Search Results (167)

Measuring antimicrobial use (AMU) in animal production can provide useful data for monitoring AMU over time, which will promote antimicrobial resistance (AMR) reduction. This study involved the daily collation and validation of active primary drug sales and prescription data from veterinary outlets and clinics of the Kaduna metropolis. In total, 83.7% of the identified antimicrobials were in the form of oral medication, and most were registered antibiotics (52.8%). Parenteral and topical forms were also identified, with 94% also being antibiotics. The estimated AMU was 282 mg/kg population correction unit (PCU). Poultry represented the most significant population, constituting 99% (31,502,004) of the study population. The class-specific AMU was antibiotics, with 274 mg/kg PCU. The antiprotozoal AMU was 418 mg/kg PCU. The anthelminthic AMU was the highest at 576 mg/kg PCU. This study has provided useful and practical information on the trends in antimicrobial use in animals, with poultry being the most important animal population involved in AMU and oxytetracycline being the most abused antibiotic in animal production. Antimicrobial stewardship (AMS) should be targeted at poultry populations, with an emphasis on reducing antibiotic use/consumption. Full article

Background: Congenital diarrhea is persistent diarrhea that manifests during the neonatal period. Mutations in DGAT1, which is crucial for triglyceride synthesis and lipid absorption in the small intestine, are causal factors for congenital diarrhea. In this study, we aimed to determine the value of tissue RNA sequencing (RNA-seq) for assisting with the clinical diagnosis of some genetic variants of uncertain significance. Methods: We clinically evaluated a patient with watery diarrhea, vomiting, severe malnutrition, and total parenteral nutrition dependence. Possible pathogenic variants were detected using whole-exome sequencing (WES). RNA-seq was utilized to explore the transcriptional alterations in DGAT1 variants identified by WES with unknown clinical significance, according to the American College of Medical Genetics guidelines. Systemic examinations, including endoscopic and histopathological examinations of the intestinal mucosa, were conducted to rule out other potential diagnoses. Results: We successfully diagnosed a patient with congenital diarrhea and protein-losing enteropathy caused by a DGAT1 mutation and reviewed the literature of 19 cases of children with DGAT defects. The missense mutation c.620A>G, p.Lys207Arg located in exon 15, and the intronic mutation c.1249-6T>G in DGAT1 were identified by WES. RNA-seq revealed two aberrant splicing events in the DGAT1 gene of the patient’s small intestinal tissue. Both variants lead to loss-of-function consequences and are classified as pathogenic variants of congenital diarrhea. Conclusions: Rare DGAT1 variants were identified as pathogenic evidence of congenital diarrhea, and the detection of tissue-specific mRNA splicing and transcriptional effects can provide auxiliary evidence. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

Background/Objective: We sought to address ongoing gaps in understanding the relationship between first-week percent maximal weight loss (MWL) and average first-week total fluid intake (TFI), enteral intake, and parenteral intake among premature newborns with adverse in-hospital outcomes born in low- and middle-income countries (LMICs). Methods: We evaluated newborns born <34 weeks gestation or <1500 g who survived at least 7 days at the St. Paul’s Hospital Millennium Medical College (SPHMMC) neonatal intensive care unit in Ethiopia. We performed univariate and multivariate regression models analyzing the first-week MWL, average TFI, parenteral, and enteral intake and their relationships with adverse in-hospital outcomes. Results: Among N = 490 moderately and very preterm newborns, multivariate regression models demonstrated that >13% MWL was associated with significantly increased odds of suspected necrotizing enterocolitis (NEC), culture-positive sepsis, retinopathy of prematurity (ROP), and a longer length of stay (LOS). An average enteral intake of >60 mL/kg/day was significantly associated with reduced odds of all-cause mortality, suspected NEC, culture-positive sepsis, ROP, and a shorter LOS, whereas an average parenteral intake of >60 mL/kg/day was associated with increased odds of in-hospital mortality, culture-positive sepsis, ROP, and a longer LOS. Conclusions: In moderately and very preterm neonates in an LMIC setting, >13% MWL is associated with adverse health outcomes. Increasing the average parenteral intake over the first week after birth among moderately and very preterm neonates is significantly associated with adverse in-hospital outcomes whereas increasing the average enteral intake is associated with improved outcomes. Full article

Background/Objectives: The administration of parenteral medications is essential in managing acute arousal within the Behavioral Assessment Unit (BAU) of the emergency department (ED), where timely and effective intervention is critical. This study aims to evaluate current practices surrounding the use of parenteral medications for patients with acute agitation, focusing on adherence to protocols, medication safety, documentation accuracy, and patient outcomes. Methods: A retrospective analysis was conducted on 177 cases from December 2023 to February 2024. The study assessed the demographics, diagnoses, treatment protocols, and patient outcomes, with a particular emphasis on the use of parenteral medications such as benzodiazepines and antipsychotics. The relationship between medication administration and involuntary admission, mechanical restraint usage, and patient outcomes was also explored. Results: The majority of patients were aged between 21 and 30 years, and there was a predominance of male patients across both groups. Schizophrenia was the most common diagnosis, with a higher prevalence in the parenteral group (34%) compared to the oral-only group (24%), and personality disorders were more frequent in the parenteral group. Intramuscular (IM) medication administration was strongly associated with the use of mechanical restraint, with patients receiving IM medication being 35 times more likely to require restraint, emphasizing the link between more intensive treatment approaches and behavioral challenges. The most frequently administered medications were diazepam (40.6%) and olanzapine (36.5%), with olanzapine, droperidol, and diazepam most commonly used parenterally. Documentation of physical assessments prior to parenteral administration was present in most cases, though comprehensive evaluations such as ECGs were inconsistently performed. Conclusions: Parenteral medications, including benzodiazepines and antipsychotics, were effective in rapidly stabilizing patients, but the study emphasizes reducing dependency on mechanical restraints. Tailoring treatment to patient characteristics and employing alternative de-escalation strategies can improve safety and align with recovery-oriented care. This study highlights the need for evidence-based practices to optimize care and improve patient outcomes in ED settings. Further research is needed to explore long-term outcomes and refine non-coercive care approaches. Full article

Objectives: This study aimed to describe the prevalence of malnutrition and its impact on postoperative outcomes in infants and children with congenital heart diseases (CHDs) undergoing cardiac surgeries. Methods: We conducted a single-center, retrospective review of medical records of children aged 1 month to 5 years with CHDs who underwent cardiac surgery at the American University of Beirut Medical Center (AUBMC) between January 2015 and January 2017. Anthropometric data were collected and z-scores for weight-for-age (WAZ), height-for-age (HAZ), weight-for-height (WHZ), and BMI-for-age were calculated. Malnutrition was classified based on the World Health Organization (WHO) definitions and the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. The postoperative outcomes were analyzed using bivariate and multivariable models. Results: The prevalence of malnutrition was 33.8%, with children younger than 24 months having significantly higher odds of malnutrition. The most common CHDs were ventricular septal defect (VSD) and tetralogy of Fallot (TOF), with malnutrition being significantly more prevalent in the children with VSD. Malnutrition was significantly associated with a prolonged pediatric intensive care unit (PICU) stay, with underweight being the strongest predictor. Malnourished children also had a significantly longer mechanical ventilation time (median 9.0 vs. 5.0 h, p = 0.017). Lower weight-for-age (WAZ) and BMI-for-age z-scores were associated with longer hospital stay, PICU stay, and mechanical ventilation durations. Conclusions: Malnutrition is prevalent among children with CHDs and is independently associated with longer hospital and PICU stays, as well as extended mechanical ventilation. Early nutritional assessment and intervention may improve postoperative outcomes in this vulnerable population. Full article

Background: Patients with arrhythmias, particularly paroxysmal supraventricular tachycardia (PSVT), face an increased risk of cardiac complications. Currently, non-parenteral medications for rapid PSVT cessation are lacking. Etripamil, a novel intranasal, short-acting calcium channel blocker, offers a rapid onset and the potential for unsupervised PSVT management. However, data on its use in arrhythmia management remain limited. Aims: We aimed to assess the efficacy and safety of 70 mg of etripamil compared with placebo in the treatment of PSVT. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) from inception to April 2025. We calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs) using random or common effects models, depending on the heterogeneity. Results: Four RCTs including 540 patients were analyzed. Etripamil demonstrated higher conversion rates to the sinus rhythm at 15 min (RR 1.84 [95% CI: 1.32–2.48]), 30 min (RR 1.80 [95% CI: 1.38–2.35]), and 60 min (RR 1.24 [95% CI: 1.04–1.48]). PSVT recurrence rates were similar between groups (RR 0.52 [95% CI: 0.20–1.34]). Adverse events (AEs) and severe AEs were comparable between etripamil and the placebo. Etripamil was associated with higher rates of nasal discomfort, nasal congestion, rhinorrhea, and epistaxis but not with increased bradyarrhythmia, atrial fibrillation, or non-sustained ventricular tachycardia. Conclusions: Etripamil appears to be a promising treatment for cardiac arrhythmias. Larger long-term RCTs are needed to confirm its safety and efficacy in clinical practice. Full article

Short bowel syndrome (SBS) is a malabsorptive condition resulting from reduced functional small intestinal length. SBS is closely related to intestinal failure (IF), defined as the reduction of functional intestinal mass below that which can sustain life, resulting in parenteral nutrition (PN) support for 60 days or greater within a consecutive 74-day period. IF frequently results from intestinal resection necessitated by such diseases as necrotizing enterocolitis in children and Crohn’s disease in adults. Clinical manifestations of IF may include diarrhea, growth failure, bacterial overgrowth, and vitamin deficiencies. Nutritional rehabilitation is the cornerstone of IF management. Surgical interventions are aimed at preserving intestinal length and restoring continuity. Medical management involves individualized enteral and parenteral nutrition therapy, GLP-2 agonists (e.g., teduglutide) that promote mucosal growth, and drugs for symptom management such as antidiarrheals. Experimental therapies such as the use of devices to induce intestinal growth through distraction enterogenesis are under development for the treatment of IF. An interdisciplinary approach involving surgeons, gastroenterologists, dietitians, nurses, and social workers is crucial in the management of these complex patients. Ultimately, a combination of nutritional, medical, and surgical management may be necessary to improve clinical outcomes in patients with IF. Full article

Background: Vascular Ehlers–Danlos syndrome (vEDS) is a rare connective tissue disorder characterized by collagen type III deficiency, predisposing to spontaneous arterial, uterine, and intestinal ruptures. While intestinal complications are recognized in vEDS, intestinal failure (IF) secondary to these complications is a rare and potentially life-threatening occurrence. This study aimed to describe the clinical presentation, surgical management, and outcomes of pediatric patients with IF secondary to vEDS and to provide a comprehensive review of the limited existing literature on this challenging clinical scenario. Methods: This study comprises a case series of pediatric patients with IF due to vEDS complications and a comprehensive literature review. Clinical data were collected from medical records, including age at diagnosis, surgical history, complications, nutritional status, and long-term outcomes. A literature review was performed to identify studies reporting gastrointestinal complications, surgical outcomes in pediatric vEDS patients, and cases of intestinal failure. Results: Two pediatric patients with vEDS and IF were included. Both patients experienced intestinal perforations and surgical complications and required long-term parenteral nutrition (PN). One patient required PN for 18 months before achieving enteral autonomy, while the other remains dependent. The literature review included four articles and revealed a high risk of complications, including anastomotic leaks, fistulae, and recurrent perforations, in patients with vEDS undergoing intestinal surgery. Delayed diagnosis of vEDS was common. Conclusions: Intestinal complications in pediatric patients with vEDS can lead to severe short bowel syndrome and long-term PN dependence. Early diagnosis and a multidisciplinary approach are crucial for optimizing patient care and minimizing complications. Full article

Obesity is a growing global health challenge, necessitating effective treatment options beyond lifestyle interventions. This narrative review explores established and emerging pharmacotherapies for weight management, including parenteral agents like Liraglutide, Semaglutide, Setmelanotide, and Tirzepatide, as well as peroral medications such as Phentermine, Phentermine/Topiramate, Bupropion/Naltrexone, Orlistat, and Metformin. Newer treatments like Cagrilintide and Bimagrumab show promise for enhancing weight loss outcomes. Parenteral GLP-1 receptor agonists demonstrate superior efficacy compared to traditional peroral medications, with gastrointestinal side effects being the most common. Artificial intelligence presents intriguing opportunities to enhance weight loss strategies; however, its integration into clinical practice remains investigational and requires rigorous clinical validation. While current anti-obesity medications deliver significant benefits, future research must determine the efficacy, safety, and cost-effectiveness of AI-driven approaches. This includes exploring how AI can complement combination therapies and tailor personalized interventions, thereby grounding its potential benefits in robust clinical evidence. Future directions will focus on integrating AI into clinical trials to refine and personalize obesity management strategies. Full article

Large-volume parenterals (LVPs), as essential medical products, are widely used in healthcare settings, making their safety inspection crucial. Current methods for detecting foreign particles in LVP solutions through image analysis primarily rely on single-frame detection or simple temporal smoothing strategies, which fail to effectively utilize spatiotemporal correlations across multiple frames. Factors such as occlusion, motion blur, and refractive distortion can significantly impact detection accuracy. To address these challenges, this paper proposes a multi-frame object detection framework based on spatiotemporal collaborative learning, incorporating three key innovations: a YOLO network optimized with deformable convolution, a differentiable cross-frame association module, and an uncertainty-aware feature fusion and re-identification module. Experimental results demonstrate that our method achieves a 97% detection rate for contaminated LVP solutions on the LVPD dataset. Furthermore, the proposed method enables end-to-end training and processes five bottles per second, meeting the requirements for real-time pipeline applications. Full article

Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they are categorized as high-risk for leachables. Method: These external foreign chemical substances (leachables) may adversely affect and alter patient safety. Results: These primary container closure systems and manufacturing process equipment mainly comprise rubber elastomers, polypropylene, resin, ink, adhesives, glass, or plastic material. To establish the ID of detected compounds and their quantity in the finished parenteral drug formulation and then to assess the formulation for toxicological safety, broad-scope non-specific analytical screening methods are required that are capable of screening out and quantifying the predicted/unpredicted leachable compounds at the levels that pose anticipated toxicological concerns for human patients. Before the selection of the final primary packaging system for the parenteral drug product, their extractable screening profile/knowledge is required to minimize leachable compounds in the finished drug product formulation and to develop and manufacture a safe product for human patients. The adverse effect or toxicity of leachables proportionally increases with an increase in the dose of the drug product or the duration of therapy because the volume of the drug product administered to a patient in a larger quantity is directly proportional to the concentration of the detected leachable. Conclusion: This document outlines the detailed process/scientific approach for conducting an organic leachable screening profile for parenteral drug products with respect to the chemical nature of leachables, i.e., polarity, propensity, volatility, and techniques. Full article

Food cobalamin malabsorption (FCM) represents a prevalent, often underdiagnosed, etiology of vitamin B12 deficiency, particularly within an aging population. Unlike pernicious anemia, an autoimmune disorder targeting intrinsic factor, FCM stems from the impaired release of cobalamin from food proteins, primarily due to age-related gastric changes, medication-induced gastric hypochlorhydria, metformin, or non-immune atrophic gastritis. The clinical presentation of FCM mirrors that of general cobalamin deficiency, encompassing a spectrum of neurological (peripheral neuropathy, cognitive decline), hematological (megaloblastic anemia), and gastrointestinal (glossitis, anorexia) manifestations. Given the potential for irreversible neurological sequelae, early detection and intervention are paramount. High-dose oral cobalamin (125–250 mcg daily) has demonstrated efficacy, offering a convenient and cost-effective alternative to parenteral administration. Full article