scholarly journals Dose Banding -- weighing up benefits, therapeutic failure and risks

2021 ◽  
Author(s):  
Stephen Duffull
Keyword(s):  
Pharmacokinetic Model ◽  
Therapeutic Benefit ◽  
Average Concentration ◽  
Therapeutic Failure ◽  
Future Application ◽  
Target Attainment ◽  
Therapeutic Success ◽  
Dose Individualisation ◽  
Better Than ◽  
State Average

Aim Dose banding is a commonly used method of dose individualisation in which all patients with similar characteristics are allocated to the same dosing group. Dose banding results in some patients receiving less intensive treatment with the potential for a reduction in therapeutic benefit (iatrogenic therapeutic failure). This study aims to explore the effects of dose banding on therapeutic success and failure. Methods This was a simulation study conducted using MATLAB. Virtual patients were simulated under a simple pharmacokinetic model with a predefined target steady-state average concentration (c_(ss,ave)). Clearance was correlated with a covariate used for dosing. Dose individualisation was based on: one-dose-fits-all, covariate based dosing, empirical dose banding, dose banding optimised for benefit:risk only and dose banding optimised for both benefit:risk and minimising iatrogenic therapeutic failure. Results The lowest and highest probabilities of target attainment (PrTA) were 46% for one-dose-fits-all and 72% for fully individualised covariate-based dosing. Neither dosing approach would result in iatrogenic therapeutic failure as lower dose intensities do not occur. Empirical dose banding performed better than once-dose-fits-all with 59% PTA but not as good as either optimised method (64-69% PrTA) while carrying a risk of iatrogenic therapeutic failure in 25% of patients. Optimising for benefit:risk (only) improved PrTA but carried a risk of iatrogenic therapeutic failure of up to 10%. Optimising for benefit:risk and minimising iatrogenic therapeutic failure provided the best balance. Conclusion Future application of dose banding needs to consider both the probability of benefit:risk as well the risk of causing iatrogenic therapeutic failure.

scholarly journals Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia

2005 ◽  
Vol 49 (8) ◽  
pp. 3171-3177 ◽  
Author(s):  
Cornelius J. Clancy ◽  
Victor L. Yu ◽  
Arthur J. Morris ◽  
David R. Snydman ◽  
M. Hong Nguyen
Keyword(s):  
Therapeutic Response ◽  
Geometric Mean ◽  
Therapeutic Failure ◽  
Response To Therapy ◽  
Success Rates ◽  
Therapeutic Success ◽  
Data Set ◽  
In Vitro Susceptibility ◽  
Dose Dependent

ABSTRACT We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (≤200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 μg/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 μg/ml and 219.36 [P = 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC ≤ 8 μg/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 μg/ml), and resistant (MIC ≥ 64 μg/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio ≤50 (P = 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.

A History Matching Framework to Characterize Fracture Network and Reservoir Properties in Tight Oil

2019 ◽  
Vol 142 (4) ◽  
Author(s):  
Xu Shiqian ◽  
Li Yuyao ◽  
Zhao Yu ◽  
Wang Sen ◽  
Feng Qihong
Keyword(s):  
History Matching ◽  
Fracture Network ◽  
Future Application ◽  
Tight Oil ◽  
Oil Reservoir ◽  
Fracture Permeability ◽  
Reservoir Properties ◽  
Matrix Permeability ◽  
Tight Oil Reservoir ◽  
Better Than

Abstract Accurately characterizing hydraulic fracture network and tight oil reservoir properties can lay the foundation for the production forecast and development design. In this work, we proposed a history matching framework for tight oil. We first use the Hough transform method to characterize complex fracture network from microseismic data. Then, we put the fracture network into an embedded discrete fracture model (EDFM) to build a tight oil reservoir simulation model. After that, we further couple whale optimization algorithm (WOA) and EDFM to match the field production data. In this way, we can accurately estimate reservoir properties, including matrix permeability and porosity, as well as fracture permeability. We apply the framework to two-field applications in China. One is fractured vertical well in the Songliao Basin of Daqing oilfield. The other one is multi-stage fractured horizontal well in the Jimsar Sag of the Xinjiang oilfield. Results show that if we do not consider tight oil characteristics, the estimated fracture permeability, matrix permeability, and matrix porosity will underestimate 73%, 20%, and 47%, respectively. Because we apply WOA to history matching for the first time, we compare the performance of WOA with ensemble–smoother with multiple data–assimilation (ES-MDA). When we fit six parameters, ES-MDA performs better than WOA. However, when we fit three parameters, WOA performs better than ES-MDA. In addition, for engineering problem, WOA performs well on both convergence speed and stability. Therefore, WOA is recommended in the future application of history matching.

scholarly journals Evaluation of the agrarian businesses results according to their legal form

2013 ◽  
Vol 59 (No. 9) ◽  
pp. 396-402
Author(s):  
P. Adamišin ◽  
R. Kotulič
Keyword(s):  
Legal Status ◽  
Agricultural Land ◽  
Average Concentration ◽  
Economic Indicators ◽  
Social Changes ◽  
Economic Success ◽  
Legal Form ◽  
Technical Performance ◽  
Significant Difference ◽  
Better Than

The entry into the new market environment after 1990 marked the beginning of complicated structural, economic and social changes for agricultural companies that brought a measurable improvement in only few aspects of the technical performance and competitiveness. New forms of enterprise were created, the number of subjects increased and their average concentration decreased. Based on the analysis, it is claimed that in the majority of selected economic indicators, there was a significant difference in the reached parameters among the groups of the analyse subjects using land, differentiated according to their legal status. Based on the results of testing, it is possible to claim that business companies show a higher extent of economic success evaluated through the selected economic indicators. Only in one case – the indicator of the amount of subsidies per 1 ha of agricultural land – it is impossible to establish a statistically significant difference. This impossibility in that particular indicator only shows even more notably the fact that business companies are able to manage better than cooperatives even with subsidies per hectare of agricultural land that have not been statistically significantly different.  

scholarly journals Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

2017 ◽  
Vol 56 (10) ◽  
pp. 1197-1206 ◽  
Author(s):  
Lisa C. Martial ◽  
Rob ter Heine ◽  
Jeroen A. Schouten ◽  
Nicole G. Hunfeld ◽  
Henk J. van Leeuwen ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Target Attainment

scholarly journals Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae

2016 ◽  
Vol 60 (7) ◽  
pp. 4128-4139 ◽  
Author(s):  
James Albiero ◽  
Sherwin K. B. Sy ◽  
Josmar Mazucheli ◽  
Silvana Martins Caparroz-Assef ◽  
Bruno Buranello Costa ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Clinical Utility ◽  
Multidrug Resistant ◽  
Target Attainment ◽  
Content Type ◽  
Serious Infections ◽  
High Death ◽  
Potential Clinical Utility ◽  
Better Than

ABSTRACTKPC-producingKlebsiella pneumoniaecauses serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no dosages for the combination have been defined. The MICs of meropenem and fosfomycin were evaluated against 18 clinical isolates of KPC-2-producingK. pneumoniae. The activities of combination antimicrobials were also determined by the checkerboard method. The MIC50and MIC90of each agent alone and in combination were challenged against short (1.5-h) or prolonged (3-h) infusion regimens of meropenem (1 g every 8 h [q8h], 1.5 g q6h, 2 g q8h) and fosfomycin (4 g q8h, 6 g q6h, 8 g q8h) by Monte Carlo simulation to evaluate the time above the MIC of the free drug concentration as a percentage of the dosing interval (fT>MIC). The monotherapy MIC50s and MIC90s were 32 and 256 mg/liter for meropenem and 64 and 512 mg/liter for fosfomycin, respectively. Antimicrobial combination increased bacterial susceptibility to 1/4 the MIC50s and to 1/8 to 1/16 the MIC90s of monotherapy. The antimicrobial combination demonstrated a synergistic effect for at least two-thirds of the isolates. In combination therapy, fosfomycin regimens of 6 g q6h and 8 g q8h as a 3-h infusion against the MIC50and MIC90had better chances of achieving ≥90% probability of target attainment (PTA) of 70%fT>MIC. Meropenem regimens of 1.5 g q6h and 2 g q8h in prolonged infusion can achieve close to 90% PTA of 40%fT>MIC for MIC50but not MIC90. The significant reduction in the MIC values and the achievement of appropriate PTA demonstrated that regimens containing fosfomycin with meropenem can be effective against KPC-2-producingK. pneumoniae.

scholarly journals Urinary Bactericidal Activity of Doripenem versus That of Levofloxacin in Patients with Complicated Urinary Tract Infections or Pyelonephritis

2009 ◽  
Vol 53 (4) ◽  
pp. 1567-1573 ◽  
Author(s):  
Florian M. E. Wagenlehner ◽  
Christine Wagenlehner ◽  
Rebecca Redman ◽  
Wolfgang Weidner ◽  
Kurt G. Naber
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Bactericidal Activity ◽  
Good Alternative ◽  
Antimicrobial Activities ◽  
Control Strain ◽  
Target Attainment ◽  
Therapeutic Success ◽  
Time Curve ◽  
Tract Infections

ABSTRACT The aim of this study was to investigate the urinary bactericidal titers (UBTs) and 24-h area under the UBT-versus-time curve (AUBT) of intravenous doripenem (500 mg every 8 h [q8h]), a new carbapenem, versus those of intravenous levofloxacin (250 mg q24h) in patients with complicated urinary tract infections (cUTIs) or pyelonephritis. UBTs and AUBTs are pharmacokinetic/pharmacodynamic parameters able to reflect the activity of an antimicrobial substance in the urine. Doripenem and levofloxacin show comparable urinary excretion of approximately 80% and are therefore registered for the treatment of UTIs. In order to assess and compare the urinary antimicrobial activities of the two substances, UBTs were investigated for 24 patients (10 treated with doripenem and 14 with levofloxacin) for 31 uropathogens and one control strain. Eight strains were tested for all patients and 27 only in the urine of the corresponding patient. Median UBTs (AUBTs) of doripenem for the uropathogens tested ranged between 1.5 and 65,536 (224 and 909,312) and were significantly higher than median UBTs (AUBTs) of levofloxacin, ranging between 0 and 128 (0 and 2,208). Eight microbiological failures were observed, three after doripenem treatment and five after levofloxacin treatment. For levofloxacin, microbiological failures correlated well with low UBTs and AUBTs, whereas for doripenem there was no correlation. From this study, a calculated target attainment rate for levofloxacin predicting therapeutic success in patients with UTIs approximated mean UBTs of 100 over 24 h or AUBTs of 2,240. Doripenem demonstrated excellent urinary bactericidal activity with the dose administered and appears to be a good alternative in the empirical treatment of cUTI.

scholarly journals Target Attainment in the Production of English Vowels by Polish Students: The Influence of Language Instruction in the Time of Covid-19, Imitation, and Musicality

2021 ◽  
Vol 69 (5 Zeszyt specjalny) ◽  
pp. 23-42
Author(s):  
Eugeniusz Cyran ◽  
Martyna Michalska
Keyword(s):  
Experimental Study ◽  
Likert Scale ◽  
Language Instruction ◽  
Statistical Testing ◽  
Future Research ◽  
Target Attainment ◽  
English Vowels ◽  
Reading Experiment ◽  
Research Questions ◽  
Better Than

This pilot experimental study pursues a number of goals. Firstly, it aims to assess the phonetic attainment of selected English vowels among twelve Polish students of English philology after one term of intensive online pronunciation training in pandemic conditions. Secondly, it looks at potential differences between production outcomes in two experimental contexts, that is, reading and imitation. Finally, it seeks to determine if there is any correlation between musicality and target attainment with a view to identifying a broader scope for potential future research questions. For this purpose, recorded samples of read and imitated English words containing vowels in a uniform context /h_d/ were assessed by six raters using a 5-point Likert scale. The results, including those of an online musicality test, were analysed and subjected to statistical testing. The majority of total scores exceed the assumed acceptability benchmark of 50%. The study yielded a number of unexpected results. Firstly, female participants performed significantly better than male ones in the reading experiment, but not in imitation. Secondly, a stronger correlation was found between the reading results and musicality than between imitation results and musicality.

scholarly journals Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

2008 ◽  
Vol 50 (3) ◽  
pp. 157-160 ◽  
Author(s):  
Alan César Teixeira ◽  
Marcilene Gomes Paes ◽  
Jorge de Oliveira Guerra ◽  
Aluízio Prata ◽  
Mario León Silva-Vergara
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Therapeutic Failure ◽  
Controlled Clinical Trial ◽  
Intramuscular Dose ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Group I ◽  
Leishmania Spp ◽  
Group Ii ◽  
Better Than

A non-randomized controlled clinical trial was carried outin order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5%) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5%) cases. In group II, antimony cured eight of 19 (42.1%) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9%) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

scholarly journals Intensive blood-pressure lowering in patients with acute cerebral hemorrhage

CJEM ◽  
2017 ◽  
Vol 20 (2) ◽  
pp. 256-259 ◽  
Author(s):  
Sufyan Alrahbi ◽  
Rashid Alaraimi ◽  
Abdalla Alzaabi ◽  
Sophie Gosselin
Keyword(s):  
Blood Pressure ◽  
Cerebral Hemorrhage ◽  
Antihypertensive Treatment ◽  
Therapeutic Benefit ◽  
Blood Pressure Lowering ◽  
Pressure Lowering ◽  
Acute Intracerebral Hemorrhage ◽  
Better Than ◽  
Intensive Blood Pressure

Clinical questionIs intensive blood pressure (BP) treatment (systolic BP target 110-139 mm Hg) better than standard antihypertensive treatment (systolic BP target 140-179 mm Hg) in reducing mortality and disability in patients with acute intracerebral hemorrhage (ICH)?Article chosenQureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med 2016;375(11):1033-43.ObjectiveTo determine the therapeutic benefit of intensive BP treatment compared to standard BP treatment in reducing death and disability after 3 months of follow-up among patients with ICH treated within 4.5 hours from onset of symptoms.

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