-
The Journal of Antimicrobial... Nov 2023The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For...
BACKGROUND
The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.
OBJECTIVES
To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).
METHODS
Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.
RESULTS
Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.
CONCLUSIONS
These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.
Topics: Humans; Cefepime; Aztreonam; Anti-Bacterial Agents; Ceftazidime; Piperacillin; Microbial Sensitivity Tests; Monte Carlo Method
PubMed: 37796958
DOI: 10.1093/jac/dkad300 -
European Archives of... Mar 2023To investigate the dosages of swallowing exercises reported in intervention studies on post-stroke dysphagia through systematic review. (Review)
Review
PURPOSE
To investigate the dosages of swallowing exercises reported in intervention studies on post-stroke dysphagia through systematic review.
METHODS
Five electronic databases were searched from inception until February 2022 with reference tracing of included studies. Studies were included, where adults with post-stroke dysphagia received rehabilitative, behavioural swallowing exercises, pre/post outcomes were reported, and intervention dosage was described in detail, including frequency, intensity, time, and type of exercise. Two reviewers independently screened studies and rated quality using ASHA Levels of Evidence tool. Data was tabulated and narratively described.
RESULTS
54 studies were included with a total 1501 participants. Studies included 28 randomised controlled trials, 8 non-randomised controlled trials, 12 pre/post studies, 3 retrospective case controls and 3 case studies. Results showed inconsistent reporting of intervention dosage, with intensity the least consistently reported dosage component. While swallowing intervention was most commonly provided five times per week for four weeks, there was a wide breadth of type, frequency, intensity and duration of swallowing exercises reported. Dosage under-reporting and variation was particularly observed in "standard care" co-interventions or control groups. Study strengths included following PRISMA guidelines, providing a comprehensive review of swallowing exercise methodology and dosages, and including non-English studies. The limitation was lack of meta-analysis due to the heterogeneity of included studies.
CONCLUSIONS
Dosages of swallowing exercises are inconsistently reported and vary significantly in post-stroke dysphagia studies. Results indicate the need for consistent and comprehensive dosage reporting in dysphagia studies, and for further research into evidence-based principles to optimise swallowing exercise dosages.
SYSTEMATIC REVIEW REGISTRATION NUMBER
131294.
Topics: Adult; Humans; Deglutition Disorders; Deglutition; Stroke Rehabilitation; Retrospective Studies; Stroke
PubMed: 36471047
DOI: 10.1007/s00405-022-07735-7 -
Pediatric Nephrology (Berlin, Germany) Sep 2021The use of diuretics is extremely frequent in sick neonates, the more so in very premature newborn infants. The use of diuretics in patients whose kidney function is... (Review)
Review
The use of diuretics is extremely frequent in sick neonates, the more so in very premature newborn infants. The use of diuretics in patients whose kidney function is immature necessitates a thorough knowledge of renal developmental physiology and pathophysiology. This review presents the basic aspects of body fluid homeostasis in the neonate, discusses the development of kidney function, and describes the mechanisms involved in electrolyte and water reabsorption along the nephron. Diuretics are then classified according to the site of their action on sodium reabsorption. The use of diuretics in sodium-retaining states, in oliguric states, in electrolyte disorders, and in arterial hypertension, as well as in a few specific disorders, is presented. Common and specific adverse effects are discussed. Recommended dosages for the main diuretics used in the neonatal period are given. New developments in diuretic therapy are briefly mentioned.
Topics: Diuretics; Humans; Infant, Newborn; Infant, Premature
PubMed: 33481099
DOI: 10.1007/s00467-021-04921-3 -
Revue Medicale Suisse Jun 2021Sex-related differences affecting pharmacokinetic and pharmacodynamic processes result mostly from sex dimorphisms in body composition, and liver and kidney function, in...
Sex-related differences affecting pharmacokinetic and pharmacodynamic processes result mostly from sex dimorphisms in body composition, and liver and kidney function, in addition to hormonal regulation of enzymes, transporters and drug receptors. Gender biases have long compromised the identification of these differences in clinical trials. They also modulate prescription patterns and therapeutic benefits. Men and women would benefit from different standard dosages of some anti-infectives, anticancer agents and other treatments requiring precise dosage adjustment. This would alleviate the well-documented excess of adverse reactions affecting women. However, the variability of pharmacological responses within each sex exceeds the average male-female difference, highlighting the importance of other criteria for therapeutic individualisation.
Topics: Antineoplastic Agents; Female; Humans; Liver; Male; Sex Characteristics; Sex Factors
PubMed: 34219420
DOI: No ID Found -
Drug and Alcohol Dependence Nov 2023Buprenorphine reduces risk of opioid overdose mortality. However, its benefits are limited by low retention, particularly in early treatment. Optimizing initial dosage...
BACKGROUND
Buprenorphine reduces risk of opioid overdose mortality. However, its benefits are limited by low retention, particularly in early treatment. Optimizing initial dosage may impact retention. However, little is known about the prescription characteristics of new buprenorphine treatment episodes.
METHODS
In a US sample of commercial and employer-sponsored pharmacy claims, we identified new buprenorphine treatment episodes (days 1-30) from individuals ≥16 years following 90 days without buprenorphine from 2010 to 2019. Outcomes included first prescription average days supplied, first prescription average daily dosage, and average dosage on days 2, 8, 15 and 30.
RESULTS
We identified 117,793 new episodes among 96,451 unique individuals. Episodes per 10,000 person-years decreased slightly over time. Stratifying by age, sex and region demonstrated decreasing episodes among individuals ≤34 years and increasing episodes among individuals ≥35 years. From 2010-2019, first prescription average days supplied and daily dosage decreased from 17.1 to 15.3 days and 13.6mg to 11.6mg, respectively. Simultaneously, the proportion of episodes without possession and with dosages <16mg increased across all days and years. By day 30, episodes without buprenorphine possession grew from 27.9% to 30.8% and episodes involving dosages of <16mg grew from 26.4% to 33.4%.
CONCLUSIONS
We found that buprenorphine dosage and days supplied for new treatment episodes decreased from 2010 to 2019 while buprenorphine possession worsened. Further investigation examining the relationship between buprenorphine dosage and retention in the early treatment period is needed.
Topics: Humans; Adult; Buprenorphine; Opioid-Related Disorders; Opiate Substitution Treatment; Opiate Overdose; Analgesics, Opioid; Retrospective Studies
PubMed: 37839942
DOI: 10.1016/j.drugalcdep.2023.110981 -
Journal of Cancer 2023Although sorafenib is adopted as the first-line treatment for unresectable liver cancer, the antitumor efficacy is severely limited by the pro-invasive side effect. To...
Although sorafenib is adopted as the first-line treatment for unresectable liver cancer, the antitumor efficacy is severely limited by the pro-invasive side effect. To explore the underlying mechanisms, various-dosage sorafenib was applied to survey its effect on cell invasion in HCCLM3 and PLC cell models. Our results revealed that high-dosage sorafenib inhibited liver cancer cell invasion. By contrast, sorafenib with low and median dosages promoted the invasion. studies showed that sorafenib with a median dosage increased the intrahepatic metastasis (IHM) and lung metastasis (LM) of liver cancer cells, while sorafenib with a high dosage inhibited IHM and LM. Then, bioinformatics analysis indicated that HIF-1α, IL-6, and PFKFB3 were associated with the sorafenib resistance. models showed that the pro-invasive effect was mediated by IL-6/HIF-1α/PFKFB3 regulation in dosage- and time-dependent manners. PFKFB3 knockdown confirmed that PFKFB3 promoted HCCLM3 cell migration via modulating EMT-related markers. Furthermore, we found that sorafenib upregulated PFKFB3 by IL-6/HIF-1α in a time-dependent manner, without direct effect on PFKFB3 expression. In summary, these results demonstrated that sorafenib could dose-dependently promote cell invasion, intrahepatic and lung metastasis in hepatocellular carcinoma through IL-6/HIF-1α mediated PFKFB3 activation, providing novel insights to improve the therapeutic efficacy of sorafenib.
PubMed: 37476196
DOI: 10.7150/jca.84451 -
The Urologic Clinics of North America Nov 2022Androgenic steroids have been abused by elite athletes for decades. Their performance-enhancing properties for sports that involve strength and power have been... (Review)
Review
Androgenic steroids have been abused by elite athletes for decades. Their performance-enhancing properties for sports that involve strength and power have been confirmed, and this class has been banned from most elite athletic competitions since the mid-1970s. There is a risk of a withdrawal syndrome that includes severe depression, and there seems to be an increased risk of cardiovascular disease associated with chronic abuse. In contrast to high-dosage androgen abuse, androgen therapy at near-physiological dosages is generally safe and effective for male hypogonadism and potential use in sarcopenia and male hormonal contraception.
Topics: Male; Humans; Anabolic Agents; Androgens; Doping in Sports; Athletes; Steroids
PubMed: 36309421
DOI: 10.1016/j.ucl.2022.07.008 -
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 -
Frontiers in Molecular Neuroscience 2022Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism...
Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), intellectual disability, attention-deficit/hyperactivity disorder, and schizophrenia. -mutant mice show ASD-like behavioral deficits and altered synaptic and neuronal functions, but little is known about how different brain regions and gene dosages affect the transcriptomic phenotypes of these mice. Here, we performed RNA-Seq-based transcriptomic analyses of the prefrontal cortex, hippocampus, and striatum in adult heterozygous (HT)- and homozygous (HM)-mutant mice lacking exons 6-7. The prefrontal cortical, hippocampal, and striatal regions showed distinct transcriptomic patterns associated with synapse, ribosome, mitochondria, spliceosome, and extracellular matrix (ECM). The three brain regions were also distinct in the expression of ASD-related and ASD-risk genes. These differential patterns were stronger in the prefrontal cortex where the HT transcriptome displayed increased synaptic gene expression and reverse-ASD patterns whereas the HM transcriptome showed decreased synaptic gene expression and ASD-like patterns. These results suggest brain region- and gene dosage-differential transcriptomic changes in -mutant mice.
PubMed: 36311025
DOI: 10.3389/fnmol.2022.977305