Pharmacoepidemiology and Drug Safety最新文献

Background: Drug-induced immune hemolytic anemia (DIIHA), a rare complication of beta-lactams, lacks population-level data on subclinical antibody prevalence.

Objective: To quantify drug-induced antibody incidence and hematologic impact in beta-lactam-treated patients.

Methods: Prospective cohort of 4040 patients receiving ceftriaxone, piperacillin/trizobactam, piperacillin/sulbactam 2:1 and piperacillin/tazobactam at a Chinese tertiary hospital (2020.1-2020.9). Antibodies were detected via immunoadsorption assays. The primary outcomes were changes in hemoglobin, bilirubin, and lactate dehydrogenase (LDH) levels.

Results: Antibody positivity occurred in 18.07% (730/4040), highest with piperacillin/sulbactam 2:1 (24.02% vs. 0.43% Ceftriaxone, p < 0.001). Seropositive patients had a significant hemoglobin decline (Δ = -5.00 g/L, 95% CI -6.2 to -3.8) and bilirubin elevation (Δ = +0.95 μmol/L, 95% CI +0.4 to +1.5), but only 0.2% (2/730) progressed to severe anemia. Subclinical hemolysis (LDH > 250 U/L) was prevalent (89.3%).

Conclusion: Beta-lactams exhibit high asymptomatic antibody rates (18.07%) with minimal severe hemolysis risk (0.2%). Protocolized monitoring and HLA screening may optimize safety. This first large-scale prospective cohort quantifies the underrecognized epidemic of subclinical antibody formation, challenging traditional pharmacovigilance frameworks that focus solely on overt hemolysis.

Purpose: This nationwide cohort study examined the effects of discontinuation versus continuation of renin-angiotensin system inhibitors (RASis) on major renal and cardiovascular outcomes after the estimated glomerular filtration rate (eGFR) decreased to below 45 mL/min/1.73 m² in patients with type 2 diabetes and treated with RASis.

Methods: Using linked Taiwanese databases with claims and clinical data, we identified patients with type 2 diabetes who used RASis during 2016-2020, and either discontinued or continued RASis within 180 days when their eGFR fell below 45 mL/min/1.73 m². The outcomes of interest included end-stage renal disease (ESRD), myocardial infarction, stroke, heart failure, and all-cause mortality. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for RASi discontinuation versus RASi continuation using on-treatment and intention-to-treat analyses and inverse probability weighting to adjust for baseline and time-varying covariates.

Results: We identified 251 853 eligible patients, of whom 37 108 (15%) discontinued RASis and 214 745 (85%) continued RASis. The on-treatment HR associated with RASi discontinuation was 2.52 (95% CI, 2.33-2.73) for ESRD, 1.18 (1.08-1.30) for myocardial infarction, 1.28 (1.19-1.37) for stroke, 1.18 (1.13-1.24) for heart failure, and 1.77 (1.70-1.84) for all-cause mortality. Results from the intention-to-treat analysis were similar, albeit more conservative. Findings remained consistent across eGFR strata (≥ 30 to < 45 and < 30 mL/min/1.73 m²), urine albumin-creatinine ratio categories (≥ 300 and < 300 mg/g), and patient subgroups with various baseline characteristics.

Conclusion: Our results support continuing RASi treatment even when the eGFR declines to below 45 mL/min/1.73 m² based on potential renal, cardiovascular, and survival benefits.

Purpose: To assess the prevalence of psychotropic use among classroom teachers and to identify associated factors.

Methods: A cross-sectional study was conducted between January and February 2024 in Espírito Santo, Brazil. The study included teachers from 20 state schools selected through probabilistic sampling. Data were collected in person using a self-administered questionnaire that addressed sociodemographic characteristics, working conditions, mental health history, mental health screening scales, and the use of psychotropic medications. Poisson regression with robust variance was employed to estimate the prevalence ratio of psychotropic and antidepressant use. The study was approved by the research ethics committee.

Results: The study included 453 teachers. The prevalence of psychotropic medication use was 20.0% (95% CI: 16.9%-22.9%), while the prevalence of antidepressant use was 16.9% (95% CI: 13.8%-19.8%). In the multivariate analysis, a higher prevalence of psychotropic use was observed among cisgender women (PR = 1.91; 95% CI: 1.07-3.39) and teachers with depressive symptoms (PR = 2.30; 95% CI: 1.26-4.22). Antidepressant use was also more frequent among cisgender women (PR = 2.07; 95% CI: 1.12-3.85) and those with depressive symptoms (PR = 2.01; 95% CI: 1.05-3.82), while teachers working in schools located in Santa Teresa showed a lower prevalence compared to those in Vitória (PR = 0.31; 95% CI: 0.10-0.90).

Conclusion: The findings indicate a considerable prevalence of psychotropic and antidepressant use among teachers, particularly among cisgender women and those presenting depressive symptoms.

Background: Accurate pharmaco-epidemiological assessment of the safety of biological treatments is essential but methodologically challenging.

Aims: This study evaluated how different assumptions regarding treatment switching and treatment episode definitions affect outcome estimates in psoriasis patients, focusing on malignancies and serious infections.

Methods: Data from Danish national registers (2009-2022) were analyzed for hospitalized psoriasis patients treated with ustekinumab, non-biologics, tumor necrosis factor-α inhibitors, and other interleukin inhibitors excluding ustekinumab. Various as-treated approaches were assessed and compared to the Intention-to-Treat (ITT) approach. The as-treated approaches included: (1) RC-switch, considering switching only between ustekinumab and the comparator in question, (2) Bio-switch, considering switches among all biologics, (3) Multi-switch, analyzing all groups simultaneously, and (4) Hierarchy-switch, analyzing switching by a predefined hierarchy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using Cox models. Sensitivity analyses incorporated treatment episodes based on the defined daily dose (DDD) and grace periods.

Results: Broader treatment switching allowances affected outcome estimates. For malignancies, the Bio-switch approach yielded the largest HR changes relative to the ITT. For serious infections, also, Bio-switch produced the largest HR shifts, for example, HR 1.32 (CI 1.09, 1.58) versus ITT HR 1.08 (CI 0.91, 1.29). Sensitivity analyses showed that accounting for episode gaps influenced HRs and widened CIs.

Conclusion: The number of events within the exposure group varied by approaches, influencing the HR estimates. The multi-switch approach effectively captured treatment switching and reduced statistical uncertainty, supporting clearer safety conclusions. Tracking each treatment period with gaps reflects real-world practice but may lower statistical power and should be carefully considered in analyses.

Background: Poor blood pressure control and low adherence to antihypertensives increase the risk for anthracycline-induced cardiotoxicity (AIC) in hypertensive cancer patients. Little is known about whether past adherence to antihypertensive medications can reduce the risk of AIC in patients initiating anthracyclines. We examined adherence to antihypertensives pre-anthracycline initiation and its association with the risk of AIC.

Methods: We conducted a retrospective cohort study using a 25% random sample of IQVIA PharMetrics Plus for Academics US health plan claims, 2006-2022. We identified individuals 18- 64 years old, with hypertension, diagnosed with breast cancer or lymphoma (Hodgkin's or Non-Hodgkin's) 9 months before the anthracycline treatment initiation (index date). Group-based trajectory modeling was used to estimate latent subgroups of antihypertensive adherence before the index date, using monthly proportions of days covered over the 9 months (baseline). Using Cox regression models, we examined the risk of AIC in the 12 months after the index date.

Results: We identified four distinct antihypertensive adherence trajectory groups in the baseline period. In the adjusted model, the risk of AIC was higher in the early decline group (hazard ratio [HR] = 1.67, 95% CI [1.11-2.49]) and the moderate adherence (HR = 1.62, 95% CI [1.16-2.26]) groups compared to the near-perfect adherence group. Comorbidities associated with an increased risk of AIC include diabetes and chronic kidney failure.

Conclusion: Poor adherence to antihypertensives prior to anthracycline use was associated with AIC. Future studies should explore whether select antihypertensive classes are more cardioprotective than others.

Purpose: This study aimed to investigate the proportions of polypharmacy in the macroregions of Brazil, considering socioeconomic and demographic factors and their associations.

Methods: A cross-sectional analysis was conducted using data from the second wave (2019-2021) of ELSI-Brazil. The outcome was self-reported polypharmacy. Independent variables included sociodemographic, health, and behavioral factors, such as diabetes and hypertension. Descriptive analyses incorporated sample weights, and Poisson regression was employed to assess associations between polypharmacy and the independent variables. Analyses were stratified by the five macroregions of Brazil: North, Northeast, Southeast, South, and Central-West.

Results: The study included 6917 participants aged 50 years or older. Differences in polypharmacy prevalence were observed across Brazilian macroregions. In the Central-West, polypharmacy was less frequent among rural residents (PR = 0.84; 95% CI: 0.82-0.85) than among urban residents. In the North, polypharmacy was more frequent among non-white individuals (PR = 1.08; 95% CI: 1.02-1.15) and less frequent among Black individuals (PR = 0.92; 95% CI: 0.88-0.96) compared with white individuals. In the Southeast and South, polypharmacy was more frequent among adults aged 80 years or older (PR = 1.14; 95% CI: 1.08-1.19 and PR = 1.17; 95% CI: 1.08-1.27, respectively) than among younger groups. Although no formal statistical comparisons between regions were performed, the observed estimates and their confidence intervals indicate regional variation in polypharmacy.

Conclusion: This study identified regional disparities in polypharmacy prevalence across Brazil's macroregions, influenced by factors such as age, chronic conditions, and socioeconomic status. Strengthening primary care, promoting rational medication use, addressing inequalities, and integrating prevention strategies are crucial to mitigating its negative impacts.

Purpose: Missing information is common in real-world claims data, particularly on behavioral confounders, for example, smoking. Often one category of the variable, "yes" is partially observed while the other "no" remains completely missing-a pattern we call missing with truncation. A common way to handle these missing values is to naïvely treat missing values as absence of the risk factor, which may lead to substantial misclassification. Standard multiple imputation is impossible as only one level of the variable is observed.

Methods: A case study was conducted using data from the NOVELTY study, including 12 224 people with physician diagnosed asthma and/or COPD (NCT02760329). From this cohort, 9733 patients with complete information were included. This dataset was split into two where the first part was used to train an imputation model and the second part was used to evaluate the imputations based on the model (1) when used to impute a truncated and amputated smoking variable against the naïvely classifying missing as "no" (2) when varying the percent smokers retained, q.

Results: The accuracy of approaches (1) and (2) was 0.79 and 0.43, respectively; for q = 90%, the accuracy of approaches (1) and (2) was 0.89 and 0.94, respectively. Transfer learning showed better accuracy than the naïve approach when the percentage of true smokers being recorded as smokers was < 80%.

Conclusions: The added value of transfer learning was greatest when low proportions of true ever-smokers were recorded, with its advantage depending on both the true prevalence of true smokers and the predictive model's performance.

Purpose: Our study aimed to investigate the knowledge, attitudes, and information sources about adverse drug reactions (ADRs) among healthcare professionals (HCPs) and non-healthcare professionals (non-HCPs) in Poland.

Methods: A self-administered questionnaire was designed in two versions (non-HCPs and HCPs). The questionnaire, available in electronic and paper format, was distributed between August 2023 and April 2024 using various means, including HCP and patient organisations, senior citizens centres, and community pharmacies. The anonymous survey included a series of statements regarding ADRs and single- and multiple-choice questions.

Results: Answers collected from 981 non-HCPs and 481 HCPs were analysed. Most respondents correctly identified the essential aspect of the ADR definition regardless of their medical education (non-HCP, n = 700 (71.36%) vs. HCP, n = 346 (71.93%) p = 0.818). Still, few respondents in both groups identified additional elements of the definition, with less than one-third of HCP respondents believing an ADR can result from improper medication use (non-HCP, n = 338 (34.45%) vs. HCP, n = 128 (26.61%) p = 0.002). Most respondents did not identify a "common ADR" as defined in the current rules of communicating about the frequency of ADRs. Most respondents indicate a lack of specific information in summary of product characteristics or package leaflet, with only 15.46% (n = 226) stating that they believe nothing is missing from those resources.

Conclusions: Our survey results show the need to effectively educate HCPs and non-HCPs on ADRs. Exploring ways to communicate about ADRs may help patients and HCPs better understand the risks of pharmacotherapy and their role in the pharma covigilance system.