Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study.

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.

Antiseizure adverse drug reaction and associated factors among epileptic patients at Jimma Medical Center: a prospective observational study.

A growing body of evidence suggests that adverse drug reactions (ADRs) are a major cause of morbidity and mortality in the healthcare system. Fifteen to twenty-five percent of patients with epilepsy discontinued antiseizure drugs (ASDs) within 6 months of therapy owing to intolerable adverse drug reactions. In Ethiopia, the prevalence of antiseizure adverse drug reactions and associated factors was not extensively conducted in advanced settings like Jimma Medical Centers. Hence, the objective of this study is to assess patterns of adverse drug reactions and associated factors among ambulatory epileptic patients at tertiary hospitals in Ethiopia. A hospital-based prospective observational study was spanned for 1 year. Two hundred ninety patients were consecutively recruited into the study from all epileptic patients attending the ambulatory clinic. Relevant data were collected through patient interviews and medical chart reviews. The causality assessment was done by using the Naranjo Probability Scale. Epi-Data manager version 4.6.0.4 was used for data entry and statistical analysis was performed by Statistical Package for Social Science version 25.0 (SPSS). Stepwise backward logistic regression analysis was done to identify factors that increase the risk of antiseizure adverse drug reactions. The mean (± SD) age of the participants were 29.91(± 11.26) years. The overall prevalence of ADR was 33.8% (95% CI 29.2-39.9%). A total of 110 adverse drug reactions were identified among 98 patients with an average of 1.12 per patient. ADRs were frequently reported with phenobarbital (52.04%) and phenytoin (34.70%). The commonly identified adverse drug reactions were epigastric pain (27.55%) and central nervous system drowsiness (23.46%). Comorbidity (AOR = 5.91, 95% CI (2.14-16.32), seizure-free period of fewer than 2 years (AOR = 1.94, 95% CI (1.18-3.19), and polytherapy (AOR = 1.35, 95% CI (1.80-2.26) were significantly associated with adverse drug reactions. This trial had a comparatively high percentage of adverse medication reactions. Adverse medication reactions were more common in patients with polytherapy, comorbidities, and seizure-free durations less than two years. Therefore, medical practitioners should advise patients who exhibit these traits on how to reduce or avoid bad drug responses or provide comfort in the event of small incidents.

Monitoring of Adverse Events and Safety in Autoinflammatory Diseases: Real-Life Data from the Eurofever Registry.

OBJECTIVES: The study is aimed to evaluate the impact of safety events in the Eurofever registry for Autoinflammatory diseases. METHODS: This was a retrospective and longitudinal observational multicentre study. Data were retrieved from the international registry Eurofever, starting patients' enrolment since 2009. All moderate, severe, or very severe AEs reported by treating physician in Eurofever were analyzed regardless of a possible suspected causal relationship to any therapies and according to the latest release of the Medical Dictionary for Regulatory Activities. RESULTS: Complete information on safety were available in 2464 patients enrolled in the registry. In 1499 of them retrospective data encompassing the period from disease onset to enrolment were available, whereas 965 consecutive patients entered in the longitudinal part of the study. A total of 479 AEs have been reported in 275 patients. Eighty-two AEs were reported as serious and 99 were drug-related according to the physicians. Infections or infestations (94; 19.6%), gastrointestinal disorders (66; 13.8%), nervous system disorders (41; 8.6%) and systemic disorders or administration site reactions (35; 7.3%) were the most frequent reported events. The highest absolute number of drug-related AEs were related to biologic DMARDs (40/99 reports, 40,4%) and colchicine (31/99 reports, 31.3%). CONCLUSIONS: Present study shows the importance of a longitudinal and homogeneous registration of the AEs in rare conditions, with a particular focus on the safety profile of the treatments used in these conditions.

Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system.

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.

Mortality and years of life lost related to adverse drug events in Brazil.

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.

Rare and severe adverse events in children with inflammatory bowel disease: analysis of data from the PIBD-SETQuality Safety Registry.

BACKGROUND: Rare and severe adverse events can occur in children with inflammatory bowel disease (IBD), and the relationship with disease or drug treatment is often uncertain. We aimed to establish a method of reporting adverse events of interest in children with IBD, allowing for estimates of incidence rates with comparison between different regions, and, if possible, to compare with published data on rates of adverse events in children overall. METHODS: For this analysis, we used data from the Paediatric Inflammatory Bowel Disease Network for Safety, Efficacy and Treatment and Quality improvement of care (PIBD-SETQuality) Safety Registry, which collects data on multiple rare and severe adverse events in children younger than 19 years with IBD. Overall, the registry collected data on ten prespecified rare and severe adverse events in children with IBD, as established by a panel of paediatric IBD experts, via reports from paediatric gastroenterologists at participating hospitals between Nov 1, 2016, and March 31, 2023. Reporting physicians, who could only be paediatric gastroenterologists or IBD nurses reporting on behalf of paediatric gastroenterologists, were recruited through invitations sent to both national and international IBD networks and at conferences. Once per month, participating paediatric gastroenterologists received an email with an anonymous and unique link to an online survey asking them to report whether any of ten rare and severe adverse events had occurred in a patient in their paediatric-IBD population in the previous month. Prevalent or retrospective rare and severe adverse events were excluded, as were events occurring in children with an unconfirmed diagnosis of IBD or for whom inflammatory colitis was part of a monogenic immunodeficiency disorder. Duplicates and events that did not meet the definitions and criteria were excluded. Physicians could also report other, non-categorised adverse events if they considered them rare and severe. In case of no response, up to two reminders were sent for each per-month survey. Annual denominator data surveys were sent to obtain the total number of person-years for the estimation of incidence rates, which were calculated via Poisson regression models. FINDINGS: Responses were gathered from 220 paediatric gastroenterologists from 167 centres. 121 centres were in Europe, 23 centres were in North America, 17 centres were in Asia, and six centres were in Oceania. Combined, the total population with paediatric IBD consisted of an estimated 30 193 children with 114 528 person-years of follow-up. 451 adverse events were initially reported. After excluding and reorganising adverse events, 402 were eligible; 261 (65%) were categorised and 141 (35%) were non-categorised. The most frequently reported adverse events were venous-thromboembolic events (n=66), renal failure (n=43), opportunistic infections (n=42), and cancer (n=33). Haemophagocytic lymphohistiocytosis (n=4) and liver failure (n=3) were the least frequently reported adverse events. Incidence rates per 10 000 person-years were 5·50 (95% CI 4·25-6·97) for venous-thromboembolic events, 3·75 (2·74-4·99) for renal failure, 3·67 (2·67-4·89) for opportunistic infection, and 2·88 (2·01-3·98) for cancer. Of 66 venous-thromboembolic events, 31 (47%) involved cerebral venous sinus thrombosis at an incidence rate of 2·71 (95% CI 1·86-3·77). INTERPRETATION: The PIBD-SETQuality Safety Registry enabled us to identify incidence rates of rare and severe adverse events in children with IBD. Our findings can guide physicians and enhance awareness of the incidence of adverse events in children with IBD that are considered to be rare. FUNDING: EU Horizon 2020 Research and Innovation Programme.

Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

Adverse drug reactions in paediatric surgery: prospective study on frequency and risk related factors.

BACKGROUND: Paediatric patients are especially prone to experiencing adverse drug reactions (ADRs), and the surgical environment gathers many conditions for such reactions to occur. Additionally, little information exists in the literature on ADRs in the paediatric surgical population. We aimed to quantify the ADR frequency in this population, and to investigate the characteristics and risk factors associated with ADR development. METHODS: A prospective observational study was conducted in a cohort of 311 paediatric patients, aged 1-16 years, admitted for surgery at a tertiary referral hospital in Spain (2019-2021). Incidence rates were used to assess ADR frequency. Odds ratios (ORs) were calculated to evaluate the influence of potential risk factors on ADR development. RESULTS: Distinct ADRs (103) were detected in 80 patients (25.7%). The most frequent being hypotension (N = 32; 35%), nausea (N = 16; 15.5%), and emergence delirium (N = 16; 15.5%). Most ADRs occurred because of drug-drug interactions. The combination of sevoflurane and fentanyl was responsible for most of these events (N = 32; 31.1%). The variable most robustly associated to ADR development, was the number of off-label drugs prescribed per patient (OR = 2.99; 95% CI 1.73 to 5.16), followed by the number of drugs prescribed per patient (OR = 1.26, 95% CI 1.13 to 1.41), and older age (OR = 1.26, 95% CI 1.07 to 1.49). The severity of ADRs was assessed according to the criteria of Venulet and the Spanish Pharmacovigilance System. According to both methods, only four ADRs (3.9%) were considered serious. CONCLUSIONS: ADRs have a high incidence rate in the paediatric surgical population. The off-label use of drugs is a key risk factor for ADRs development.

Determination of drug-related problems in the hematology service: a prospective interventional study.

BACKGROUND: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey. METHODS: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version. RESULTS: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033-20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125-1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%). CONCLUSIONS: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

Trends in Adverse Event Reporting Before and After the Introduction of the Med Safety App in Nigeria.

INTRODUCTION: Spontaneous reporting of adverse events (AEs) is a mainstay of pharmacovigilance, and an ongoing challenge is how to ensure that more high-quality reports are collected for comprehensive information provision. The Med Safety App, a smartphone-based application, was launched in Nigeria in November 2020 to provide an electronic platform for users to seamlessly report AEs. There has been a paucity of evidence on the use of this application or other mobile applications for reporting adverse drug reactions/AEs following immunization in the Nigerian environment. OBJECTIVE: The aim of this study was to evaluate the trends in adverse event reporting before and after the introduction of the Med Safety App in Nigeria. METHODS: This was a retrospective, observational study using data from the VigiFlow database to compare adverse event reporting in Nigeria before and after the deployment of the Med Safety App. The baseline period was 1st April 2019 to 30th October 2020 and the comparison period was 1st November 2020 to 31st May 2022. We used Vigilance Hub, the back-end system for the Med Safety App, to extract data on App downloads and de-identified user statistics. Data were summarized using descriptive statistics, frequencies and proportions. Quality was assessed by assigning a completeness score to each individual case safety report. The Kruskal-Wallis test was used to test for differences in medians between groups. RESULTS: Following deployment of the App, the Nigerian National Pharmacovigilance Centre recorded an increase in the total number of adverse event reports received in VigiFlow, from 2051 in the baseline period to 18,995 following deployment of the App, with 81.7% of those reported via the Med Safety App. There was a reduction in the proportion of paper-based reporting from 98.4 to 15.7% post-deployment, and direct reporting by consumers increased from 2.7 to 17.6%. Of the 15,526 reports submitted via the App, 15,111 (97.3%) had a completeness score above 70% and 6993 (45%) had a completeness score of 100%. The median completeness score of adverse event reports on the Med Safety App was 6 out of 7. On bivariate analysis using the Kruskal-Wallis test, there was an association between means of reporting and completeness score, and this association was significant, with a p value of 0.0001, which may reflect the validation rules that are applied within the App. CONCLUSION: Deployment of the Med Safety App increased both the number and quality of adverse event reports; however, more awareness and capacity building are needed to strengthen and sustain reporting on the tool by all categories of healthcare professionals and consumers/patients.

Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

Adverse event signal mining and serious adverse event influencing factor analysis of fulvestrant based on FAERS database.

Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack of relevant reports on adverse reaction data mining for fulvestrant. To perform data mining on adverse events (AEs) associated with fulvestrant and explore the risk factors contributing to severe AEs, providing a reference for the rational use of fulvestrant in clinical practice. Retrieved adverse event report information associated with fulvestrant from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the period from market introduction to September 30, 2023. Suspicious AEs were screened using the reporting odds ratio (ROR) and proportional reporting ratio methods based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe AEs to explore the risk factors associated with fulvestrant-induced severe AEs. A total of 6947 reports related to AEs associated with fulvestrant were obtained, including 5924 reports of severe AEs and 1023 reports of non-severe AEs. Using the disproportionality analysis method, a total of 210 valid AEs were identified for fulvestrant, with 45 AEs (21.43%) not listed in the product labeling, involving 11 systems and organs. The AEs associated with fulvestrant were sorted by frequency of occurrence, with neutropenia (325 cases) having the highest number of reports. By signal strength, injection site pruritus showed the strongest signal (ROR = 658.43). The results of the logistic regression analysis showed that concurrent use of medications with extremely high protein binding (≥ 98%) is an independent risk factor for severe AEs associated with fulvestrant. Age served as a protective factor for fulvestrant-related AEs. The co-administration of fulvestrant with CYP3A4 enzyme inhibitors did not show statistically significant correlation with the occurrence of severe AEs. Co-administration of drugs with extremely high protein binding (≥ 98%) may increase the risk of severe adverse reactions of fulvestrant. Meanwhile, age (60-74 years) may reduce the risk of severe AEs of fulvestrant. However, further clinical research is still needed to explore and verify whether there is interaction between fulvestrant and drugs with high protein binding through more clinical studies.

A Real-world Toxicity Atlas Shows that Adverse Events of Combination Therapies Commonly Result in Additive Interactions.

PURPOSE: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. EXPERIMENTAL DESIGN: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects. To capture these patterns, we trained a convolutional neural network (CNN) autoencoder using 7,300 single-drug heat maps. In addition, statistical synergy analyses were performed on the basis of BLISS independence or χ2 testing. RESULTS: The trained CNN model was able to decode patterns, showing that adverse events occur in global rather than isolated and unique patterns. Patterns were not likely to be attributed to disease symptoms given their relatively limited contribution to drug-associated adverse events. Pattern recognition was validated using trial data from ClinicalTrials.gov and drug combination data. We examined the adverse event interactions of 140 drug combinations known to be avoided in the clinic and found that near all of them showed additive rather than synergistic interactions, also when assessed statistically. CONCLUSIONS: Our study provides a framework for analyzing adverse events and suggests that adverse drug interactions commonly result in additive effects with a high level of overlap of adverse event patterns. These real-world insights may advance the implementation of new combination therapies in clinical practice.

[Risk factors associated to adverse drug events in hospitalized patients]. / Factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados.

OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients. METHODS: Analytical, observational, case-control study of patients with ADE. For statistical analysis, the following were calculated: percentages, frequencies, averages; odds ratio, χ2 test and multiple binary logistic regression. Data analysis was carried out with the Statistical Package, for the Social Sciences 23 program. RESULTS: A 132 patients were registered: 66 cases (26 EM and 40 RAM) and 66 controls; with average age of 35 years (SD 17.41). The prevalence of adverse drug events was 3.6%. The most frequently reported medications: antibiotics and anti-inflammatories. The frequency of adverse events by gender was: 39.3% men and 60.7% women. The services with the greatest patient care: emergencies, surgery; the most frequent route of administration: intravenous (32.3%). The main symptoms: skin. (32.3%) frequent symptoms: cutaneous. Associated symptoms RAM: type A pruritus (OR: 8.5; p = 0.001; IC95%: 0.035-0.393), type B pruritus (OR: 11; p = 0.001; CI95%: 0.021-0.368) urticaria (OR: 19; p = 0.005; IC95%: 0.007-0.412). Risk factors Associated EAM: female (OR: 2.6; p = 0.05; CI95%: 1.33-5.43), history of allergy (OR: 3.4; p = 0.033; CI95%: 1.04-8.40), prolonged hospital stays (OR: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONS: Patient safety is a priority when prescribing any drug, which represents a key point in prevention.

OBJETIVO: Determinar la prevalencia, causas y factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados. MÉTODOS: Estudio de casos y controles, observacional, analítico, llevado a cabo en pacientes con eventos adversos a medicamentos. Para el análisis estadístico se calcularon: porcentajes, frecuencias, promedios; razón de momios, prueba de χ2 y regresión logística binaria múltiple. El análisis de los datos se efectuó con el programa Statistical Package, for the Social Sciencies 23. RESULTADOS: Se registraron 132 pacientes: 66 casos (26 EM y 40 RAM) y 66 controles, con edad promedio de 35 años (DS 17.41). La prevalencia de eventos adversos a medicamentos fue del 3.6%. Los medicamentos reportados con mayor frecuencia: antibióticos y antiinflamatorios. La frecuencia de eventos adversos por género fue: 39.3% hombres y 60.7% mujeres. Los servicios con mayor atención de pacientes: urgencias y cirugía; vía de administración más frecuente: intravenosa (32.3%). Los principales síntomas fueron los cutáneos. Los síntomas asociados con reacción adversa a medicamentos: prurito tipo A (RM: 8.5; p = 0.001; IC95%: 0.035-0.393), prurito tipo B (RM: 11; p = 0.001; IC95%: 0.021-0.368) urticaria (RM: 19; p = 0.005; IC95%: 0.007-0.412). Los factores de riesgo asociados con eventos adversos a medicamentos: mujer (RM: 2.6; p = 0.05; IC95%: 1.33-5.43), antecedente de alergia (RM: 3.4 p = 0.033; (IC95%: 1.04-8.40) y estancia hospitalaria prolongada (RM: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONES: La seguridad de los pacientes es una prioridad al momento de prescribir cualquier fármaco, lo que representa un punto clave en la prevención.

The temporal association between adverse drug reactions and antirheumatic drugs utilisation in Western Australia: a retrospective study from real-world data (1995-2015).

BACKGROUND/OBJECTIVES: Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US). METHODS: Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2). RESULTS: A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period. CONCLUSIONS: The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Medication use among the oldest old in the Faroe Islands-A national cross-sectional study.

Aging is often associated with an increasing number of comorbidities that warrant use of multiple drugs which increases the use of potentially inappropriate medications (PIMs), drug-drug interactions (DDIs) and drug-related problems (DRPs). The aim is to assess the prevalence of polypharmacy, PIMs, DDIs and DRPs among Faroese residents aged ≥90 years. In this population-based cross-sectional study, 494 individuals ≥90 years were invited and 298 (60%) participated. A pharmacist-led medication review was performed based on self-information, electronic patient journal and the Faroese Prescription Registry. The prevalence of polypharmacy was 74% with no sex-difference. Approximately 60% of participants used PIMs, primarily benzodiazepines and proton pump inhibitors, the latter being a frequently implicated medication in DRPs. Opioid use was low compared with other Nordic studies. DRPs were observed for 79% with discrepancies in the medication lists as the most common cause, and DDIs were identified for 47% of participants, mostly moderately clinically relevant DDIs. In conclusion, the medication use among the oldest old Faroese resembled that in other Nordic countries with a high prevalence of polypharmacy and use of PIMs, especially PPIs and benzodiazepines. However, no sex-difference was noted in medication use and the use of opioids was low.

Side effects of drug-antibody conjugates enfortumab-vedotin and sacituzumab-govitecan in targeted therapy in cancer.

OBJECTIVE: Antibody-drug conjugates (ADC), enfortumab-vedotin (EV) and sacituzumab-govitecan are new drugs in the treatment of urologic tumors, whose safety profile has not been fully investigated. Therefore, the aim of our study was to evaluate adverse events related to both agents reported to VigiBase, the World Health Organization's global pharmacovigilance database. METHODS: We employed Bayesian disproportionality analysis based on the information component (IC) to explore the safety profile associated with both therapies. Additionally, we used the proportional reporting ratio approach to examine the safety profile further. RESULTS: We identified 41,752 reports connected to ADC therapy (EV: n=5359; SG: n=36,393). In the EV subgroup, most reports were associated with dermatologic (38.6%), neurologic adverse events (16.5%), or adverse laboratory assessments (19.4%). In contrast, reports in the SG subgroup were mainly associated with gastrointestinal adverse events (24.2%) and adverse laboratory assessments (39.0%). Adverse laboratory assessments in both cohorts were often based on haematotoxic adverse events. CONCLUSION: We could provide a comprehensive real-world safety profile of EV and SG using a global pharmacovigilance database. Based on the safety signals explored in this study, further research regarding the impact of these side effects on patient outcomes is justified.