Medicines

1 pages, 150 KB

Open AccessCorrection

Correction: Zulfiqar et al. Association of Frailty Status with Risk of Fall among Hospitalized Elderly Patients: A Cross-Sectional Study in an Acute Geriatric Unit. Medicines 2022, 9, 48

by Abrar-Ahmad Zulfiqar, Perla Habchi, Ibrahima Amadou Dembele and Emmanuel Andres

Medicines 2026, 13(1), 5; https://doi.org/10.3390/medicines13010005 - 2 Feb 2026

Abstract

There was an error in the original publication [...] Full article

10 pages, 468 KB

Open AccessArticle

Significant Impact of Previous Major Cardiovascular Events (MACEs) and Viremia on Risk of New MACEs in People Living with HIV on Antiretroviral Therapy

by Caterina Candela, Alessia Siribelli, Tommaso Clemente, Riccardo Lolatto, Michele Bellomo, Vincenzo Stabile, Hamid Hasson, Vincenzo Spagnuolo, Antonella Castagna, Silvia Nozza and Camilla Muccini

Medicines 2026, 13(1), 4; https://doi.org/10.3390/medicines13010004 - 29 Jan 2026

Abstract

Background: Major cardiovascular events (MACEs) in people with HIV (PWH) may be partly related to antiretroviral therapy (ART) and persistent inflammation. The aim of the study was to evaluate the association between targeted variables and MACEs. Methods: Retrospective, single-center study conducted on PWH [...] Read more.

Background: Major cardiovascular events (MACEs) in people with HIV (PWH) may be partly related to antiretroviral therapy (ART) and persistent inflammation. The aim of the study was to evaluate the association between targeted variables and MACEs. Methods: Retrospective, single-center study conducted on PWH receiving ART between January 2010 and April 2024, classified according to HIV-RNA levels: virological suppression (<50 copies/mL), low-level viremia (50–200 or 200–1000 copies/mL), and non-suppression (≥1000 copies/mL). Viremia was considered as a time-dependent variable and by cumulative years in each category. A Cox proportional hazards model for multivariate time-to-event analysis assessed associations between virological status and MACEs. Results: We included 3349 PWH followed for a median time of 14 years (interquartile range, IQR 11.2–14.2). At baseline, 2794 (83.4%) were virologically suppressed, 189 (5.6%) and 90 (2.7%) presented 50–200 and 200–1000 copies/mL, respectively, and 276 (8.2%) were non-suppressed. During the follow-up, virological suppression was documented at least once in 3295 (98.4%), low-level viremia in 1579 (47.1%) with 50–200 copies/mL and 794 (23.7%) with 200–1000 copies/mL, and HIV-RNA > 1000 copies/mL in 844 (25.2%). Overall, 300 MACEs occurred, including 53 (17.7%) repeated events, with total incident rate of 0.00976 events per person-year. The risk of MACEs was significantly associated with previous MACEs (Hazard Ratio, HR 3.385, p-value < 0.001) and viremia > 1000 copies/mL at baseline (HR 2.209, p-value 0.039). Their onset was also significantly associated with greater age at baseline and years on ART, hypertension, diabetes, lower HDL, and higher triglycerides. Conclusions: PWH on ART with HIV-RNA > 1000 copies/mL at baseline and a previous MACE presented higher risk of developing MACEs. Full article

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15 pages, 1265 KB

Open AccessSystematic Review

Anticonvulsant Therapy in Trigeminal Neuralgia: A Class-Oriented Systematic Review

by Miguel Pinto Moreira, Bruno Daniel Carneiro, Carlos Silva Faria, Daniel Humberto Pozza and Sara Fonseca

Medicines 2026, 13(1), 3; https://doi.org/10.3390/medicines13010003 - 26 Jan 2026

Abstract

Background/Objectives: Trigeminal Neuralgia (TN) is a chronic neuropathic condition characterized by sudden, severe facial pain. Anticonvulsants are the cornerstone of pharmacological management, yet comparative evidence based on pharmacological class remains scarce. This systematic review aimed to evaluate the efficacy and safety of anticonvulsants [...] Read more.

Background/Objectives: Trigeminal Neuralgia (TN) is a chronic neuropathic condition characterized by sudden, severe facial pain. Anticonvulsants are the cornerstone of pharmacological management, yet comparative evidence based on pharmacological class remains scarce. This systematic review aimed to evaluate the efficacy and safety of anticonvulsants in TN, stratified by their mechanism of action. Methods: A systematic search in PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines. Studies employing a pharmacological approach including human patients with TN, published in English since 2000, were included. Risk of bias was assessed using the Cochrane RoB 2, the ROBINS-I and the ROBINS-E tools, according to the study design. Results: Out of 922 initial records, 12 studies met the eligibility criteria. Sodium channel inhibitors showed high efficacy but frequent adverse effects, particularly hyponatremia and central nervous system symptoms. Calcium channel modulators offered a more favorable safety profile. Combination therapies showed benefits, levetiracetam and topiramate were moderately effective and well tolerated. Although the evidence has limitations, anticonvulsants continue to be the primary treatment for TN. Sodium-channel blockers demonstrate strong efficacy, whereas alternative agents generally provide superior tolerability. Conclusions: These findings support selecting drugs according to their underlying mechanisms of action. Equally important is tailoring therapy to pain phenotype and patient characteristics, balancing mechanism with tolerability and efficacy. Full article

(This article belongs to the Section Neurology and Neurologic Diseases)

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17 pages, 801 KB

Open AccessPerspective

Antioxidant Delivery Revisited: The Promise of Nanostructured Lipid Carriers

by Leif Behar and Holly Siddique

Medicines 2026, 13(1), 2; https://doi.org/10.3390/medicines13010002 - 22 Jan 2026

Abstract

Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug [...] Read more.

Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug delivery systems. Therefore, encapsulation of natural products in a carrier addresses the above concern. Drug delivery systems, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are promising carriers for effective release, consisting of solid and liquid lipids, which enhance efficiency, stability, and controlled release, thereby minimising bioavailability limitations. This review consolidates current studies on the formulation methodologies, mechanisms of action, and therapeutic applications of NLCs, emphasizing their use in the treatment of conditions such as cancer, neurological disorders, and cardiovascular diseases. The results demonstrate that NLCs substantially enhance the bioavailability and therapeutic efficacy of antioxidants, thereby improving their targeted administration and clinical effects. Nonetheless, difficulties in clinical translation remain, including drug loading capacity, regulatory authorisation, and the need for pervasive research on cytotoxicity. This article highlights important areas for future inquiry, specifically the optimisation of NLC formulations, the enhancement of targeting accuracy, and the resolution of safety issues to enhance their clinical application. Full article

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12 pages, 747 KB

Open AccessReview

Treatment of Symptomatic Male Hypogonadism with New Oral Testosterone Therapies: A Comparative Review of Jatenzo, Tlando, and Kyzatrex

by Samantha H. Rosen and Kian Asanad

Medicines 2026, 13(1), 1; https://doi.org/10.3390/medicines13010001 - 22 Dec 2025

Abstract

Symptomatic male hypogonadism, defined by low serum testosterone with associated clinical symptoms, is increasingly treated with testosterone replacement therapy. Traditional oral formulations were limited by hepatotoxicity and poor bioavailability, leading to reliance on injectable and transdermal routes. Recent advances in oral testosterone undecanoate [...] Read more.

Symptomatic male hypogonadism, defined by low serum testosterone with associated clinical symptoms, is increasingly treated with testosterone replacement therapy. Traditional oral formulations were limited by hepatotoxicity and poor bioavailability, leading to reliance on injectable and transdermal routes. Recent advances in oral testosterone undecanoate formulations have introduced safer and more effective options. This review compares Jatenzo, Tlando, and Kyzatrex, highlighting their pharmacology, efficacy, safety, and clinical utility. Clinical trial data demonstrate restoration of eugonadal testosterone levels in most patients (80–88%), with shared risks including hypertension, polycythemia, and lipid changes. Differences in dosing regimens, titration requirements, and insurance coverage influence choice of therapy and patient adherence. Kyzatrex offers flexible titration and self-pay access, Tlando provides a fixed-dose regimen, and Jatenzo combines titratability with established clinical data. Collectively, these agents expand the therapeutic landscape of hypogonadism, offering effective, non-invasive alternatives that support individualized treatment strategies. Full article

(This article belongs to the Topic New Compounds Discovery and Development in Medicine — Advances in Research on Potential Therapeutic Agents and Drug Candidates, 2nd Edition)

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14 pages, 2428 KB

Open AccessArticle

Preliminary Evaluation of an Injectable Therapeutic for Cisplatin Ototoxicity Using Neuronal SH-SY5Y Cells

by Michelle Hong, Katherine Kedeshian, Larry Hoffman and Ashley Kita

Medicines 2025, 12(4), 30; https://doi.org/10.3390/medicines12040030 - 9 Dec 2025

Abstract

Background/Objectives: Though ototoxic, cisplatin is a mainstay of chemotherapy for a variety of cancers. One suggested mechanism of cisplatin ototoxicity involves damage to the spiral ganglion afferent neurons in the inner ear. There is a need for a high-throughput model to screen medications [...] Read more.

Background/Objectives: Though ototoxic, cisplatin is a mainstay of chemotherapy for a variety of cancers. One suggested mechanism of cisplatin ototoxicity involves damage to the spiral ganglion afferent neurons in the inner ear. There is a need for a high-throughput model to screen medications for efficacy against cisplatin and to develop a local therapeutic to mitigate cisplatin’s debilitating side effects. Microparticles encapsulating a therapeutic medication are an injectable and tunable method of sustained drug delivery, and thus a promising treatment. Methods: SH-SY5y human neuroblastoma cells were used as a cell line model for the spiral ganglion neurons. The cells were dosed with cisplatin and four potential therapeutics (melatonin, metformin, cyclosporine, and N-acetylcysteine), with cell viability measured by CCK-8 assay. The most promising therapeutic, N-acetylcysteine (NAC), was then encapsulated into multiple poly(lactic-co-glycolic acid) (PLGA) microparticle subtypes of varied lactide–glycolide (L:G) ratios and NAC amounts. The elution profile of each microparticle subtype was determined over two months. Results: Of the therapeutics screened, only cells dosed with 1 or 10 mM NAC prior to cisplatin injury demonstrated an improvement in cell viability (73.8%, p < 1 × 10⁻⁸) when compared to cells dosed with cisplatin alone. The 75:25 L:G microparticles demonstrated an increase in the amount of NAC released compared to the 50:50 L:G microparticles. Conclusions: NAC is a potential therapeutic agent for cisplatin toxicity when tested in a neuronal cell line model. NAC was encapsulated into PLGA microparticles and eluted detectable concentrations of NAC for 6 days, which is a first step towards otoprotection for the weeks long duration of chemotherapy treatment. This work describes a method of screening potential therapeutics and a strategy to develop local drug eluting treatments to protect against cisplatin ototoxicity. Full article

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12 pages, 1617 KB

Open AccessArticle

Identification of Active Components in Connarus ruber Extract Exhibiting Anti-Glycation Effects

by Ryoji Taniguchi, Ryusuke Nakatsuka, Yuka Sasaki, Mariko Takenokuchi, Takashi Maoka, Tomio Iseki, Hirohito Kubo and Tadashige Nozaki

Medicines 2025, 12(4), 29; https://doi.org/10.3390/medicines12040029 - 3 Dec 2025

Abstract

Background: Glycation, a non-enzymatic reaction between sugars and biomolecules, leads to the formation of advanced glycation end-products (AGEs), which are implicated in the progression of chronic diseases. Connarus ruber (Poepp.) Planch (C. ruber), a traditional medicinal plant used for diabetes, has [...] Read more.

Background: Glycation, a non-enzymatic reaction between sugars and biomolecules, leads to the formation of advanced glycation end-products (AGEs), which are implicated in the progression of chronic diseases. Connarus ruber (Poepp.) Planch (C. ruber), a traditional medicinal plant used for diabetes, has shown anti-glycation activity. This study aimed to identify the active components in C. ruber extract and elucidate their anti-glycation mechanisms. Methods: Using NMR and LC-MS analyses, we identified epicatechin and procyanidin A2 as major polyphenolic constituents. Collagen glycation assays were performed to evaluate the inhibitory effects of these compounds on fructose- and glyceraldehyde (GA)-induced glycation. Additionally, their cytoprotective effects were assessed using GA-induced cytotoxicity assays in dental pulp stem cells (DPSCs). Results: Both epicatechin and procyanidin A2 inhibited fructose- and GA-induced glycation in a dose-dependent manner, showing greater efficacy than aminoguanidine. Furthermore, these compounds significantly alleviated GA-induced cytotoxicity in DPSCs. Conclusions: These findings suggest that epicatechin and procyanidin A2 are candidate contributors to the anti-glycation and cytoprotective effects of C. ruber. The results support the potential of C. ruber extract as a source of therapeutic agents for glycation-related diseases and for enhancing stem cell viability. Full article

(This article belongs to the Section Oral Medicine and Dentistry)

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31 pages, 1106 KB

Open AccessReview

AΙ-Driven Drug Repurposing: Applications and Challenges

by Paraskevi Keramida, Nikolaos K. Syrigos, Marousa Kouvela, Garyfallia Poulakou, Andriani Charpidou and Oraianthi Fiste

Medicines 2025, 12(4), 28; https://doi.org/10.3390/medicines12040028 - 13 Nov 2025

Abstract

Drug repurposing is the process of discovering new therapeutic indications for already existing drugs. By using already approved molecules with known safety profiles, this approach reduces the time, costs, and failure rates associated with traditional drug development, accelerating the availability of new treatments [...] Read more.

Drug repurposing is the process of discovering new therapeutic indications for already existing drugs. By using already approved molecules with known safety profiles, this approach reduces the time, costs, and failure rates associated with traditional drug development, accelerating the availability of new treatments to patients. Artificial Intelligence (AI) plays a crucial role in drug repurposing by exploiting various computational techniques to analyze and process big datasets of biological and medical information, predict similarities between biomolecules, and identify disease mechanisms. The purpose of this review is to explore the role of AI tools in drug repurposing and underline their applications across various medical domains, mainly in oncology, neurodegenerative disorders, and rare diseases. However, several challenges remain to be addressed. These include the need for a deeper understanding of molecular mechanisms, ethical concerns, regulatory requirements, and issues related to data quality and interpretability. Overall, AI-driven drug repurposing is an innovative and promising field that can transform medical research and drug development, covering unmet medical needs efficiently and cost-effectively. Full article

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13 pages, 252 KB

Open AccessArticle

Cannabis Use and Analgesic Prescribing in UK Primary Care: A Retrospective Cohort Study of Patients with Osteoarthritis

by Simon Erridge, Joht Singh Chandan, Krishna M. Gokhale, Christian Billinghurst and Mikael H. Sodergren

Medicines 2025, 12(4), 27; https://doi.org/10.3390/medicines12040027 - 10 Nov 2025

Abstract

Objectives: This study aims to assess differences in analgesia prescribing in UK primary care between individuals with osteoarthritis who have a recorded exposure to cannabis use and those who do not. Methods: This population-based retrospective cohort study included opioid-naïve patients with osteoarthritis (aged [...] Read more.

Objectives: This study aims to assess differences in analgesia prescribing in UK primary care between individuals with osteoarthritis who have a recorded exposure to cannabis use and those who do not. Methods: This population-based retrospective cohort study included opioid-naïve patients with osteoarthritis (aged 25–85 years) who were active in Clinical Practice Research Datalink Aurum between 1 January 1995 and 15 December 2023. Patients with osteoarthritis who had current or historic cannabis use recorded were matched to two unexposed individuals by age, sex, smoking status, and health authority. Patients were followed up to assess prescriptions of analgesia. Cox regression was performed adjusted for age, sex, and ethnicity. Results: 662 exposed patients were matched to 1319 unexposed patients. Cannabis-exposed individuals were more likely to be prescribed opioids (adjusted hazard ratio (HR): 2.06; 95% confidence interval (CI): 1.74–2.43; p < 0.001), gabapentinoids (HR: 3.31; 95% CI: 2.34–4.67; p < 0.001), non-steroidal anti-inflammatory drugs (HR: 1.99; 95% CI: 1.72–2.31; p < 0.001), tricyclic antidepressants (HR: 2.64; 95% CI: 2.03–3.44; p < 0.001), other antidepressants (HR: 7.22; 95% CI: 5.24–9.94; p < 0.001), and paracetamol (HR: 3.30; 95% CI: 2.43–4.48; p < 0.001). Conclusions: This study suggests there is an association between coded exposure to cannabis in UK primary care records and increased prescribing of analgesia. Given the relative scarcity of recorded cannabis use relative to its prevalence in the general population, these findings must be interpreted cautiously. The increased hazard of using analgesia and mortality within the cannabis-exposed cohort may be confounded by socioeconomic status and a higher likelihood of coding cannabis use in those experiencing adverse effects after consumption or cannabis misuse disorder. Full article

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Open AccessArticle

HDAC5 Inhibition as a Therapeutic Strategy for Titin Deficiency-Induced Cardiac Remodeling: Insights from Human iPSC Models

by Arif Ul Hasan, Sachiko Sato, Mami Obara, Yukiko Kondo and Eiichi Taira

Medicines 2025, 12(4), 26; https://doi.org/10.3390/medicines12040026 - 27 Oct 2025

Abstract

Background/Objectives: Dilated cardiomyopathy (DCM) is a prevalent and life-threatening heart muscle disease often caused by titin (TTN) truncating variants (TTNtv). While TTNtvs are the most common genetic cause of heritable DCM, the precise downstream regulatory mechanisms linking TTN [...] Read more.

Background/Objectives: Dilated cardiomyopathy (DCM) is a prevalent and life-threatening heart muscle disease often caused by titin (TTN) truncating variants (TTNtv). While TTNtvs are the most common genetic cause of heritable DCM, the precise downstream regulatory mechanisms linking TTN deficiency to cardiac dysfunction and maladaptive fibrotic remodeling remain incompletely understood. This study aimed to identify key epigenetic regulators of TTN-mediated gene expression and explore their potential as therapeutic targets, utilizing human patient data and in vitro models. Methods: We analyzed RNA sequencing (RNA-seq) data from left ventricles of non-failing donors and cardiomyopathy patients (DCM, HCM, PPCM) (GSE141910). To model TTN deficiency, we silenced TTN in human iPSC-derived cardiomyocytes (iPSC-CMs) and evaluated changes in cardiac function genes (MYH6, NPPA) and fibrosis-associated genes (COL1A1, COL3A1, COL14A1). We further tested the effects of TMP-195, a class IIa histone deacetylase (HDAC) inhibitor, and individual knockdowns of HDAC4/5/7/9. Results: In both human patient data and the TTN knockdown iPSC-CM model, TTN deficiency suppressed MYH6 and NPPA while upregulating fibrosis-associated genes. Treatment with TMP-195 restored NPPA and MYH6 expression and suppressed collagen genes, without altering TTN expression. Among the HDACs tested, HDAC5 knockdown was most consistently associated with improved cardiac markers and reduced fibrotic gene expression. Co-silencing TTN and HDAC5 replicated these beneficial effects. Furthermore, the administration of TMP-195 enhanced the modulation of NPPA and COL1A1, though its impact on COL3A1 and COL14A1 was not similarly enhanced. Conclusions: Our findings identify HDAC5 as a key epigenetic regulator of maladaptive gene expression in TTN deficiency. Although the precise mechanisms remain to be clarified, the ability of pharmacological HDAC5 inhibition with TMP-195 to reverse TTN-deficiency-induced gene dysregulation highlights its promising translational potential for TTN-related cardiomyopathies. Full article

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12 pages, 892 KB

Open AccessArticle

Checklist-Based Identification of Adverse Drug Reactions in Emergency Department Patients

by Benjamin J. Hellinger, Thilo Bertsche, Yvonne Remane and André Gries

Medicines 2025, 12(4), 25; https://doi.org/10.3390/medicines12040025 - 17 Oct 2025

Abstract

Background: Patients presenting at the emergency department (ED) have a wide variety of complaints. In some of those patients a possible reason for their complaints might be an adverse drug reaction (ADR). An appropriate identification of ADR in this setting is required to [...] Read more.

Background: Patients presenting at the emergency department (ED) have a wide variety of complaints. In some of those patients a possible reason for their complaints might be an adverse drug reaction (ADR). An appropriate identification of ADR in this setting is required to optimize drug therapy and to prevent serious harm deriving from an overlooked ADR. Methods: This retrospective study assessed medical records of patients for ADR as a reason for the ED presentation in two assessments. In the first assessment, medical records were evaluated for potential ADR leading to ED presentation with a predefined checklist by an examiner not involved in initial patient treatment. In the second assessment the same medical records were assessed for ADR identified by the physician in the initial patient presentation. Discrepancies in identified ADR were compared. For descriptive data analysis and statistical evaluation, the McNemar test was performed. Results: From 35,333 patients admitted to the ED, full data were available from 34,747 patients for evaluation. In those patients, 2071 (6.0%) ADR were identified as being the reason for ED presentation by using the checklist. In 828 (2.4%) patients, emergency department physicians had documented an ADR in the medical records. By using the checklist, ADR identification could be improved significantly as compared to routine care, at 6.0% vs. 2.4%, respectively (p < 0.001). The most common chief complaint in patients with an ADR was worsened general condition. Most common drug class causing ADR were antithrombotics. Conclusions: ADR seem to be overlooked in routine care since a significantly higher number of ADR were found by using a checklist-based method as compared to ADR documented as part of routine examination. Therefore, implementing the checklist in the routine process might improve ADR identification. Full article

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13 pages, 1524 KB

Open AccessArticle

Impact of Sampling Strategy and Population Model on Bayesian Estimates of Vancomycin AUC in Patients with BMI > 40 kg/m²: A Single-Center Retrospective Study

by Sarah A. Ekkelboom, Soraya M. Hobart, Laurie J. Barten and Staci L. Hemmer

Medicines 2025, 12(4), 24; https://doi.org/10.3390/medicines12040024 - 30 Sep 2025

Abstract

Background/Objectives: Growing evidence supports the use of a single trough concentration, rather than both a peak and trough, to estimate the 24 h area under the curve (AUC₂₄) of vancomycin using Bayesian software (InsightRx^® Ver.1.71). However, patients with body [...] Read more.

Background/Objectives: Growing evidence supports the use of a single trough concentration, rather than both a peak and trough, to estimate the 24 h area under the curve (AUC₂₄) of vancomycin using Bayesian software (InsightRx^® Ver.1.71). However, patients with body mass index (BMI) ≥ 40 kg/m² are underrepresented in validation studies. Studies in patients with obesity have produced mixed results, potentially because of different population models used. Methods: This single-center, retrospective study evaluated adult inpatients with BMI ≥ 40 kg/m². Steady-state AUC₂₄ estimates generated by Bayesian software using both two-concentration and one-concentration inputs were compared. Agreement was defined as a percent difference within ±20%. Subgroup analyses were conducted for patients with defined peak and trough concentrations and for comparisons between two Bayesian population models (Carreno vs. Hughes). Linear regression assessed covariates associated with percent difference. Results: Among 82 encounters, 97.5% of one-concentration estimates based on the smaller concentration were within ±20% of the two-concentration AUC_24,SS (mean difference: 2.9%, 95% CI: 0.14 to 3.8%). Similar agreement was observed using the larger concentration (97.5%, mean difference: −3.1%, 95% CI: −4.7 to −0.1.5%). Subgroup analysis for encounters with true peak/trough levels (n = 22) also showed 100% agreement within ±20%. The percent difference did not correlate with BMI or other covariates. Comparison of Hughes vs. Carreno models showed larger variability (only 59.1% within ±20%). Conclusions: In patients with BMI ≥ 40 kg/m², Bayesian AUC_24,SS estimation using a single vancomycin concentration is feasible. Greater caution is warranted in the setting of acute kidney injury, poor model fit, or targeting AUC at the extremes of the therapeutic range. The population model used to generate the Bayesian AUC estimate has a much greater influence than the number of concentrations analyzed. Furthermore, measuring two concentrations does not ensure concordance between models. Full article

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17 pages, 1617 KB

Open AccessSystematic Review

Levosimendan in Decompensated Heart Failure with Reduced Ejection Fraction in Older Adults: A Systematic Review of Safety and Efficacy

by Esteban Zavaleta-Monestel, Jeaustin Mora-Jiménez, Kevin Cruz-Mora, Ernesto Martinez-Vargas, José Pablo Díaz-Madriz, Sebastián Arguedas-Chacón, Abigail Fallas-Mora, Carlos Wu-Chin and Jose Miguel Chaverrí-Fernandez

Medicines 2025, 12(4), 23; https://doi.org/10.3390/medicines12040023 - 30 Sep 2025

Abstract

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of hospitalization and functional decline in older adults, accounting for over 80% of all heart failure cases. Given the narrow therapeutic window of currently available inotropes and the vulnerability of this [...] Read more.

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of hospitalization and functional decline in older adults, accounting for over 80% of all heart failure cases. Given the narrow therapeutic window of currently available inotropes and the vulnerability of this population, levosimendan has been proposed as a potential alternative. This systematic review aimed to evaluate the clinical efficacy and safety of levosimendan in older adults with decompensated HFrEF. Methods: A systematic search of PubMed, Embase, Scopus, and the Cochrane Library was conducted between January and May 2025, following PRISMA 2020 guidelines. The review was registered in PROSPERO (CRD420251032329). Of 379 articles initially identified, 8 studies (randomized, observational, and single-arm designs) enrolling patients aged ≥65 years with decompensated HFrEF met the inclusion criteria. Study quality was assessed using the Cochrane RoB-2 tool and JBI Critical Appraisal Checklists. No meta-analysis was performed due to heterogeneity in study designs, populations, and interventions. Results: A total of 2838 patients were analyzed. Levosimendan was associated with short-term improvements in hemodynamic parameters, including an increase in cardiac index (from 1.65 to 2.37 L/min/m²) and a reduction in pulmonary capillary wedge pressure (from 31 to 16 mmHg) within 24–72 h (p < 0.002). However, no statistically significant differences were observed in 30-, 90-, or 180-day mortality (p > 0.05), and findings on rehospitalization were inconsistent. Reported adverse events included hypotension (36–57%) and atrial arrhythmias (9–50%), with low treatment discontinuation rates (5–8%). Conclusions: Levosimendan may improve short-term hemodynamic parameters in older adults with decompensated HFrEF, but the available evidence is limited and heterogeneous. Its effects on mortality and rehospitalization remain inconclusive. Clinical use should be individualized and closely monitored, particularly in frail patients. Full article

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12 pages, 622 KB

Open AccessArticle

Non-Induction Basiliximab to Facilitate Renal Recovery via Temporary Tacrolimus Cessation in Cardiothoracic Transplant Patients

by Tanner A. Melton, Molly W. Fenske, Stacy A. Bernard, Kristin C. Cole, Kelly M. Pennington and Adley I. Lemke

Medicines 2025, 12(3), 22; https://doi.org/10.3390/medicines12030022 - 28 Aug 2025

Abstract

Introduction: Reversible and irreversible nephrotoxicity are known complications of tacrolimus. Approaches to reduce the incidence of nephrotoxicity include the reduction or avoidance of tacrolimus but must be weighed against risk of rejection. Infrequently, basiliximab has been used outside of the induction period to [...] Read more.

Introduction: Reversible and irreversible nephrotoxicity are known complications of tacrolimus. Approaches to reduce the incidence of nephrotoxicity include the reduction or avoidance of tacrolimus but must be weighed against risk of rejection. Infrequently, basiliximab has been used outside of the induction period to facilitate temporary tacrolimus cessation in the setting of acute kidney injury (AKI). Objective: The primary objective of this study was to describe renal recovery after temporary tacrolimus cessation with non-induction basiliximab (NIB) compared to a matched cohort. Methods: We conducted a single-center study of adult cardiothoracic transplant recipients that received basiliximab beyond post-operative day 7 for temporary tacrolimus cessation in the setting of AKI between January 2019 and November 2023 and matched them to acontrol cohort. Results: Twelve patients underwent temporary tacrolimus cessation with NIB. In total, 7 (58%) patients achieved initial renal recovery at tacrolimus resumption compared to 15 (42%) patients in the matched cohort at an equivalent time point. No difference between treated rejection (17% vs. 19%, p = 0.80) or infection (75% vs. 50%, p = 0.32) was observed between tacrolimus cessation and its matched cohort. Conclusions: The use of NIB for tacrolimus cessation can allow for potential renal recovery after an AKI or in patients at risk of AKI. This approach does not appear to significantly increase the risk of rejection but may increase the risk of infection in the long term. Full article

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12 pages, 514 KB

Open AccessArticle

Duration of DKA and Insulin Use in People with and Without SGLT2 Inhibitor Medications

by Yeung-Ae Park, Anya Kitt Lee, Rahul D. Barmanray, Frank Gao, Spiros Fourlanos and Chris Gilfillan

Medicines 2025, 12(3), 21; https://doi.org/10.3390/medicines12030021 - 19 Aug 2025

Abstract

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 [...] Read more.

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. Full article

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9 pages, 911 KB

Open AccessBrief Report

Evaluation of a Febrile Neutropenia Protocol Implemented at Triage in an Emergency Department

by Stefanie Stramel-Stafford, Heather Townsend, Brian Trimmer, James Cohen and Jessica Thompson

Medicines 2025, 12(3), 20; https://doi.org/10.3390/medicines12030020 - 1 Aug 2025

Cited by 1

Abstract

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 [...] Read more.

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

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22 pages, 1317 KB

Open AccessReview

Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies

by Mohammad Iftekhar Ullah and Sadeka Tamanna

Medicines 2025, 12(3), 19; https://doi.org/10.3390/medicines12030019 - 28 Jul 2025

Cited by 4

Abstract

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 [...] Read more.

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

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10 pages, 546 KB

Open AccessArticle

First-Ever Stroke Outcomes in Patients with Atrial Fibrillation: A Retrospective Cross-Sectional Study

by Ivanka Maduna, Dorotea Vidaković, Petra Črnac, Christian Saleh and Hrvoje Budinčević

Medicines 2025, 12(3), 18; https://doi.org/10.3390/medicines12030018 - 24 Jul 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Cardiology and Vascular Disease)

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19 pages, 328 KB

Open AccessReview

Multi-Drug Resistant Gram-Negative Sepsis in Neonates: The Special Role of Ceftazidime/Avibactam and Ceftolozane/Tazobactam

by Niki Dermitzaki, Foteini Balomenou, Anastasios Serbis, Natalia Atzemoglou, Lida Giaprou, Maria Baltogianni and Vasileios Giapros

Medicines 2025, 12(3), 17; https://doi.org/10.3390/medicines12030017 - 26 Jun 2025

Abstract

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: [...] Read more.

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

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