Search Results (301)

Background: Pneumococcal vaccination rates in the United States (US) remain suboptimal, especially for adults aged 19 to 64 with high-risk medical conditions. Community-pharmacy-based immunization services increase vaccine access, particularly in rural areas. This study describes the provision of pneumococcal immunization services, assesses the processes used to identify and confirm patient eligibility, and determines barriers to immunization services in rural community pharmacies. Methods: A cross-sectional survey was emailed to members of the Rural Research Alliance of Community Pharmacies, located in the southeastern US. The survey assessed which pneumococcal vaccines were offered, age groups, prescription requirements, and how patient eligibility was determined. In addition, participants were asked to rate a series of patient-related and organizational barriers to pneumococcal vaccination. Results: Ninety-four pharmacies completed the survey, with most (96.8%) offering pneumococcal vaccines, most commonly PCV20 (95.6%). Most pharmacies vaccinated patients upon request (98.9%) or when patients presented with a prescription (82.4%), but few proactively contacted patients to schedule the vaccination (17.6%). Pharmacists most often administered pneumococcal vaccines to patients aged 65 and older and used patient age and immunization information systems to identify eligible patients. The most common patient-related barrier was the patient’s belief that they do not need the vaccine. The most common organizational barriers were inadequate reimbursements for vaccine administration and vaccine products. Conclusions: Pneumococcal vaccinations are commonly offered in rural community pharmacies, which play an important role in immunization access. With recent guideline changes to the age-based recommendation, there is an opportunity to optimize strategies to increase vaccine uptake. Full article

In the United States, the Clozapine Risk Evaluation and Mitigation Strategy (REMS) program was implemented to ensure safe prescription and monitoring; however, its administrative complexity has often resulted in unintended barriers to access. Clozapine remains the most effective antipsychotic for treatment-resistant schizophrenia (TRS), yet its use continues to be constrained by outdated regulatory frameworks, cultural inertia, and clinical hesitancy. This perspective article revisits the pharmacokinetic foundations of clozapine, re-examines its association with fatal outcomes, and critiques the persistence of obsolete monitoring systems such as the U.S. REMS program. Drawing on recent consensus publications endorsed by over 120 international clozapine experts, this article outlines the proposed changes to the U.S. prescription information and contextualizes them within broader global practices. This article argues that many barriers to clozapine use stem not from evidence, but from regulatory conservatism and the perpetuation of clinical myths. The dismantling of the REMS program in early 2025 represents a pivotal moment, yet further reforms are urgently needed to align regulatory guidance with contemporary science. Ultimately, this article is a call to rediscover the clinical value of clozapine and to translate decades of knowledge into regulatory and clinical action. Full article

Pharmacogenomics (PGx) has emerged as a powerful tool to personalize drug selection and dosing based on a patient’s genetic profile. However, there are a range of challenges that impede uptake in current clinical practice. For example, clinicians often express frustration with commercially available PGx panel tests, which fail to consistently include all key actionable PGx genes (according to the Clinical Pharmacogenetics Implementation Consortium (CPIC), Food and Drug Administration (FDA) PGx guidelines, or The Dutch Pharmacogenetics Working Group (DPWG) guidelines) and instead are too long with clinically unimportant information (unvalidated genotypes). Additionally, the lack of EMR integration, clinician education and awareness of the benefits of PGx impedes uptake. This paper examines key challenges identified in clinical practice and proposes future directions, focusing on limiting PGx reports to essential data, providing point-of-prescription alerts, and establishing reimbursement pathways that encourage adoption. Future directions include leveraging large language models, integrating point-of-prescription alerts and phenoconversion calculators into the electronic medical record, increasing the genomic diversity of PGx study populations, and streamlining coverage by payers. Full article

Propolis is a natural resinous substance produced by honeybees that has many biological activities. For thousands of years, it has been widely used as a dietary supplement and traditional medicine to treat a variety of ailments due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and wound-healing properties. Nutritional supplements and foods may interact with drugs both pharmacodynamically and pharmacokinetically, which could raise clinical concerns. Background/Objectives: This study aimed to investigate the effect of propolis on the plasma disposition of enrofloxacin and to assess the potential pharmacokinetic interaction in rabbits. Methods: In this study, enrofloxacin was applied per os (20 mg/kg) and IM (10 mg/kg) and with propolis (100 mg resin/kg) administration in four groups of rabbits (each of six individuals). Heparinized blood samples were collected at 0, 0.1, 0.3, 0.5, 1, 2, 4, 8, 12, and 24 h post-administration. HPLC-FL was used to analyze the plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin following liquid–liquid phase extraction, i.e., protein precipitation with acetonitrile and partitioning with sodium sulfate. Results: The results revealed that propolis coadministration significantly affected the plasma disposition of enrofloxacin and its active metabolite after both per os and intramuscular administration routes. Significantly greater AUC (48.91 ± 11.53 vs. 26.11 ± 12.44 µg.h/mL), as well as longer T_1/2λz (11.75 ± 3.20 vs. 5.93 ± 2.51 h) and MRT (17.26 ± 4.55 vs. 8.96 ± 3.82 h) values of enrofloxacin and its metabolite ciprofloxacin, were observed after the coadministration of propolis compared to enrofloxacin alone following both per os and IM routes in rabbits. Conclusions: The concurrent use of propolis and prescription medications may prolong the half-life (T_1/2λz) and increase the systemic availability of chronically used drugs with narrow therapeutic indices. The repeated use of drugs such as antibiotics, heart medications, and antidepressants, or drugs with a narrow therapeutic index such as antineoplastic and anticoagulant agents, can cause toxic effects by raising blood plasma levels. Considering the varied metabolism of rabbits and humans, further validation of this study may require thorough clinical trials in humans. Full article

Background/Objectives: Sepsis is one of the most common causes of death worldwide, and its diagnosis remains a challenge for clinicians. The main purpose of this study was to appraise the diagnosis and antibiotic prescription pattern for sepsis admitted to the Emergency Department (ED), comparing Sepsis-2 to Sepsis-3 criteria. Methods: The study was conducted in an ED of a tertiary care medical center in Hungary. We included all adult patients who were diagnosed with sepsis in 2023. Data collection was made manually from UD MED System. Diagnosis was assessed based on Sepsis-2 and Sepsis-3 criteria, then compared. Further analyses were made only in cases with confirmed sepsis diagnosis. Antibiotic guideline adherence was determined according to the local guideline in force. Fisher’s exact test, t-test, and ANOVA were applied to compare categorical and continuous variables between groups. The Kaplan–Meier test was applied for probability of survival. Significant p-values were defined as below 0.05. Results: The substantial majority of patients recorded with sepsis in the ED met both the Sepsis-2 and Sepsis-3 criteria (80%), while the rate of misdiagnosis was similar (Sepsis-2: 16/91, 17.6% and Sepsis-3: 14/91, 15.4%). The most important identified risk factors in sepsis were old age (60+ years) and comorbidities (CCI ≥ 4). Elevated LDH (median 325 mg/dL) and decreased albumin levels (median 26 g/L) can be used as early indicators of sepsis. Although the time to first antibiotic administration was not associated with significantly better clinical outcomes, the guideline-adherent agent selection (Sepsis-2: 18/43, 41.9% and Sepsis-3: 19/46: 41.3%) led to a significantly longer survival (median 37 vs. 4 days). Conclusions: No significant differences were found in diagnostic accuracy or prediction of mortality between Sepsis-2 and Sepsis-3. Guideline-adherent antibiotics may lead to significantly higher survival rate in sepsis. Full article

Delta-9-tetrahydrocannabinol (THC) is a psychoactive element of Cannabis sativa and affects the human cannabinoid system through its receptors, CB1R and CB2R. CB1R was found in several brain areas, including the hippocampal formation (HF), and it is responsible for most THC side effects. We investigated THC’s effects in the HF of female Wistar rats to assess changes in its neurotransmission. Female Wister rats (n = 20) were gonadectomized under anesthesia at 8 weeks old. Afterwards, they received estradiol benzoate (EB) and/or THC. Immunohistochemistry was performed to assess the expression of the cholinergic receptor alpha 7 subunit (CHRNA7), the vesicular acetylcholine transporter (VAChT), the vesicular glutamate transporter (VGLUT), the gamma-aminobutyric acid type A receptor (GABRA), the CB1 receptor, and estradiol receptor alpha (EBα). In the HF, the expression of CHRNA7 was increased by EB and by THC in the Oil groups but decreased by THC in the EB groups. The same is true for VGLUT expression in the DG and hilum and for GABRA expression in the hilum. The expression of VAChT and CB1 is reduced by EB, while the concomitant administration of THC increases it. GAD expression is reduced by EB administration in CA1, CA3, and DG. Our results may help with decision-making regarding the prescription of low doses of THC as a therapeutical approach. Full article

Background: Pain is a prevalent issue among breast cancer patients and survivors, with a significant proportion receiving hydrocodone for pain management. However, the rescheduling of hydrocodone from Schedule III to Schedule II by the U.S. Drug Enforcement Administration (DEA) in October 2014 raised concerns about potential barriers to opioid access for cancer patients, particularly among vulnerable populations such as dually eligible Medicare–Medicaid beneficiaries and racial/ethnic minorities. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data including 52,306 early-stage breast cancer patients from 2011 to 2019. We employed multivariable logistic regression models with model specification tests to stratify the subgroups and evaluate the differential effects of the policy change by Medicaid dual eligibility and race–ethnicity, while adjusting for other patient demographics, clinical characteristics, and cancer treatments. Results: The rescheduling of hydrocodone was associated with significantly different effects on prescription opioid use across subgroups, with the most pronounced reduction in hydrocodone prescription observed among dual-eligible racial/ethnic minority patients (adjusted odds ratio [AOR] = 0.57; 95% confidence interval [CI]: 0.44–0.74; p < 0.001). Non-dual-eligible patients experienced a smaller reduction in hydrocodone use (AOR = 0.84; 95% CI: 0.78–0.90; p < 0.001). Concurrently, non-hydrocodone opioid use significantly increased among non-dual-eligible non-Hispanic White patients (AOR = 1.29; 95% CI: 1.19–1.40; p < 0.001), suggesting a substitution effect, while smaller non-significant increases were observed among other subgroups. Conclusions: Hydrocodone rescheduling led to the greatest reduction in hydrocodone use among dual-eligible racial–ethnic minority patients. The corresponding increase in non-hydrocodone opioid use was limited to non-dual-eligible non-Hispanic White patients. These findings highlight the need for opioid policies that balance misuse prevention with equitable access to pain relief, particularly among underserved populations. Full article

Osteoporosis therapy is a crucial component of fragility fracture patients’ care. A Quality Improvement Project (QIP) was undertaken to review and improve such bone protection practice within a busy UK hospital orthopaedic department. Full-loop audit cycles, totalling 216 patients, were conducted before and after the implementation of a single-page checklist. This intervention significantly increased consultant-led osteoporosis plans by 37%, enhanced bone-sparing treatment administration by 20%, and eliminated unsafe prescriptions. Provision timeliness was not affected, but the communication of correct discharge information was significantly improved by 27%, and staff surveys showed the checklist was well-received, easy-to-use, and educational. Hopefully this will encourage other orthogeriatric teams to utilise a similarly effective and simple QI strategy. Full article

Background: Oral semaglutide, a GLP1-receptor agonist (GLP1-RA), shows promise in efficacy and compliance, especially amid the global shortage of injectable GLP-1 RAs. Its short-term effectiveness remains unexplored. Objective: This real-world observational study assessed the short-term effectiveness of oral semaglutide after three months of therapy. Methods: Patients with type 2 diabetes from four Italian diabetes centers, who received an initial prescription of oral semaglutide, were reassessed after three months. Primary outcomes included glycated hemoglobin (HbA1c) and body weight reduction; secondary outcomes involved changes in lipid parameters and cardiovascular risk. Results: Among 167 participants (mean age 66.5 years, mostly obese, baseline HbA1c 8.4% ± 1.5), 83.2% received a 7 mg dose. After three months, HbA1c significantly declined (8.4% to 7.1%, −1.3%, p < 0.001), alongside body mass index (BMI) (30.9 kg/m² to 29.6 kg/m², p < 0.0001). The target HbA1c ≤ 7% was achieved by 54.5%, and 34.7% reached ≤6.5%. Patients losing >5% of their initial weight (30.5%) saw the largest HbA1c drop (−1.9%). Those with newly diagnosed diabetes or a duration < 5 years showed superior responses (p = 0.001), while no significant differences were found based on the timing of drug administration. Oral semaglutide replaced or supplemented prior therapies, allowing discontinuation of dipeptidyl peptidase 4 inhibitors (DPP4i), sulfonylureas, glinides, and acarbose, and deprescription of thiazolidinediones. A significant reduction in cardiovascular risk was observed (p = 0.04), together with a significant reduction in lipid parameters. Conclusions: Oral semaglutide showed significant short-term efficacy, reducing HbA1c, body weight, and cardiovascular risk in three months, making it a valuable therapeutic option. Full article

The rapid pace of modern life has contributed to a significant decline in sleep quality, which has become an urgent global public health issue. Melatonin, an endogenous hormone that regulates circadian rhythms, is vital in maintaining normal sleep cycles. While oral melatonin supplementation is widely used, transdermal delivery systems present advantages that include the avoidance of first-pass metabolism effects and enhanced bioavailability. In this study, a novel melatonin transdermal delivery system was successfully developed using a thermosensitive poly(N-vinylcaprolactam) [p(NVCL)]-based carrier. The p(NVCL) polymer was synthesized through free radical polymerization and characterized for its structural properties and phase transition temperature, in alignment with skin surface conditions. Orthogonal optimization experiments identified 3% azone, 3% menthol, and 4% borneol as the optimal enhancer combination for enhanced transdermal absorption. The formulation demonstrated exceptional melatonin loading characteristics with high encapsulation efficiency and stable physicochemical properties, including an appropriate pH and optimal moisture content. Comprehensive in vivo evaluation using normal mouse models revealed significant sleep quality improvements, specifically a shortened sleep latency and extended non-rapid eye movement sleep duration, with elevated serum melatonin and serotonin levels. Safety assessments including histopathological examination, biochemical analysis, and 28-day continuous administration studies confirmed excellent biocompatibility with no adverse reactions or systemic toxicity. Near-infrared fluorescence imaging provided direct evidence of enhanced transdermal absorption and superior biodistribution compared to oral administration. These findings indicate that the p(NVCL)-based melatonin transdermal gel system offers a safe, effective and convenient non-prescription option for sleep regulation, with promising potential for clinical translation as a consumer sleep aid. Full article

Background and Objectives: Medication errors are a critical issue in healthcare systems worldwide, contributing to significant patient harm, with studies indicating that medication-related incidents are among the most common causes of adverse events in medical practice. There are between 80 and 200 steps in providing a single patient with a single dose of drugs, with five stages, including prescription, preparation, dispensation, administration and monitoring. This study aims to describe and validate the MAEs (Medication Administration Error Scale) tool, which investigates the most common causes of medication errors in medication administration. Materials and Methods: Independent translators translated the original version of the scale using language verification. The agreed-upon version of the translation was then assessed by a team of nurses, specialists in anaesthetic and intensive care nursing, in terms of understanding the translated content. After introducing changes resulting from linguistic and organisational differences, a survey questionnaire was prepared and used in the pilot study. Eighty-six respondents participated in the pilot study via the Office 365 platform and the Forms programme. The research was led by nurses who work in highly specialised units. The reliability of the translated version of the questionnaire was examined by calculating the Cronbach’s alpha coefficient. Results: The tool’s internal consistency across ranges was within acceptable limits. For part A (questions 1–29), it was 0.93; for part B (questions 30–45), it was 0.94. In part C, regarding the percentages of the type of error occurring in a given medical facility, Cronbach’s alpha coefficient was 0.97. When the factor loadings of the items were evaluated, they were determined to be in the range of 0.602–0.783. In this context, the factor loading levels of the items in the 5-factor model were high and sufficient. Conclusions: The statistical analyses suggest that the Polish version of the Medication Administration Error Survey demonstrates satisfactory reliability and is a promising tool for assessing the cause of medication administration errors. Full article

Background: Tapentadol is an atypical opioid with a dual mechanism as a mu agonist and norepinephrine reuptake inhibitor. This study characterized tapentadol use in the United States (US) using three databases. Methods: Drug distribution data from 2010 to 2020 were extracted from the Drug Enforcement Administration (DEA)’s Automated Reports and Consolidated Orders System (ARCOS), including use per region (mg/person) and business activity (i.e., pharmacy). Tapentadol prescription claims from the Medicare and Medicaid programs for 2010–2020 were also examined. Results: The distributed amount of tapentadol was 3.5 tons in 2020. Distribution was over twice as high in southern (South Atlantic = 29.0 mg/person, East South Central = 28.8) relative to Pacific (12.9) or New England (12.8) states. Tapentadol use decreased nationally between 2012 and 2020 by −53.8%. Adult diabetes prevalence was significantly associated with tapentadol distribution in 2012 (r(50) = +0.44, p < 0.01) and 2020 (r(50) = +0.28, p < 0.05). Tapentadol prescribing to Medicaid patients declined −55.2% from the peak year, 2011, until 2020. Tapentadol prescribed by Nurse Practitioners accounted for over one-sixth (18.0%) of 2019 in Medicare. Conclusions: There has been a substantial decline over the past decade in tapentadol distribution and prescribing. However, the substantial regional differences may warrant further attention by opioid stewardship programs. Full article

Objective: Tuo-Min-Ding-Chuan decoction (TMDC), a traditional Chinese prescription, has demonstrated significant clinical efficacy in treating allergic asthma. This study aimed to investigate the mechanism of TMDC in treating asthma from the perspective of Treg cells and gut microbiota across distinct gut segments (jejunum, ileum, cecum, and colon). Methods: An ovalbumin (OVA)-induced asthma model was established in mice, followed by oral administration of TMDC at high, medium, and low dose. Immune cells and lung inflammation were examined to assess asthma severity. Microbial composition was determined by 16S rRNA sequencing. Antibiotic cocktail and Lactobacillus rhamnosus GG (LGG) were administrated to confirm the key role of specific bacteria. Results: TMDC attenuated lung inflammation (p < 0.01) and eosinophilic infiltration (p < 0.01) as well as IL-4 and IL-5 secretion (p < 0.01); it was also associated with an increase in Treg cells in the lung, small intestine (SI), and colon (p < 0.05). Meanwhile, TMDC restored the number of microbiota species and the Shannon index in the hindgut and reinstated beneficial bacteria, such as Allobaculum and Turicibacter, which were diminished in asthmatic mice. Notably, TMDC significantly enriched Bifidobacterium and Lactobacillus, particularly in the hindgut. Lactobacillus abundance was significantly correlated (p < 0.05) with Treg cells, IL-4, IL-5, and eosinophils. Furthermore, LGG supplementation restored elevated lung inflammation (p < 0.05) and decreased Treg cells (p < 0.01) due to antibiotic-induced microbiota depletion. Conclusion: TMDC alleviated asthma by promoting Treg cell expansion in a Lactobacillus-dependent manner across different gut segments, providing new insights into its therapeutic mechanisms. Full article

Yinhua Pinggan Granules (YPG) is a patented traditional Chinese medicine (TCM) compound prescription, with wide clinical application against cold, cough, and relevant diseases. However, the chemical profiles of YPG in vivo are still unknown, hindering further pharmacological and quality control (QC) researches. This study presents an ultra-high-performance liquid chromatography coupled with high-resolution orbitrap mass spectrometry (UHPLC-MS)-based method. Using the Compound Discoverer platform and a self-built ‘in-house’ compound database, the metabolic profiles and pharmacokinetics characters of YPG were investigated. Consequently, a total of 230 compounds (including 39 prototype components and 191 metabolites) were tentatively identified, in which the parent compounds were mainly flavonoids, alkaloids, and terpenoids, and the main metabolic pathways of metabolites include hydration, dehydration, and oxidation. The serum concentration of seven major representative compounds, including quinic acid, chlorogenic acid, amygdalin, 3′-methoxypuerarin, puerarin, glycyrrhizic acid, and polydatin, were also measured, to elucidate their pharmacokinetics behaviors in vivo. The pharmacokinetic study showed that the seven representative compounds were quantified in rat plasma within 5 min post-administration, with T_max of less than 2 h, followed by a gradual decline in concentration over a 10 h period. The method demonstrated excellent linearity (R² > 0.998), precision, and recovery (RSD < 15%). As the first systematic characterization of YPG’ s in vivo components and metabolites using UHPLC-MS, this study may contribute to comprehensively elucidate the metabolic profiles of the major components in YPG, and provide a critical foundation for further investigation on the QC and bioactivity research of YPG. Full article

Background/Objectives: Multi-lumen devices that limit physicochemical incompatibilities (PCIs) are frequently used in neonatal intensive care units where premature infants receive numerous infusions. The aim of the study was to investigate a PCI that occurred despite the use of a device of this type (EDELVAISS^® Multiline NEO, Doran International, Toussieu, France). Case Summary: A 7-week-old preterm infant received ganciclovir at therapeutic dosage for cytomegalovirus (CMV) infection. After the fifth administration of ganciclovir, a PCI occurred, leading to a white precipitate. The peripheral inserted central catheter (PICC) (PREMICATH^®2Fr, Vygon, Ecouen, France) had to be replaced. Laboratory reproduction of the administrations during 72 h, nuclear magnetic resonance (NMR) analysis and particle counting were carried out to analyse the occurrence of events leading to PCIs. The precipitate was linked to a PCI of parenteral nutrition associated with a dilution error of ganciclovir (omission of a 10-fold dilution step, resulting in ganciclovir being administered at 30 mg/L instead of 3 mg/L). Due to the presence of lipids in the parenteral nutrition, visual detection of the white precipitate was difficult. Conclusions: Multi-lumen infusion devices limit but do not prevent the occurrence of PCIs, particularly in the event of a preparation error. Despite the use of this type of device, great vigilance is still required, particularly with regard to prescription analysis and reconstitution procedures. Full article