Search Results (1,574)

Purpose: This post-marketing surveillance study evaluated the real-world safety and descriptive outcomes of a fixed 2:1 recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) combination among Korean women undergoing assisted reproductive technology with severe LH and FSH deficiency (baseline endogenous serum LH < 1.2 IU/L). Methods: A prospective, multicenter, observational study was conducted across 24 Korean fertility centers between August 2011 and May 2018. Safety outcomes included adverse events (AEs), adverse drug reactions (ADRs), and ovarian hyperstimulation syndrome (OHSS). Descriptive outcomes included endpoint-specific evaluable sets for follicular response and ultrasound-confirmed clinical pregnancy. Analyses were performed in safety (n = 600), follicular-response evaluable (n = 537), and pregnancy-evaluable (n = 486) sets. Results: Among patients in the safety set (mean age, 34.6 years), AEs occurred in 2.7% (16/600; 95% confidence interval [CI], 1.6–4.3), ADRs in 2.2% (13/600; 95% CI, 1.3–3.7), and OHSS in 1.3% (8/600; 95% CI, 0.7–2.6), including one severe case. In the follicular-response evaluable set, follicular response (≥1 follicle ≥17 mm) occurred in 99.3% (533/537; 95% CI, 98.1–99.7). In the pregnancy-evaluable set, clinical pregnancy occurred in 42.0% (204/486; 95% CI, 37.7–46.4), biochemical-only pregnancies in 3.1% (15/486; 95% CI, 1.9–5.0), and total pregnancies (clinical + biochemical-only, reported descriptively) in 45.1% (219/486; 95% CI, 40.7–49.5). Conclusions: In this historically constrained post-marketing surveillance cohort, the fixed 2:1 r-hFSH and r-hLH combination showed a favorable post-marketing safety profile and provided descriptive outcome information within endpoint-specific evaluable sets in women meeting the severe LH-deficiency criterion. Full article

Background: The purpose of this preliminary study was to evaluate the use of the Zipf–Mandelbrot (ZM) law to mathematically model the percentage occurrence of adverse drug reactions (ADRs), as a function of rank, reported to the United States Food and Drug Administration Adverse Event Monitoring System (US FDA AEMS). Methods: Six commonly used but pharmacologically different hospital-based medications were examined. Nonlinear curve fitting of the two ZM coefficients was utilized to model the percentage occurrence of ADRs in a hierarchical or rank order for each drug examined. Results: The reported complications and their associated occurrence rates for all six medications were accurately modeled using the ZM law. Those medications that have a greater percentage of reported ADRs within their first ten ranks were also found to have a greater negative slope. Furthermore, a natural logarithmic transformation of both the reported FDA data and the ZM law-derived predicted values demonstrated a consistent near-linear relationship, which was statistically significant. The ratio of the coefficients of the ZM law, $a·b^{-1}$, was also found to be a potentially useful index that allows for describing and comparing the overall shape of the medication-specific distributions. Conclusions: Based upon this preliminary examination, the ZM law appears to be applicable to the mathematical modeling of US FDA-reported ADRs. Additional research to assess and utilize this law for the analysis, economic management, and possible improvement in patient outcomes may be warranted. Full article

Background/Objectives: Omalizumab is an effective treatment for antihistamine-refractory chronic urticaria. However, post-injection urticaria exacerbation and related adverse reactions remain inconsistently reported. This scoping review mapped evidence on clinical presentation, timing, mechanisms, management strategies, rechallenge outcomes, treatment discontinuation, and patient outcomes associated with these reactions. Methods: The review followed the Joanna Briggs Institute methodology and was registered prospectively in INPLASY (INPLASY202650060). PubMed, Scopus, and the Directory of Open Access Journals were searched from inception to April 2026. Eligible studies included English-language case reports, case series, observational studies, cohort studies, registry or pharmacovigilance studies, postmarketing surveillance studies, and clinical trials reporting urticaria-related or hypersensitivity-type adverse reactions during omalizumab treatment for chronic urticaria. Data were charted descriptively and synthesized narratively. Results: Seventeen studies published between 2015 and 2026 included 2790 patients with chronic urticaria, 60 of whom experienced urticaria-related adverse reactions, corresponding to a mapped proportion of 2.2%. Clinical phenotypes included transient urticaria exacerbation, urticaria flare or worsening, localized urticarial plaques at the injection area, angioedema, anaphylaxis or anaphylaxis-like reactions, and serum sickness-like reactions. Reactions occurred within minutes to several hours, within 24 h, several days, or up to 1 week after injection or dose escalation. Reactions occurred following the first dose, repeated doses, and dose escalation. Proposed mechanisms included delayed hypersensitivity, possible IgE-mediated delayed-onset anaphylaxis, serum sickness-like reaction, paradoxical worsening, infection-associated flare, excipient-related reactions, and severe underlying CSU exacerbation mimicking anaphylaxis. Management strategies ranged from observation or symptomatic treatment to discontinuation of omalizumab and systemic interventions. Conclusions: Omalizumab-associated urticaria-related adverse reactions were infrequently reported across the mapped evidence but were clinically heterogeneous. Standardized definitions and detailed case reporting are needed to clarify causality, recurrence risk, rechallenge safety, and long-term outcomes. Full article

Drug recall is a critical regulatory mechanism implemented to protect public health by removing defective, unsafe, or non-compliant pharmaceutical products from the market. Despite stringent regulatory approval processes, issues related to manufacturing defects, contamination, labeling errors, stability failures, and post-marketing safety concerns may lead to drug recalls. Regulatory authorities across the world, including the Central Drugs Standard Control Organization (CDSCO), the United States Food and Drug Administration (US FDA), the European Medicines Agency (EMA), and other national agencies, have developed structured recall guidelines and rapid alert systems to ensure timely withdrawal of defective products. Drug recalls are typically classified based on the level of health risk and may be executed at different levels of the distribution chain, including wholesale, retail, and consumer levels. Effective recall management involves risk assessment, recall communication, product traceability, documentation, and recall effectiveness checks. Pharmacovigilance systems also play an important role in identifying adverse drug reactions and quality defects that may lead to product recalls. This review article provides a comprehensive overview of drug recall systems, including causes of recalls, regulatory frameworks in India and other countries, recall classification, recall procedures, rapid alert systems, and global recall trends. The article also discusses challenges in recall implementation and provides recommendations to strengthen drug recall systems and regulatory coordination worldwide. The review additionally summarizes major official sources of recall information, including recall alerts, safety communications, and regulatory databases maintained by the Food and Drug Administration (FDA), EMA, CDSCO, Medicines and Healthcare products Regulatory Agency (MHRA), and World Health Organization (WHO), and provides a comparative global perspective on contemporary pharmaceutical recall practices. Full article

Background/Objectives: Hydroxychloroquine is widely used in the treatment of autoimmune and dermatologic diseases; however, it may rarely induce severe cutaneous adverse reactions. Acute Generalized Exanthematous Pustulosis is an uncommon, acute pustular eruption most frequently associated with antibiotics. Hydroxychloroquine-induced AGEP remains relatively rare and diagnostically challenging due to its atypical and prolonged clinical course. Case presentation: We report the case of a 45-year-old woman with rheumatoid arthritis and a complex medical history who developed generalized urticarial and pustular dermatosis following re-exposure to hydroxychloroquine. Notably, the patient had experienced a similar cutaneous reaction after previous exposure to the same medication several years earlier. Ten days after completing a treatment course of hydroxychloroquine, she developed rapidly progressive pruritic erythematous and urticarial plaques that evolved into generalized annular lesions with peripheral scaling and grouped sterile pustules. Laboratory evaluation demonstrated leukocytosis, intermittent eosinophilia, and elevated IgE levels, while the infectious workup was negative. Histopathological examination revealed subcorneal pustules with neutrophilic infiltration, mild spongiosis, and scattered individual eosinophils, perivascular inflammatory infiltrates, findings consistent with AGEP. Retrospective assessment using the EuroSCAR scoring system classified the reaction as probable AGEP, while the Naranjo adverse drug reaction scale supported a probable causal relationship with hydroxychloroquine. Clinical improvement was achieved after withdrawal of the drug and treatment with systemic corticosteroids and supportive therapy. Conclusions: This case highlights the importance of recognizing atypical presentations compatible with hydroxychloroquine-induced probable AGEP and emphasizes the diagnostic value of a positive rechallenge as supportive evidence of drug causality. Early recognition and prompt discontinuation of the offending agent are essential to prevent severe complications and recurrence. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has transformed haematological-malignancy care, but its dermatologic safety profile remains incompletely characterised across products and indications. Methods: We analysed 8,431,841 deduplicated FDA Adverse Event Reporting System reports from 2016 Q3 to 2026 Q1. Seven approved CAR T-cell products were identified. The primary outcome was any dermatologic adverse event, defined using the MedDRA Skin and subcutaneous tissue disorders system organ class. Secondary outcomes included broad severe cutaneous adverse reactions, narrow Stevens-Johnson syndrome/toxic epidermal necrolysis, and 14 phenotype-specific categories. Multivariable models adjusted for demographics, polypharmacy, cancer, immune checkpoint inhibitor exposure, lymphodepleting chemotherapy and cytokine release syndrome. Additional sensitivity analyses evaluated HSCT/GVHD co-reporting proxies, infection and cytopenia/bleeding proxies, severe-event clinical characteristics, comparator robustness and multiplicity correction. Results: Dermatologic adverse events were identified in 996,654 reports, including 425 CAR-T-associated cases. CAR T-cell exposure was associated with reduced adjusted reporting odds for the primary outcome (adjusted odds ratio 0.13, 95% confidence interval 0.09–0.20) and broad severe cutaneous adverse reactions (0.35, 0.23–0.52). The primary SKIN_ANY reduced-reporting pattern was consistent across all-FAERS, haematological-malignancy and active haematology-oncology comparators. HSCT/GVHD proxy co-reporting was uncommon and did not materially alter estimates. Severe dermatologic reports frequently co-mentioned CRS and serious outcomes. The tisagenlecleucel vascular cutaneous signal was nominally significant but attenuated after excluding infection-attributable and cytopenia/bleeding-proxy reports. Conclusions: Within spontaneous reporting systems, CAR T-cell therapy showed reduced relative reporting of dermatologic adverse events across broad, phenotype-specific and product-level analyses. These results should be interpreted as differences in reporting behaviour, not as evidence of reduced true clinical incidence or lower patient-level risk. Early severe cutaneous reports frequently overlapped with cytokine release syndrome, while infection, cytopenia/bleeding proxies and supportive-care drugs were important alternative explanations for selected cutaneous signals. Full article

Background/Objectives: Special populations, including pediatric, geriatric, and organ-impaired patients, are consistently underrepresented in randomized controlled trials (RCTs), resulting in limited evidence for safe and effective dosing. Off-label use is common, and variability in drug exposure and response increases the risk of adverse drug reactions (ADRs). This review aims to examine how integrating pharmacometrics (PMX) with real-world data (RWD) can address evidence gaps by supporting dose optimization, population expansion, and safety evaluation in these vulnerable groups. Methods: A narrative literature review was conducted using PubMed, Embase, and Web of Science (January 2000–November 2025). Using Boolean combinations of PMX and RWD-related search terms, approximately 200–300 records were identified across the three databases; approximately 30 full-text articles were reviewed, and representative case studies were selected based on population diversity, methodological variation, and regulatory or clinical impact. Results: RWD–PMX integration has been applied across three domains: (i) dosing optimization through therapeutic drug monitoring (TDM)-informed PopPK modeling and model external validation in pediatric and neonatal populations; (ii) population expansion supporting dose extrapolation and regulatory decision-making for unapproved groups; and (iii) safety evaluation enabling identification of exposure–toxicity risk factors in vulnerable cohorts. Conclusions: Integrating PMX with RWD provides a practical and mechanistically grounded framework for evaluating dosing, treatment eligibility, and safety in populations insufficiently represented in clinical trials. Accumulating evidence indicates that RWD–PMX methodologies can complement traditional clinical research and inform regulatory decision-making. Continued refinement of data quality standards, validation practices, and guidance frameworks will be essential for broader adoption. Full article

Background: Adverse drug reactions (ADRs) represent a major and often underestimated source of morbidity, hospitalization, and functional decline in older adults. The convergence of age-related pharmacokinetic and pharmacodynamic changes, multimorbidity, polypharmacy, and frailty creates a clinical environment in which ADR risk is not static but evolves along progressive trajectories—from mild, early manifestations toward severe, potentially irreversible outcomes. Understanding these trajectories is essential for rational geriatric prescribing. Methods: This narrative review synthesizes evidence from epidemiological studies, systematic reviews, Cochrane analyses, and clinical trials published between 2000 and 2025, focusing on adults aged 65 years and older with two or more chronic conditions. Sources were identified through a structured, non-systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus using the terms ‘adverse drug reactions’, ‘polypharmacy’, ‘multimorbidity’, ‘frailty’, ‘deprescribing’, and ‘pharmacokinetics’ in older adults, alone and in combination. Evidence quality was assessed narratively, distinguishing trial evidence from observational and expert consensus data. Results: ADRs in older adults are best classified using complementary frameworks—the augmented Type A to withdrawal Type E and failure-of-therapy Type F taxonomy (Types A–F), the Dose-Time-Susceptibility (DoTS) classification, and the EIDOS mechanistic scheme—which together capture the heterogeneity of drug-related harm in this population. Age-related pharmacokinetic changes (altered absorption, increased volume of distribution of lipophilic drugs, reduced hepatic and renal clearance) and pharmacodynamic shifts (heightened receptor sensitivity, baroreflex impairment, increased blood–brain barrier permeability) interact with polypharmacy and frailty to amplify ADR trajectories from mild to severe. Anticholinergic burden, prescribing cascades, and inappropriate polypharmacy function as structural accelerators of these trajectories. Medication review and deprescribing improve prescribing quality but evidence for hard outcome benefits remains of low to very low certainty. Emerging AI-enabled digital tools show promising accuracy for identifying frailty and pharmacological vulnerability, but this performance relates to frailty classification and has not yet been shown to prevent ADR trajectories; they require validation for routine clinical use. Conclusions: Recognizing ADRs in older adults as dynamic trajectories rather than isolated events repositions prescribing review and deprescribing from optional to essential clinical acts. An integrated approach combining pharmacological vigilance, comprehensive geriatric assessment, structured deprescribing, and emerging digital decision-support tools offers the most realistic pathway to reduce the trajectory-related burden of drug-related harm in complex older patients. Full article

Objective: Icariin (ICA) is an active small molecule extracted from Epimedium, possessing therapeutic potential for inflammatory bone destruction. Small extracellular vesicles (MEVs) derived from bovine milk are safe and efficient drug delivery carriers. We aimed to explore the potential of ICA-loaded bovine milk EVs (ICA-MEVs) to repair inflammatory bone defects in an inflammatory microenvironment and investigated the underlying molecular mechanism, providing new ideas for the treatment of inflammatory bone defects. Methods: We fabricated icariin (ICA)-loaded milk-derived extracellular vesicles (ICA-MEVs) embedded in GelMA hydrogel and systematically evaluated the in vivo repairing efficacy against lipopolysaccharide (LPS)-induced inflammatory calvarial bone defects via micro-CT, HE staining, Masson staining and immunohistochemistry. Subsequent in vitro cellular experiments were carried out to uncover the regulatory mechanism by which ICA-MEVs promotes LPS-inhibited osteoblast proliferation and osteogenic differentiation. Results: ICA-MEVs significantly promoted the repair of inflammatory bone defects, upregulated osteogenic factors such as BMP-2, OCN, and Runx-2, and reduced the levels of IL-1β and TNF-α. ICA-loaded MEVs facilitated the proliferation and osteogenic differentiation of MC3T3-E1 osteoblasts while alleviating cellular inflammatory activation. Mechanistically, ICA-MEVs promoted bone repair by elevating LIM1 expression. Elevated LIM1 bound to the endogenous HIF-1α promoter and triggered subsequent transcriptional activation of HIF-1α. Conclusions: Under inflammatory conditions, ICA-MEVs effectively promoted the proliferation and differentiation of MC3T3-E1 cells and inhibited the expression of inflammatory factors. Mechanistically, ICA-MEVs upregulated HIF-1α transcription and expression by potentiating the LIM1-mediated transcriptional activation of the HIF-1α promoter, thereby facilitating inflammatory bone repair. Although milk-derived EVs exhibited favorable safety profiles in this preclinical study, comprehensive detection of immunogenicity and long-term adverse reactions will be necessary in follow-up research to support clinical transformation. Full article

Background: Previous trials of prophylactic norepinephrine have compared it with volume loading or non-norepinephrine vasopressors. Thus, it remains unclear whether a preemptive norepinephrine strategy provides incremental benefit over conventional management permitting reactive norepinephrine use. We evaluated whether preemptive low-dose norepinephrine infusion reduces hemodynamic instability during craniotomy for brain tumor resection under propofol–remifentanil total intravenous anesthesia (TIVA). Methods: Adult patients undergoing craniotomy for brain tumor resection under propofol–remifentanil TIVA were randomized to preemptive continuous infusion of norepinephrine (CINE; started at 0.02 µg/kg/min and titrated to remain below 0.05 µg/kg/min) or conventional management, in which norepinephrine was administered at the anesthesiologist’s discretion in response to hypotension. The primary endpoint was moderate or severe hemodynamic instability, defined as mean arterial pressure outside 80–120% and 70–130% of baseline, respectively. Secondary endpoints included rescue medication use, postoperative complications, and safety. Results: Compared with conventional management, the CINE group showed less moderate hemodynamic instability, both in the number of episodes per patient (median [interquartile range]: 6 [3–11] vs. 9 [5–13], p = 0.045) and in the proportion of anesthesia time affected (7.4% [3.6–12.4] vs. 12.2% [6.8–21.4], p = 0.017), but not less severe instability. Rescue medication was required less frequently in the CINE group (16.7% vs. 100%, p < 0.001). Complication rates were similar between the groups, and no adverse drug reactions occurred. Conclusions: Preemptive low-dose norepinephrine infusion reduced moderate hemodynamic instability during propofol–remifentanil TIVA for brain tumor resection, even against a control group receiving conventional management with reactive norepinephrine use, suggesting potential hemodynamic benefit that warrants confirmation in larger trials. Full article

Background/Objectives: In situ vaccines that directly release endogenous tumor antigens in situ to elicit anti-tumor immune responses without exogenous antigen preparation have emerged as a promising cancer immunotherapy strategy, due to their enhanced safety by local immunization that minimizes systematically adverse reactions. However, the anti-tumor efficacy of most in situ vaccines is affected by their limited access to tumors in distant sites and the toxicity of the adjuvants contained. Methods: To overcome these shortcomings, the present study explored the feasibility of utilizing extracellular vesicles from the probiotic bacteria Lactococcus lactis as both immune activators and drug carriers, which were formulated into nanoparticles to target distant tumors. Results: Using confocal microscopy and flow cytometry, we confirmed that the Lactococcus lactis-derived extracellular vesicles possess adjuvant activity that promoted the maturation of dendritic cells without affecting their viability or apoptosis rate. Moreover, the Lactococcus lactis-derived extracellular vesicles, both alone and when carrying the drug doxorubicin, could target and accumulate in solid tumor tissues via the enhanced permeability and retention effect. Interestingly, compared to healthy cells, the Lactococcus lactis-derived extracellular vesicles tended to be taken up more by tumor cells and readily released their encapsulated doxorubicin in the acidic tumor environment, which resulted in their enhanced reactive oxygen species production and immunogenic cell death. Ultimately, systemic administration of Lactococcus lactis-derived extracellular vesicle-encapsulated doxorubicin greatly increased the anti-tumor efficacy by boosting the number of infiltrating dendritic cells and CD8⁺ T cells in the tumor tissues and doxorubicin-mediated immunogenic cell death. Conclusions: Collectively, this study demonstrated that the probiotic Lactococcus lactis-derived extracellular vesicles are both safer adjuvants and effective drug carriers with immunostimulatory activity and tumor-targeting capability, shedding an interesting light on this vaccine design platform for future cancer immunotherapy. Full article

Background: Despite increasing opioid use in Brazil, the national epidemiological profile of opioid-related poisonings remains insufficiently characterized. Objective: To characterize opioid-notified poisonings reported in the Sistema de Informações sobre Agravos de Notificação (SINAN—Notifiable Diseases Information System), accessed through Departamento de Informática do Sistema Único de Saúde (DATASUS—Department of Informatics of the Unified Health System), between 2019 and 2025. Methods: This retrospective descriptive study used secondary national surveillance data from publicly accessible databases. Records of exogenous poisonings related to medications and drugs of abuse were screened, and notifications involving opioid analgesics were identified and standardized. Descriptive analyses were performed for demographic, clinical, and exposure-related variables. Bivariate analyses and multivariable logistic regression, regression models were conducted for selected outcomes. Incidence rates were estimated by year and federative unit, and temporal trends were assessed using generalized linear mixed models. Results: Between 2019 and 2025, 1,127,265 poisonings related to medications and drugs of abuse were reported in Brazil, of which 12,645 involved opioids. The opioids most frequently implicated in notifications were codeine (38.65%), tramadol (33.98%), and morphine (17.86%). Most cases occurred in women (70.3%), in individuals aged 26–50 years (47.8%), and in residences (85.6%). Digestive exposure predominated (92.3%), and suicide attempt was the main circumstance (73.5%). Most patients recovered without sequelae (75.1%), whereas 1.6% died due to exogenous intoxication. Co-exposure information was classifiable in 9573 records, most commonly involving opioids and medications. In multivariable analyses, suicide attempts were associated with female sex (aOR = 1.98; 95% CI: 1.68–2.34), residence-based exposure (aOR = 8.95; 95% CI: 6.29–12.72), and co-exposure (aOR = 2.17; 95% CI: 1.82–2.60). Hospitalization was less likely among females (aOR = 0.83; 95% CI: 0.75–0.91) and more likely with co-exposure (aOR = 1.14; 95% CI: 1.02–1.27). Serious outcomes were associated with older age (aOR = 1.017; 95% CI: 1.009–1.026), while residence-based exposure and suicide attempt showed lower odds. A significant increasing temporal trend was identified, with higher reported notification rates observed in the South and Southeast regions. Discussion: The predominance of suicide attempts and residential digestive exposures suggests that the notification profile captured by SINAN/DATASUS is predominantly shaped by intentional self-poisoning and household medication availability, while still representing a broader toxicovigilance scenario involving abuse, habitual use, adverse reactions, and other exposure contexts. The contrast between the most frequent notification profile and the profile associated with serious outcomes indicates that occurrence and severity may follow different epidemiological patterns. Therefore, these findings should be interpreted as a toxicovigilance signal reflecting multiple exposure contexts rather than as evidence of a single opioid-use pattern. Conclusions: Reported opioid-notified poisonings in Brazil increased over the study period and were predominantly associated with domestic exposure, suicide attempts, and co-exposure to other substances. These findings highlight the clinical and public health relevance of opioid-notified poisonings and support the need for strengthened surveillance, improved reporting quality, and preventive strategies addressing both opioid use and mental health. Limitations: Underreporting, missing data, regional reporting differences, and possible misclassification in SINAN/DATASUS records; therefore, associations, temporal increases, and projections should be interpreted as exploratory, and hypothesis generating. Full article

Background: Health literacy plays an important role in medication understanding, self-management, and engagement with healthcare services among older adults. Limited health literacy may contribute to medication-related problems and reduced utilization of pharmacist-led services in geriatric populations. Methods: A cross-sectional, questionnaire-based survey was conducted among geriatric outpatients (≥60 years) attending a tertiary-care teaching hospital in Saudi Arabia. Health literacy was assessed using a four-domain functional tool—covering prescription label comprehension, understanding of healthcare instructions, confidence in completing medical forms, and comprehension of written health information—developed in alignment with established health literacy frameworks, including the Health Literacy Survey—European Union (HLS-EU) model and Baker’s conceptual framework. Participants were classified as having higher health literacy (0–2 domains impaired) or lower health literacy (3–4 domains impaired). Sociodemographic characteristics, clinical burden, medication self-management behaviors, and awareness of clinical pharmacist services were recorded. Multivariable logistic regression was used to identify factors independently associated with lower health literacy. Results: A total of 200 participants were included. Impairment in three or more domains was observed in 55.5% of participants. Lower health literacy was independently associated with older age, lower educational attainment, lower income, female sex, multimorbidity, and polypharmacy. Participants with lower health literacy reported higher rates of missed or incorrect medication dosing and unreported adverse drug reactions and lower use of medication management aids. Awareness of clinical pharmacist services and prior exposure to pharmacist counseling were significantly lower among participants with lower health literacy. Willingness to receive pharmacist counseling was higher among participants with higher health literacy and greater awareness of pharmacist roles. Conclusions: Health-literacy impairment is common among geriatric outpatients and is associated with medication self-management behaviors and engagement with pharmacist-led services. These findings highlight the relevance of functional health literacy in geriatric medication use and support further research on literacy-sensitive pharmacist-led interventions. Full article

Background: Portal hypertension can lead to complications such as ascites, hepatic encephalopathy, esophageal varices, and gastrointestinal (GI) bleeding, all of which are associated with significant morbidity and mortality. Variceal bleeding is the most severe complication, with an estimated mortality of up to 30%. In children, evidence-based guidelines for the management of GI bleeding secondary to portal hypertension are lacking. In this con-text, octreotide, a synthetic somatostatin analog approved for other indications, has been increasingly used off-label and represents a paradigmatic example of drug re-purposing in pediatrics. Methods: Following the 2020 PRISMA guidelines, this systematic review evaluated the efficacy and safety of octreotide for the treatment of portal hyperten-sion-related GI bleeding in children. A comprehensive search of six sources, including five bibliographic databases (PubMed, Embase, Web of Science, Cochrane Library, and EBSCOhost) and the ClinicalTrials.gov registry, was conducted to identify studies in-cluding pediatric patients with GI bleeding secondary to portal hypertension. Results: Three non-randomized observational studies were included, assessing bleeding recurrence, packed red blood cell requirements, and adverse events following octreotide admin-istration. Overall, 33 patients were analyzed, with a mean age of 6.3 years. One study reported a reduction in rebleeding episodes and transfusion requirements after oc-treotide treatment. Across all included studies, no serious adverse events were ob-served; mild and reversible hyperglycemia was the only reported drug-related effect. Quantitative synthesis was not feasible due to substantial heterogeneity, missing data, and a serious risk of bias, resulting in very low certainty of evidence. Conclusions: Octreotide may represent a feasible therapeutic option for portal hypertension-related GI bleeding in children; however, further prospective and standardized studies are needed to establish its long-term safety and efficacy. Full article

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recommended for the treatment of acute (low) back pain, despite modest effectiveness and well-known safety concerns, particularly in older patients. Pridinol is a centrally acting antispasmodic with a mechanism-oriented approach targeting muscle spasm, a key component of acute back pain. While a previous real-world analysis demonstrated a significantly better tolerability and effectiveness of pridinol compared with NSAIDs, age-dependent effects have not yet been systematically evaluated. Objective: To assess the age dependency of effectiveness, safety, and tolerability of pridinol versus NSAIDs in patients with acute (low) back pain under real-world conditions, based on already available data. Methods: This secondary analysis used propensity score-matched real-world data from the German Pain e-Registry (PROVIDENCE study; EUPAS identifier: 49718). A total of 934 patients with acute (low) back pain treated for four weeks with either pridinol (n = 467) or NSAIDs (n = 467) were stratified by age (<65 vs. ≥65 years). Outcomes included the incidence of adverse drug reactions (ADRs), ADR-related treatment discontinuations, time to ADR occurrence, and clinically meaningful improvement in pain-related disability (≥50% reduction in modified Pain Disability Index). Analyses were performed within and between age strata. Results: Overall, ADRs were reported by 9.0% of pridinol-treated patients and 20.8% of NSAID-treated patients (p < 0.001). In the pridinol cohort, ADR rates were virtually identical in patients <65 and ≥65 years (8.9% vs. 9.2%; p = 0.940). In contrast, NSAID-treated patients showed a pronounced age-related increase in ADR incidence (17.3% vs. 32.1%; p < 0.001). ADR-related treatment discontinuation rates under NSAIDs increased markedly with age (5.9% vs. 21.1%; p < 0.001), whereas rates under pridinol remained low and age independent (3.1% vs. 4.6%; p = 0.447). Gastrointestinal and cardiovascular ADRs were the main contributors to the age-related risk increase under NSAIDs, while corresponding events under pridinol were rare across age groups. Clinically meaningful improvement in pain-related disability was achieved with pridinol/NSAIDs in 91.9/48.0% (<65 years) and 88.1/47.7% (≥65 years; p < 0.001 for both). Conclusions: Age is a major modifier of NSAID-related risk but not of pridinol tolerability in acute (low) back pain. While NSAID-associated ADRs and treatment discontinuations increase substantially in patients aged 65 years or older, pridinol demonstrates a stable, age-independent safety profile combined with significantly better functional outcomes. These findings suggest that, particularly in older patients, mechanism-oriented alternatives such as pridinol may offer a more favorable benefit–risk profile than NSAIDs. Full article