Journal Description
Medicines
Medicines
is an international, peer-reviewed, open access journal on drug discovery and clinical application published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within PubMed, PMC, CAPlus / SciFinder, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 28.6 days after submission; acceptance to publication is undertaken in 6.6 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Medicines is a companion journal of Pharmaceutics.
Latest Articles
Is the Impact of Sodium–Glucose Co-Transporter 2 (SGLT2) Inhibitors on Bone Metabolism and Fracture Incidence a Class or Drug Effect? A Narrative Review
Medicines 2025, 12(2), 10; https://doi.org/10.3390/medicines12020010 - 16 Apr 2025
Abstract
Background/Objectives: Type 2 diabetes mellitus (T2DM) has a growing prevalence, even in developed countries. Because of the increase in life expectancy, the number of older people with T2DM is also increasing. The management and handling of these patients is challenging due to
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Background/Objectives: Type 2 diabetes mellitus (T2DM) has a growing prevalence, even in developed countries. Because of the increase in life expectancy, the number of older people with T2DM is also increasing. The management and handling of these patients is challenging due to its co-morbidities. Aim: In the present study, we reviewed the literature in order to investigate the impact of sodium–glucose co-transporter 2 inhibitors (SGLT-2 inhibitors) on bone metabolism and fracture incidence. Methods: We searched the literature using the databases of PubMed, CENTRAL and Cochrane Central Register of Controlled Trials up to December 2024. Results: There is a controversial position in the literature concerning the effects of SGLT2 inhibitors when administered in T2DM, with respect to bone metabolism and bone fracture incidence. Multiple studies suggest the SGLT2 inhibitors have a disadvantageous effect on bone metabolism and fracture incidence, while several others suggest a beneficial effect. Conclusions: Patients with type 2 diabetes mellitus are at high risk of alterations in their bone metabolism. SGLT2 inhibitors are a novel class with pleiotropic effects in many organs, such as the kidneys and heart, although their effect on bone metabolism and fracture incidence is still unclear. Until we have more clinical data, all caregivers (medical and nursing staff) should be aware of possible bone fractures in patients receiving this class of agents.
Full article
(This article belongs to the Section Endocrinology and Metabolic Disorders)
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Open AccessArticle
Retrospective Bayesian Reanalysis of Single Gentamicin Concentrations: A Neonatal Case Series
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Staci L. Hemmer and Sarah K. Scoular
Medicines 2025, 12(2), 9; https://doi.org/10.3390/medicines12020009 - 10 Apr 2025
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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
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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.
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Open AccessReview
Common Bacterial Infections in Persons Who Inject Drugs
by
Michael P. Lorenzo, Kathleen K. Adams and Seth T. Housman
Medicines 2025, 12(2), 8; https://doi.org/10.3390/medicines12020008 - 28 Mar 2025
Abstract
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
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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
(This article belongs to the Special Issue The 10th Anniversary of Medicines: Future Directions)
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Open AccessCase Report
Hyponatraemia Induced by Terlipressin in Patients Diagnosed with Decompensated Liver Cirrhosis and Acute Variceal Bleeding
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Mahmoud Elshehawy, Richel Merin Panicker, Alaa Amr Abdelgawad, Patrick Anthony Ball and Hana Morrissey
Medicines 2025, 12(2), 7; https://doi.org/10.3390/medicines12020007 - 28 Mar 2025
Abstract
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
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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
Open AccessArticle
New Synthetic Compounds with Psychoactive Action—Preliminary Results Among Primary and High School Students on the Territory of Novi Sad
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Igor Kelečević, Ljubica Gugleta, Ana-Marija Vejnović and Vesna Mijatović Jovin
Medicines 2025, 12(1), 6; https://doi.org/10.3390/medicines12010006 - 14 Mar 2025
Abstract
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
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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
(This article belongs to the Special Issue Clinical Psychopharmacology and Toxicology)
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Open AccessReview
Justice for Placebo: Placebo Effect in Clinical Trials and Everyday Practice
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Nebojsa Nick Knezevic, Aleksandar Sic, Samantha Worobey and Emilija Knezevic
Medicines 2025, 12(1), 5; https://doi.org/10.3390/medicines12010005 - 24 Feb 2025
Cited by 1
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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
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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.
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Open AccessReview
Beyond the Needle: Innovative Microneedle-Based Transdermal Vaccination
by
Hiep X. Nguyen
Medicines 2025, 12(1), 4; https://doi.org/10.3390/medicines12010004 - 7 Feb 2025
Cited by 1
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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
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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.
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Open AccessCase Report
Thrombosed Mechanical Aortic Valve Treated with Low-Dose Ultraslow Alteplase Infusion
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Nicholas Pavlatos, Pawan Daga, Aangi Shah, Muhammad Khan and Jishanth Mattumpuram
Medicines 2025, 12(1), 3; https://doi.org/10.3390/medicines12010003 - 2 Feb 2025
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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
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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.
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Open AccessArticle
Hypomyelinating Leukodystrophy 14 (HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype Reversable with Hesperetin
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Yuri Ichihara, Maho Okawa, Minori Minegishi, Hiroaki Oizumi, Masahiro Yamamoto, Katsuya Ohbuchi, Yuki Miyamoto and Junji Yamauchi
Medicines 2025, 12(1), 2; https://doi.org/10.3390/medicines12010002 - 16 Jan 2025
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Introduction: In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations
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Introduction: In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths. Among these, an amino acid mutation of the ubiquitin-fold modifier conjugating enzyme 1 (UFC1) is associated with HLD14-related disease, characterized by hypomyelination and delayed myelination in the brain. UFC1 is a critical component of the UFMylation system, functioning similarly to E2-conjugating enzymes in the ubiquitin-dependent protein degradation system. Methodology: We describe how a missense mutation in UFC1 (p.Arg23Gln) leads to the aggregation of UFC1 primarily in lysosomes in FBD-102b cells, which are undergoing oligodendroglial cell differentiation. Results: Cells with mutated UFC1 exhibit reduced Akt kinase phosphorylation and reduced expression of differentiation and myelination marker proteins. Consistently, these cells exhibit impaired morphological differentiation with a reduced ability to extend widespread membranes. Interestingly, hesperetin, a citrus flavonoid with known neuroprotective properties, was found to restore differentiation abilities in cells with the UFC1 mutation. Conclusions: These findings indicate that the HLD14-related mutation in UFC1 causes its lysosomal aggregation, impairing its morphological differentiation. Furthermore, the study highlights potential therapeutic insights into the pathological molecular and cellular mechanisms underlying HLD14 and suggests hesperetin as a promising candidate for treatment.
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Open AccessReview
The Pharmacokinetic Changes in Cystic Fibrosis Patients Population: Narrative Review
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Ayda Awaness, Rania Elkeeb, Sepehr Afshari and Eman Atef
Medicines 2025, 12(1), 1; https://doi.org/10.3390/medicines12010001 - 31 Dec 2024
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Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs’ absorption, distribution, metabolism, and excretion (ADME). This review aims to identify
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Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs’ absorption, distribution, metabolism, and excretion (ADME). This review aims to identify the ADME data that compares the pharmacokinetics (PK) of different drugs in CF and healthy subjects. The published data highlight multiple factors that affect absorption, such as the bile salt precipitation and the gastrointestinal pH. Changes in CF patients’ protein binding and body composition affected the drug distribution. The paper also discusses the factors affecting metabolism and renal elimination, such as drug–protein binding and metabolizing enzyme capacity. The majority of CF patients are on multidrug therapy, which increases the risk of drug–drug interactions (DDI). This is particularly true for those receiving the newly developed transmembrane conductance regulator (CFTR), as they are at a higher risk for CYP-related DDI. Our research highlights the importance of meticulously evaluating PK variations and DDIs in drug development and the therapeutic management of CF patients.
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Open AccessRetraction
RETRACTED: Zulfiqar et al. Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care. Medicines 2022, 9, 38
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Abrar-Ahmad Zulfiqar, Perla Habchi and Ibrahima Amadou Dembele
Medicines 2024, 11(8), 22; https://doi.org/10.3390/medicines11080022 - 18 Dec 2024
Abstract
The journal retracts the article titled “Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care” [...]
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Open AccessArticle
Utility of Aprepitant in the Management of Pediatric Patients with Cyclical Vomiting Syndrome
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Aravind Thavamani, Sindhoosha Malay, Jasmine Khatana, Sujithra Velayuthan and Senthilkumar Sankararaman
Medicines 2024, 11(8), 21; https://doi.org/10.3390/medicines11080021 - 11 Dec 2024
Abstract
Introduction: Cyclical vomiting syndrome (CVS) is a recurrent debilitating illness characterized by intense episodes of nausea and emesis with widely varied pharmacological management across the country. Aprepitant is now increasingly used in patients with CVS. The impact of aprepitant as an abortive
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Introduction: Cyclical vomiting syndrome (CVS) is a recurrent debilitating illness characterized by intense episodes of nausea and emesis with widely varied pharmacological management across the country. Aprepitant is now increasingly used in patients with CVS. The impact of aprepitant as an abortive therapy in the readmission of pediatric patients with CVS is currently unknown. Methodology: We analyzed all pediatric patients with a primary diagnosis of CVS using the ICD-10 code in the Pediatric Health Information System database of the Children’s Hospital Association. We evaluated the demographic data, comorbid conditions, and management details during the inpatient stay. CVS patients who received aprepitant during their inpatient hospitalization were compared with patients without aprepitant use. Seven-day readmission rate for CVS was used as the outcome variable to assess the effectiveness of the aprepitant in aborting an episode. Propensity score matching was used to match the two cohorts. Results: We analyzed 1775 patients of which 96 received aprepitant during the inpatient hospitalization. The aprepitant group had a more severe hospitalization course as evidenced by an increased duration of hospital stay (5 vs. 3 days) and total hospitalization costs ($11,790 vs. $6380). There were no significant differences in the 7-day (17% vs. 16%, p = 0.91) readmission rate and results were not altered by propensity score matching. Conclusions: Aprepitant use as an abortive therapy did not affect the 7-day CVS-related readmission rate. Further prospective studies are needed to explore the role of aprepitant as an abortive agent in the management of CVS in the pediatric population.
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Open AccessReview
Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review
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Vítor Silva, Ricardo Madeira, João Joaquim and Cristiano Matos
Medicines 2024, 11(8), 20; https://doi.org/10.3390/medicines11080020 - 15 Nov 2024
Abstract
In recent years, the off-label use of medications in sports has increased significantly, primarily driven by psychological and social factors. Athletes frequently misuse drugs without adequate medical supervision, relying on unreliable sources of information, which leads to improper usage and serious health risks.
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In recent years, the off-label use of medications in sports has increased significantly, primarily driven by psychological and social factors. Athletes frequently misuse drugs without adequate medical supervision, relying on unreliable sources of information, which leads to improper usage and serious health risks. This narrative review analyzes literature from PubMed® (Medline), Scopus®, and Web of Science® databases, focusing on studies up to December 2023, to examine the safety concerns related to off-label drug use in sports. The review presents an overview of the off-label use of pharmacological substances by athletes, focusing on both hormonal and non-hormonal drugs. Hormonal substances such as anabolic steroids and growth hormones, and non-hormonal agents like diuretics and β2-agonists, are frequently abused. These practices are associated with severe side effects, including infections, cardiovascular complications, hormonal imbalances, psychological disorders, dependence, and even cases of death. The study emphasizes the need for stronger regulation, public awareness initiatives, and preventive strategies to mitigate the health risks associated with this growing trend.
Full article
Open AccessArticle
Does Ortho-Substitution Enhance Cytotoxic Potencies in a Series of 3,5-Bis(benzylidene)-4-piperidones?
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Subhas S. Karki, Umashankar Das, Jan Balzarini, Erik De Clercq, Hiroshi Sakagami, Yoshihiro Uesawa, Praveen K. Roayapalley and Jonathan R. Dimmock
Medicines 2024, 11(8), 19; https://doi.org/10.3390/medicines11080019 - 30 Oct 2024
Abstract
Background: A series of 3,5-benzylidene-4-piperidones, 1a–n, were prepared to evaluate the hypothesis that the placement of different groups in the ortho-location of the aryl rings led to compounds with greater cytotoxic potencies than structural analogs. Methods: The bioevaluation of 1a
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Background: A series of 3,5-benzylidene-4-piperidones, 1a–n, were prepared to evaluate the hypothesis that the placement of different groups in the ortho-location of the aryl rings led to compounds with greater cytotoxic potencies than structural analogs. Methods: The bioevaluation of 1a–n was undertaken using human Molt/4C8 and CEM cells as well as murine L1210 cells. Correlations were sought between the interplanar angles θA and θB and the cytotoxic potencies. A QSAR analysis was also undertaken. In order to evaluate whether these compounds demonstrated greater toxicity to neoplasms than non-malignant cells, 1a–n were evaluated against HSC-2, HSC-3, HSC-4 and HL60 neoplasms as well as non-malignant HGF, HPC and HPLF cells. Results: A positive correlation was noted between the interplanar angle θA of one of the aryl rings and the adjacent olefinic linkage with IC50 values in the Molt4/C8 screens. The QSAR analysis revealed a positive correlation between the Hansch pi (π) value of the aryl substituents and the IC50 values of the compounds towards the Molt4/C8 and CEM cells. The dienones in series 1 demonstrated higher tumor-selective toxicity towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC and HPLF cells. Conclusions: The bioevaluations revealed some support for greater cytotoxic potencies to be displayed by compounds having ortho-substituents.
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(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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Open AccessReview
Breathing for Two: Asthma Management, Treatment, and Safety of Pharmacological Therapy during Pregnancy
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Jovan Javorac, Dejan Živanović, Biljana Zvezdin and Vesna Mijatović Jovin
Medicines 2024, 11(7), 18; https://doi.org/10.3390/medicines11070018 - 5 Sep 2024
Abstract
The primary objectives of asthma management during pregnancy are to achieve adequate symptom control, reduce the risk of acute exacerbations, and maintain normal pulmonary function, all of which contribute to ensuring the health and well-being of both the mother and the baby. The
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The primary objectives of asthma management during pregnancy are to achieve adequate symptom control, reduce the risk of acute exacerbations, and maintain normal pulmonary function, all of which contribute to ensuring the health and well-being of both the mother and the baby. The Global Initiative for Asthma (GINA) recommends that pregnant women with asthma continue using asthma medications throughout pregnancy, as the benefits of well-controlled asthma for both the mother and fetus outweigh the potential risks of medication side effects, poorly controlled asthma, and exacerbations. The classification of asthma medications by the US Food and Drug Administration (FDA) into categories A, B, C, D, and X is no longer applied. Instead, the potential benefits and risks of each medication during pregnancy and lactation are considered individually. The use of medications to achieve good asthma control and prevent exacerbations during pregnancy is justified, encompassing inhaled corticosteroids (ICS), some leukotriene receptor antagonists (LTRA), short-acting beta-2 agonists (SABA), long-acting beta-2 agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA), and, recently, biological therapies, even in the absence of definitive safety data during pregnancy.
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Open AccessCommentary
GDF15 Targeting for Treatment of Hyperemesis Gravidarum
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Jamie Thygerson, Dallin Oyler, Jackson Thomas, Brandon Muse, Benjamin D. Brooks and Jessica E. Pullan
Medicines 2024, 11(7), 17; https://doi.org/10.3390/medicines11070017 - 30 Aug 2024
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Nausea and vomiting during pregnancy (NVP), particularly its severe form, Hyperemesis gravidarum (HG), affects up to 70% of pregnancies and significantly impacts the quality of life for those with the condition as well as generates a great economic burden, with annual costs exceeding
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Nausea and vomiting during pregnancy (NVP), particularly its severe form, Hyperemesis gravidarum (HG), affects up to 70% of pregnancies and significantly impacts the quality of life for those with the condition as well as generates a great economic burden, with annual costs exceeding $1.7 billion in the United States. Despite the available treatments targeting neurotransmitters like serotonin and dopamine, many patients experience inadequate relief and suffer from severe side effects, including headaches and dizziness. Recent research has underscored the role of GDF15, a protein mainly produced by the placenta and linked to NVP symptoms. This protein, part of the TGF-β superfamily, has been implicated in appetite and weight regulation and is altered in those with HG due to specific genetic mutations. Addressing the challenges of delivering effective treatments, current innovations focus on targeting GDF15 to reduce symptoms while ensuring fetal safety. Promising therapeutic strategies include non-IgG immunotherapies, small peptide and molecule antagonists, and novel administration methods such as transdermal patches. These approaches aim to optimize dosage and reduce adverse effects. The effective development and testing of these treatments necessitate advanced animal models that closely resemble human pregnancy physiology, highlighting the need for further research and funding. This ongoing research holds significant potential to improve the clinical outcomes for HG patients and decrease the economic impact on healthcare systems, urging a dedicated response from the scientific and medical communities to advance these promising treatments.
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Open AccessReview
Postoperative Nausea and Vomiting in the Ambulatory Surgery Center: A Narrative Review
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Justin Bell, Adam Bindelglass, Jennifer Morrone, Sherwin Park, Ana Costa and Sergio Bergese
Medicines 2024, 11(7), 16; https://doi.org/10.3390/medicines11070016 - 9 Aug 2024
Abstract
Postoperative nausea and vomiting (PONV) is a common complication of ambulatory surgery, leading to numerous deleterious effects such as decreased patient satisfaction, prolonged recovery unit stays, and rarely, more serious complications such as aspiration pneumonia or wound dehiscence. In this paper, we present
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Postoperative nausea and vomiting (PONV) is a common complication of ambulatory surgery, leading to numerous deleterious effects such as decreased patient satisfaction, prolonged recovery unit stays, and rarely, more serious complications such as aspiration pneumonia or wound dehiscence. In this paper, we present a narrative review of the literature regarding common risk factors for PONV including patient factors, surgical factors, and anesthetic factors. We then will review anesthetic techniques and antiemetic drugs demonstrated to mitigate the risk of PONV. Finally, we discuss the potential economic benefits of PONV prophylaxis in the perioperative ambulatory setting.
Full article
(This article belongs to the Special Issue The 10th Anniversary of Medicines: Future Directions)
Open AccessReview
Deciphering Mechanisms, Prevention Strategies, Management Plans, Medications, and Research Techniques for Strokes in Systemic Lupus Erythematosus
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Ola A. Al-Ewaidat and Moawiah M. Naffaa
Medicines 2024, 11(7), 15; https://doi.org/10.3390/medicines11070015 - 31 Jul 2024
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range
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Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke.
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(This article belongs to the Section Neurology and Neurologic Diseases)
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Open AccessReview
Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines
by
Qingyuan Yu, Xian Zhou, Rotina Kapini, Anthony Arsecularatne, Wenting Song, Chunguang Li, Yang Liu, Junguo Ren, Gerald Münch, Jianxun Liu and Dennis Chang
Medicines 2024, 11(7), 14; https://doi.org/10.3390/medicines11070014 - 18 Jul 2024
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Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and
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Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.
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Open AccessCase Report
An Unusual Case of Immune Complex-Mediated Membranoproliferative Glomerulonephritis as Renal Manifestation of Idiopathic Hypereosinophilic Syndrome: A Case Report and Literature Review
by
Michael Cieza-Terrones, José C. De La Flor, Christian Requejo, Daniel Villa, Jacqueline Apaza, Pablo Rodríguez-Doyágüez, Rocío Zamora, Carmen Asato-Higa, David Rivera-Estrella and Antonio Carrasco-Yalán
Medicines 2024, 11(6), 13; https://doi.org/10.3390/medicines11060013 - 2 Jun 2024
Abstract
Background: Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5 × 109/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of
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Background: Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5 × 109/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of unknown cause. IHES affects different organs such as the heart, lungs, nervous system, and skin, with renal involvement being rare in this condition. Case Presentation: We present a case of a young patient with IHES and immune complex-mediated membranoproliferative glomerulonephritis with nephrotic syndrome, as a rare renal manifestation. We discuss the clinical, analytical, and histopathologic renal and hematologic features, comparing them with other reported cases in the literature.
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(This article belongs to the Section Nephrology and Urology)
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