Dosing time matters.
Ontology highlight
ABSTRACT:
SUBMITTER: Ruben MD
PROVIDER: S-EPMC8011856 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Dosing time matters.
Ruben Marc D MD Smith David F DF FitzGerald Garret A GA Hogenesch John B JB
Science (New York, N.Y.) 20190801 6453
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Project description:BackgroundInitiation of oncologic care is often delayed, yet little is known about delays in hepatopancreatobiliary (HPB) cancers or their impact. This retrospective cohort study describes trends in time to treatment initiation (TTI), assesses the association between TTI and survival, and identifies predictors of TTI in HPB cancers.MethodsThe National Cancer Database was queried for patients with cancers of the pancreas, liver, and bile ducts between 2004 and 2017. Kaplan-Meier survival analysis and Cox regression were used to investigate the association between TTI and overall survival for each cancer type and stage. Multivariable regression identified factors associated with longer TTI.ResultsOf 318,931 patients with HPB cancers, median TTI was 31 days. Longer TTI was associated with increased mortality in patients with stages I-III extrahepatic bile duct (EHBD) cancer and stages I-II pancreatic adenocarcinoma. Patients treated within 3-30, 31-60, and 61-90 days had median survivals of 51.5, 34.9, and 25.4 months (log-rank P<0.001), respectively, for stage I EHBD cancer, and 18.8, 16.6, and 15.2 months for stage I pancreatic cancer, respectively (P<0.001). Factors associated with increased TTI included stage I disease (+13.7 days vs. stage IV, P<0.001), treatment with radiation only (β=+13.9 days, P<0.001), Black race (+4.6 days, P<0.001) and Hispanic ethnicity (+4.3 days, P<0.001).ConclusionsSome HPB cancer patients with longer time to definitive care experienced higher mortality than patients treated expeditiously, particularly in non-metastatic EHBD cancer. Black and Hispanic patients are at risk for delayed treatment. Further research into these associations is needed.
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Project description:Fluconazole is frequently used for the treatment of invasive Candida infections in critically ill patients. However, alterations in renal functions might influence fluconazole clearance. Therefore, our objective was to study the impact of renal function on the population pharmacokinetics of fluconazole in critically ill patients with various degrees of renal function or undergoing continuous renal replacement therapy (CRRT). This was an open-label, multicenter observational study. Critically ill patients receiving fluconazole were included. Baseline and clinical data were collected. At days 3 and 7 of enrollment, blood samples were drawn for pharmacokinetic curves. Additionally, daily trough samples were taken. A nonlinear mixed-effects model was built, followed by Monte Carlo simulations for assessment of exposure to various dosages of fluconazole. Nineteen patients were included with a median age of 64.4 (range, 23 to 81) years and median weight of 82.0 (range, 44.0 to 119.5) kg. A linear two-compartment model best described fluconazole pharmacokinetics and demonstrated higher clearance than expected in critically ill patients. Simulations showed that daily dosages of 600 mg and 800 mg are needed for intensive care unit (ICU) patients with normal renal function and patients on CRRT, respectively, to achieve the EUCAST-recommended target fAUC (area under the concentration-time curve for the free, unbound fraction of the drug)/MIC ratio of 100. In conclusion, fluconazole clearance is highly variable in ICU patients and is strongly dependent on renal function and CRRT. Trough concentrations correlated well with the AUC, opening up opportunities for tailored dosing using therapeutic drug monitoring. We recommend doses of 400 mg for patients with poor to moderate renal function, 600 mg for patients with adequate renal function, and 800 mg for patients treated with CRRT. (This study has been registered at ClinicalTrials.gov under identifier NCT02666716.).
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Project description:In this study, we investigated whether working memory capacity (WMC), personality characteristics (grit) and number of matches played (time on task) can predict performance score (matchmaking rating [MMR]) in experienced players of a popular video game called Dota 2. A questionnaire and four online-based cognitive tasks were used to gather the data, and structural equation modelling (SEM) was used to investigate the interrelationships between constructs. The results showed that time on task was the strongest predictor of MMR, and grit also significantly influenced performance. However, WMC did not play a substantial role in predicting performance while playing Dota 2. These results are discussed in relation to sample characteristics and the role of deliberate practice and skill acquisition within the domain of playing Dota 2. Further, we suggest that future research investigates the social aspects of attaining skill, the relationship between personality and performance, and the qualitative aspects of time spent on a task.
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Project description: Not available
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Project description:BackgroundPreviously, consensus MS care standards were defined by MS specialist neurologists from 19 countries. We developed, piloted and refined an Excel-based quality improvement tool to enable MS services to benchmark against these standards. Here, we examine the refined tool.ObjectiveTo determine the applicability of the quality improvement tool in different healthcare settings.MethodsMS centres across the globe were invited to pilot the quality improvement tool by coding the medical records of 36 adults with MS. We invited feedback on user friendliness, quality improvement tool usefulness and relevance of data collected.ResultsSeventeen centres from 14 countries participated; 14 completed the post-service evaluation survey. Over 50% of responders rated the tool 'very easy' or 'easy' to use and 'very relevant' to their service. Almost 85% of responders (11/13) planned to introduce changes to their service, including improvements in documentation, communication, interactions with colleagues and referrals; 85% would use a future shorter version of the tool.ConclusionsThe quality improvement tool can enable MS centres globally to benchmark their services. Widespread uptake of a shorter tool may help MS centres to work towards achieving consensus standards for brain health-focused care. Incorporation into routine clinical practice would drive adoption.
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