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La Revue de Medecine Interne Mar 2018While we are confronted with the major increase in antibiotic resistance, the preservation of existing antibiotics has become an absolute necessity both to achieve... (Review)
Review
While we are confronted with the major increase in antibiotic resistance, the preservation of existing antibiotics has become an absolute necessity both to achieve therapeutic success and to limit the risks of the emergence of resistance. The optimization of antibiotic use and dosages must have a threefold objective: guarantee antibacterial efficacy, limit toxicities and limit emergence of resistant strains. However, with the increase in the number of multipathological patients, particularly those with renal or hepatic impairment, the increase in the number of patients with extreme weights and the use of antibiotics with narrower therapeutic margins, the adaptation of antibiotic dosages is becoming increasingly important. By reminding some principles of pharmacokinetics and pharmacodynamics of antibiotics (PK/PD), the necessary objectives for clinical effectiveness of most antibiotic classes are reviewed and several examples of situations where dosage adjustments are necessary will be given. In particular, adjustment of antibiotic dosages in obese patients will be discussed. Adaptation is not limited to the adaptation of the total daily dose. The PK/PD parameters also tell us that the mode of administration (intermittent versus continuous, number of injections per day, etc.) is also an essential point to consider. By taking examples concerning some molecules, infections and difficult clinical situations, we review situations in which dosage adjustments appear necessary.
Topics: Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Resistance, Microbial; Humans; Precision Medicine
PubMed: 28693837
DOI: 10.1016/j.revmed.2017.06.009 -
Heliyon Apr 2022In this study, we investigated a mathematical model for chemoimmunotherapy (a combination of chemotherapy and immunotherapy) for brain cancer. In most cases, the...
In this study, we investigated a mathematical model for chemoimmunotherapy (a combination of chemotherapy and immunotherapy) for brain cancer. In most cases, the standard protocol for cancer treatment is fixed in terms of treatment time intervals and dosages. We offer a wide range of non-fixed protocols, which essentially vary in terms of time intervals and dosages (i.e., personalised medicine). The functions that describe this treatment are explicit and analytical. Hence, the parameters of the function can be easily changed and a new protocol can be obtained. We compared different protocols and obtained an optimal solution. In addition, we applied the singular perturbed vector field (SPVF) method to determine the hierarchy of the system of equations, which enabled us to identify the equilibrium points of the mathematical model and investigate their stability.
PubMed: 35520602
DOI: 10.1016/j.heliyon.2022.e09288 -
Journal of Food Biochemistry May 2021The thymus regulates a specific microenvironment for the growth and maturation of naive T cells. Involution of immune function was an important factor during body aging....
The thymus regulates a specific microenvironment for the growth and maturation of naive T cells. Involution of immune function was an important factor during body aging. Preventing the senescence of immune organs has become a major medical issue. Resveratrol (RSV) has been proved to delay the aging of many organs including the thymus. However, the underlying mechanism remains indefinite and the dosages of RSV on thymus involution need to be further clarified. In the current study, the senescence-accelerated mice were produced using d-galactose for two months. RSV at different dosages (25, 50, 100 mg kg day ) was then administered. The alteration of the thymic morphological structure was observed. It showed that three dosages of RSV significantly decreased cellular senescence of the thymus and no dosage difference was detected. For cellular proliferation and apoptosis of the thymus, 50 and 25 mg/kg per day of RSV displayed the best effects on cellular proliferation and apoptosis in the thymus, respectively. Furthermore, 50 mg/kg per day of RSV increased the expression of FoxN1 both at transcription and translation levels. These findings indicated that RSV could delay thymus atrophy in a dosage-dependent pattern and FoxN1 might involve in the beneficial mechanism of RSV, which was of great significance for the enhancement of thymic health and organic immunity. PRACTICAL APPLICATIONS: Resveratrol has been proved to delay aging of many organs including of thymus. In the present study, we explored the dosage of resveratrol on thymus involution and the expression of transcription factors forkhead box protein N1 (FoxN1) in the senescenceaccelerated mice induced by D-galactose. The results indicated that resveratrol could delay thymus atrophy in a dosage-dependent pattern within a certain dose range, and higher RSV concentration may have drug toxicity, which suggests that the dosage of RSV requires attention, And FoxN1 might involve in the beneficial mechanism of resveratrol supplement, which was of great significance to explore the mechanism for the enhancement of thymus immunity.
Topics: Animals; Cellular Senescence; Forkhead Transcription Factors; Galactose; Mice; Resveratrol; T-Lymphocytes
PubMed: 33778958
DOI: 10.1111/jfbc.13709 -
Zeitschrift Fur Rheumatologie Feb 2024Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs.... (Review)
Review
Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective product information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.
Topics: Humans; Consensus; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Drug Interactions; Biological Products
PubMed: 37831190
DOI: 10.1007/s00393-023-01417-3 -
CMAJ Open 2022There is little evidence describing the technical aspects of medical assistance in dying (MAiD) in Canada, such as medications, dosages and complications. Our objective...
BACKGROUND
There is little evidence describing the technical aspects of medical assistance in dying (MAiD) in Canada, such as medications, dosages and complications. Our objective was to describe clinical practice in providing MAiD in Ontario and Vancouver, Canada, and explore relations between medications used, time until death and complications.
METHODS
We conducted a retrospective cohort study of a sample of adult (age ≥ 18 yr) patients who received MAiD in Ontario between 2016 and 2018, and patients who received MAiD in 1 of 3 Canadian academic hospitals (in Hamilton and Ottawa, Ontario, and Vancouver, British Colombia) between 2019 and 2020. We used de-identified data for 2016-2018 from the Office of the Chief Coroner for Ontario MAiD Database and chart review data for 2019-2020 from the 3 centres. We used multivariable parametric survival analysis to identify relations between medications, dosages and time from procedure start until death.
RESULTS
The sample included 3557 patients (1786 men [50.2%] and 1770 women [49.8%] with a mean age of 74 [standard deviation 13] yr). The majority of patients (2519 [70.8%]) had a diagnosis of cancer. The medications most often used were propofol (3504 cases [98.5%]), midazolam (3251 [91.4%]) and rocuronium (3228 [90.8%]). The median time from the first injection until death was 9 (interquartile range 6) minutes. Standard-dose lidocaine (40-60 mg) and high-dose propofol (> 1000 mg) were associated with prolonged time until death (prolonged by a median of 1 min and 3 min, respectively). Complications occurred in 41 cases (1.2%), mostly related to venous access or need for administration of a second medication.
INTERPRETATION
In a large sample of patients who died with medical assistance, certain medications were associated with small differences in time from injection to death, and complications were rare. More research is needed to identify the medication protocols that predict outcomes consistent with patient and family expectations for a medically assisted death.
Topics: Aged; Anesthetics, Intravenous; Canada; Cross-Sectional Studies; Drug Dosage Calculations; Drug Utilization; Female; Humans; Male; Neoplasms; Palliative Care; Patient Care Management; Suicide, Assisted; Time-to-Treatment
PubMed: 35042691
DOI: 10.9778/cmajo.20200268 -
Dysphagia Apr 2023This study investigated how swallowing exercise dosage is recorded, and what swallowing exercise dosages are reported in a stroke rehabilitation setting. We additionally...
This study investigated how swallowing exercise dosage is recorded, and what swallowing exercise dosages are reported in a stroke rehabilitation setting. We additionally explored the relation between mean daily swallowing repetitions and likelihood of improvement in functional swallowing status and considered how swallowing exercise dosages in practice compared to evidence-based principles of neural plasticity and strength training. We audited medical records for 42 patients with post-stroke dysphagia admitted to an inpatient rehabilitation unit over 18 months. Data were collected on participant characteristics, swallowing exercises and dosages, and clinical outcomes. The relation between dosage and outcomes was investigated using logistic regression analysis. On average, patients were seen for a median of 2.4 swallowing intervention sessions per week (IQR: 1.7) over 21 days (IQR: 16) and received a median 44.5 swallowing exercise repetitions per session (IQR: 39.6). Results indicated variable reporting of swallowing exercise dosages. Frequency, intervention duration, exercise type, and number of repetitions were routinely recorded in medical records, while intensity, session length, content, and adherence to home exercise programs were not. Frequency of swallowing intervention was lower in practice compared to research studies, and swallowing exercises did not follow specificity or progressive resistance principles. Likelihood of improvement in swallowing status was partially explained by age (B = -.015, p = .007) but not by mean daily swallowing exercise repetitions. This study illustrates dosages of swallowing exercises used in clinical practice. Results highlight the need for improved consideration and reporting of dosage, and application of evidence-based principles to swallowing exercise dosages.
Topics: Humans; Stroke Rehabilitation; Deglutition Disorders; Deglutition; Stroke; Exercise Therapy
PubMed: 35951119
DOI: 10.1007/s00455-022-10500-x -
Journal of Pharmacokinetics and... Dec 2021Optimization of antibiotic administration helps minimizing cases of bacterial resistance. Dosages are often selected by trial and error using a pharmacokinetic (PK)...
Optimization of antibiotic administration helps minimizing cases of bacterial resistance. Dosages are often selected by trial and error using a pharmacokinetic (PK) model. However, this is limited to the range of tested dosages, restraining possible treatment choices, especially for the loading doses. Colistin is a last-resort antibiotic with a narrow therapeutic window; therefore, its administration should avoid subtherapeutic or toxic concentrations. This study formulates an optimal control problem for dosage selection of colistin based on a PK model, minimizing deviations of colistin concentration to a target value and allowing a specific dosage optimization for a given individual. An adjoint model was used to provide the sensitivity of concentration deviations to dose changes. A three-compartment PK model was adopted. The standard deviation between colistin plasma concentrations and a target set at 2 mg/L was minimized for some chosen treatments and sample patients. Significantly lower deviations from the target concentration are obtained for shorter administration intervals (e.g. every 8 h) compared to longer ones (e.g. every 24 h). For patients with normal or altered renal function, the optimal loading dose regimen should be divided into two or more administrations to attain the target concentration quickly, with a high first loading dose followed by much lower ones. This regimen is not easily obtained by trial and error, highlighting advantages of the method. The present method is a refined optimization of antibiotic dosage for the treatment of infections. Results for colistin suggest significant improvement in treatment avoiding subtherapeutic or toxic concentrations.
Topics: Anti-Bacterial Agents; Colistin; Humans
PubMed: 34156631
DOI: 10.1007/s10928-021-09769-6 -
Drugs Mar 2017Dabigatran etexilate (Pradaxa) is approved in the EU for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) and one... (Review)
Review
Dabigatran etexilate (Pradaxa) is approved in the EU for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) and one or more risk factors. Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. In patients with NVAF in the phase III RE-LY trial, dabigatran etexilate dosages of 110 and 150 mg twice daily were noninferior to warfarin with regard to the risk of stroke or systemic embolism (primary efficacy endpoint). The higher dosage was associated with a significantly lower risk of stroke or systemic embolism than warfarin, with no significant between-group difference in the risk of major bleeding (primary safety endpoint). Both dosages of dabigatran etexilate were associated with significantly lower rates of haemorrhagic stroke, intracranial bleeding and life-threatening major bleeding than warfarin. Dabigatran etexilate was also effective and generally well tolerated across various patient subgroups. The efficacy and tolerability of dabigatran etexilate was maintained for up to 6.7 years in the RELY-ABLE extension study. Routine anticoagulation monitoring is not required in patients receiving dabigatran etexilate, and it is currently the only non-vitamin K antagonist oral anticoagulant (NOAC) with a specific reversal agent available. Although direct comparisons with other NOACs would be beneficial, dabigatran etexilate is a useful option for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
Topics: Antithrombins; Atrial Fibrillation; Dabigatran; Humans
PubMed: 28185082
DOI: 10.1007/s40265-017-0699-z -
Nature Reviews. Endocrinology Aug 2017Vitamin D is essential for calcium and bone homeostasis. Humans are largely dependent on UVB-radiation-induced photosynthesis of vitamin D, as few foods contain vitamin... (Comparative Study)
Comparative Study Review
Vitamin D is essential for calcium and bone homeostasis. Humans are largely dependent on UVB-radiation-induced photosynthesis of vitamin D, as few foods contain vitamin D. However, the same radiation that produces vitamin D is also carcinogenic, albeit with a long lag time, and causes DNA damage. In view of the increasing life expectancy, avoiding excessive sun exposure is prudent. Several groups of people have a shortfall between their requirements for vitamin D and their combined endogenous synthesis and intake from natural foods, and therefore need vitamin D supplementation. Governments and scientific societies are regularly updating their recommendations for intake of vitamin D, especially for groups that should (infants) or prefer to (especially elderly individuals) avoid direct sunlight. An overview of such guidelines is presented in this Review. A fairly large consensus exists that all infants should receive 400 international units (IU) (10 μg) daily during their first year of life and that elderly individuals should have access to vitamin D supplementation (at recommended dosages varying from 400 IU to 800 IU daily in most governmental guidelines but at higher dosages in other guidelines). All guidelines unanimously agree that serum levels of 25-hydroxyvitamin D (25OHD) <25 nmol/l (10 ng/ml) should be avoided at all ages. Children and adults who have limited sun exposure should receive vitamin D supplementation, but the recommended doses vary widely (from 200 IU to 2,000 IU daily), in line with disagreement regarding the minimal desirable serum concentration of 25OHD (which varies from 25 nmol/l to >100 nmol/l).
Topics: Calcium, Dietary; Dietary Supplements; Humans; Nutrition Policy; Sunlight; Vitamin D; Vitamin D Deficiency
PubMed: 28387318
DOI: 10.1038/nrendo.2017.31 -
Nurse Education in Practice Sep 2016A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is... (Review)
Review
A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety.
Topics: Anxiety; Clinical Competence; Drug Dosage Calculations; Education, Nursing, Baccalaureate; Humans; Mathematics; Medication Errors; Nursing Education Research; Patient Safety; Students, Nursing
PubMed: 27589091
DOI: 10.1016/j.nepr.2016.08.005