Rev Saude Publica. 2024 May 13;58:20. doi: 10.11606/s1518-8787.2024058005458. eCollection 2024.

ABSTRACT

OBJECTIVE: To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil.

METHODS: This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis.

RESULTS: For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal.

CONCLUSIONS: The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender.

PMID:38747868 | DOI:10.11606/s1518-8787.2024058005458

Front Immunol. 2024 Apr 30;15:1396752. doi: 10.3389/fimmu.2024.1396752. eCollection 2024.

ABSTRACT

OBJECTIVES: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice.

METHODS: Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality.

RESULTS: The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs.

CONCLUSION: These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.

PMID:38745663 | PMC:PMC11091284 | DOI:10.3389/fimmu.2024.1396752

Int J Nurs Stud Adv. 2022 Apr 18;4:100079. doi: 10.1016/j.ijnsa.2022.100079. eCollection 2022 Dec.

ABSTRACT

BACKGROUND: Despite good evidence that supports improved clinical health outcomes and the cost effectiveness of nurse-pharmacist collaboration for promoting medication safety among adults in acute care settings, there is limited research in community settings.

OBJECTIVE: This scoping review examines, maps, and identifies gaps in the existing literature on nurse-pharmacist collaboration to augment medication safety among community-dwelling adults.

DESIGN: Setting(s): Community setting.

PARTICIPANTS: This review consists of 3,464 participants across 23 studies.

METHODS: We used the enhanced Arksey and O'Malley framework by Levac and colleagues. Studies from MEDLINE, CINAHL, ProQuest, Scopus, and PubMed databases implementing medication safety through nurse-pharmacist collaboration for community-dwelling adults were included. We extracted data according to country of origin, intervention, and relevance to the current review.

RESULTS: Twenty-three studies were included in this review. Nurse-pharmacist collaborations in community settings are still evolving and are in a nascent form. Five sub-themes emerged from literature review of collaboration between nurses and pharmacists in community settings for medication safety. They are creating new opportunities to address gaps in community medication safety, enabling complementary interprofessional roles in medication safety, facilitating of efficient and cost-effective measures for medication safety, diverse nature of assessments done by nurses and pharmacists, and incohesive teams due to poor collaborative practices.

CONCLUSIONS: Nurse-pharmacist collaborations in community settings improved disease management, prevented adverse drug events, and reduced hospitalizations. They resulted in early identification and correction of medication safety related issues, reduced wait periods to see general practitioners, and enhanced chronic disease self-management skills among community-dwelling adults. There is a need to improve existing systems and policies through research for sustaining such collaborations especially in community settings.

PMID:38745597 | PMC:PMC11080473 | DOI:10.1016/j.ijnsa.2022.100079

J Cancer Res Clin Oncol. 2024 May 14;150(5):252. doi: 10.1007/s00432-024-05713-6.

ABSTRACT

INTRODUCTION: Adjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.

METHODS: In the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients' ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.

RESULTS: The preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60-65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18-22% for ICI and + 15% for TT.

CONCLUSION: Our study highlights the importance of understanding the patient's perspective and a potential difference to the doctor's view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

PMID:38743104 | DOI:10.1007/s00432-024-05713-6

JIMD Rep. 2024 Apr 16;65(3):156-162. doi: 10.1002/jmd2.12421. eCollection 2024 May.

ABSTRACT

Type II D-2-Hydroxyglutaric aciduria (T2D2HGA) is caused by a gain-of-function pathogenic variant in Isocitrate Dehydrogenase 2 (IDH2). Patients with T2D2HGA commonly present with developmental delay, seizures, cardiomyopathy, and arrhythmias. The recently approved IDH2-inhibitor Enasidenib targets the p.Arg140Gln pathogenic IDH2 variant and decreases production of D2HGA. We present a 7-year-old female with T2D2HGA due to the p.Arg140Gln variant. She was diagnosed at 3-years-old after presenting with global developmental delay, leukoencephalopathy, communicating hydrocephalus, seizures, and dilated cardiomyopathy. At age 3 years 11 months, 50 mg Enasidenib daily was initiated. Primary outcomes included seizure frequency, hospital admissions, development, and cardiac structure. Laboratories were monitored biweekly for common Enasidenib side effects. Our patient tolerated Enasidenib well. Urine 2-HGA decreased significantly from 244 mg/g creatinine to undetectable within 2 weeks of treatment. Inpatient admissions decreased from 8 during the 2 years preceding treatment to 1 during treatment. She has been seizure-free since Enasidenib initiation. Echocardiography showed improvement in dilated cardiomyopathy with normal left ventricular systolic function. Developmental assessment demonstrated improvements in gross motor, fine motor, language, and socialization domains. Treatment was complicated by mild elevations in alanine transaminase (118 IU/L, range 0-28) and creatine kinase (334 U/L, range 45-198) that resolved by decreasing Enasidenib dosing frequency to three times weekly. Enasidenib is a viable treatment for Type II D2HGA with benefits including developmental gains, fewer acute medical interventions, and cardiomyopathy improvement. While drug-induced hepatitis is a novel adverse effect of Enasidenib, it can be ameliorated by decreasing dose frequency.

PMID:38736636 | PMC:PMC11078709 | DOI:10.1002/jmd2.12421

Cancer Immunol Immunother. 2024 May 11;73(7):126. doi: 10.1007/s00262-024-03707-4.

ABSTRACT

BACKGROUND: Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development.

METHODS: This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs.

RESULTS: Our study included 181 patients (median age: 82 years, range: 80-94), mostly men (73%), with a performance status of 0-1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/μL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118.

CONCLUSION: IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

PMID:38733406 | DOI:10.1007/s00262-024-03707-4

JCO Clin Cancer Inform. 2024 May;8:e2300159. doi: 10.1200/CCI.23.00159.

ABSTRACT

PURPOSE: We present and validate a rule-based algorithm for the detection of moderate to severe liver-related immune-related adverse events (irAEs) in a real-world patient cohort. The algorithm can be applied to studies of irAEs in large data sets.

METHODS: We developed a set of criteria to define hepatic irAEs. The criteria include: the temporality of elevated laboratory measurements in the first 2-14 weeks of immune checkpoint inhibitor (ICI) treatment, steroid intervention within 2 weeks of the onset of elevated laboratory measurements, and intervention with a duration of at least 2 weeks. These criteria are based on the kinetics of patients who experienced moderate to severe hepatotoxicity (Common Terminology Criteria for Adverse Events grades 2-4). We applied these criteria to a retrospective cohort of 682 patients diagnosed with hepatocellular carcinoma and treated with ICI. All patients were required to have baseline laboratory measurements before and after the initiation of ICI.

RESULTS: A set of 63 equally sampled patients were reviewed by two blinded, clinical adjudicators. Disagreements were reviewed and consensus was taken to be the ground truth. Of these, 25 patients with irAEs were identified, 16 were determined to be hepatic irAEs, 36 patients were nonadverse events, and two patients were of indeterminant status. Reviewers agreed in 44 of 63 patients, including 19 patients with irAEs (0.70 concordance, Fleiss' kappa: 0.43). By comparison, the algorithm achieved a sensitivity and specificity of identifying hepatic irAEs of 0.63 and 0.81, respectively, with a test efficiency (percent correctly classified) of 0.78 and outcome-weighted F1 score of 0.74.

CONCLUSION: The algorithm achieves greater concordance with the ground truth than either individual clinical adjudicator for the detection of irAEs.

PMID:38728613 | DOI:10.1200/CCI.23.00159

J Immunother Precis Oncol. 2024 May 2;7(2):73-81. doi: 10.36401/JIPO-23-16. eCollection 2024 May.

ABSTRACT

INTRODUCTION: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance.

METHODS: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The primary objective of dose escalation phase Ib was to assess safety, tolerability, and recommended phase II dose. The primary objective of the phase II expansion study was to assess the combination's antitumor activity, including objective response rate and clinical benefit rate.

RESULTS: A total of eight patients (five in phase Ib and three in phase II) were evaluable for adverse events (AEs) at our study site. All eight patients experienced at least grade 1 AE. The most common treatment-related AEs were increased serum aspartate aminotransferase (38%), fatigue (38%), anemia (25%), increased alkaline phosphatase (25%), hyperbilirubinemia (25%), hypocalcemia (25%), and hypoalbuminemia (25%). Most of these AEs were grade 1 or 2. None of the patients experienced grade 4 AEs and no drug-related fatal AEs were reported among the eight patients treated in the study. One (13%) patient had stable disease (SD) (captured as unknown by the study sponsor because the evaluation criteria set per protocol was not met) and three (38%) patients had progressive disease. Four (50%) patients developed clinical disease progression based on investigator evaluation. One patient with pancreatic cancer achieved immune-related SD for 26 months while on the study treatments.

CONCLUSION: The study completed phase Ib dose escalation and phase II. However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored.

PMID:38721402 | PMC:PMC11075470 | DOI:10.36401/JIPO-23-16

Drug Saf. 2024 Jun;47(6):571-573. doi: 10.1007/s40264-024-01441-5. Epub 2024 May 8.

NO ABSTRACT

PMID:38720115 | DOI:10.1007/s40264-024-01441-5

Clin Rheumatol. 2024 May 8. doi: 10.1007/s10067-024-07000-8. Online ahead of print.

ABSTRACT

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.

PMID:38720163 | DOI:10.1007/s10067-024-07000-8

BMJ. 2024 May 7;385:e074892. doi: 10.1136/bmj-2023-074892.

ABSTRACT

Polypharmacy is common in older adults and is associated with adverse drug events, cognitive and functional impairment, increased healthcare costs, and increased risk of frailty, falls, hospitalizations, and mortality. Many barriers exist to deprescribing, but increased efforts have been made to develop and implement deprescribing interventions that overcome them. This narrative review describes intervention components and summarizes findings from published randomized controlled trials that have tested deprescribing interventions in older adults with polypharmacy, as well as reports on ongoing trials, guidelines, and resources that can be used to facilitate deprescribing. Most interventions were medication reviews in primary care settings, and many contained components such as shared decision making and/or a focus on patient care priorities, training for healthcare professionals, patient facing education materials, and involvement of family members, representing great heterogeneity in interventions addressing polypharmacy in older adults. Just over half of study interventions were found to perform better than usual care in at least one of their primary outcomes, and most study interventions were assessed over 12 months or less.

PMID:38719530 | DOI:10.1136/bmj-2023-074892

Drug Ther Bull. 2024 May 6:dtb-2024-000031. doi: 10.1136/dtb.2024.000031. Online ahead of print.

NO ABSTRACT

PMID:38719337 | DOI:10.1136/dtb.2024.000031

Am J Public Health. 2024 Jun;114(6):587-589. doi: 10.2105/AJPH.2024.307673.

NO ABSTRACT

PMID:38718337 | DOI:10.2105/AJPH.2024.307673

JMIR Med Inform. 2024 May 1;12:e50164. doi: 10.2196/50164.

ABSTRACT

BACKGROUND: Tolvaptan is the only US Food and Drug Administration-approved drug to slow the progression of autosomal dominant polycystic kidney disease (ADPKD), but it requires strict clinical monitoring due to potential serious adverse events.

OBJECTIVE: We aimed to share our experience in developing and implementing an electronic health record (EHR)-based application to monitor patients with ADPKD who were initiated on tolvaptan.

METHODS: The application was developed in collaboration with clinical informatics professionals based on our clinical protocol with frequent laboratory test monitoring to detect early drug-related toxicity. The application streamlined the clinical workflow and enabled our nursing team to take appropriate actions in real time to prevent drug-related serious adverse events. We retrospectively analyzed the characteristics of the enrolled patients.

RESULTS: As of September 2022, a total of 214 patients were enrolled in the tolvaptan program across all Mayo Clinic sites. Of these, 126 were enrolled in the Tolvaptan Monitoring Registry application and 88 in the Past Tolvaptan Patients application. The mean age at enrollment was 43.1 (SD 9.9) years. A total of 20 (9.3%) patients developed liver toxicity, but only 5 (2.3%) had to discontinue the drug. The 2 EHR-based applications allowed consolidation of all necessary patient information and real-time data management at the individual or population level. This approach facilitated efficient staff workflow, monitoring of drug-related adverse events, and timely prescription renewal.

CONCLUSIONS: Our study highlights the feasibility of integrating digital applications into the EHR workflow to facilitate efficient and safe care delivery for patients enrolled in a tolvaptan program. This workflow needs further validation but could be extended to other health care systems managing chronic diseases requiring drug monitoring.

PMID:38717378 | DOI:10.2196/50164

J Assoc Physicians India. 2023 Oct;71(10):96-98. doi: 10.59556/japi.71.0309.

ABSTRACT

Statins are drugs for preventing cardiac events in the elderly population. Statins are well tolerated with a lower reported incidence of serious side effects (<0.15%) like myopathy and elevated transaminases [>3× upper limit of normal (ULN)]. Serious adverse effects of statins like statin-associated myopathy range from mild muscle pain to rhabdomyolysis. Drug-induced liver injury (DILI) is another adverse effect of statin use, typically presenting with an acute hepatocellular liver injury pattern as mixed or cholestatic injury. Symptoms usually disappear after 3 months of discontinuation of statins. Some patients require immunosuppression with steroids, intravenous immunoglobulin, or rituximab for management of rhabdomyolysis. DILI can be rapidly reversed by the stoppage of the statins if the enzyme elevation is more than twice the normal. Elderly patients are particularly at increased risk of such adverse effects, emphasizing a need for rational prescription of statins in older adults and close monitoring. We report a case of an elderly presenting with paraparesis and later diagnosed to be a case of statin-induced myositis that significantly improved with prompt management. How to cite this article: Kashyap K, Bisht K, Dhar M, et al. Atorvastatin-induced Myositis and Drug-induced Liver Injury. J Assoc Physicians India 2023;71(10):96-98.

PMID:38716533 | DOI:10.59556/japi.71.0309

Front Public Health. 2024 Apr 23;12:1392180. doi: 10.3389/fpubh.2024.1392180. eCollection 2024.

ABSTRACT

INTRODUCTION: Social media platforms serve as a valuable resource for users to share health-related information, aiding in the monitoring of adverse events linked to medications and treatments in drug safety surveillance. However, extracting drug-related adverse events accurately and efficiently from social media poses challenges in both natural language processing research and the pharmacovigilance domain.

METHOD: Recognizing the lack of detailed implementation and evaluation of Bidirectional Encoder Representations from Transformers (BERT)-based models for drug adverse event extraction on social media, we developed a BERT-based language model tailored to identifying drug adverse events in this context. Our model utilized publicly available labeled adverse event data from the ADE-Corpus-V2. Constructing the BERT-based model involved optimizing key hyperparameters, such as the number of training epochs, batch size, and learning rate. Through ten hold-out evaluations on ADE-Corpus-V2 data and external social media datasets, our model consistently demonstrated high accuracy in drug adverse event detection.

RESULT: The hold-out evaluations resulted in average F1 scores of 0.8575, 0.9049, and 0.9813 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. External validation using human-labeled adverse event tweets data from SMM4H further substantiated the effectiveness of our model, yielding F1 scores 0.8127, 0.8068, and 0.9790 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively.

DISCUSSION: This study not only showcases the effectiveness of BERT-based language models in accurately identifying drug-related adverse events in the dynamic landscape of social media data, but also addresses the need for the implementation of a comprehensive study design and evaluation. By doing so, we contribute to the advancement of pharmacovigilance practices and methodologies in the context of emerging information sources like social media.

PMID:38716250 | PMC:PMC11074401 | DOI:10.3389/fpubh.2024.1392180

Int J Crit Illn Inj Sci. 2024 Jan-Mar;14(1):32-36. doi: 10.4103/ijciis.ijciis_57_23. Epub 2024 Mar 27.

ABSTRACT

BACKGROUND: Multiple factors influence the fall risk in end-stage kidney disease. This study aims to investigate how medication factors influence the interpretation of fall risk due to age, gender, and years of dialysis treatment among patients undergoing hemodialysis (HD).

METHODS: A cross-sectional study was carried out in 2023 using the Johns Hopkins Fall Risk Assessment tool. Participants were recruited from the HD unit at a tertiary care academic medical center in Ajman, UAE. Data were analyzed between different ages, genders, and years on HD categories with or without medication factors.

RESULTS: Data were collected and analyzed for 44 patients. The fall risk of the study population assessed with the Kruskal-Wallis test showed no difference between different age groups (P = 0.43) but did show a significant difference when the score of medication factor was removed from the fall risk estimation (P = 0.002). A pairwise analysis showed fall risk score of the age group 46-60 years was differing from the age cohort >60 (P < 0.001). A positive moderate correlation (Spearman's correlation coefficient 0.514 was found, with a P < 0.001) was seen with an increase in age and fall risk only when the medication factor was removed from the fall risk estimation. Results on gender or duration of dialysis were insignificant.

CONCLUSION: Medication factors being a significant contributor to fall risk among the study population was found to mask the fall risk difference between age groups 46-60 years and >60 years. Such influence was not found for gender or duration of dialysis.

PMID:38715751 | PMC:PMC11073637 | DOI:10.4103/ijciis.ijciis_57_23

Ther Adv Drug Saf. 2024 May 6;15:20420986241244585. doi: 10.1177/20420986241244585. eCollection 2024.

ABSTRACT

BACKGROUND: Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to antidepressants. Therefore, drug-induced liver injury (DILI) caused by antidepressants deserves more attention.

OBJECTIVES: To investigate DILI adverse events reported due to antidepressant use in the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database.

RESEARCH DESIGN: A disproportionality analysis of spontaneously reported adverse events was conducted to assess the association between antidepressant drugs and DILI.

METHODS: FAERS data from 1 January 2004 to 31 December 2021 were compiled and analyzed using the reporting odds ratio (ROR) and information component (IC).

RESULTS: As per the FAERS database, of the 324,588 cases that were administered antidepressants, 10,355 were identified as cases with DILI. Among the identified 42 antidepressants, nefazodone (n = 47, ROR = 7.79, IC = 2.91), fluvoxamine (n = 29, ROR = 4.69, IC = 2.20), and clomipramine (n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin (n = 3, ROR = 21.46, IC = 3.99), nefazodone (n = 264, ROR = 18.67, IC = 3.84), and maprotiline (n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone (n = 187, ROR = 12.71, IC = 0.48), clomipramine (n = 35, ROR = 2.07, IC = 0.26), and mirtazapine (n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders. Only nefazodone elicited hepatic failure signals (n = 48, ROR = 18.64, IC = 4.16). There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine.

CONCLUSION: A significant association was observed between DILI and nefazodone. Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite causal link between antidepressants and DILI. Additional research is required to assess new-generation antidepressants for their propensity to cause DILI.

PMID:38715707 | PMC:PMC11075604 | DOI:10.1177/20420986241244585

Drug Saf. 2024 Jun;47(6):585-599. doi: 10.1007/s40264-024-01423-7. Epub 2024 May 7.

ABSTRACT

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

PMID:38713347 | DOI:10.1007/s40264-024-01423-7

Drug Saf. 2024 Jun;47(6):575-584. doi: 10.1007/s40264-024-01421-9. Epub 2024 May 7.

ABSTRACT

BACKGROUND AND AIM: Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts.

METHODS: We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting.

RESULTS: Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts.

CONCLUSIONS: The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence.

PMID:38713346 | DOI:10.1007/s40264-024-01421-9