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INTRODUCTION: Identification of optimal drug doses and drug combinations is crucial for optimized treatment of tuberculosis. AREAS COVERED: An unprecedented level of research activity involving multiple approaches is seeking to improve tuberculosis treatment. This report is a review of the quantitative methods currently used on clinical data sets to identify drug exposure targets and optimal drug combinations for tuberculosis treatment. A high-level summary of the methods, including the strengths and weaknesses of each method and potential methodological improvements is presented. Methods incorporating data generated from multiple sources such as in vitro and clinical studies, and their potential to provide better estimates of pharmacokinetic/pharmacodynamic (PK/PD) targets, are discussed. PK/PD relationships identified are compared between different studies and data analysis methods. EXPERT OPINION: The relationships between drug exposures and tuberculosis treatment outcomes are complex and require analytical methods capable of handling the multidimensional nature of the relationships. The choice of a method is guided by its complexity, interpretability of results, and type of data available.

Introduction: Cystic Fibrosis is a recessive monogenetic disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), a chloride ion channel expressed by epithelial cells throughout the body. Although it is a multisystem disease, for most patients the pulmonary manifestations of CF account for the major incidences of morbidity and mortality.Areas covered: In this review, the authors discuss new and emerging therapies that target CFTR and describe ex vivo models that have been developed to evaluate the efficacy of precision medicines for people with CF.Expert commentary: Pharmacological and genetic medical technologies to overcome CF have been developed. These treatments are expensive but for people with CF, and especially those with rare CFTR mutations, strategies exist to test appropriate drug doses and combinations thereof ex vivo. The current challenges are to identify the correct CFTR therapy for each patient and make a clinical decision abou...

The use of a length/weight-based tape (LBT) for equipment size and drug dosing for pediatric patients is recommended in a joint statement by multiple national organizations. A new system, known as Handtevy™, allows for rapid determination of critical drug doses without performing calculations.To compare two LBT systems for dosing errors and time to medication administration in simulated prehospital scenarios.This was a prospective randomized trial comparing the Broselow Pediatric Emergency Tape™ (Broselow) and Handtevy LBT™ (Handtevy). Paramedics performed 2 pediatric simulations: cardiac arrest with epinephrine administration and hypoglycemia mandating dextrose. Each scenario was repeated utilizing both systems with a 1-year-old and 5-year-old size manikin. Facilitators recorded identified errors and time points of critical actions including time to medication.We enrolled 80 paramedics, performing 320 simulations. For Dextrose, there were significantly more errors with Broselow (63.8%) compared to Handtevy (13.8%) and time to administration was longer with the Broselow system (220 seconds vs. 173 seconds). For epinephrine, the LBTs were similar in overall error rate (Broselow 21.3% vs. Handtevy 16.3%) and time to administration (89 vs. 91 seconds). Cognitive errors were more frequent when using the Broselow compared to Handtevy, particularly with dextrose administration. The frequency of procedural errors was similar between the two LBT systems.In simulated prehospital scenarios, use of the Handtevy LBT system resulted in fewer errors for dextrose administration compared to the Broselow LBT, with similar time to administration and accuracy of epinephrine administration.

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q(m)) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC: drug ratios were 10:1, 5:1, 3:1, 2:1, and 1:1. The mixed-drug adsorption vials contained the same AC: paracetamol ratios, but amitriptyline was added as fixed dose (0.080 g) to all samples. Drug concentrations in the liquid phase were analyzed using high-performance liquid chromatography (HPLC)/UV-detection. Results. Q(m), amitriptyline, were 0.49 g/g Carbomix® and 0.70 g/g Norit Ready-To-Use, and Q(m), paracetamol, were 0.63 g/g Carbomix® and 0.72 g/g Norit Ready-To-Use. The tested pH differences had minor effect on the adsorption. The mixed-drug adsorption showed about 40% Q(m) reduction of each drug with increasing amounts of drug/g AC, but the total gram of drug adsorbed to AC was increased compared to one-drug conditions. Conclusion. The adsorption of the two compounds to AC seems to compete resulting in lower maximum adsorption capacity for both drugs when mixed. However, a great adsorptive capacity was noted and might be explained by adsorption of the drugs to different AC surface sites. Furthermore, the Norit Ready-To-Use preparation, with less volume and total weight for the same AC dose as Carbomix®, showed a higher Q(m). This might be clinically significant in terms of preventing nausea, vomiting, and subsequent aspiration.

Calculating weight-based drug doses for pediatric patients is difficult, with significant error potential. In the prehospital setting, few safeguards currently avert pediatric drug administration errors. We sought to determine whether use of a protocol-specific pediatric code card enables prehospital care providers to calculate more consistently accurate weight-based drug doses, volumes of administration, and age-appropriate endotracheal tube sizes.Questionnaires requiring calculations of medication doses, volumes, and endotracheal tube sizes were administered to prehospital care providers between June and November 2006 in fire department continuing education classes in the State of Maryland and the District of Columbia. Half of the participants performed the calculations with the pediatric code card as an aid, and half without. Calculations done by the two groups were compared for rate and extent of errors. We evaluated the error frequency in calculations of pediatric medication doses and endotracheal tube sizes.Of the 523 advanced life support prehospital care providers questioned, 246 answered questions using the pediatric code card, and 277 answered questions without using the card. The mean individual percentages of correct responses were 94% for the group aided by the code card and 65% for the group unaided by the card (percentage difference, 29%; 95% confidence interval [CI], 25-31%; p0.001). Ninety-eight percent of the aided group and 23% of the unaided group calculated the correct endotracheal tube size (percentage difference, 75%; 95% CI, 70-81%; p0.001).The use of the pediatric code card enabled prehospital care providers to determine weight-based drug doses, volumes of administration, and endotracheal tube sizes more accurately than peers without access to the code card.

Isolated hepatic perfusion (IHP) involves a method of complete vascular isolation of the liver to enable treatment of liver tumors with high drug doses without systemic toxicity. Recent clinical studies have mainly employed IHP with melphalan with or without tumor necrosis factor-alpha and mild hyperthermia. The results of these studies demonstrate that high response and survival rates can be achieved with IHP. The current status, recent developments and future perspectives of IHP are discussed in this review.

The great majority of adverse drug reactions are dose-related and occur in patients taking standard doses of medications. These facts suggest that for many patients, standard drug doses may be excessive. The principle of variability among individuals, which requires tailoring the dose to the patient, needs to be reasserted in clinical medicine to reduce the incidence of side effects. Physicians should obtain patients' histories of drug reactions and have at hand information on the full range of effective drug doses, including data on low doses gathered in prerelease and postrelease drug studies. Whenever possible, manufacturers should provide a range of doses and breakable tablets to facilitate flexible dosing.

Middle Tennessee State University, Tennessee, USAOnline Publication Date: 01 June 2007To cite this Article: Sheng, Qin and Khaliq, Abdul Q. M. (2007) 'Preface: Splittingmethods for differential equations', International Journal of Computer Mathematics,84:6, 709 - 711To link to this article: DOI: 10.1080/00207160701489067URL: http://dx.doi.org/10.1080/00207160701489067PLEASE SCROLL DOWN FOR ARTICLEFull terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdfThis article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction,re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expresslyforbidden.The publisher does not give any warranty express or implied or make any representation that the contents will becomplete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should beindependently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings,demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with orarising out of the use of this material.

Universite Paris 6, Geologie Appliquee, B 123, Paris Cedex 05, FranceOnline Publication Date: 01 March 1997To cite this Article: Segers, H. and Pourriot, R. (1997) 'On a new and puzzlingAmerican rotifer (Rotifera: Monogononta, Lecanidae)', Journal of Natural History,31:3, 383 - 388To link to this article: DOI: 10.1080/00222939700770181URL: http://dx.doi.org/10.1080/00222939700770181PLEASE SCROLL DOWN FOR ARTICLEFull terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdfThis article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction,re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expresslyforbidden.The publisher does not give any warranty express or implied or make any representation that the contents will becomplete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should beindependently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings,demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with orarising out of the use of this material.

The antidepressants clomipramine hydrochloride (Anafranil), fluoxetine hydrochloride (Prozac), and sertraline hydrochloride (Zoloft) are the main choices for pharmacologic treatment of obsessive-compulsive disorder. Often, drug doses for obsessive-compulsive disorder are higher than for depression, and improvement occurs more slowly and is often only partial. Behavior therapy involving exposure to feared objects or situations and prevention of ritualistic behavior complements pharmacologic treatment. Referral to a behavioral therapist may be necessary to achieve recovery.

This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.

It is plausible that, for pharmacologic and physiologic reasons, antisecretory treatment reduces the chances of rebleeding from gastric and duodenal ulcers and thereby reduces operation and death rates. Currently available evidence is not strong enough to confirm this, in part because trials have been too small to detect any differences present, and perhaps in part because drug doses have been too low to achieve the desired antisecretory potential.