Dosage optimization of treatments using population pharmacokinetic modeling and simulation.

Pharmacokinetic variability in drug levels represent for some drugs a major determinant of treatment success, since sub-therapeutic concentrations might lead to toxic reactions, treatment discontinuation or inefficacy. This is true for most antiretroviral drugs, which exhibit high inter-patient variability in their pharmacokinetics that has been partially explained by some genetic and non-genetic factors. The population pharmacokinetic approach represents a very useful tool for the description of the dose-concentration relationship, the quantification of variability in the target population of patients and the identification of influencing factors. It can thus be used to make predictions and dosage adjustment optimization based on Bayesian therapeutic drug monitoring (TDM). This approach has been used to characterize the pharmacokinetics of nevirapine (NVP) in 137 HIV-positive patients followed within the frame of a TDM program. Among tested covariates, body weight, co-administration of a cytochrome (CYP) 3A4 inducer or boosted atazanavir as well as elevated aspartate transaminases showed an effect on NVP elimination. In addition, genetic polymorphism in the CYP2B6 was associated with reduced NVP clearance. Altogether, these factors could explain 26% in NVP variability. Model-based simulations were used to compare the adequacy of different dosage regimens in relation to the therapeutic target associated with treatment efficacy. In conclusion, the population approach is very useful to characterize the pharmacokinetic profile of drugs in a population of interest. The quantification and the identification of the sources of variability is a rational approach to making optimal dosage decision for certain drugs administered chronically.

Agreed-upon procedures report on the Iowa Sheep and Wool Promotion Board for the period July 1, 2011 through June 30, 2013

Agreed-upon procedures report on the Iowa Sheep and Wool Promotion Board for the period July 1, 2011 through June 30, 2013

Agreed-upon procedures report on the City of Urbana, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Urbana, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Pomeroy, Iowa for the period August 1, 2013 through July 31, 2014

Agreed-upon procedures report on the City of Pomeroy, Iowa for the period August 1, 2013 through July 31, 2014

Utilité de la prophylaxie antibiotique avant un geste dentaire pour tes porteurs de prothèses totales du genou ou de la hanche [Antibiotic prophylaxis before dental procedures in arthroplasty patients]

Antibiotic prophylaxis is commonly prescribed to patients with total arthroplasties before a dental intervention. This attitude is not evidence-based for several reasons: 1) the usual pathogens of prosthetic joint infections are not of oral origin; 2) even if given, systemic antibiotic do not completely suppress the occult bacteraemia occurring during dental intervention and 3) humans may have up to twelve episodes of occult bacteraemia of dental origin per day. Routine antibiotic prophylaxis should be clearly distinguished from the antibiotic treatment required in case of established oral cavity infection. A constant optimal oral and dental hygiene is more important in terms of prevention and should be routinely recommended to every patient carrying a joint arthroplasty.

Agreed-upon procedures report on the City of Vincent, Iowa for the period August 1, 2013 through July 31, 2014

Agreed-upon procedures report on the City of Vincent, Iowa for the period August 1, 2013 through July 31, 2014

Agreed-upon procedures report on the City of Walcott, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Walcott, Iowa for the period July 1, 2013 through June 30, 2014

Optimization of HS-SPME/GC-MS analysis and its use in the profiling of illicit ecstasy tablets (Part 1)

A headspace solid-phase microextraction procedure (HS-SPME) was developed for the profiling of traces present in 3,4-methylenedioxymethylampethamine (MDMA). Traces were first extracted using HS-SPME and then analyzed by gas chromatography-mass spectroscopy (GC-MS). The HS-SPME conditions were optimized using varying conditions. Optimal results were obtained when 40 mg of crushed MDMA sample was heated at 80 °C for 15 min, followed by extraction at 80 °C for 15 min with a polydimethylsiloxane/divinylbenzene coated fibre. A total of 31 compounds were identified as traces related to MDMA synthesis, namely precursors, intermediates or by-products. In addition some fatty acids used as tabletting materials and caffeine used as adulterant, were also detected. The use of a restricted set of 10 target compounds was also proposed for developing a screening tool for clustering samples having close profile. 114 seizures were analyzed using an SPME auto-sampler (MultiPurpose Samples MPS2), purchased from Gerstel GMBH & Co. (Germany), and coupled to GC-MS. The data was handled using various pre-treatment methods, followed by the study of similarities between sample pairs based on the Pearson correlation. The results show that HS-SPME, coupled with the suitable statistical method is a powerful tool for distinguishing specimens coming from the same seizure and specimens coming from different seizures. This information can be used by law enforcement personnel to visualize the ecstasy distribution network as well as the clandestine tablet manufacturing.

Agreed-upon procedures report on the City of Kimballton, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Kimballton, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Glidden, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Glidden, Iowa for the period July 1, 2013 through June 30, 2014

Critical values of nitrogen indices in tomato plants grown in soil and nutrient solution determined by different statistical procedures

The objective of this study was to establish critical values of the N indices, namely soil-plant analysis development (SPAD), petiole sap N-NO3 and organic N in the tomato leaf adjacent to the first cluster (LAC), under soil and nutrient solution conditions, determined by different statistical approaches. Two experiments were conducted in randomized complete block design with four repli-cations. Tomato plants were grown in soil, in 3 L pot, with five N rates (0, 100, 200, 400 and 800 mg kg-1) and in solution at N rates of 0, 4, 8, 12 and 16 mmol L-1. Experiments in nutrient solution and soil were finished at thirty seven and forty two days after transplanting, respectively. At those times, SPAD index and petiole sap N-NO3 were evaluated in the LAC. Then, plants were harvested, separated in leaves and stem, dried at 70ºC, ground and weighted. The organic N was determined in LAC dry matter. Three statistical procedures were used to calculate critical N values. There were accentuated discrepancies for critical values of N indices obtained with plants grown in soil and nutrient solution as well as for different statistical procedures. Critical values of nitrogen indices at all situations are presented.

Agreed-upon procedures report on the City of Bertram, Iowa for the period August 1, 2013 through July 31, 2014

Agreed-upon procedures report on the City of Bertram, Iowa for the period August 1, 2013 through July 31, 2014

Agreed-upon procedures report on the City of Olin, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Olin, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Griswold, Iowa for the period July 1, 2013 through June 30, 2014

Agreed-upon procedures report on the City of Griswold, Iowa for the period July 1, 2013 through June 30, 2014