Pharmacoepidemiology and Drug Safety最新文献

Purpose: Biological treatment has been a game changer in the management of moderate-to-severe psoriasis. In Denmark, biological treatment for psoriasis is registered in two data sources. We aimed to describe the utilization of biologics for psoriasis in Denmark using data from both data sources separately.

Methods: We used data from two different nationwide Danish data sources: The healthcare registries and the clinical quality database, Dermbio. Utilization patterns were described by three different parameters: (1) distribution of drugs used in the first treatment episodes, (2) treatment cascade on a population level, and (3) drug survival using Kaplan Meier (KM) analysis and the proportion of patients covered (PPC) method.

Results: From January 1, 2011, to December 31, 2018, we found 1878 users of biologics in the healthcare registries and 2264 in Dermbio. Adalimumab, ustekinumab, and secukinumab were the most common first-choice treatments throughout the study period. According to the healthcare registries, it was most common to have more than one treatment episode with the same drug. In Dermbio, most were registered to have only one observable treatment episode overall in the study period. Ustekinumab showed the longest drug survival in both databases. Drug survival was longer for all biologics in Dermbio than in the healthcare registries.

Conclusion: Adalimumab, ustekinumab, and secukinumab were the most common first-choice treatments in Denmark. Overall, ustekinumab showed the longest drug survival. We observed important differences in treatment cascades and drug survival between Dermbio and the healthcare registries, which should be considered when using these data sources to perform drug utilization studies on biologics.

Purpose: Uncontrolled hypertension causes significant morbidity and mortality worldwide. Several prescribing guidelines have been created to address this, however, prescriber adherence to guidelines is influenced by various sociodemographic patient factors. This study aims to determine the effects of these patient factors on prescriber adherence to antihypertensive prescription guidelines.

Methods: A secondary analysis of data from the first wave of The Irish Longitudinal Study on Ageing (TILDA), was conducted. Participants were included if they reported previous hypertension diagnoses. Antihypertensive medication regimes were compared with the prescribing guidance in the 2011 NICE hypertension guidelines. The effects of patient sociodemographic factors on prescriber adherence to guidelines, and the effect of prescriber adherence on blood pressure control (≥ 140/90 mmHg), were determined using binomial logistic regression models.

Results: A total of 2992 participants were included in this analysis; 54.9% female with mean age 65.7 years (±9.23). Male sex and older age, and lower socioeconomic status were associated with increased prescriber guideline adherence. Prescribers were less likely to adhere to guidelines in female patients ≥ 55 years (Relative Risk [RR] 0.75 [0.62, 0.91]), and female patients across all age groups (RR 0.80 [0.67, 0.95]). Better blood pressure control was seen with medication regimes adherent to prescription guidelines (140.38 (±18.98)/83.09 (±11.02) mmHg adherent vs. 141.66 (±19.86)/84.77 (±11.71) mmHg non-adherent).

Conclusions: This study highlights the effect of patient sex on prescriber adherence to antihypertensive prescription guidelines, emphasizing a larger issue of systemic undertreatment of females observed within healthcare. Further research is needed to determine the reasons for such differences in hypertensive care.

Background and purpose: The aim of the study was to provide valuable real-world long-term safety data of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in comparison of monotherapy with statins of moderate intensity.

Materials and methods: POSE study was an observational, comparative study conducted in three European countries. Patients treated or planned to be treated with pravastatin 40 mg/fenofibrate 160 mg or with a moderate-intensity statin in monotherapy were assessed over 3 years. The main safety endpoints included the incidence of renal or urinary disorder, musculoskeletal or connective tissue disorder, hepatobiliary disorder and cardiovascular events.

Results: The study included 3075 patients treated for dyslipidaemia, with diabetes mellitus (47%), hypertension (56%) and/or established cardiovascular disease (61%). Over the 3 years of follow-up, the difference in incidence rate of safety events between the pravastatin 40 mg/fenofibrate 160 mg group and the statin group was not statistically significant (RR = 1.366 [95% CI = 0.967-1.929]). The most frequently occurring events were musculoskeletal and connective tissue disorders (AR = 0.030 in the pravastatin 40 mg/fenofibrate 160 mg group and 0.024 in the statin group), renal and urinary disorders (AR = 0.019 vs. 0.016, respectively) and aggravated diabetes mellitus (0.021 vs. 0.014). Most events occurred during the first year, then incidence decreased over the 3-year period. No statistically significant difference was observed between treatment groups regarding the cardiovascular events (RR = 1.209 [95% CI = 0.596-2.453]) and no new signal emerged from the long-term follow-up.

Conclusions: This study demonstrates a reassuring long-term safety profile of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in routine clinical practice, with low and similar incidence of events over the 3 years follow-up compared to a monotherapy with statins of moderate intensity.

Purpose: This study examined the prevalence of headache medicine use among Danish adolescents and explores the link between mental health, frequent headaches, and medicine use for headache. We hypothesized that poor mental health increases headache occurrence, leading to greater medicine use.

Methods: The 2022 Danish Health Behaviour in School-aged Children (HBSC) study surveyed 5292 students aged 11, 13, and 15. Self-reported data included headache frequency, medicine use for headache, and five mental health indicators: life satisfaction, emotional symptoms, loneliness, self-efficacy, and self-esteem. Multivariate logistic regression analyses assessed the association between mental health indicators and headache medicine use, adjusting for headache frequency.

Results: Weekly headaches were reported by 33.1%, and 43.6% used headache medicine in the past month. Poor mental health correlated with higher headache and medicine use rates. Analyses adjusted for sex, age group, and occupational social class found significantly increased odds ratios (95% confidence interval) for medicine use for headache among students with low life satisfaction (2.27; 1.88-2.75), among students with 2+ emotional symptoms (2.28; 1.92-2.69), students who often felt lonely (2.08; 1.69-2.55), students with low self-efficacy (1.37; 1.16-1.61) and students with low self-esteem (1.59; 1.36-1.85). When accounting for headache frequency, the association between poor mental health and medicine use diminished and became nonsignificant.

Conclusions: Poor mental health was linked to increased medicine use for headache. The findings suggest that frequent headaches may explain the association between poor mental health and the use of headache medicine. Promoting rational medicine use and enhancing mental health among adolescents is essential.

Background and objectives: This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy.

Methods: Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results: The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease.

Discussion: Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Purpose: While potential harm from high doses of systemic dexamethasone for clinical management of COVID-19 is an important concern, little is known about real world dexamethasone dosing in patients hospitalized with COVID-19 in the United States.

Methods: Descriptive study to assess dexamethasone daily dose in adults with COVID-19 in a large US hospital network, overall and by respiratory support requirements, extracted using semi- structured nursing notes.

Results: Of 332 430 hospitalizations with a COVID-19 diagnosis, 201 637 (60.7%) hospitalizations included dexamethasone administration. The mean age of recipients was 63 years, 53.0% were male, and 64.5% White. Median time from admission to dexamethasone administration was 0 day (interquartile range [IQR], 0-1 days) and median duration of use was 5 (IQR, 3-9) days. Almost 80% of hospitalizations received standard daily doses (≤ 6 mg daily), 12.7% moderately high daily doses (> 6- ≤ 10 mg daily), and 8.1% high (> 10- ≤ 20 mg daily) or very high daily dose (> 20 mg daily). Over 20% of COVID-19 hospitalizations requiring no oxygen or simple oxygen received high doses of systemic dexamethasone.

Conclusions: Given the findings from the UK RECOVERY trial, and the general uncertainty around safety of higher dexamethasone doses in those requiring more intense respiratory support, standard daily dexamethasone doses of 6 mg or less for hospitalized COVID-19 requiring supplemental oxygen are recommended.

Pharmacoepidemiological studies provide important information on the safety and effectiveness of medications, but the validity of study findings can be threatened by residual bias. Ideally, biases would be minimized through appropriate study design and statistical analysis methods. However, residual biases can remain, for example, due to unmeasured confounders, measurement error, or selection into the study. A group of sensitivity analysis methods, termed quantitative bias analyses, are available to assess, quantitatively and transparently, the robustness of study results to these residual biases. These approaches include methods to quantify how the estimated effect would be altered under specified assumptions about the potential bias, and methods to calculate bounds on effect estimates. This article introduces quantitative bias analyses for unmeasured confounding, misclassification, and selection bias, with a focus on their relevance and application to pharmacoepidemiological studies.

Purpose: We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART).

Methods: Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT] ≥5 times upper limit of normal [ULN]/ALT ≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury.

Results: We included 48 participants. All were people with HIV (PWH). Twenty-seven were on concomitant ART and ATT, with a median of six potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 7% and 100% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4) and lopinavir/ritonavir (1/0).

Conclusions: PWH with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicate causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury.