scholarly journals Predicting the Outcome of Voriconazole Individualized Medication Using Integrated Pharmacokinetic/Pharmacodynamic Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ping Yang ◽  
Wei Liu ◽  
Jiajia Zheng ◽  
Yuanyuan Zhang ◽  
Li Yang ◽  
...  

Therapeutic drug monitoring is considered to be an effective tool for the individualized use of voriconazole. However, drug concentration measurement alone doesn’t take into account the susceptibility of the infecting microorganisms to the drug. Linking pharmacodynamic data with the pharmacokinetic profile of individuals is expected to be an effective method to predict the probability of a certain therapeutic outcome. The objective of this study was to individualize voriconazole regimens by integrating individual pharmacokinetic parameters and pathogen susceptibility data through Monte Carlo simulations The individual pharmacokinetic parameters of 35 hospitalized patients who received voriconazole were calculated based on a validated population pharmacokinetic model. The area under the concentration-time curve for free drug/minimal inhibitory concentration (fAUCss/MIC) > 25 was selected as the pharmacokinetic/pharmacodynamic (PK/PD) parameter predicting the efficacy of voriconazole. The cumulative fraction of response (CFR) of the target value was assessed. To verify this conclusion, a logistic regression analysis was used to explore the relationship between actual clinical efficiency and the CFR value. For the 35 patients, the area under the free drug concentration-time curve (fAUCss) was calculated to be 34.90 ± 21.67 mgh/L. According to the dualistic logistic regression analysis, the minimal inhibitory concentration (MIC) value of different kinds of fungi had a great influence on the effectiveness of clinical treatment. It also showed that the actual clinical efficacy and the CFR value of fAUCss/MIC had a high degree of consistency. The results suggest that it is feasible to individualize voriconazole dosing and predict clinical outcomes through the integration of data on pharmacokinetics and antifungal susceptibility.

2012 ◽  
Vol 116 (5) ◽  
pp. 1124-1133 ◽  
Author(s):  
Bruce Hullett ◽  
Sam Salman ◽  
Sean J. O'Halloran ◽  
Deborah Peirce ◽  
Kylie Davies ◽  
...  

Background Parecoxib is a cyclooxygenase-2 selective inhibitor used in management of postoperative pain in adults. This study aimed to provide pediatric pharmacokinetic information for parecoxib and its active metabolite valdecoxib. Methods Thirty-eight children undergoing surgery received parecoxib (1 mg/kg IV to a maximum of 40 mg) at induction of anesthesia, and plasma samples were collected for drug measurement. Population pharmacokinetic parameters were estimated using nonlinear mixed effects modeling. Area under the valdecoxib concentration-time curve and time above cyclooxygenase-2 in vitro 50% inhibitory concentration for free valdecoxib were simulated. Results A three-compartment model best represented parecoxib disposition, whereas one compartment was adequate for valdecoxib. Age was linearly correlated with parecoxib clearance (5.0% increase/yr). There was a sigmoid relationship between age and both valdecoxib clearance and distribution volume. Time to 50% maturation was 87 weeks postmenstrual age for both. In simulations using allometric-based doses the 90% prediction interval of valdecoxib concentration-time curve in children 2-12.7 yr included the mean for adults given 40 mg parecoxib IV. Simulated free valdecoxib plasma concentration remained above the in vitro 50% inhibitory concentrations for more than 12 h. In children younger than 2 yr, a dose reduction is likely required due to ongoing metabolic maturation. Conclusions The final pharmacokinetic model gave a robust representation of parecoxib and valdecoxib disposition. Area under the valdecoxib concentration-time curve was similar to that in adults (40 mg), and simulated free valdecoxib concentration was above the cyclooxygenase-2 in vitro 50% inhibitory concentration for free valdecoxib for at least 12 h.


2019 ◽  
Vol 2 (1) ◽  
pp. 27-33
Author(s):  
Megawati Sinambela ◽  
Evi Erianty Hasibuan

Antenatal care is a service provided to pregnant women to monitor, support maternal health and detect mothers whether normal or problematic pregnant women. According to the WHO, globally more than 70% of maternal deaths are caused by complications of pregnancy and childbirth such as hemorrhage, hypertension, sepsis, and abortion. Based on data obtained from the profile of the North Sumatra provincial health office in 2017, in the city of Padangsidimpuan in 2017 the coverage of ANC visits reached (76.58%) and had not reached the target in accordance with the 2017 Provincial Health Office strategy plan (95%). This type of research was an observational analytic study with a cross sectional design. The population in this study were independent practice midwives who were in the Padangsidimpuan, the sample in this study amounted to 102 respondents. The technique of collecting data used questionnaires and data analysis used univariate, bivariate and multivariate analysis with logistic regression analysis. Based on bivariate analysis showed that there was a relationship between facilities, knowledge and attitudes of independent midwives with compliance with the standards of antenatal care services with a value of p <0.05. The results of the study with multivariate logistic regression analysis showed that the factors associated with the compliance of independent midwives in carrying out antenatal care service standards were attitudes with values (p = 0.026).


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Atsushi Kotera

Abstract Background Postanesthetic shivering is an unpleasant adverse event in surgical patients. A nonsteroidal anti-inflammatory drug has been reported to be useful in preventing postanesthetic shivering in several previous studies. The aim of this study was to evaluate the efficacy of flurbiprofen axetil being a prodrug of a nonsteroidal anti-inflammatory drug for preventing postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries. Method This study is a retrospective observational study. I collected data from patients undergoing gynecologic laparotomy surgeries performed between October 1, 2019, and September 30, 2020, at Kumamoto City Hospital. All the patients were managed with general anesthesia with or without epidural analgesia. The administration of intravenous 50 mg flurbiprofen axetil for postoperative pain control at the end of the surgery was left to the individual anesthesiologist. The patients were divided into two groups: those who had received intravenous flurbiprofen axetil (flurbiprofen group) and those who had not received intravenous flurbiprofen axetil (non-flurbiprofen group), and I compared the frequency of postanesthetic shivering between the two groups. Additionally, the factors presumably associated with postanesthetic shivering were collected from the medical charts. Intergroup differences were assessed with the χ2 test with Yates’ correlation for continuity category variables. The Student’s t test was used to test for differences in continuous variables. Furthermore, a multivariate logistic regression analysis was performed to elucidate the relationship between the administration of flurbiprofen axetil and the incidence of PAS. Results I retrospectively examined the cases of 141 patients aged 49 ± 13 (range 21-84) years old. The overall postanesthetic shivering rate was 21.3% (30 of the 141 patients). The frequency of postanesthetic shivering in the flurbiprofen group (n = 31) was 6.5%, which was significantly lower than that in the non-flurbiprofen group (n = 110), 25.5% (p value = 0.022). A multivariate logistic regression analysis showed that administration of flurbiprofen axetil was independently associated with a reduced incidence of postanesthetic shivering (odds ratio 0.12; 95% confidence interval, 0.02-0.66, p value = 0.015). Conclusions My result suggests that intraoperative 50 mg flurbiprofen axetil administration for postoperative pain control is useful to prevent postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries.


2021 ◽  
Vol 12 ◽  
pp. 215145932199616
Author(s):  
Robert Erlichman ◽  
Nicholas Kolodychuk ◽  
Joseph N. Gabra ◽  
Harshitha Dudipala ◽  
Brook Maxhimer ◽  
...  

Introduction: Hip fractures are a significant economic burden to our healthcare system. As there have been efforts made to create an alternative payment model for hip fracture care, it will be imperative to risk-stratify reimbursement for these medically comorbid patients. We hypothesized that patients readmitted to the hospital within 90 days would be more likely to have a recent previous hospital admission, prior to their injury. Patients with a recent prior admission could therefore be considered higher risk for readmission and increased cost. Methods: A retrospective chart review identified 598 patients who underwent surgical fixation of a hip or femur fracture. Data on readmissions within 90 days of surgical procedure and previous admissions in the year prior to injury resulting in surgical procedure were collected. Logistic regression analysis was used to determine if recent prior admission had increased risk of 90-day readmission. A subgroup analysis of geriatric hip fractures and of readmitted patients were also performed. Results: Having a prior admission within one year was significantly associated (p < 0.0001) for 90-day readmission. Specifically, logistic regression analysis revealed that a prior admission was significantly associated with 90-day readmission with an odds ratio of 7.2 (95% CI: 4.8-10.9). Discussion: This patient population has a high rate of prior hospital admissions, and these prior admissions were predictive of 90-day readmission. Alternative payment models that include penalties for readmissions or fail to apply robust risk stratification may unjustly penalize hospital systems which care for more medically complex patients. Conclusions: Hip fracture patients with a recent prior admission to the hospital are at an increased risk for 90-day readmission. This information should be considered as alternative payment models are developed for hip fracture care.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rongxin Wang ◽  
Jing Wang ◽  
Shuiqing Hu

Abstract Background The etiology of reflux esophagitis (RE) is multi-factorial. This study analyzed the relationship of depression, anxiety, lifestyle and eating habits with RE and its severity and further explored the impact of anxiety and depression on patients’ symptoms and quality of life. Methods From September 2016 to February 2018, a total of 689 subjects at Xuanwu Hospital Capital Medical University participated in this survey. They were divided into the RE group (patients diagnosed with RE on gastroscopy, n = 361) and the control group (healthy individuals without heartburn, regurgitation and other gastrointestinal symptoms, n = 328). The survey included general demographic information, lifestyle habits, eating habits, comorbidities, current medications, the gastroesophageal reflux disease (GERD) questionnaire (GerdQ), the Patient Health Questionnaire-9 depression scale and the General Anxiety Disorder-7 anxiety scale. Results The mean age and sex ratio of the two groups were similar. Multivariate logistic regression analysis identified the following factors as related to the onset of RE (p < 0.05): low education level; drinking strong tea; preferences for sweets, noodles and acidic foods; sleeping on a low pillow; overeating; a short interval between dinner and sleep; anxiety; depression; constipation; history of hypertension; and use of oral calcium channel blockers. Ordinal logistic regression analysis revealed a positive correlation between sleeping on a low pillow and RE severity (p = 0.025). Depression had a positive correlation with the severity of symptoms (rs = 0.375, p < 0.001) and patients’ quality of life (rs = 0.306, p < 0.001), whereas anxiety showed no such association. Conclusions Many lifestyle factors and eating habits were correlated with the onset of RE. Notably, sleeping on a low pillow was positively correlated with RE severity, and depression was positively related to the severity of symptoms and patients’ quality of life.


Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 105
Author(s):  
Kun Mi ◽  
Da Sun ◽  
Mei Li ◽  
Haihong Hao ◽  
Kaixiang Zhou ◽  
...  

Haemophilus parasuis can cause high morbidity and mortality in swine. Cefquinome possesses excellent antibacterial activity against pathogens causing diseases of the respiratory tract. This study aimed to establish the clinical breakpoint (CBP) of cefquinome against H. parasuis and to monitor the resistance change. Referring to the minimum inhibitory concentration (MIC) distribution of cefquinome against 131 H. parasuis isolates, the MIC50 and MIC90 were determined to be 0.125 and 1 μg/mL, respectively. And the epidemiological cutoff (ECOFF) value was 1 μg/mL. HPS42 was selected as a representative strain for the pharmacodynamic (PD) experiment, pharmacokinetic (PK) experiment and clinical experiments. The PK/PD index values, area under concentration-time curve (AUC)/MIC, of the bacteriostatic, bactericidal, and bacterial elimination effects were 23, 41, and 51 h, respectively. The PK/PD cutoff was calculated as 0.125 μg/mL by Monte Carlo simulation (MCS), and the clinical cutoff was 0.25−4 μg/mL by WindoW. Combing these three values, the CBP of cefquinome against H. parasuis was found to be 1 μg/mL. In conclusion, this was the first study to integrate various cutoffs to establish the CBP in the laboratory. It is helpful to distinguish wild type H. parasuis and reduce the probability of treatment failure.


2021 ◽  
Vol 10 (5) ◽  
pp. 933
Author(s):  
Byung Woo Cho ◽  
Du Seong Kim ◽  
Hyuck Min Kwon ◽  
Ick Hwan Yang ◽  
Woo-Suk Lee ◽  
...  

Few studies have reported the relationship between knee pain and hypercholesterolemia in the elderly population with osteoarthritis (OA), independent of other variables. The aim of this study was to reveal the association between knee pain and metabolic diseases including hypercholesterolemia using a large-scale cohort. A cross-sectional study was conducted using data from the Korea National Health and the Nutrition Examination Survey (KNHANES-V, VI-1; 2010–2013). Among the subjects aged ≥60 years, 7438 subjects (weighted number estimate = 35,524,307) who replied knee pain item and performed the simple radiographs of knee were enrolled. Using multivariable ordinal logistic regression analysis, variables affecting knee pain were identified, and the odds ratio (OR) was calculated. Of the 35,524,307 subjects, 10,630,836 (29.9%) subjects experienced knee pain. Overall, 20,290,421 subjects (56.3%) had radiographic OA, and 8,119,372 (40.0%) of them complained of knee pain. Multivariable ordinal logistic regression analysis showed that among the metabolic diseases, only hypercholesterolemia was positively correlated with knee pain in the OA group (OR 1.24; 95% Confidence Interval 1.02–1.52, p = 0.033). There were no metabolic diseases correlated with knee pain in the non-OA group. This large-scale study revealed that in the elderly, hypercholesterolemia was positively associated with knee pain independent of body mass index and other metabolic diseases in the OA group, but not in the non-OA group. These results will help in understanding the nature of arthritic pain, and may support the need for exploring the longitudinal associations.


2021 ◽  
Vol 40 (S1) ◽  
Author(s):  
Siew Man Cheong ◽  
Rashidah Ambak ◽  
Fatimah Othman ◽  
Feng J. He ◽  
Ruhaya Salleh ◽  
...  

Abstract Background Excessive intake of sodium is a major public health concern. Information on knowledge, perception, and practice (KPP) related to sodium intake in Malaysia is important for the development of an effective salt reduction strategy. This study aimed to investigate the KPP related to sodium intake among Malaysian adults and to determine associations between KPP and dietary sodium intake. Methods Data were obtained from Malaysian Community Salt Survey (MyCoSS) which is a nationally representative survey with proportionate stratified cluster sampling design. A pre-tested face-to-face questionnaire was used to collect information on socio-demographic background, and questions from the World Health Organization/Pan American Health Organization were adapted to assess the KPP related to sodium intake. Dietary sodium intake was determined using single 24-h urinary sodium excretion. Respondents were categorized into two categories: normal dietary sodium intake (< 2000 mg) and excessive dietary sodium intake (≥ 2000 mg). Out of 1440 respondents that were selected to participate, 1047 respondents completed the questionnaire and 798 of them provided valid urine samples. Factors associated with excessive dietary sodium intake were analyzed using complex sample logistic regression analysis. Results Majority of the respondents knew that excessive sodium intake could cause health problems (86.2%) and more than half of them (61.8%) perceived that they consume just the right amount of sodium. Overall, complex sample logistic regression analysis revealed that excessive dietary sodium intake was not significantly associated with KPP related to sodium intake among respondents (P > 0.05). Conclusion The absence of significant associations between KPP and excessive dietary sodium intake suggests that salt reduction strategies should focus on sodium reduction education includes measuring actual dietary sodium intake and educating the public about the source of sodium. In addition, the relationship between the authority and food industry in food reformulation needs to be strengthened for effective dietary sodium reduction in Malaysia.


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