Pharmacoepidemiology

Background: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal (GI) disorders. Omeprazole is one of the most commonly prescribed PPIs in Thailand. However, it is frequently overprescribed in hospital settings, increasing the risk of adverse effects. Moreover, such overuse imposes unnecessary healthcare costs. Objectives: To determine the prevalence of potentially inappropriate omeprazole prescribing and its associated factors, and to assess the financial impact of its overuse. Methods: This retrospective cross-sectional study was conducted in a general hospital in Thailand. Outpatients who received omeprazole between 1 January 2025 and 30 June 2025 were included. Descriptive statistics were used to summarize the data. The Chi-square test and Fisher’s exact test were used to compare categorical variables, as appropriate. Factors associated with inappropriate omeprazole prescribing were evaluated using logistic regression analysis. Results: A total of 229 patients receiving 347 omeprazole prescriptions were included. The mean age was 61.35 ± 17.17 years, and 59.4% were female. Inappropriate omeprazole prescribing was identified in 58.2% of prescriptions, primarily due to lack of appropriate indications (75.2%), followed by inappropriate duration. Antiplatelet use (OR 0.21, 95% CI 0.11–0.38, p < 0.001) and dual antiplatelet therapy (OR 0.05, 95% CI 0.01–0.37, p = 0.004) were significantly associated with a lower likelihood of inappropriate prescribing. Conclusion: Inappropriate omeprazole prescribing was common and largely driven by the absence of a clear indication, which was the main contributor to excess costs. Targeted interventions focusing on appropriate initiation, GI risk assessment, and regular reassessment may improve prescribing quality and reduce unnecessary healthcare expenditure. Full article

Background/Objectives: We described adverse event reporting patterns for insulin glargine marketed as 100 units/mL (Lantus), 300 units/mL (Toujeo), and 100 units/mL biosimilars (Basaglar/Semglee). Methods: We analyzed Food and Drug Administration Adverse Event Reporting System (FAERS) reports received from 2015 through 2025 that listed insulin glargine as a primary or secondary suspect. Reports were grouped by trade name into standard-strength originator (Lantus), high-strength (Toujeo), and biosimilar products. We defined a composite serious outcome (death, life-threatening event, hospitalization, or disability). Logistic regression adjusted for age, sex, reporter type, and year received; Firth’s penalized regression was used for sparse death and hospitalization outcomes. Sensitivity analyses restricted to reports without concomitant suspect products, overlapping calendar windows, and healthcare professional reports. Geographic reporting patterns were analyzed by country. Results: We included 43,905 eligible reports (Lantus: 35,927; Toujeo: 3699; biosimilars: 4279). Unadjusted death was highest for Lantus (8.2%) followed by biosimilars (6.0%) and Toujeo (3.2%). In the primary adjusted model (n = 28,519), reports listing Toujeo had lower adjusted reporting odds of the composite serious outcome compared with Lantus (aOR 0.88, 95% CI 0.81–0.96), while biosimilars showed higher odds (aOR 1.24, 95% CI 1.11–1.38). The biosimilar association was not robust: it attenuated without concomitant drugs (aOR 1.07, 95% CI 0.92–1.23) and reversed in healthcare professional reports (aOR 0.65, 95% CI 0.49–0.87). Device-related events were lower for biosimilars (aOR 0.58) and Toujeo (aOR 0.85). Geographic heterogeneity was extreme (Egypt 76.9% death vs. Italy 0.8%), and the US protective association reversed in recent years. Conclusions: After adjustment for report-level characteristics, Toujeo was associated with lower reporting odds of serious outcomes, while biosimilar findings were inconsistent across sensitivity analyses and driven by consumer reporting. Geographic heterogeneity and the Egypt outlier underscore the fragility of cross-country comparisons in spontaneous reporting data. These findings reflect reporting-behavior heterogeneity rather than differential product safety. Full article

Background/Objectives: Medication adherence is a critical determinant of therapeutic outcomes in type 2 diabetes mellitus (T2DM); however, its relationship with glycemic control remains inconsistent, particularly in real-world and socially vulnerable settings. This study aimed to evaluate medication adherence using multiple validated instruments, assess disease-related knowledge, and examine their relationship with glycemic control, with a focus on potential discordance between self-reported adherence and objective metabolic outcomes. Methods: A cross-sectional analytical study was conducted with 237 adults with T2DM receiving care in a primary health care (PHC) unit in the Brazilian Amazon. Medication adherence was assessed using the Almeida Adherence Scale, ARMS-12, and the Haynes–Sackett test, while disease-related knowledge was evaluated using the Batalla–Martínez questionnaire. Glycemic control was determined based on glycated hemoglobin (HbA1c) values obtained from clinical records within the previous three months. Descriptive and comparative analyses were performed. Results: The study population was predominantly female (64.1%) and aged 40–59 years (55.7%), with a high prevalence of socioeconomic vulnerability. Non-adherence was identified in 55.7% of participants using the Almeida Adherence Scale, whereas higher adherence rates were observed with ARMS-12 (91.1%) and the Haynes–Sackett test (72.2%). Inadequate disease-related knowledge was found in 77.2% of participants. Among individuals with available HbA1c data (n = 116), the mean HbA1c was 8.63% (SD = 1.65), and 81.9% presented inadequate glycemic control (HbA1c ≥ 7%). Notably, among participants classified as adherent by the ARMS-12 scale (91.1%), inadequate glycemic control was nonetheless present in 81.9% of those with available HbA1c data, illustrating the magnitude of the observed discordance between self-reported adherence and objective metabolic outcomes. Cross-tabulation of each adherence instrument against glycemic control showed no statistically significant associations (chi-square with Yates correction; ARMS-12: p = 0.631, φ = 0.045; Almeida Adherence Scale: p = 0.301, φ = 0.096; Haynes–Sackett: p = 0.800, φ = 0.024). Multivariable logistic regression (Nagelkerke R² = 0.321; AUC = 0.834) identified older age (aOR = 0.92; 95% CI: 0.87–0.96; p < 0.001) and higher income (aOR = 9.96; 95% CI: 2.05–48.32; p = 0.004) as independent predictors of glycemic outcome, while no adherence measure was independently associated with HbA1c ≥ 7%. A sensitivity analysis using HbA1c ≥ 8.0% revealed poor control in 59.5% of participants (n = 69/116). Conclusions: Despite varying levels of self-reported medication adherence, inadequate glycemic control was highly prevalent. The absence of statistically significant associations between self-reported adherence and HbA1c, combined with the high prevalence of poor glycemic control regardless of adherence status, is consistent with the hypothesis that adherence alone does not fully explain metabolic outcomes in T2DM. Given the cross-sectional design, no causal inferences can be drawn. These findings highlight the need for integrated care strategies in primary health care, including improved health literacy, structured pharmacotherapeutic follow-up, and the use of multiple adherence assessment tools to better inform clinical decision-making. Full article

Background: The COVID-19 pandemic was associated with extensive empirical antibiotic exposure despite the predominantly viral etiology of the disease. Evaluating patterns of azithromycin use, prescribing determinants, and appropriateness provides insight into real-world antibiotic use under conditions of diagnostic uncertainty. Methods: We performed a retrospective cohort study including 3200 adult patients hospitalized with laboratory-confirmed COVID-19 at the General Hospital in Ferizaj between June 2020 and June 2022. Demographic characteristics, comorbidities, markers of disease severity, laboratory parameters, and antibiotic exposure were extracted from medical records. Azithromycin prescriptions were classified as appropriate, potentially appropriate, or inappropriate based on predefined clinical and laboratory indicators suggestive of bacterial co-infection. Drug utilization patterns, temporal trends, and independent determinants of inappropriate prescribing were assessed using descriptive analyses and multivariable logistic regression modeling. Results: Among 3200 hospitalized patients, 1968 (61.5%) received azithromycin. Of these prescriptions, 612 (31.1%) were classified as appropriate, 418 (21.3%) as potentially appropriate, and 938 (47.6%) as inappropriate. The proportion of inappropriate use decreased over time, from 52.4% in 2020–2021 to 38.7% in 2022 (p < 0.001). However, a substantial proportion of prescriptions remained inappropriate throughout the study period. In multivariable analysis, absence of laboratory markers suggestive of bacterial infection (OR 2.41; 95% CI 1.98–2.93), concomitant use of more than one antibiotic (OR 1.67; 95% CI 1.32–2.11), and lower clinical severity at admission (OR 1.54; 95% CI 1.21–1.95) were independently associated with inappropriate azithromycin prescribing. Conclusions: Azithromycin use was frequent among hospitalized adults with COVID-19, and a considerable proportion of prescriptions lacked clinical or laboratory justification. Although prescribing patterns changed over time, the persistence of inappropriate use highlights ongoing challenges in aligning antibiotic use with emerging evidence. These findings contribute to the understanding of antibiotic utilization patterns in acute care settings and underscore the importance of integrating objective diagnostic indicators into antimicrobial decision-making to strengthen stewardship practice. Full article

Background and Objective: Perioperative antibiotics are widely used in pediatric surgical practice; however, inappropriate selection and prolonged use may contribute to antimicrobial resistance and unnecessary exposure. Appropriate use of perioperative antibiotics is essential to prevent surgical site infections while minimizing antimicrobial resistance, adverse drug reactions, and unnecessary healthcare costs. Despite existing international recommendations, deviations from guideline-based practice remain frequent in pediatric surgical settings. This study aimed to describe patterns of perioperative antibiotic use and assess the appropriateness of prescribing practices in a tertiary care setting, and to identify factors associated with inappropriate antibiotic use. Methods: A retrospective pharmacoepidemiological study was conducted by reviewing medical records of pediatric patients admitted to a tertiary care hospital in Kosovo between January 2022 and December 2025 (data lock: December 2025). A total of 650 patients aged 0–18 years who underwent surgical interventions and received perioperative antibiotics for prophylaxis or empirical treatment (defined as antibiotic therapy initiated in the presence of suspected infection) were included. Data collected comprised demographic characteristics, surgical diagnoses, type of surgery, antibiotics prescribed, weight-adjusted dosing, route of administration, timing of initiation, and duration of therapy. Appropriateness of antibiotic use was evaluated based on available documentation and compliance with WHO (2018) and CDC (2017) guidelines regarding indication, antibiotic selection, dosage, timing, and duration. Statistical analyses included descriptive statistics, chi-square tests, and multivariable logistic regression to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs), with statistical significance set at p < 0.05. Results: Among the 650 patients, 378 (58.2%) were male and 272 (41.8%) were female, with a mean age of 6.8 ± 4.3 years. The most common types of surgery were abdominal (35.7%), otorhinolaryngological (29.4%), urological (19.1%), and orthopedic (15.8%). Perioperative antibiotics were administered predominantly for prophylaxis (91.5%), while 8.5% of patients received empirical treatment. The most frequently prescribed antibiotics were cefazolin (42.6%), ceftriaxone (34.8%), ampicillin/sulbactam (12.3%), and gentamicin (6.1%). Notably, ceftriaxone was frequently prescribed for prophylactic purposes despite international recommendations generally favoring narrow-spectrum first-line agents for perioperative prophylaxis. Intravenous administration was used in 87.9% of cases. Antibiotic duration was ≤24 h in 61.2% of patients, whereas 38.8% received antibiotics for more than 24 h. Overall, appropriate antibiotic use was identified in 62.9% of cases, while 37.1% were classified as inappropriate. Prolonged antibiotic use beyond 24 h (adjusted OR = 3.87; 95% CI: 2.68–5.58; p < 0.001) and ceftriaxone use (adjusted OR = 2.41; 95% CI: 1.63–3.55; p < 0.001), were independently associated with inappropriate antibiotic use. Conclusions: Perioperative antibiotic use in pediatric tertiary care is highly prevalent, with more than one-third of prescriptions not fully aligned with international recommendations. Prolonged antibiotic duration and the preferential use of broad-spectrum agents, particularly ceftriaxone, were the factors most strongly associated with inappropriate prescribing patterns. These findings highlight the need for improved adherence to guideline-based perioperative antibiotic protocols; however, causal inferences regarding stewardship interventions cannot be drawn from this retrospective study. The findings should be interpreted within the limitations inherent to retrospective observational studies. Full article

Background/Objectives: Medication discrepancies at hospital discharge are common and may contribute to adverse drug events and avoidable healthcare use. Patients with mental health conditions may be at increased risk because of greater clinical complexity, polypharmacy, and fragmented care, but comparative evidence during general hospital admissions is limited. Our primary objective was to determine whether adults with mental health conditions were more likely than those without such conditions to experience unintended medication discrepancies at hospital discharge. Secondary objectives were to examine discrepancy subtypes, assess whether associations differed for serious mental illness versus other mental health conditions, and explore whether associations varied by reconciliation arm. Methods: We conducted a retrospective cohort study using linked data from the RightRx cluster-randomized trial at the McGill University Health Centre (2014–2016) and Quebec administrative databases. Adults with continuous provincial drug coverage for at least 12 months before admission who met study eligibility criteria were included. The primary exposure was any documented mental health condition; secondary analyses distinguished serious mental illness (SMI) from other mental health conditions. The primary outcome was any unintended medication discrepancy at discharge; subtype analyses examined omissions, therapeutic duplications, and unintended dose changes. Results: Among 3567 patients, 877 (24.6%) had a mental health condition. Crude discrepancy prevalence was similar between groups. In the prespecified primary analysis, mental health condition status was associated with lower observed odds of any unintended discrepancy at discharge. This unexpected inverse association should not be interpreted as evidence of a protective effect and may reflect differences in documentation, residual confounding, selection, or other unmeasured processes. Secondary and supplementary analyses, including omission and SMI subgroup comparisons, did not remain statistically significant after Holm correction. Conclusions: These findings suggest that documentation-based discrepancy measures may relate to mental health status in heterogeneous ways, but they require confirmation in independent settings. Full article

Background/Objectives: Pregnant and breastfeeding people require special considerations for enrollment in clinical trials. However, the baseline proportion of cardiovascular clinical trials including pregnant and breastfeeding people remains unclear. The objective of this study was to characterize the representation of pregnant and breastfeeding people in cardiovascular randomized clinical trials (RCTs) and to determine whether inclusion has increased following the 2018 removal of pregnancy from the FDA’s “vulnerable population” designation. Methods: We screened eight high-impact general medicine and specialty journals for cardiovascular RCTs published between 1 January 2019 and 31 December 2023. We included RCTs examining pharmacological, behavioral, educational, device, or procedural interventions. We excluded RCTs that recruited exclusively male, pediatric, geriatric, or postmenopausal populations, and those specifically designed for obstetrical populations. We also excluded publications reporting follow-up or subgroup, pooled, or secondary analyses of previously published trials. Data from RCTs were independently extracted in duplicate following the PRISMA guidelines. We examined each RCT for pregnancy and breastfeeding inclusion criteria, rationale for exclusion, and contraception requirements. Results: Of 3764 citations identified, 586 met the inclusion criteria. In total, four (0.7%) RCTs permitted inclusion of pregnant people, 382 (65%) explicitly stated their exclusion, and 200 (34%) did not provide specific enrolment criteria for them. The few studies that explicitly stated exclusion of pregnant people (31/382, 8.1%) provided a rationale. 225 (38%) RCTs explicitly stated exclusion of breastfeeding people, and none explicitly permitted inclusion. There was no significant difference in the proportion of pregnant or breastfeeding people included or excluded from RCTs that began enrollment before 2018 versus after 2018. Conclusions: Pregnant and breastfeeding people are primarily excluded from cardiovascular RCTs, and the justification for their exclusion is rarely provided. Full article

Objective: To evaluate adverse effects associated with biologic therapy (Etanercept, Adalimumab, and Secukinumab) in patients with psoriasis, psoriatic arthritis, and hidradenitis suppurativa. Methods: This retrospective observational study included 58 patients receiving biologic therapy: 40 with generalized plaque psoriasis, 13 with psoriatic arthritis, and 3 with hidradenitis suppurativa. Eligibility was based on national treatment protocols (Psoriasis Area and Severity Index [PASI] > 10; Hurley stage II–III). Demographic data, treatment duration, therapy modifications, discontinuations, and adverse events were collected from medical records. Patients were monitored for both efficacy and safety outcomes. Results: Treatment discontinuation due to severe hepatotoxicity occurred in four patients (three receiving Etanercept and one Adalimumab), corresponding to 6.9% of the cohort. Adalimumab was discontinued in one patient due to cutaneous leishmaniasis after 24 months and in another due to pregnancy after 26 months. Upper limb edema was observed following a switch from Adalimumab to Secukinumab. One patient discontinued Etanercept due to lack of efficacy and subsequently died from a fatal methotrexate overdose. Treatment switches included Etanercept to Adalimumab for granulomatous uveitis (one case) and Adalimumab to Etanercept due to generalized urticaria (two cases). Conclusion: Adverse events were relatively infrequent, with an overall incidence below 10% (6.9% for the most common event and <2% for other events). Most adverse events were mild and reversible following dose adjustment or temporary discontinuation. No unexpected or fatal adverse events were directly attributable to biologic therapy. Full article

Background: A significant percentage of patients with major depressive disorder (MDD) fail to achieve remission with antidepressant monotherapy and frequently experience residual mood and cognitive symptoms that impair their functional recovery. Thus, an augmentation with vortioxetine, a multimodal antidepressant with reported cognitive benefits, might be a useful strategy for such patients. Methods: We conducted a 12-week naturalistic, prospective observational study in a Malaysian university hospital; 40 adults with MDD and inadequate response to at least eight weeks of antidepressant therapy received either adjunctive vortioxetine or optimization of their existing antidepressant as part of treatment-as-usual care. Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), cognitive symptoms using the Perceived Deficits Questionnaire-5 (PDQ-D5), and global improvement using the Clinical Global Impressions—Improvement (CGI-I) scale. Results: Both groups demonstrated significant improvements in MADRS and PDQ-D5 scores over 12 weeks (p < 0.001). Remission rates at Week 12 were high in both groups (93.8% adjunctive vortioxetine vs. 86.7% control). Both groups demonstrated significant improvements in depressive and cognitive symptoms over 12 weeks. Although between-group differences were not statistically significant, descriptive trends toward earlier symptomatic improvement were observed in the adjunctive vortioxetine group in several core depressive symptoms, including apparent sadness, suicidal ideation, and appetite disturbance. Greater clinician-rated global improvement was observed in the vortioxetine group at Week 12 (87.5% vs. 40.0%, p < 0.001). Conclusions: In this outpatient clinical setting, adjunctive vortioxetine was associated with earlier improvement of core depressive symptoms and greater global clinical improvement compared with optimization of existing antidepressant therapy. Collectively, these findings suggest adjunctive vortioxetine as a clinically relevant option for patients with MDD who show an inadequate response to antidepressant monotherapy; however, findings are exploratory and not causal, and thus larger RCTs are needed for affirmation. Full article

Background/Objectives: The accumulation of unused and expired pharmaceuticals in households is a growing public health concern with implications for patient safety, rational drug use, and environmental health. However, systematic risk characterization integrating clinical and environmental perspectives at the community level remains limited, particularly in low- and middle-income settings. This study aimed to develop and apply a composite risk index, grounded in an eco-pharmacovigilance framework, for the assessment of health risks associated with accumulated household pharmaceuticals in southeastern Mexico. Methods: A cross-sectional study was conducted in 526 randomly selected households using stratified sampling. Guided in-home medication inventories were performed with participant collaboration, and pharmaceuticals were classified according to the Anatomical Therapeutic Chemical (ATC) system. A composite risk index (CRI = Fr × PR) was developed within an eco-pharmacovigilance framework. The frequency of accumulation (Fr) for each therapeutic group was multiplied by a potential risk score (PR) derived through a structured multidisciplinary expert consensus process integrating clinical toxicity, environmental persistence, and antimicrobial resistance potential. Results: A total of 2184 pharmaceutical units were recorded during the household inventories, of which 28.7% were expired. Expired medications were primarily retained rather than actively used, representing a latent risk for inappropriate self-medication and accidental exposure. The therapeutic groups with the highest CRI values were antihypertensives (CRI = 42.3), antidiabetics (CRI = 37.8), and antibiotics (CRI = 31.5), indicating a relatively higher contribution within the composite risk index framework to overall household pharmaceutical risk. These findings highlight priority therapeutic groups driven by the combined effect of high accumulation frequency, distinct accumulation patterns, and intrinsic hazard. Conclusions: Household pharmaceutical accumulation can be characterized using a composite, eco-pharmacovigilance-based approach that integrates exposure and hazard dimensions. The proposed framework functions as a prioritization tool rather than a precise quantitative measure, enabling the identification of therapeutic groups requiring targeted intervention. Findings should be interpreted as indicative of relative risk patterns rather than precise estimates, given the exploratory design and guided data collection approach. The proposed framework provides a practical tool for prioritizing interventions aimed at improving rational drug use, reducing accumulation, and mitigating environmental impact. Further validation in diverse settings is warranted to strengthen its applicability. Full article

Background: Medial-compartment knee osteoarthritis (KOA) carries substantial disability and long-term cost. High tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) are key joint-preserving or joint-replacing options for selected patients, but their comparative economic ranking remains uncertain. Methods: This critical narrative review synthesized comparative economic evidence on HTO versus UKA for isolated medial-compartment KOA. PubMed and Web of Science were searched as primary sources for English-language studies published from 1 January 2000 to 15 January 2026, while Google Scholar and citation tracking were used supplementarily to identify potentially missed records. Eligible studies were direct economic evaluations or comparative cost/resource studies with clear decision relevance to the HTO–UKA choice. Burden and cost-of-illness studies were used for contextual framing only and were not included in the core comparative synthesis. Results: The direct evidence base was small and methodologically heterogeneous and was dominated by decision-analytic models that differed in perspective, time horizon, utility metric, and assumptions regarding reoperation, revision, and conversion to total knee arthroplasty (TKA). These structural differences largely explain why a U.S. lifetime societal model favored HTO, a UK age-stratified 10-year model produced age-dependent findings, and a recent Canadian public-payer model favored UKA. Observational studies suggest that UKA episode costs can fall substantially in outpatient or ambulatory pathways, whereas HTO costs may rise when reoperations and technique-specific resource use are explicitly captured. Conclusions: Current evidence does not support a context-free economic ranking of HTO and UKA. Because the available studies are heterogeneous and incremental utility differences are often small, the findings should be interpreted cautiously and as scenario-dependent rather than definitive. Future comparative analyses should use contemporary pathway data, transparent and standardized costing, and explicit downstream event definitions for both procedures. Full article

Background: The introduction of targeted therapy in oncology has led to several challenges. These medicines are relatively new in clinical practice and are not well known to specialists with regard to adverse drug reactions (ADRs) and potential drug–drug interactions (pDDIs). In addition, cancer affects multiple body systems, including weight loss, anemia, liver and kidney function, depression, and pain. Patients frequently have comorbidities, leading to polypharmacy and the use of special foods, nutritional supplements, and herbal products for self-medication. Identification of pDDIs is essential, as concomitant use of multiple medicinal products increases the risk of ADRs and may compromise treatment. Objective: This study aims to retrospectively review and analyze data on ADRs and pDDIs in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors and to evaluate the relationship between them. Method: EudraVigilance and UpToDate^® Lexidrug™ application were used to screen suspected ADRs and pDDIs, respectively. Descriptive statistical analysis was performed. Results: After reviewing Line Listing Reports (LLRs) from 2021 to 2023 in EudraVigilance, the number of suspected adverse drug reactions (ADRs) reported was higher when drug interactions classified as risk categories D and X were identified, compared with cases involving EGFR inhibitor monotherapy or other drug combinations. Of the 144 cases involving category D and/or X interactions, 63 demonstrated a possible association with the reported ADRs of EGFR inhibitors. The most common pDDIs detected were erlotinib–ranitidine (14 cases, category D) and osimertinib–amiodarone (13 cases, category D). Conclusions: Although EGFR inhibitors improve overall and progression-free survival in NSCLC, screening for pDDIs before treatment is essential to improve safety and quality of life. Full article

Background/Objectives: The study’s goal is to assess the association between long-term statin therapy and influenza incidence, influenza severity, and all-cause mortality. Methods: Two population-based dynamic cohorts (exposed and unexposed to statins) were followed from 2010 to 2019. Participants were 60 years or older; frail patients were excluded. The primary outcomes were influenza incidence, influenza-related intensive care unit (ICU) admission as a proxy for severity, and all-cause mortality. The exposed cohort comprised new statin users with a minimum of two pharmacy invoices within 90 days of enrollment. Adjusted risk ratios (aRRs) for influenza incidence, ICU admission, and mortality rate were calculated using Poisson regression. Results: The initial study population of 639,564 individuals was evenly split into exposed (319,782) and unexposed (319,782) cohorts; mean age was 71 years (standard deviation: 8 years), and 57% were women. Compared to non-users, new statin users showed a higher influenza incidence [9.39 (95% confidence interval: 9.36–9.42) vs. 7.64 (7.61–7.66) per 1000 person-years], ICU admission [1.65 (1.65–1.66) vs. 1.36 (1.35–1.36) per 1000 person-years], and overall mortality rate [97.09 (96.75–97.43) vs. 94.15 (93.82–94.47) per 1000 person-years]. Adjusted analysis revealed no significant association between statin use and influenza incidence [aRR: 1.04 (0.98–1.10)] or influenza-related ICU admission [aRR: 1.03 (0.89–1.19)] and shifted the effect on mortality from harmful to beneficial [aRR: 0.88 (0.87–0.89)]. Conclusions: Despite new users’ greater vulnerability at the start of treatment, our findings indicate that statins do not influence influenza incidence or severity but reduce all-cause mortality, warranting further exploration of their anti-inflammatory properties. Full article

Background: Furosemide is one of the most frequently prescribed loop diuretics for cardiovascular conditions, particularly in the management of volume overload and acute elevations in blood pressure. However, detailed real-world data describing its utilization characteristics and documented safety outcomes in primary healthcare settings remain limited, especially in underrepresented health systems. Objective: This study aimed to describe real-world patterns of furosemide utilization, including indications and concomitant treatment patterns, and to document associated adverse drug events and short-term clinical outcomes in routine primary healthcare practice. Methods: A retrospective pharmacoepidemiological observational study was conducted between January and December 2025 in a primary healthcare center. Medical records of 1300 adult patients who received furosemide for cardiovascular indications were reviewed. Indications included arterial hypertension, hypertensive crises, and conditions related to volume overload. Utilization characteristics were operationalized as indication distribution, monotherapy versus combination therapy, and recurrence patterns within the study period. Data collected included demographic characteristics, primary and comorbid diagnoses, blood pressure values recorded before and after administration, furosemide dose and route of administration, concomitant antihypertensive therapy, documented adverse drug events as recorded in routine clinical documentation, recurrent presentations related to hypertensive crises, and the need for hospital referral. Descriptive statistics and paired comparative analyses were performed, with statistical significance set at p < 0.05. Results: The mean patient age was 62.4 ± 11.8 years, with a male predominance (54.1%). Arterial hypertension was the most frequent recorded indication (78.6%), while 32.4% of patients had multiple cardiovascular diagnoses. A statistically significant reduction in systolic blood pressure (from 176.3 ± 18.5 mmHg to 148.7 ± 16.2 mmHg, p < 0.001) and diastolic blood pressure (from 101.2 ± 11.4 mmHg to 89.6 ± 9.8 mmHg, p < 0.001) was observed between measurements recorded before and after administration during the same clinical episode. Recurrent presentations related to hypertensive crises were documented in 27.9% of patients during the study period. Adverse drug events were documented in 9.6% of cases, most commonly dehydration and suspected electrolyte disturbances as noted in routine clinical records. Hospital referral was required in 6.8% of patients. Conclusions: In this real-world primary healthcare cohort, furosemide was commonly used across a heterogeneous mix of cardiovascular indications, predominantly in combination with other antihypertensive agents. Observed temporal reductions in blood pressure and documented adverse events reflect routine clinical practice rather than controlled treatment effects. These findings provide descriptive pharmacoepidemiological evidence from a primary care setting and underscore the importance of careful monitoring, documentation, and rational prescribing in patients receiving loop diuretics. Full article

Background: Preterm prelabour rupture of membranes (PPROM) is the spontaneous rupture of fetal membranes prior to 37 weeks of pregnancy. Latency antibiotics, including macrolides with or without group B streptococcus (GBS)-covering antibiotics, are recommended as part of expectant management. Currently, there is no consensus on whether GBS-covering antibiotics should be prescribed. The primary objective of this retrospective cohort study was to characterize practice variation in GBS-covering antibiotic prescribing in PPROM. The secondary objective was to explore the association between maternal characteristics and GBS-covering antibiotic prescribing. Methods: Pregnant women with PPROM prescribed azithromycin (institutional standard antibiotic regimen) in 2024 and not in active labour were included. Maternal characteristics, stratified by GBS status, were compared. The association between antibiotic prescribing for GBS coverage and maternal factors was assessed using odds ratios. Two-sided p-values < 0.05 were considered statistically significant. Results: Out of the 181 admissions assessed for eligibility, 146 patients were included. Their GBS status at PPROM diagnosis was negative (19/146; 13%), positive (8/146; 5%), or unknown (119/146; 82%). The frequency of GBS-covering antibiotics prescribing was 5/8 (63%) in the positive group, 4/19 (21%) in the negative group, and 65/119 (55%) in those with an unknown GBS status. Aminopenicillin-based and penicillin regimens accounted for (69/74; 93%) of antibiotic regimens. Half (38/74; 51%) of the GBS-covering antibiotics were prescribed for 3–7 days, with a 33/74 (45%) completion rate as prescribed at PPROM diagnosis. The main reason for antibiotic discontinuation was negative GBS recto-vaginal swabs or urine cultures collected in those with an unknown GBS status at PPROM diagnosis, highlighting the role of microbiology laboratory testing in adjusting antibiotic therapy and facilitating antimicrobial stewardship. Aside from GBS status, no maternal characteristics were associated with GBS-covering antibiotic prescribing. Conclusions: At PPROM diagnosis, GBS coverage was prescribed in 21%, 63%, and 55% of patients with a negative, positive, and unknown GBS status, respectively. Only GBS status was associated with GBS-covering antibiotic prescribing. Further research is required to determine the impact of GBS coverage on perinatal outcomes. Full article

Background: Acalabrutinib is a selective Bruton tyrosine kinase inhibitor widely used for chronic lymphocytic leukemia and mantle cell lymphoma. Real-world safety evidence from Latin America remains limited, which restricts local benchmarking and pharmacovigilance planning. In this study we aimed to assess exposure-adjusted adverse events in routine care in Mexico. Methods: We analyzed postmarketing surveillance datasets and spontaneous reports from March 2020 to August 2024, classifying events with MedDRA and summarizing seriousness, severity, and incidence per 100 patient-years. Results: A total of 266 patients were registered; 193 had evaluable exposure and safety data, contributing 242.73 patient-years. The overall adverse event incidence was 24.71 per 100 patient-years. Twenty-eight individual case safety reports documented 60 events. Forty-four events were serious. Among 33 events with reported severity, 14 were severe, 14 moderate, and five mild. Frequently affected system organ classes were blood and lymphatic, vascular, and infections. Seven deaths were reported; most were associated with COVID-19 complications or disease progression. Conclusions: The adverse event profile observed aligns with published trial experience and supports the tolerability of acalabrutinib in Mexican practice. These country-level, exposure-adjusted estimates provide actionable context for clinicians, institutional pharmacists and pharmacovigilance teams and point to the value of strengthening report completeness to improve signal detection in routine oncology care. Full article

Background: Pharmacovigilance is a critical component of patient safety, particularly among older adults with chronic diseases who are frequently exposed to polypharmacy. In Kosovo, adverse drug reactions (ADRs) reported by patients remain insufficiently recognized within the healthcare system. Polypharmacy, limited access to pharmaceutical counseling, and self-medication practices may contribute to increased medication-related harm. Capturing ADRs directly from patients provides valuable insight into medication safety challenges and communication gaps in clinical care. Objective: To assess the frequency, characteristics, and reporting behavior of adverse drug reactions among adults aged 60–75 years with chronic diseases in Kosovo, and to identify factors associated with awareness and reporting practices. Methods: A multicenter cross-sectional study was conducted between January and September 2025 in four major cities in Kosovo (Prishtina, Prizren, Peja, and Gjilan). A total of 1024 patients receiving continuous therapy for at least one chronic condition were surveyed using a structured questionnaire covering demographic characteristics, drug exposure, ADR experience, and reporting behavior. Statistical analyses included descriptive statistics, chi-square testing, and multivariable logistic regression to identify predictors of ADR reporting. Results: Overall, 47.3% of participants reported experiencing at least one ADR in the preceding 12 months. Among those, 39.5% reported the event to a healthcare professional, whereas 60.5% did not seek professional advice. The most frequently implicated drug classes were antihypertensives (32.8%), analgesics and non-steroidal anti-inflammatory drugs (27.4%), and antirheumatic agents (14.6%), with mainly gastrointestinal (24.1%) and cardiovascular (18.9%) manifestations. Approximately 19.8% of participants reported discontinuing medication due to adverse effects. Female patients were more likely to report ADRs compared to males (p < 0.01). Lack of prior counseling about potential side effects was independently associated with lower reporting (OR = 2.17; 95% CI: 1.41–3.33). Patients using more than six medications had a higher prevalence of ADRs (61.2%). Conclusion: Adverse drug reactions were frequently reported by older patients, while formal reporting to healthcare professionals remained limited. Strengthening patient education, improving patient–provider communication, and integrating clinical pharmacists into primary care may enhance pharmacovigilance practices and medication safety. Full article

Background/Objectives: To evaluate the incidence, characteristics, and clinical outcomes of intraocular inflammation (IOI) associated with intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Web of Science, Scopus, Embase, and CENTRAL databases was performed from their inception to February 2025. Using the random-effects model, weighted proportions, standardized mean differences, and weighted log odds ratios (OR) were pooled and calculated. A two-tailed p-value of <0.05 was considered statistically significant. The χ² (z) test and the Higgins I² test were used to assess studies heterogeneity. Results: We conducted a systematic review and meta-analysis of 24 studies (4761 patients; 5652 eyes). The most common diagnoses were nAMD (n = 4782, 94.6%) and DME (n = 845, 37.1%). The pooled proportion for IOI incidence in eyes receiving IVF was 3.0% (95% CI: 1.0–6.0). The odds of developing IOI did not differ significantly between the DME and nAMD groups (OR: 1.13, p = 0.78). Unspecified IOI was the most common sign (n = 210, 2.9% [95% CI: 1.2–7.3]), followed by anterior uveitis (n = 80, 1.9% [95% CI: 0.1–34.8]), vitritis (n = 63, 2.9% [95% CI: 0.2–32.1]), retinal hemorrhage (n = 27, 0.7% [95% CI: 0.0–15.3]), and endophthalmitis (n = 8, 0.5% [95% CI: 0.3–1.1]). Conclusions: While IVF demonstrates therapeutic efficacy, our findings highlight a clinically relevant risk of IOI. We, therefore, recommend vigilant clinical monitoring in patients receiving this therapy. Full article

Background: According to the literature, adverse drug reactions (ADRs) account for 5–10% of hospital admissions and affect 25–30% of hospitalized patients, but no data are available for Gabon. Objectives: To estimate the incidence of ADRs among hospitalized patients at the Libreville University Hospital Center (CHUL) and to classify them according to their frequency, severity, mechanism and preventability, while proposing appropriate risk minimization strategies. Patients and Methods: A 14-month, single-center, prospective study included all patients experiencing ADRs, excluding those without ADRs or with intentional overdoses. ADRs were analyzed using the World Health Organization (WHO) causality assessment, the ATC classification, and Rawlins and Thompson criteria. Data were actively collected from patients and hospital records. Results: Among 4999 patients, 105 experienced 177 adverse events (incidence: 3.5%, 95% CI: 1.7–2.5%). Among the identified ADRs, 42% were serious. Nausea and vomiting were the most frequent ADRs, mainly caused by analgesics (nefopam, tramadol) and antibiotics (amoxicillin–clavulanic acid). The gastrointestinal and nervous systems were the most affected. According to the Rawlins and Thompson classification, 90% of ADRs were type A, 8% type B, and 2% type E (withdrawal syndrome). Overall, 90% of ADRs were preventable. Conclusions: This study highlights the importance of pharmacovigilance at CHUL, Gabon, and emphasizes the role of healthcare professionals in ADR reporting and risk minimization. Full article