity of isoniazid (INH), the drug-induced hepatotoxicity and peripheral neuropathy pose a significant challenge to its wider clinical use. The primary cause of INH-induced hepatotoxicity is in vivo metabolism involving biotransformation on its terminal -NH2 group owing to its high nucleophilic nature. The human N-acetyltransferase-2 enzyme (NAT-2) exploits the reactivity of INH's terminal -NH2 functional group and inactivates it by transferring the acetyl group, which subsequently converts to toxic metabolites. This -NH2 group also tends to react with vital endogenous molecules such as pyridoxine, leading to their deficiency, a major cause of peripheral neuropathy. The elevation of liver functional markers is observed in 10%-20% of subjects on INH treatment. INH-induced risk of fatal hepatitis is about 0.05%-1%. The incidence of peripheral neuropathy is 2%-6.5%. In this review, we discuss the genesis and historical development of INH, and different reported mechanisms of action of INH. This is followed by a brief review of various clinical trials in chronological order, highlighting treatment-associated adverse events and their occurrence rates, including details such as geographical location, number of subjects, dosing concentration, and regimen used in these clinical studies. Further, we elaborated on various known metabolic transformations highlighting the involvement of the terminal -NH2 group of INH and corresponding host enzymes, the structure of different metabolites/conjugates, and their association with hepatotoxicity or neuritis. Post this deliberation, we propose a hydrolysable chemical derivatives-based approach as a way forward to restrict this metabolism.

PMID:39364056 | PMC:PMC11447295 | DOI:10.3389/fphar.2024.1441147

Ann Pharmacother. 2024 Oct 3:10600280241284923. doi: 10.1177/10600280241284923. Online ahead of print.

ABSTRACT

BACKGROUND: Hypoalbuminemia is common in patients with advanced solid tumor malignancies. However, despite the increased use of highly protein-bound tyrosine kinase inhibitors (TKIs) in cancer treatments, the tolerability of these agents in patients with hypoalbuminemia is not fully known.

OBJECTIVE: Our aim is to assess whether patients on oral TKIs with hypoalbuminemia are at higher risk for experiencing medication-related adverse events, therefore requiring careful considerations.

METHODS: This is a single-center, retrospective study including patients ≥18 years of age with a solid tumor malignancy who had taken at least one dose of oral TKIs with a protein binding of ≥90% between June 1, 2016, and June 1, 2021. The primary outcome was to compare time to TKI discontinuation due to adverse events between patients with and without hypoalbuminemia. Key secondary outcomes include TKI discontinuation and dose reduction rates, time to TKI dose reduction, and severity of adverse events.

RESULTS: Out of 282 included patients, 134 (48%) patients had hypoalbuminemia and 148 (52%) had normal albumin levels. Compared with patients without hypoalbuminemia, patients with hypoalbuminemia had shorter median time on treatment at 2.8 months (95% CI = 2.3-4.5 months) versus 4.3 months (95% CI = 2.8-6.4 months; P = 0.003). In patients who had TKI discontinuation, dose reduction was associated with longer time on treatment in patients in the normal albumin group compared with patients in the hypoalbuminemia group or patients without dose reduction (P < 0.0001). Patients in the hypoalbuminemia group experienced significantly more grade 3/4 adverse events compared with those in the normal albumin group (73% vs 27%, P < 0.0001).

CONCLUSION AND RELEVANCE: Hypoalbuminemia is a risk factor for both shorter time on treatment and more severe adverse events in patients with solid tumor malignancies taking highly protein-bound oral TKIs. This study highlights the need for closer monitoring of this patient population by health care providers.

PMID:39363502 | DOI:10.1177/10600280241284923

BMC Womens Health. 2024 Oct 3;24(1):545. doi: 10.1186/s12905-024-03355-x.

ABSTRACT

BACKGROUND: In the breast cancer treatment, there may be a gap between patients' information needs and physicians' perceptions. To address this issue, we conducted a comprehensive questionnaire survey aimed to assess the specific information needs of patients regarding the adverse events (AEs) associated with treatment.

METHODS: A web-based questionnaire survey (UMIN000049280: Registered on October 31, 2022) was conducted in patients with a history of breast cancer treatment. Responses were obtained regarding AEs experienced, AEs for which remedies were identified, AEs patients sought to prevent, and pre-treatment information on AEs patients desired to have.

RESULTS: Data from 435 breast cancer patients were analyzed. The most common AEs reported included hair loss (93.3%), malaise/fatigue (89.4%), nail changes (83.2%), dysgeusia (69.0%), leukopenia/white blood cell decreased (65.1%), neuropathy (62.3%), and nausea/vomiting (61.4%). Financial anxiety was reported in 35.2% of the participants. AEs for which a minority of patients found effective solutions included neuropathy (20.3%), financial anxiety (21.6%), edema (24.3%), joint pain (26.0%), and malaise/fatigue (26.7%). Patients expressed the greatest desire to avoid hair loss (34.7%), followed by nausea/vomiting (23.7%), interstitial lung disease/pneumonitis (5.5%), malaise/fatigue (5.1%), and dysgeusia (5.1%). The most commonly requested pre-treatment information regarding AEs was their duration, followed by prevention methods, management strategies, time to onset, and the impact on daily life.

CONCLUSIONS: This survey highlights the existence of significant unmet medical needs among breast cancer patients, due to the inadequate solutions available for managing AEs associated with various therapeutic agents. In addition, the survey revealed that patients have different information needs regarding different types of AEs.

PMID:39363303 | PMC:PMC11447999 | DOI:10.1186/s12905-024-03355-x

PLoS One. 2024 Oct 3;19(10):e0309796. doi: 10.1371/journal.pone.0309796. eCollection 2024.

ABSTRACT

BACKGROUND: Adverse drug reaction is one of the emerging challenges in antiretroviral treatment. Determining the incidence rate and predictors among children on antiretroviral treatment (ART) is essential to improve treatment outcomes and minimize harm. And also, evidence regarding the time to major adverse drug reactions and its predictors among children on antiretroviral treatment is limited in Ethiopia.

OBJECTIVE: This study aimed to assess the time to major adverse drug reaction and its predictors among children on antiretroviral treatment at selected public hospitals in Northwest Amhara, Ethiopia, 2023.

METHOD: A retrospective cohort study was conducted among 380 children on antiretroviral treatment who enrolled from June 27, 2017, to May 31, 2022. Data was collected using a structured data extraction checklist. Data were entered into Epidata 4.6 and analyzed using STATA 14. The incidence rate of major adverse drug reactions was determined per person/months. The Cox proportional hazards regression model was used to identify predictors of major adverse drug responses. A p-value less than 0.05 with a 95% CI was used to declare statistical significance.

RESULT: The minimum and maximum follow-up time was 6 and 59 months, respectively. The study participants were followed for a total of 9916 person-months. The incidence rate of major adverse drug reactions was 3.5 /1000 person-months. Advanced clinical stages of HIV/AIDS (III and IV) [adjusted hazard ratio = 7.3, 95% CI: 2.74-19.60)], poor treatment adherence [adjusted hazard ratio = 0.33, 95% CI: 0.21-0.42], taking antiretroviral treatment twice and more [adjusted hazard ratio = 3.43, 955 CI: (1.26-9.33)] and not taking opportunistic infection prophylaxis [adjusted hazard ratio = 0.35, 95% CI: 0.23-0.52)] were predictors of major adverse drug reactions.

CONCLUSION: The incidence rate of major adverse drug reactions among children on antiretroviral treatment was congruent with studies in Ethiopia. Advanced clinical stages of HIV/AIDS, poor treatment adherence, taking antiretroviral treatment medications twice or more, and not taking opportunistic infection prophylaxis were predictors of major adverse drug reactions.

PMID:39361573 | PMC:PMC11449323 | DOI:10.1371/journal.pone.0309796

J Lipid Atheroscler. 2024 Sep;13(3):215-231. doi: 10.12997/jla.2024.13.3.215. Epub 2024 Sep 4.

ABSTRACT

Elevated blood cholesterol and triglyceride levels induced by secondary causes are frequently observed. The identification and appropriate handling of these causes are essential for secondary dyslipidemia treatment. Major secondary causes of hypercholesterolemia and hypertriglyceridemia include an unhealthy diet, diseases and metabolic conditions affecting lipid levels, and therapeutic side effects. It is imperative to correct secondary causes prior to initiating conventional lipid-lowering therapy. Guideline-based lipid therapy can then be administered based on the subsequent lipid levels.

PMID:39355405 | PMC:PMC11439749 | DOI:10.12997/jla.2024.13.3.215

Clin Toxicol (Phila). 2024 Oct;62(10):615-624. doi: 10.1080/15563650.2024.2398119. Epub 2024 Oct 1.

ABSTRACT

INTRODUCTION: Poisoning is a leading cause of morbidity and mortality that is increasing in many countries. Better data are needed to understand epidemiology and outcomes of poisoning. This work describes a new poisoning data linkage cohort in New South Wales, Australia (population approximately 8 million).

METHODS: This is a longitudinal health record linkage, 2011-2020, including data from: ambulance call-outs, emergency department presentations, hospital admissions, death registrations, the poisons centre, and four tertiary toxicology units. Individuals with poisoning, venomous animal/plant exposures, or adverse drug reaction events were included.

RESULTS: There were 845,217 linkable events relating to 400,642 ambulance, 688,484 emergency department, 682,013 admission, 40,456 toxicology, and 11,879 death records. There were 572,841 people with events; the median age at the time of first event was 57 years, and 51.9% were female. Events leading to patient admission were most commonly adverse drug reactions (n = 511,263), intentional poisonings (n = 68,646), unintentional poisonings (n = 54,840) and animal/plant exposures (n = 11,092). Demographics varied by cause: intentional poisoning (median age 33 years, 61.7% female); unintentional poisoning/animals/plants (median age 43 years, 45% female); and adverse drug reactions (median age 70 years, 54% female). Adolescent females had highest rates of intentional poisoning, while unintentional poisoning had a bimodal distribution, highest in children <5 years old and males aged 20 to 50 years. Substance use disorders were documented comorbidities for 44% of intentional poisoning, 29% of unintentional poisoning, and 13% of adverse drug reaction-related admissions; mood disorders were documented for 54%, 17% and 10% of these admissions, respectively.

DISCUSSION: Poisonings and hospitalised adverse drug reactions are common in New South Wales, affecting approximately 8% of the population in 10 years. This linkage improves understanding of poisoning risks and outcomes in Australia.

CONCLUSIONS: This novel data linkage provides a unique opportunity to study poisoning across multiple settings for an individual over an extended period.

PMID:39350754 | DOI:10.1080/15563650.2024.2398119

Eur J Hosp Pharm. 2024 Sep 30:ejhpharm-2024-004335. doi: 10.1136/ejhpharm-2024-004335. Online ahead of print.

NO ABSTRACT

PMID:39349010 | DOI:10.1136/ejhpharm-2024-004335

Lung Cancer. 2024 Oct;196:107966. doi: 10.1016/j.lungcan.2024.107966. Epub 2024 Sep 24.

ABSTRACT

OBJECTIVES: KRAS (G12C) inhibitors (sotorasib and adagrasib) have approved treatment in patients with KRAS (G12C)-mutated non-small cell lung cancer (NSCLC). The post-marketing data concerning KRAS (G12C) inhibitors remain limited, and the outcomes of relevant studies are yet to yield conclusive evidence supporting the long-term safety of KRAS (G12C) inhibitors.

MATERIALS AND METHODS: This investigation comprehensively assessed adverse events (AEs) attributed to KRAS (G12C) inhibitors by employing advanced data mining techniques, utilizing the FDA Adverse Event Reporting System (FAERS). The dataset encompasses the period from the first quarter of 2021 to the first quarter of 2024. A disproportionality analysis was conducted to quantify the correlation between KRAS (G12C) inhibitors and AEs. The metrics employed for the evaluation of disproportionality comprise the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM).

RESULTS: A total of 2,253 and 486 reports were identified as related to sotorasib and adagrasib, with the identification of 51 and 26 preferred terms, respectively. The most frequent AEs of sotorasib comprised diarrhoea (ROR 5.27), hepatotoxicity (ROR 38.09), alanine aminotransferase increased (ROR 17.41), aspartate aminotransferase increased (ROR 20.88), and hepatic function abnormal (ROR 19.88). The most common AEs of adagrasib included diarrhoea (ROR 4.21), nausea (ROR 3.84), vomiting (ROR 5.36), decreased appetite (ROR 4.79), and dehydration (ROR 7.00). A relatively reduced risk of hepatotoxicity but a increased risk of serious AEs in adagrasib compared to sotorasib (P < 0.001).

CONCLUSION: Our findings would provide valued evidence for healthcare professionals to recognize AEs associated with KRAS (G12C) inhibitors and differences between sotorasib and adagrasib, and guide their clinical practice.

PMID:39342769 | DOI:10.1016/j.lungcan.2024.107966

Drugs Aging. 2024 Oct;41(10):833-846. doi: 10.1007/s40266-024-01148-3. Epub 2024 Sep 29.

ABSTRACT

BACKGROUND: Older inpatients with dementia are at an increased risk of an adverse drug reaction (ADR) during hospitalization.

OBJECTIVE: To quantify the prevalence of ADRs in older inpatients according to dementia status and ADR definition approach and to identify risk factors of ADRs during hospitalization.

METHODS: This was a retrospective cohort study of 2000 inpatients aged ≥ 75 years admitted consecutively to six Sydney hospitals (1 July 2016 to 31 May 2017). Dementia was defined by diagnosis in electronic medical records. ADRs were defined according to two approaches: the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) and classification by a research pharmacist (subset cohort, n = 600). A binary logistic regression was conducted to determine risk factors of ADRs.

RESULTS: Among 2000 patients, 25.9% (n = 517) were reported to have dementia. ADRs defined by ICD-10-AM were identified in 8.3% (n = 43) and 14.6% (n = 217) of inpatients with and without dementia respectively (p < 0.001). A total of 13.0% (n = 260) and 12.5% (n = 75) of patients had ADRs defined by ICD-10-AM and a research pharmacist, respectively. Key risk factors of ADRs were longer hospital stay [odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01, 1.02) and a greater number of regular potentially inappropriate medicines (PIMs) on admission (OR 1.17, 95% CI 1.00, 1.38).

CONCLUSIONS: ADRs were more prevalent among inpatients without dementia and when assessed by a research pharmacist. Our findings underline the need for improved ADR detection in older inpatients.

PMID:39342531 | DOI:10.1007/s40266-024-01148-3

Maxillofac Plast Reconstr Surg. 2024 Sep 29;46(1):34. doi: 10.1186/s40902-024-00445-6.

ABSTRACT

BACKGROUND: Xerostomia, or dry mouth, can be a temporary or persistent symptom resulting from various factors, such as medication use, therapeutic radiation, chemotherapy, autoimmune conditions (e.g., Sjögren's syndrome), and hormonal imbalances. Xerostomia often leads to associated mucositis, which significantly impacts patients' quality of life. The nano-bio-fusion (NBF) gingival gel, a gel-type functional toothpaste containing vitamins C, E, propolis, and herbal extracts in a nano-emulsion state, has shown potential in accelerating the healing of oral mucosal lesions.

METHODS: A total of 127 patients (102 females, 25 males) with persistent xerostomia were treated from 2018 to 2023. Of these, 32 patients were treated exclusively with NBF Gel, while 95 patients received NBF Gel in combination with other medications, such as pilocarpine. The underlying causes of xerostomia included irradiation and chemotherapy (12 patients), medication (40 patients), hormonal imbalance (28 patients), and Sjögren's syndrome (47 patients). NBF Gel was applied 2-3 times daily to the tongue and oral mucosa. Treatment effectiveness was evaluated through physical examinations and a patient-reported scale ranging from 1 (no improvement) to 10 (complete improvement), focusing on the healing of mucosal lesions rather than saliva production.

RESULTS: Both treatment groups showed significant improvements in the healing of xerostomia-associated mucositis, particularly in severe cases with visible lesions. Patients treated with NBF Gel reported improved symptoms related to mucosal health, while those who received combination therapy also experienced reduced side effects of pilocarpine due to dose reduction. The most substantial improvements were observed in patients with drug-induced and hormonally-caused xerostomia-related mucositis. No adverse side effects from NBF Gel were reported during the study.

CONCLUSION: NBF gingival gel proved to be beneficial in accelerating the healing of mucositis associated with xerostomia, regardless of the underlying cause, including medication use, radiotherapy, chemotherapy, hormonal imbalances, and Sjögren's syndrome. It presents a promising adjunctive treatment to improve mucosal health and quality of life for patients suffering from xerostomia-associated mucositis.

PMID:39342518 | PMC:PMC11439858 | DOI:10.1186/s40902-024-00445-6

BMC Pharmacol Toxicol. 2024 Sep 27;25(1):71. doi: 10.1186/s40360-024-00790-2.

ABSTRACT

OBJECTIVE: Tafamidis-associated adverse events (AEs) were investigated retrospectively by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS) to inform clinical safety.

METHODS: Data were gathered from the FAERS database, which spans the second quarter of 2019 to the fourth quarter of 2023. A total number of 8532 reports of Tafamidis-related adverse events were detected after evaluating 8,432,351 data. Disproportionality analyses were used to quantify the signal and assess the significance of Tafamidis-associated AEs using four algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the multi-item gamma Poisson shrinker (MGPS) and the Bayesian confidence propagation neural network (BCPNN).

RESULTS: Among the 8532 reports of AEs with Tafamidis as the primary suspected drug, Tafamidis-induced AEs were identified as occurring in 27 system organ classes (SOC). A total of 207 Tafamidis-induced AEs were detected which simultaneously complied with the four algorithms. Our analysis also identified new adverse reactions including Hypoacusis, Deafness, and Essential hypertension. The median onset of adverse reactions associated with Tafamidis was 180 days (interquartile range [IQR] 51-419 days).

CONCLUSION: Tafamidis is a drug that has shown favorable safety and tolerability results in clinical trials. However, a number of adverse reactions associated with Tafamidis have been identified through analysis of the FAERS database. In clinical applications, it is recommended to closely monitor patients' hearing while using Tafamidis. In addition, it is hoped that further experimental and clinical studies will be conducted in the future to understand the mechanism of occurrence between Tafamidis and adverse reactions such as primary hypertension, hyperlipidemia, and height reduction.

PMID:39334280 | PMC:PMC11438280 | DOI:10.1186/s40360-024-00790-2

BMC Med Inform Decis Mak. 2024 Sep 28;24(1):276. doi: 10.1186/s12911-024-02692-z.

ABSTRACT

Identifying and managing the most critical side effects encourages patients to take medications regularly and adhere to the course of treatment. Therefore, priority should be given to the more important ones, among these side effects. However, the number of studies that make a priority examination is limited. There is a need for a new study that determines which of these effects are more priority to increase the quality of the treatment. Accordingly, this study aims to define the most important side effects of antidepressant drugs with a novel model. Quantum Spherical fuzzy M-SWARA technique is considered to compute the importance weights of the items. The main contribution of this study is that the most critical side effects can be understood for antidepressant drugs by establishing a novel decision-making model. The findings demonstrate that psychological side effects are defined as the most critical side effects of antidepressant drugs. Furthermore, physical side effects also play a key role in this condition. Side effects in antidepressant treatment have a great impact on the effectiveness of treatment and patient compliance.

PMID:39342208 | PMC:PMC11438092 | DOI:10.1186/s12911-024-02692-z

Genes (Basel). 2024 Aug 24;15(9):1116. doi: 10.3390/genes15091116.

ABSTRACT

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.

PMID:39336707 | PMC:PMC11431558 | DOI:10.3390/genes15091116