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Keywords = fall-risk-increasing drugs

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26 pages, 603 KiB  
Article
Fall Risk and Knowledge of Fall-Risk-Increasing Drugs Among Saudi Older Adults
by Ayesha Yasmeen, Mamoon H. Syed, Abdulkarim M. Meraya, Saad S. Alqahtani, Nabeel Kashan Syed, Aseel J. Alfaifi, Mujeeb Alrhman I. Madkoor, Hilal A. Thaibah, Amani Khardali and Marie Claire Van Hout
Healthcare 2025, 13(13), 1549; https://doi.org/10.3390/healthcare13131549 - 29 Jun 2025
Viewed by 616
Abstract
Introduction: Falls pose a significant health risk to older adults, with a reported prevalence of 31.6% among Saudi older adults. Medication-related falls are a preventable cause of morbidity and mortality. This study aimed to assess fall risk, evaluate knowledge of fall-risk-increasing drugs, and [...] Read more.
Introduction: Falls pose a significant health risk to older adults, with a reported prevalence of 31.6% among Saudi older adults. Medication-related falls are a preventable cause of morbidity and mortality. This study aimed to assess fall risk, evaluate knowledge of fall-risk-increasing drugs, and examine the impact of pharmacist counseling on community-dwelling older adults in Jazan, Saudi Arabia. Methods: A cross-sectional survey was conducted from December 2023 to March 2024 among 391 community-dwelling individuals aged ≥60 years in Jazan, Saudi Arabia. Fall risk was assessed using the Arabic Stay Independent screening tool, which remains unvalidated in Arabic-speaking populations. Participants answered demographic questions and reported any pharmacist counseling on medication in the past six months. Knowledge of prescription and over-the-counter fall-risk-increasing drugs was evaluated. Multivariable logistic regression and ordered probit models were used to analyze factors associated with fall risk and drug knowledge. Results: Approximately 57% of the participants were at risk of falling. Only 11.5% demonstrated good knowledge of prescription fall-risk-increasing drugs, whereas 24.6% showed good knowledge of over-the-counter fall-risk-increasing drugs. Age (OR, 1.07; 95% CI, 1.00–1.14; p = 0.05), arthritis (OR, 5.73; 95% CI, 2.51–13.06; p < 0.001), obesity (OR, 6.00; 95% CI, 2.33–15.46; p < 0.001) and diabetes (OR, 2.79; 95% CI, 1.38–5.64; p = 0.004) were associated with increased fall risk. Those who received pharmacist counseling had a greater likelihood (95% CI, 0.020–0.167; p = 0.01) of being in the very likely category of willingness to discuss medication changes. Conclusions: The findings highlight the role of pharmacist counseling and recommend improving fall prevention through medication reviews for arthritis and diabetes patients, standardized counseling protocols, and implementation of the Stay Independent screening tool for risk assessment in older adults. Full article
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21 pages, 356 KiB  
Review
Overview of Oncology: Drug-Induced Cardiac Toxicity
by Nilima Rajpal Kundnani, Vincenzo Passini, Iulia Stefania Carlogea, Patrick Dumitrescu, Vlad Meche, Roxana Buzas and Daniel Marius Duda-Seiman
Medicina 2025, 61(4), 709; https://doi.org/10.3390/medicina61040709 - 12 Apr 2025
Cited by 1 | Viewed by 1366
Abstract
Cancer medications can cause cardiac issues, which are difficult to treat in oncologic patients because of the risk of complications. In some cases, this may significantly impact their well-being and treatment outcomes. Overall, these complications fall under the term “drug induced cardiotoxicity”, mainly [...] Read more.
Cancer medications can cause cardiac issues, which are difficult to treat in oncologic patients because of the risk of complications. In some cases, this may significantly impact their well-being and treatment outcomes. Overall, these complications fall under the term “drug induced cardiotoxicity”, mainly due to chemotherapy drugs being specifically toxic to the heart, causing a decrease in the heart’s capacity to pump blood efficiently and leading to a reduction in the left ventricular ejection fraction (LVEF), and subsequently possibly leading to heart failure. Anthracyclines, alkylating agents, and targeted therapies for cancer hold the potential of causing harmful effects on the heart. The incidence of heart-related issues varies from patient to patient and depends on multiple factors, including the type of medication, dosage, duration of the treatment, and pre-existing heart conditions. The underlying mechanism leading to oncologic-drug-induced cardiovascular harmful effects is quite complex. One particular group of drugs, called anthracyclines, have garnered attention due to their impact on oxidative stress and their ability to cause direct harm to heart muscle cells. Reactive oxygen species (ROS) cause harm by inducing damage and programmed cell death in heart cells. Conventional biomarkers alone can only indicate some degree of damage that has already occurred and, therefore, early detection is key. Novel methods like genetic profiling are being developed to detect individuals at risk, prior to the onset of clinical symptoms. Key management strategies—including early detection, personalized medicine approaches, and the use of novel biomarkers—play a crucial role in mitigating cardiotoxicity and improving patient outcomes. Identification of generated genetic alterations and the association to an increased likelihood of cardiotoxicity will allow treatment in a more personalized approach, aiming at decreasing rates of cardiac events while maintaining high oncological efficacy. Oncology drug-induced cardiotoxicity is managed through a combination of preventive strategies and therapeutic interventions from the union of cardiac and oncological knowledge. Full article
(This article belongs to the Special Issue New Insights into Heart Failure)
12 pages, 582 KiB  
Article
Impact of an Interprofessional Collaboration Between Physicians and Pharmacists on Fall-Risk-Increasing Drugs in Older Patients with Trauma in the Emergency Department
by Benjamin J. Hellinger, André Gries, Thilo Bertsche and Yvonne Remane
Geriatrics 2025, 10(2), 46; https://doi.org/10.3390/geriatrics10020046 - 17 Mar 2025
Viewed by 653
Abstract
Background/Objectives: In older patients, falls constitute a significant public health concern and a major cause of hospital admission. Fall-risk-increasing drugs (FRIDs) represent a key risk factor for falls. Therefore, modifying these drugs represents an important strategy for preventing recurrent falls and further [...] Read more.
Background/Objectives: In older patients, falls constitute a significant public health concern and a major cause of hospital admission. Fall-risk-increasing drugs (FRIDs) represent a key risk factor for falls. Therefore, modifying these drugs represents an important strategy for preventing recurrent falls and further patient harm. The objective of this study was to evaluate a structured interprofessional collaboration between physicians and pharmacists on managing FRIDs in older patients who present to the emergency department (ED) after a fall. Methods: This study was performed in the ED of a tertiary care hospital. Patients who were >65 years old and presented to the ED after a fall were included. A routine care group was included between 1 March 2020 and 31 May 2020. A pharmaceutical care group was included between 1 September 2023 and 30 November 2023. In the pharmaceutical care group, a clinical pharmacist supported the physicians in identifying and managing FRIDs. Possible solutions for improving FRID prescription were discussed interprofessionally. The number of FRIDs at ED admission and discharge, as well as the number of FRID modifications, were evaluated. Results: A total of 107 patients were enrolled in each group. There were 85 patients in the routine care group and 89 patients in the pharmaceutical care group, with at least 1 FRID prescribed at ED admission (p = 0.483). At ED discharge, there were 85 patients in the routine care group and 68 patients in the pharmaceutical care group, with at least 1 FRID prescribed at (p = 0.010). There were seven FRID modifications in the routine care group compared to 125 FRID modifications in the pharmaceutical care group. Conclusions: In this study, the interprofessional collaboration between physicians and pharmacists led to a reduced number of FRIDs being prescribed and more FRID modifications in older patients at ED discharge. Further research is required to ascertain the feasibility of integrating this single intervention into a multifactorial fall prevention program. Full article
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13 pages, 632 KiB  
Article
An Instant Relationship Between Hyponatremia, Geriatric Syndromes, and Drugs in Older Adults: A Cross-Sectional Analysis from a Single Geriatric Clinic
by Ali Ekrem Aydin, Esra Ates Bulut, Suleyman Emre Kocyigit, Fatma Sena Dost, Feyza Mutlay, Kubra Altunkalem Seydi, Fethiye Esenkaya and Ahmet Turan Isik
Diagnostics 2025, 15(6), 744; https://doi.org/10.3390/diagnostics15060744 - 16 Mar 2025
Viewed by 1157
Abstract
Background: Hyponatremia is a common electrolyte disorder in older adults that can lead to poor clinical outcomes and increased mortality. This study aims to evaluate the interrelationship between hyponatremia and geriatric syndromes and drugs in older adults. Methods: This study included [...] Read more.
Background: Hyponatremia is a common electrolyte disorder in older adults that can lead to poor clinical outcomes and increased mortality. This study aims to evaluate the interrelationship between hyponatremia and geriatric syndromes and drugs in older adults. Methods: This study included 1100 elderly patients admitted to a geriatric clinic. Patient records were used to obtain demographic information, comorbidities, geriatric syndromes, medications, laboratory results, and comprehensive geriatric assessment parameters. Results: The prevalence of hyponatremia was 23.9% in this study (mean age ± SD was 75.59 ± 8.13 years). The frequency of polypharmacy, dementia, falls, malnutrition and risk of malnutrition, frailty, probable sarcopenia, hypertension, cerebrovascular disease, and congestive heart failure was higher, and patients were older in the hyponatremia group (p < 0.05) than in the normonatremia group. After the adjustment of covariates, hyponatremia was shown to be related to drugs including escitalopram (odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.20–2.76), trazodone (OR: 2.27, 95% CI: 1.26–4.10), renin angiotensin aldosterone system (RAAS) inhibitors (OR: 1.71, 95% CI: 1.18–2.47), hydrochlorothiazide (OR: 1.83, 95% CI: 1.28–2.62), and opioids (OR: 4.46, 95% CI: 1.24–16.02) (p < 0.05). Polypharmacy, falls, and malnutrition with risk of malnutrition were still significantly associated with increased hyponatremia risk even after adjustment for age, sex, and comorbidity burden (p < 0.05). Conclusions: Hyponatremia seems to be associated with certain geriatric syndromes, as well as the use of some antidepressants and cardiovascular drugs in older adults. Malnourished older adults taking RAAS inhibitors, diuretics, opioids, and antidepressants may be at a higher risk of developing hyponatremia. They should be closely monitored, especially if they are taking multiple medications. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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22 pages, 1432 KiB  
Article
Individual Pharmacotherapy Management (IPM-II) for Patient and Drug Safety in Polypharmacy via Clinical Electronic Health Record Is Associated with Significant Fall Prevention
by Ursula Wolf, Luise Drewas, Hassan Ghadir, Christian Bauer, Lars Becherer, Karl-Stefan Delank and Rüdiger Neef
Pharmaceuticals 2024, 17(12), 1587; https://doi.org/10.3390/ph17121587 - 25 Nov 2024
Viewed by 2018
Abstract
Background/Objectives: Falls and fractures are emerging as a near-pandemic and major global health concern, placing an enormous burden on ageing patients and public health economies. Despite the high risk of polypharmacy in the elderly patients, falls are usually attributed to age-related changes. For [...] Read more.
Background/Objectives: Falls and fractures are emerging as a near-pandemic and major global health concern, placing an enormous burden on ageing patients and public health economies. Despite the high risk of polypharmacy in the elderly patients, falls are usually attributed to age-related changes. For the “Individual Pharmacotherapy Management (IPM)” established at the University Hospital Halle, the IPM medication adjustments and their association with in-hospital fall prevention were analysed. Methods: On the basis of the most updated digital overall patient view via his inpatient electronic health record (EHR), IPM adapts each drug’s Summary of Product Characteristics to the patient’s condition. A retrospective pre-post intervention study in geriatric traumatology on ≥70 years old patients compared 200 patients before IPM implementation (CG) with 204 patients from the IPM intervention period (IG) for the entire medication list, organ, cardiovascular and vital functions and fall risk parameters. Results: Statistically similar baseline data allowed a comparison of the average 80-year-old patient with a mean of 11.1 ± 4.9 (CG) versus 10.4 ± 3.6 (IG) medications. The IPM adjusted for drug-drug interactions, drug-disease interactions, overdoses, anticholinergic burden, adverse drug reactions, esp. from opioids inducing increased intrasynaptic serotonin, psychotropic drugs, benzodiazepines, contraindications and missing prescriptions. IPM was associated with a significant reduction in in-hospital falls from 18 (9%) in CG to 3 (1.5%) in IG, a number needed to treat of 14, relative risk reduction 83%, OR 0.17 [95% CI 0.04; 0.76], p = 0.021 in multivariable regression analysis. Factors associated with falls were antipsychotics, digitoxin, corticosteroids, Würzburg pain drip (combination of tramadol, metamizole, metoclopramide), head injury, cognitive impairment and aspects of the Huhn Fall Risk Scale including urinary catheter. Conclusion: The results indicate medication risks constitute a major iatrogenic cause of falls in this population and support the use of EHR-based IPM in standard care for the prevention of falls in the elderly and for patient and drug safety. In terms of global efforts, IPM contributes to the running WHO and United Nations Decade of Healthy Ageing (2021–2030). Full article
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13 pages, 673 KiB  
Article
Association between Polypharmacy and Adverse Events in Patients with Alzheimer’s Disease: An Analysis of the Japanese Adverse Drug Event Report Database (JADER)
by Nobuhiro Otani, Kanae Kanda, Nlandu Roger Ngatu, Akitsu Murakami, Yusuke Yamadori and Tomohiro Hirao
Medicina 2024, 60(10), 1633; https://doi.org/10.3390/medicina60101633 - 6 Oct 2024
Cited by 1 | Viewed by 2249
Abstract
Background and Objectives: Alzheimer’s disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. [...] Read more.
Background and Objectives: Alzheimer’s disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer’s disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Materials and Methods: Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer’s disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer’s disease drug combinations, as well as the number of concomitant medications. Results: Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. Conclusions: In the treatment of Alzheimer’s disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer’s disease drugs and their combination patterns. Full article
(This article belongs to the Section Neurology)
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13 pages, 1096 KiB  
Article
Frailty and Medication Appropriateness in Rural Adults: Proposing Interventions through Pharmacist–Physician Collaborative Efforts
by Cristina García, José M. Ocaña, Mónica Alacreu, Lucrecia Moreno and Luis A. Martínez
J. Clin. Med. 2024, 13(19), 5755; https://doi.org/10.3390/jcm13195755 - 27 Sep 2024
Cited by 2 | Viewed by 1561
Abstract
Background: Frailty and polymedication are closely interrelated. Addressing these concurrent conditions in primary care settings relies on the utilization of potentially inappropriate medication (PIM) lists and medication reviews (MRs), particularly in rural areas, where healthcare professionals serve as the sole point of access [...] Read more.
Background: Frailty and polymedication are closely interrelated. Addressing these concurrent conditions in primary care settings relies on the utilization of potentially inappropriate medication (PIM) lists and medication reviews (MRs), particularly in rural areas, where healthcare professionals serve as the sole point of access to the medical system. The aim of this study was to examine the relationship between medication appropriateness and variables related to frailty in a rural municipality in order to propose potential strategies for therapy optimization. Methods: This cross-sectional study included all adult community dwellers aged 50 and above officially registered in the municipality of Tiriez (Albacete, Spain) in 2023 (n = 241). The primary outcome variable was frailty (assessed using the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale). The independent variables were age, gender, medication regimen, history of falls, comorbidities, PIMs (evaluated using the screening tool of older persons’ prescriptions (STOPP) 2023 criteria), fall-risk-increasing drugs (FRID), and anticholinergic burden (ACB). Results: The prevalence of frailty was approximately 20%. FRID and ACB scores were statistically associated (p-value < 0.001) with frailty, 1.1 ± 1.3 vs. 2.5 ± 1.7, and 1.0 ± 1.3 vs. 2.8 ± 2.5, respectively. Regardless of age, frailty was observed to be more prevalent among females (odds ratio (OR) [95% confidence interval (CI)]: 3.5 [1.5, 9.0]). On average, 2.1 ± 1.6 STOPP criteria were fulfilled, with the prolonged use of anxiolytics and anti-peptic-ulcer agents being the most frequent. Priority interventions (PIs) included opioid dose reduction, benzodiazepine withdrawal, and the assessment of antidepressant and antiplatelet treatment plans. Conclusions: The optimization of medication in primary care is of paramount importance for frail patients. Interventional measures should focus on ensuring the correct dosage and combination of drugs for each therapeutic regimen. Full article
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13 pages, 639 KiB  
Review
Antibiofilm Strategies in Neonatal and Pediatric Infections
by Chrysoula Kosmeri, Vasileios Giapros, Anastasios Serbis, Foteini Balomenou and Maria Baltogianni
Antibiotics 2024, 13(6), 509; https://doi.org/10.3390/antibiotics13060509 - 30 May 2024
Cited by 3 | Viewed by 2109
Abstract
Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as Enterococcus faecalis, Pseudomonas aeruginosa, [...] Read more.
Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis commonly form biofilms on medical devices, exacerbating infection risks. Neonates and children, particularly those in intensive care units, are highly susceptible to biofilm-associated infections due to the prolonged use of invasive devices, such as central lines and endotracheal tubes. Enteral feeding tubes, crucial for neonatal nutritional support, also serve as potential sites for biofilm formation, contributing to recurrent microbial contamination. Moreover, Candida species, including Candida pelliculosa, present emerging challenges in neonatal care, with multi-drug resistant strains posing treatment complexities. Current antimicrobial therapies, while important in managing infections, often fall short in eradicating biofilms, necessitating alternative strategies. The aim of this review is to summarize current knowledge regarding antibiofilm strategies in neonates and in children. Novel approaches focusing on biofilm inhibition and dispersal show promise, including surface modifications, matrix-degrading enzymes, and quorum-sensing inhibitors. Prudent use of medical devices and exploration of innovative antibiofilm therapies are imperative in mitigating neonatal and pediatric biofilm infections. Full article
(This article belongs to the Section Antibiofilm Strategies)
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9 pages, 2073 KiB  
Article
Factors Impacting Fall Severity in Hospitalized Patients: A Retrospective Cohort Study
by Sen-Yung Liu, Yu-Kai Yang, Chew-Teng Kor, Yi-Wei Sun, Hsin-Yu Wang, Yuan-Ting Yang and Ming-Chih Chou
J. Clin. Med. 2024, 13(10), 2827; https://doi.org/10.3390/jcm13102827 - 10 May 2024
Cited by 2 | Viewed by 1732
Abstract
Objectives: This retrospective case-controlled study aimed to evaluate the association between the severity of fall-related injuries and fall-risk-increasing drugs (FRIDs) in hospitalized patients. Methods: Data were collected from Changhua Christian Hospital, Taiwan, of all adult inpatients who experienced falls between January [...] Read more.
Objectives: This retrospective case-controlled study aimed to evaluate the association between the severity of fall-related injuries and fall-risk-increasing drugs (FRIDs) in hospitalized patients. Methods: Data were collected from Changhua Christian Hospital, Taiwan, of all adult inpatients who experienced falls between January 2017 and December 2021, and were divided into two groups based on whether they sustained severe fall-related injuries. Retrospective data that may affect the severity of fall-related injuries and the use of FRIDs were investigated. Results: Among 1231 documented cases of falls, 26 patients sustained severe fall-related injuries. Older patients and those with osteoporosis were more susceptible to more severe injuries from a fall. The use of mobility aids and osteoporosis medications showed protective effects against fall injuries. No significant association was observed between fall-related injuries and comorbidities or FRIDs. Multivariate analysis confirmed the inverse correlation between the use of mobility aids, osteoporosis medications, and fall severity. Patients with osteoporosis exhibited significantly higher odds of sustaining more severe injuries with a fall (odds ratio = 3.02, 95% confidence interval: 1.21–7.53). Conclusions: This study highlights the importance of addressing risk factors associated with fall severity among hospitalized patients. Providing mobility aids to persons at greater risk. Full article
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45 pages, 487 KiB  
Review
A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review PART II—Pharmacological Approach for Management of Elderly Patients with Peripheral Atherosclerotic Lesions outside Coronary Territory
by Marcin Piechocki, Tadeusz Przewłocki, Piotr Pieniążek, Mariusz Trystuła, Jakub Podolec and Anna Kabłak-Ziembicka
J. Clin. Med. 2024, 13(5), 1508; https://doi.org/10.3390/jcm13051508 - 5 Mar 2024
Cited by 11 | Viewed by 3464
Abstract
Background: Aging is a key risk factor for atherosclerosis progression that is associated with increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in [...] Read more.
Background: Aging is a key risk factor for atherosclerosis progression that is associated with increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity, quality of life, and it is associated with reduced life expectancy. As most multicenter randomized trials exclude elderly and very elderly patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home, there is insufficient data on the management of older patients presenting with atherosclerotic lesions outside coronary territory. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment. In addition, due to a variety of severe comorbidities in the elderly, the average daily number of pills taken by octogenarians exceeds nine. Polypharmacy frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and non-adherence. Therefore, we have attempted to gather data on the medical treatment in patients with extra-cardiac atherosclerotic lesions indicating where there is some evidence of the management in elderly patients and where there are gaps in evidence-based medicine. Public PubMed databases were searched to review existing evidence on the effectiveness of lipid-lowering, antithrombotic, and new glucose-lowering medications in patients with extra-cardiac atherosclerotic occlusive disease. Full article
(This article belongs to the Section Vascular Medicine)
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19 pages, 883 KiB  
Review
Direct Oral Anticoagulants in Special Patient Populations
by Asa Kessler, Yotam Kolben, Gal Puris, Martin Ellis, Mordechai Alperin, Vered Simovich, Hila Lerman Shivek, Mordechai Muszkat, Yoram Maaravi and Yitschak Biton
J. Clin. Med. 2024, 13(1), 216; https://doi.org/10.3390/jcm13010216 - 29 Dec 2023
Cited by 6 | Viewed by 3140
Abstract
Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC [...] Read more.
Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug–drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an “abnormal” volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations. Full article
(This article belongs to the Section Cardiology)
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14 pages, 1923 KiB  
Article
Medication and the Risk of Falls: An Analysis of Adverse Drug Reactions Reported to the Portuguese Pharmacovigilance System
by Daniela Rodrigues, Samuel Silvestre, Cristina Monteiro and Ana Paula Duarte
J. Clin. Med. 2023, 12(23), 7268; https://doi.org/10.3390/jcm12237268 - 23 Nov 2023
Cited by 1 | Viewed by 2222
Abstract
Falls are not always considered direct adverse drug reactions (ADRs). However, due to their mechanism of action, certain drugs increase the risk of falls. This retrospective study aimed to evaluate the association between drugs and the risk of falls. An analysis of ADR [...] Read more.
Falls are not always considered direct adverse drug reactions (ADRs). However, due to their mechanism of action, certain drugs increase the risk of falls. This retrospective study aimed to evaluate the association between drugs and the risk of falls. An analysis of ADR reports submitted to a national pharmacovigilance database from 1992 to 2021 was performed using terms from the MedDRA dictionary. This included the word “fall” and terms related to conditions potentially predisposing patients to falls. The analysis involved examining the sex and age distribution of the population. Reports were assessed for seriousness, the class of the suspected drug, and the characterisation of fall events when they occurred. Over this period, 2217 cases were reported, with the majority occurring among females (60.71%) and the age group of 18–64 years old (38.43%). Most reports were classified as serious across all age groups, and immunomodulators (16.78%) were the most frequently reported pharmacotherapeutic class of suspected drugs. Falls were reported as ADRs in 343 cases, with fractures being the most commonly reported injuries (24.45%). In conclusion, falls can pose a significant health problem. Therefore, continuously monitoring drugs is crucial to minimise fall-associated risk factors. Full article
(This article belongs to the Section Pharmacology)
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14 pages, 1173 KiB  
Review
Inoculum-Based Dosing: A Novel Concept for Combining Time with Concentration-Dependent Antibiotics to Optimize Clinical and Microbiological Outcomes in Severe Gram Negative Sepsis
by Alwin Tilanus and George Drusano
Antibiotics 2023, 12(11), 1581; https://doi.org/10.3390/antibiotics12111581 - 31 Oct 2023
Cited by 4 | Viewed by 6701
Abstract
Certain classes of antibiotics show “concentration dependent” antimicrobial activity; higher concentrations result in increased bacterial killing rates, in contrast to “time dependent antibiotics”, which show antimicrobial activity that depends on the time that antibiotic concentrations remain above the MIC. Aminoglycosides and fluoroquinolones are [...] Read more.
Certain classes of antibiotics show “concentration dependent” antimicrobial activity; higher concentrations result in increased bacterial killing rates, in contrast to “time dependent antibiotics”, which show antimicrobial activity that depends on the time that antibiotic concentrations remain above the MIC. Aminoglycosides and fluoroquinolones are still widely used concentration-dependent antibiotics. These antibiotics are not hydrolyzed by beta-lactamases and are less sensitive to the inoculum effect, which can be defined as an increased MIC for the antibiotic in the presence of a relatively higher bacterial load (inoculum). In addition, they possess a relatively long Post-Antibiotic Effect (PAE), which can be defined as the absence of bacterial growth when antibiotic concentrations fall below the MIC. These characteristics make them interesting complementary antibiotics in the management of Multi-Drug Resistant (MDR) bacteria and/or (neutropenic) patients with severe sepsis. Global surveillance studies have shown that up to 90% of MDR Gram-negative bacteria still remain susceptible to aminoglycosides, depending on the susceptibility breakpoint (e.g., CLSI or EUCAST) being applied. This percentage is notably lower for fluoroquinolones but depends on the region, type of organism, and mechanism of resistance involved. Daily (high-dose) dosing of aminoglycosides for less than one week has been associated with significantly less nephro/oto toxicity and improved target attainment. Furthermore, higher-than-conventional dosing of fluoroquinolones has been linked to improved clinical outcomes. Beta-lactam antibiotics are the recommended backbone of therapy for severe sepsis. Since these antibiotics are time-dependent, the addition of a second concentration-dependent antibiotic could serve to quickly lower the bacterial inoculum, create PAE, and reduce Penicillin-Binding Protein (PBP) expression. Inadequate antibiotic levels at the site of infection, especially in the presence of high inoculum infections, have been shown to be important risk factors for inadequate resistance suppression and therapeutic failure. Therefore, in the early phase of severe sepsis, effort should be made to optimize the dose and quickly lower the inoculum. In this article, the authors propose a novel concept of “Inoculum Based Dosing” in which the decision for antibiotic dosing regimens and/or combination therapy is not only based on the PK parameters of the patient, but also on the presumed inoculum size. Once the inoculum has been lowered, indirectly reflected by clinical improvement, treatment simplification should be considered to further treat the infection. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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23 pages, 2367 KiB  
Article
A Single-Run HPLC–MS Multiplex Assay for Therapeutic Drug Monitoring of Relevant First- and Second-Line Antibiotics in the Treatment of Drug-Resistant Tuberculosis
by Niklas Köhler, Hande Karaköse, Hans-Peter Grobbel, Doris Hillemann, Sönke Andres, Christina König, Barbara Kalsdorf, Thomas Theo Brehm, Laura Böttcher, Inna Friesen, Harald Hoffmann, Dražen Strelec, Dagmar Schaub, Charles A. Peloquin, Stefan Schmiedel, Laurent A. Decosterd, Eva Choong, Sebastian G. Wicha, Rob E. Aarnoutse, Christoph Lange and Patricia M. Sánchez Carballoadd Show full author list remove Hide full author list
Pharmaceutics 2023, 15(11), 2543; https://doi.org/10.3390/pharmaceutics15112543 - 27 Oct 2023
Cited by 6 | Viewed by 3011
Abstract
The treatment of drug-resistant Mycobacterium tuberculosis relies on complex antibiotic therapy. Inadequate antibiotic exposure can lead to treatment failure, acquired drug resistance, and an increased risk of adverse events. Therapeutic drug monitoring (TDM) can be used to optimize the antibiotic exposure. Therefore, we [...] Read more.
The treatment of drug-resistant Mycobacterium tuberculosis relies on complex antibiotic therapy. Inadequate antibiotic exposure can lead to treatment failure, acquired drug resistance, and an increased risk of adverse events. Therapeutic drug monitoring (TDM) can be used to optimize the antibiotic exposure. Therefore, we aimed to develop a single-run multiplex assay using high-performance liquid chromatography–mass spectrometry (HPLC–MS) for TDM of patients with multidrug-resistant, pre-extensively drug-resistant and extensively drug-resistant tuberculosis. A target profile for sufficient performance, based on the intended clinical application, was established and the assay was developed accordingly. Antibiotics were analyzed on a zwitterionic hydrophilic interaction liquid chromatography column and a triple quadrupole mass spectrometer using stable isotope-labeled internal standards. The assay was sufficiently sensitive to monitor drug concentrations over five half-lives for rifampicin, rifabutin, levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, terizidone/cycloserine, ethambutol, delamanid, pyrazinamide, meropenem, prothionamide, and para-amino salicylic acid (PAS). Accuracy and precision were sufficient to support clinical decision making (≤±15% in clinical samples and ±20–25% in spiked samples, with 80% of future measured concentrations predicted to fall within ±40% of nominal concentrations). The method was applied in the TDM of two patients with complex drug-resistant tuberculosis. All relevant antibiotics from their regimens could be quantified and high-dose therapy was initiated, followed by microbiological conversion. In conclusion, we developed a multiplex assay that enables TDM of the relevant first- and second-line anti-tuberculosis medicines in a single run and was able to show its applicability in TDM of two drug-resistant tuberculosis patients. Full article
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18 pages, 866 KiB  
Review
Current Nutritional and Pharmacological Approaches for Attenuating Sarcopenia
by Kunihiro Sakuma, Kento Hamada, Akihiko Yamaguchi and Wataru Aoi
Cells 2023, 12(19), 2422; https://doi.org/10.3390/cells12192422 - 9 Oct 2023
Cited by 17 | Viewed by 5985
Abstract
Sarcopenia is characterized by a gradual slowing of movement due to loss of muscle mass and quality, decreased power and strength, increased risk of injury from falls, and often weakness. This review will focus on recent research trends in nutritional and pharmacological approaches [...] Read more.
Sarcopenia is characterized by a gradual slowing of movement due to loss of muscle mass and quality, decreased power and strength, increased risk of injury from falls, and often weakness. This review will focus on recent research trends in nutritional and pharmacological approaches to controlling sarcopenia. Because nutritional studies in humans are fairly limited, this paper includes many results from nutritional studies in mammals. The combination of resistance training with supplements containing amino acids is the gold standard for preventing sarcopenia. Amino acid (HMB) supplementation alone has no significant effect on muscle strength or muscle mass in sarcopenia, but the combination of HMB and exercise (whole body vibration stimulation) is likely to be effective. Tea catechins, soy isoflavones, and ursolic acid are interesting candidates for reducing sarcopenia, but both more detailed basic research on this treatment and clinical studies in humans are needed. Vitamin D supplementation has been shown not to improve sarcopenia in elderly individuals who are not vitamin D-deficient. Myostatin inhibitory drugs have been tried in many neuromuscular diseases, but increases in muscle mass and strength are less likely to be expected. Validation of myostatin inhibitory antibodies in patients with sarcopenia has been positive, but excessive expectations are not warranted. Full article
(This article belongs to the Special Issue Cellular Plasticity of the Neuromuscular System)
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