Search Results (571)

Objective: The impact of a febrile neutropenia (FN) emergency department (ED) triage screening tool and protocol on time to antibiotic administration (TTA) and patient outcomes was evaluated. Methods: This was a retrospective, quasi-experimental study of adult FN patients admitted through the ED from April 2014 to April 2017. In March 2016 a triage screening tool and protocol were implemented. In patients who screened positive, nursing initiated a protocol that included laboratory diagnostics and a pharmacy consult for empiric antibiotics prior to evaluation by a provider. Patients were evaluated pre- and post-protocol for TTA, 30-day mortality, ED length of stay (LOS), and hospital LOS. Results: A total of 130 patients were included in the study, 77 pre-protocol and 53 post-protocol. Median TTA was longer in the pre-protocol group at 174 min (interquartile range [IQR] 105–224) vs. 109 min (IQR 71–214) post-protocol, p = 0.04. Thirty-day mortality was greater at 18.8% pre-protocol vs. 7.5% post-protocol, p = 0.12. There was no difference in hospital LOS. Pre-protocol patients compared to post-protocol patients who had a pharmacy consult demonstrated a further reduction in TTA (174 min [IQR 105–224] vs. 87.5 min [IQR 61.5–135], p < 0.01) and a reduced mortality (18% vs. 0%, p = 0.04). Conclusions: To our knowledge, this is the first report of a protocol for febrile neutropenia that allows pharmacists to order antibiotics based on a nurse triage assessment. Evaluation of the protocol demonstrated a significant reduction in TTA and trend toward improved mortality. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Neonatal sepsis is a major cause of morbidity and mortality in neonates. A particular concern is the increasing prevalence of antibiotic-resistant strains among neonatal intensive care units (NICUs). Two novel beta-lactam/beta-lactamase inhibitors have recently been approved for use in neonates with multidrug-resistant infections: ceftazidime/avibactam and ceftolozane/tazobactam. These agents demonstrate efficacy against a range of multidrug-resistant gram-negative pathogens, including extended-spectrum beta-lactamases (ESBL)-producing and carbapenem-resistant Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. This narrative review aims to summarize the current knowledge concerning the utilization of ceftazidime/avibactam and ceftolozane/tazobactam in the NICU. According to the existing literature, both agents have been shown to be highly effective with a favorable safety profile in the neonatal population. Full article

Background/Objectives: Diabetes mellitus is a group of chronic metabolic disorders characterized by persistent hyperglycemia. Aldose reductase, the first enzyme in the polyol pathway, plays a key role in the onset of long-term diabetic complications. Aldose reductase inhibition has been widely established as a potential pharmacotherapeutic approach to prevent and treat diabetes mellitus-related comorbidities. Although several promising aldose reductase inhibitors have been developed over the past few decades, they have failed in clinical trials due to unacceptable pharmacokinetic properties and severe side effects. This paper describes the design, synthesis, and pharmacological evaluation of four novel 5-halogenated N-indolylsulfonyl-2-fluorophenol derivatives (3a-d) as aldose reductase inhibitors. Methods: The design of compounds was based on a previously published lead compound (IIc) developed by our research group to enhance its inhibitory capacity. Compounds 3a-d were screened for their ability to inhibit in vitro partially purified aldose reductase from rat lenses, and their binding modes were investigated through molecular docking. Results: The presence of a sulfonyl linker between indole and o-fluorophenol aromatic rings is mandatory for potent aldose reductase inhibition. The 5-substitution of the indole core with halogens resulted in a slight decrease in the inhibitory power of 3a-c compared to IIc. Among halogens, bromine was the most capable of filling the selectivity pocket through hydrophobic interactions with Thr113 and Phe115 residues. Conclusions: Although our strategy to optimize the inhibitory potency of IIc via inserting halogen atoms in the indole scaffold was not fruitful, aromatic ring halogenation can be still utilized as a promising approach for designing more potent aldose reductase inhibitors. Full article

Background/Objectives: Oppositional defiant disorder (ODD) and conduct disorder (CD) are important behavior disorders in children and adolescents, often linked with long-term psychosocial problems. Antipsychotics are frequently prescribed to manage severe symptoms and improve behavior, but their efficacy in this population is still unclear and a lot of physicians are remittent in prescribing them. This systematic review aims to assess the effectiveness of antipsychotic treatment in reducing symptoms associated with ODD and CD in children and adolescents. Methods: Studies that investigated how effective antipsychotic treatments are for children and teens diagnosed with oppositional defiant disorder (ODD) and conduct disorder (CD) were reviewed. Only studies that met a few main criteria were included: participants were between 5 and 18 years old with an ODD or CD diagnosis; the treatment could be any type of antipsychotic, whether typical or atypical; the accepted study designs were randomized controlled trials (RCTs), cohort studies, systematic reviews with meta-analysis, or observational studies. The outcomes of interest were reductions in aggressive or defiant behaviors, improvements in social functioning, and the occurrence of any adverse effects from the medications. There was no restriction on the language of publication, and studies published from 2000 to 2024 were considered. Studies that focused only on non-antipsychotic drugs or behavioral therapies, as well as case reports, expert opinions, and non-peer-reviewed articles did not meet the inclusion criteria. Results: The review consisted of 13 studies. The results suggest that some antipsychotic drugs—especially atypical antipsychotics—can substantially reduce aggressive and defiant behavior in children and adolescents who have oppositional defiant disorder (ODD) or conduct disorder (CD). Common side effects of these medications include weight gain, sedation, and metabolic problems. Conclusions: Although adverse effects are a concern, the potential of these medications to manage disruptive behaviors should not be overlooked. When used in combination with behavioral therapy and other forms of treatment, antipsychotics can markedly improve the outcomes of these very difficult-to-treat patients. Clinicians who treat these patients need to consider antipsychotics as a serious option. If they do not, they are denying their patients medication that could greatly benefit them. Full article

Background: Methicillin-resistant Staphylococcus aureus (MRSA) considered under the category of serious threats by the Centers for Disease Control and Prevention (CDC), urges for new antibiotics or alternate strategies to control MRSA. Methods: Ethosome-like liposomes have been developed and characterized using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Liposomes were confirmed for antibiotics infusion by encapsulation efficiency and release kinetics as well. Further, the antimicrobial potential of liposomes was checked by determination of minimum inhibitory concentrations (MICs), crystal violet assay, and live/dead biofilm eradication assay. Results: The specially designed liposomes consist of amphiphilic molecules, tocopherol, conjugated with ampicillin and, another antibiotic amikacin, loaded in the core. The developed liposomes exhibited good encapsulation efficiency, and sustained release while serving as ideal antibiotic carriers for advanced efficacy along with anti-inflammatory benefits from tocopherol. Conclusively, newly designed liposomes displayed potential antimicrobial activity against MRSA and its complex biofilms. Conclusions: Overall, dual antibiotic-encapsulated liposomes demonstrate the potential to eradicate MRSA and its mature biofilms by dual-targeted action. This could be developed as an efficient anti-infective agent and delivery vehicle for conventional antibiotics to combat MRSA. Full article

Introduction: A direct head-to-head comparison between potent P2Y12 inhibitors: prasugrel versus ticagrelor is still lacking. Purpose: In this single-center study, we sought to address the efficacy and safety of these two third-generation antiplatelet drugs, after about a decade of practical use. Methods: A retrospective observational study included all patients who were admitted with acute coronary syndrome between January 2010 and December 2019 and were discharged with aspirin and either prasugrel or ticagrelor after percutaneous coronary intervention. Patients were divided into two groups based on the dual antiplatelet drugs prescribed. Primary endpoint: A composite endpoint of cardiovascular death, recurrent coronary syndrome, or ischemic stroke at one year. Secondary endpoint: Significant bleeding according to the BARC classification (types 3, 4, or 5). Results: During this period, 746 patients met the inclusion criteria. The primary endpoint was reached in 70 patients (9.4%): 24 patients (8.0%) in the group treated with ticagrelor and 46 patients (10.3%) in the group treated with prasugrel (p-value = 0.303). In terms of safety events, significant bleeding was not statistically different between the ticagrelor and prasugrel groups: 13 (2.9%) vs. 9 (3%), respectively (p-value = 0.9). More patients discontinued their treatment before the end of the year among those treated with ticagrelor compared to those treated with prasugrel (16.7% vs. 9.6%, p-value = 0.003). Conclusions: There was no significant difference in the occurrence of recurrent cardiac events, stroke, or cardiovascular death, nor significant bleeding among ACS patients treated either with prasugrel or ticagrelor. Full article

Background: The introduction of medical cannabis in Greece marks a shift in healthcare policy, yet patient attitudes remain underexplored. Methods: This qualitative study examines the market readiness for medical cannabis through semi-structured interviews with 24 participants—12 users of cannabidiol (CBD)-based formulations and 12 medical cannabis-naive individuals. Results: CBD-experienced patients generally perceive cannabis-based treatments as beneficial for managing musculoskeletal pain, migraines, anxiety, stress and sleep disturbances, despite concerns over product quality, cost and limited medical guidance. Medical cannabis-naive participants express skepticism due to stigma and perceived insufficient evidence but acknowledge potential therapeutic value within a regulated framework. This study highlights the need for better patient education, physician training and clear regulatory guidelines to support responsible market entry. Conclusions: These findings offer important insights for policymakers, healthcare providers and the pharmaceutical industry, emphasizing the need for a structured, evidence-based approach to medical cannabis integration in Greece. Further research is needed to assess long-term patient experiences and the evolving impact of regulatory changes on market dynamics. Full article

Background/Objectives: Nomograms for adjusting gentamicin therapy in neonates using a single concentration are limited. The Dersch–Mills nomogram is inefficient for short-duration therapies, while the NeoFax nomogram is outdated based on the current American Academy of Pediatrics (AAP) guidelines. Bayesian software has shown accuracy for vancomycin in adults, but its performance for gentamicin in neonates is unclear. This study evaluates the accuracy of Bayesian estimation in predicting peak and trough gentamicin concentrations from a single measured level in neonates. Methods: A single-center, retrospective re-analysis was conducted of gentamicin concentrations in neonates. InsightRx^® was used to estimate maximum and minimum concentrations in a dosing interval (Cmax and Cmin) based on a single peak or trough concentration. Bias and accuracy were characterized using the mean difference (MD) between estimated and measured concentrations and the 95% limits of agreement (LOA) for the differences (±1.96 × SD). Results: Fifty-seven neonates (73 peak/trough pairs) were analyzed. Median gestational age was 34 weeks and median postnatal age was 0 days. The MD (LOA) between Cmin estimates and measured troughs was 0.03 mg/L (−0.17 to 0.13) for the trough-only analysis and 0.21 mg/L (−0.38 to 0.8) for the peak-only analysis. The MD (LOA) between Cmax estimates and measured peaks was 0.16 mg/L (−3.2 to 3.3) for the trough-only analysis and 1.2 mg/L (−0.58 to 3.0) for the peak-only analysis. Conclusions: In neonates, a Bayesian analysis of a trough concentration produces reliable Cmin estimates but is not as accurate in estimating Cmax. Analyzing a peak concentration produces Cmax and Cmin values that overestimate true concentrations. If the goal of monitoring is to ensure sufficiently low troughs, a single-level analysis is reasonable if levels are drawn near the end of the dosing interval, but Cmin predictions based on levels drawn early in the dosing interval should be avoided. Full article

Opioid use in the United States has increased dramatically. Bacterial infections are common among persons who inject drugs (PWID), and there is a disparity in the care these individuals receive. As such, outcomes associated with these infections can be poor. Healthcare providers can address these disparities through optimal pharmacotherapy recommendations and assistance with changing approaches to the management of PWID. Full article

Background: Hyponatraemia is a rare but potentially life-threatening complication of terlipressin therapy. Case history: In the current case, a 39-year-old female with decompensated liver cirrhosis (Child-Pugh C) and acute variceal bleeding experienced a precipitous decline in serum sodium—from 136 mmol/L to 115 mmol/L—within 48 h of initiating terlipressin therapy. This was accompanied by marked fluid retention, reduced urine output, and symptoms of confusion and agitation. Laboratory tests confirmed dilutional hyponatraemia, characterized by urinary sodium <20 mmol/L and urine osmolality <100 mOsm/kg, indicating excessive free water reabsorption. Outcomes: The prompt discontinuation of terlipressin, fluid restriction and the cautious administration of hypertonic sodium chloride solution (2.7% NaCl) achieved a gradual normalization of sodium levels and resolution of symptoms. Fluid balance monitoring revealed a marked diuretic response following terlipressin cessation. This case aligns with existing reports, emphasizing the dual vasopressin receptor activity of terlipressin and its capacity to induce hyponatraemia, particularly in cirrhotic patients with preserved renal function and higher baseline sodium levels. Conclusions: This case and a literature review underscored the critical need for early fluid balance monitoring to detect retention. This case highlights the importance of individualized risk assessment, multidisciplinary management, and vigilant sodium correction to avoid complications. Practical recommendations are outlined to aid clinicians in the recognition and management of terlipressin-induced hyponatraemia. Full article

Introduction: Novel psychoactive substances (NPSs) are substances not controlled by the United Nations’ 1961 Narcotic Drugs and 1971 Psychotropic Substances convention, which pose a threat to public health. The use of NPSs is growing among recreational drug users. NPSs mimic the effects of the existing illegal drugs; they are used as substitutes for the traditional drugs of use. NPSs are commonly marketed as safe substances. NPS abuse is especially risky among vulnerable individuals, such as children and adolescents. The Aim: This study aims to analyze the knowledge and attitudes of primary and high school students regarding NPSs, determining the frequency and patterns of NPS use, and examine motivational factors for their consumption. Methodology: The questionnaire was employed to primary and secondary school students of the city of Novi Sad in November 2024. The data were analyzed using the methods of descriptive and inferential statistics in the statistical software package JASP 0.18.1.0. Results: A total of 1095 participants took part in the survey (53.6% males and 46.4% females). The age range of participants was 11–18 years (mean age 14.637 years). The majority of pupils lived in the city (70.5%). The most numerous students were students with the highest overall grade. The proportion of students who were familiar with NPSs was 38.3%, while 61.7% of them were not aware of their existence. Living in cities correlated positively with the NPS knowledge. The NPS risk awareness was notably low. The proportion of students who tried one or more novel drugs was 1.918%. Conclusions: The abuse of novel psychoactive substances is a growing concern, particularly among young individuals, requiring increased awareness and education on their risks. Educational systems should provide accurate information to prevent false beliefs, while policymakers must legally regulate new drugs. A coordinated approach is crucial for effective prevention, involving education, media, and support from different organizations. Future studies should focus on the impact of education on attitudes towards NPSs. Full article

The placebo effect has been widely documented across various medical conditions, demonstrating its ability to influence both subjective and objective outcomes. Placebo responses can significantly improve symptoms in these different conditions, such as pain, Parkinson’s disease, depression, anxiety, and addiction. Psychological mechanisms, particularly the power of patient expectations, appear to play a central role, with neurobiological evidence supporting the activation of dopamine, endogenous opioids, and endocannabinoids in response to placebo interventions. Studies have demonstrated that placebo injections and more complex procedures, including sham surgeries, can produce therapeutic effects comparable to real treatments, particularly in pain management and neurological disorders. Moreover, placebo responses could be amplified when patients are aware of receiving treatment, as shown by research on open-label placebos and open versus hidden medical treatments. The effectiveness of 0.9% sodium chloride solution as a placebo in clinical trials is debated, with some studies indicating its potential to induce clinical improvements, though it may not be an ideal control in inflammatory pain conditions. Advances in neuroimaging have revealed that placebo treatments trigger tangible biological processes in the brain and body and are supported by psychological and physiological mechanisms that interact, suggesting real biological processes are involved in the observed effects. Overall, the growing understanding of placebo mechanisms suggests that incorporating placebo-based strategies, with patient awareness and appropriate ethical considerations, may offer significant potential for improving patient outcomes, particularly in chronic pain, mental health, and neurological conditions. Full article

Vaccination represents a critical preventive strategy in the current global healthcare system, serving as an indispensable intervention against diverse pathogenic threats. Although conventional immunization relies predominantly on hypodermic needle-based administration, this method carries substantial limitations, including needle-associated fear, bloodborne pathogen transmission risks, occupational injuries among healthcare workers, waste management issues, and dependence on trained medical personnel. Microneedle technology has emerged as an innovative vaccine delivery system, offering convenient, effective, and minimally invasive administration. These microscale needle devices facilitate targeted antigen delivery to epidermal and dermal tissues, where abundant populations of antigen-presenting cells, specifically Langerhans and dermal dendritic cells, provide robust immunological responses. Multiple research groups have extensively investigated microneedle-based vaccination strategies. This transdermal delivery technique offers several advantages, notably circumventing cold-chain requirements and enabling self-administration. Numerous preclinical investigations and clinical trials have demonstrated the safety profile, immunogenicity, and patient acceptance of microneedle-mediated vaccine delivery across diverse immunization applications. This comprehensive review examines the fundamental aspects of microneedle-based immunization, including vaccination principles, transcutaneous immunization strategies, and microneedle-based transdermal delivery—including classifications, advantages, and barriers. Furthermore, this review addresses critical technical considerations, such as treatment efficacy, application methodologies, wear duration, dimensional optimization, manufacturing processes, regulatory frameworks, and sustainability considerations, followed by an analysis of the future perspective of this technology. Full article

Background: Prosthetic valve thrombosis is a rare but serious complication of mechanical valve replacement. Traditionally, prosthetic valve thrombosis has been managed by surgical intervention; however, there is increasing data to support the use of thrombolytics. Methods: We present a case of a 74-year-old female with a history of rheumatic fever and subsequent mechanical aortic valve replacement on warfarin who presented to the emergency department with disequilibrium and chest pain. Results: She was found to have a subtherapeutic international normalized ratio and thrombosed mechanical aortic valve seen on transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy. Conclusions: She was treated with a low-dose ultraslow alteplase infusion of 25 mg of alteplase administered over 25 h. Post-infusion transthoracic echocardiography immediately following infusion and four months later confirmed resolution of thrombosis. Full article