Medicines (Basel, Switzerland)最新文献

Background/objectives: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are associated with increased rates of diabetic ketoacidosis (DKA). The difference in the management and outcomes of SGLT2i-associated DKA (SGLT2i DKA) from non-SGLT2i-associated DKA (non-SGLT2i DKA) remains unclear due to a lack of specific reporting on dextrose and insulin. This study aims to compare the management and outcome of SGLT2i and non-SGLT2i diabetic ketoacidosis.

Methods: In this retrospective cohort study, patients admitted to the Intensive Care Unit (ICU) for diabetic ketosis between 1 January 2020 to 31 December 2021 at a tertiary hospital were identified. For each SGLT2i diabetic ketosis, two non-SGLT2i diabetic ketosis admissions closest to the SGLT2i admission date were evaluated for comparison. Clinical data including biochemistry, ICU length of stay (LOS), time to normalize acidemia and ketonemia, dextrose and insulin requirements, were evaluated.

Results: In the SGLT2i group (n = 30), there were 22 DKA and 8 diabetic ketosis cases; in the non-SGLT2i group (n = 60), there were 54 DKA and 6 diabetic ketosis cases. SGLT2i DKA (n = 22) required 62% greater total insulin (154 [117-249] vs. 95 [59-150] units; p = 0.004), which remained statistically significant after weight adjustment (p = 0.02), and longer ICU LOS (52 [42-97] vs. 39 [23-68] hours; p = 0.01) compared to non-SGLT2i DKA (n = 54), despite a comparable time to DKA resolution (22 [15-35] vs. 20 [15-35] hours; p = 0.91). In the intercurrent illness subgroup analysis, neither total insulin dose nor ICU LOS remained statistically significantly different between SGLT2i (n = 16) and non-SGLT2i DKA (n = 21). The majority of cases received 10% dextrose and variable rate intravenous insulin infusion (VRIII).

Conclusions: The greater insulin requirement in SGLT2i DKA compared to non-SGLT2i DKA may be explained by the greater proportion of precipitating intercurrent illnesses and demographic differences in SGLT2i DKA, highlighting that SGLT2i DKA (predominantly comprising T2D) and non-SGLT2i DKA (predominantly comprising T1D) represent distinct clinical entities. Our findings in comparison to the literature imply that in SGLT2i DKA, the need for prolonged IV insulin infusion may be reduced through intensive management using intravenous 10% dextrose and VRIII. Prospective studies are warranted to evaluate the efficacy of different management strategies for SGLT2i DKA.

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.

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.

Background/Objectives: Atrial fibrillation (AF) is the most significant modifying risk factor for the development of cardioembolic stroke, which is associated with worse outcomes and higher intrahospital mortality compared to other types of ischemic stroke. Antithrombotic medications are administered as prophylactic treatment in patients with a risk of stroke. The aim of this study was to determine outcome measures in patients with first-ever ischemic stroke and AF regarding prior antithrombotic therapy. Methods: We collected data on stroke risk factors, CHADS₂ score, and international normalized ratio (INR) value in the context of warfarin therapy, as well as data related to localization, stroke severity, and functional outcome at discharge. Results: A total of 754 subjects with first-ever ischemic stroke and AF were included in this cross-sectional study (122 on warfarin, 210 on acetylsalicylic acid, and 422 without prior antithrombotic therapy). The diagnosis of AF was previously unknown in 31% of the subjects. Stroke risk factors (arterial hypertension, hyperlipidemia, diabetes mellitus, and cardiomyopathy) were significantly lower in the group without prior antithrombotic therapy. The anticoagulant group was significantly younger (p = 0.001). Overall, 45.4% of subjects with a previously known AF event and a high risk of developing stroke received anticoagulant therapy. Participants on warfarin had a significantly better functional outcome than those on antiplatelet therapy or without prior antithrombotic therapy (median mRS 4 vs. 5 vs. 5; p = 0.025) and lower NIHSS scores, although the difference was not statistically significant (median 10 vs. 12 vs. 12; p = 0.09). There was no difference between stroke localization among groups (p = 0.116). Conclusions: Our study showed that, in our cohort, first-ever ischemic stroke due to AF was more common in women. Subjects on prior anticoagulant therapy had more favorable outcomes at discharge.

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.

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.

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.

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.

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.

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.