Negative-pressure wound therapy - does it lower the risk of complications with closed wounds following breast surgery?

Breast surgery complications are important not only due to their morbidity and psychological impact, but also the delays that can occur for adjuvant treatment or the loss of implants in severe cases. There is growing evidence that negative pressure dressing on closed wounds can reduce the complications following surgery. This study aimed to assess whether negative-pressure dressings reduced complications in patients undergoing bilateral reduction mammoplasty with randomization of a side to negative pressure and standard care, fixation strips, on the contralateral side.

The Effect of Size, Maturation, Global Asphyxia, Cerebral Ischemia, and Therapeutic Hypothermia on the Pharmacokinetics of High-Dose Recombinant Erythropoietin in Fetal Sheep.

High-dose human recombinant erythropoietin (rEPO) is a promising potential neuroprotective treatment in preterm and full-term neonates with hypoxic-ischemic encephalopathy (HIE). There are limited data on the pharmacokinetics of high-dose rEPO in neonates. We examined the effects of body weight, gestation age, global asphyxia, cerebral ischemia, hypothermia and exogenous rEPO on the pharmacokinetics of high-dose rEPO in fetal sheep.

eradication therapy and risk of acquiring in young children with cystic fibrosis.

Background: While detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.

Aim: To determine the risk and explanatory factors of acquiring in children with CF by age 5 years.

Methods: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting at age 5 years.

TIGR matrix for implant-based breast reconstruction - a long-term resorbable mesh.

The use of biological and synthetic meshes to aid implant coverage in implant-based breast reconstruction is well established. This technique allows single stage implant-based reconstruction compared to the traditional technique which required tissue expansion before permanent implant placement and therefore involved two operations for the patient. They can further be used for pre-pectoral implant reconstructions in a similar direct-to-implant strategy.

Population pharmacokinetics and pharmacodynamics of linezolid-induced thrombocytopenia in hospitalized patients.

Aims: Thrombocytopenia is among the most important adverse effects of linezolid treatment. Linezolid-induced thrombocytopenia incidence varies considerably but has been associated with impaired renal function. We investigated the pharmacodynamic mechanism (myelosuppression or enhanced platelet destruction) and the role of impaired renal function (RF) in the development of thrombocytopenia.

Abdominal actinomycosis after laparoscopic cholecystectomy: an uncommon presentation of an uncommon problem.

Actinomycosis is a rare bacterial infection with a broad clinical presentation that is seldom reported after elective cholecystectomy. We present an as-of-yet unreported case of actinomycosis in an 81-year-old gentleman who was found to have right-sided peritonitis and small bowel obstruction 11 months after elective laparoscopic cholecystectomy. A complex loculated lesion was found on laparotomy with a protracted course of antibiotics being needed for treatment.

Prediction of Fat-Free Mass in Children.

Background: Fat-free mass (FFM) is an important covariate for predicting drug clearance. Models for predicting FFM have been developed in adults but there is currently a paucity of mechanism-based models developed to predict FFM in children.

Objective: The aim of this study was to develop and evaluate a model to predict FFM in children.

Evaluation of bootstrap methods for estimating uncertainty of parameters in nonlinear mixed-effects models: a simulation study in population pharmacokinetics.

Bootstrap methods are used in many disciplines to estimate the uncertainty of parameters, including multi-level or linear mixed-effects models. Residual-based bootstrap methods which resample both random effects and residuals are an alternative approach to case bootstrap, which resamples the individuals. Most PKPD applications use the case bootstrap, for which software is available.

Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization.

Purpose: Personalizing intravenous busulfan doses to a target plasma concentration at steady state (Css) is an essential component of hematopoietic cell transplantation (HCT). We sought to develop a population pharmacokinetic model to predict i.v.

The population pharmacokinetics of allopurinol and oxypurinol in patients with gout.

Purpose: The aims of this study were to develop a population pharmacokinetic model for allopurinol and oxypurinol and to explore the influence of patient characteristics on allopurinol and oxypurinol pharmacokinetics.

Methods: Data from 92 patients with gout and 12 healthy volunteers were available for analysis. A parent-metabolite model with a two-compartment model for allopurinol and a one-compartment model for oxypurinol was fitted to the data using non-linear mixed effects modelling.

A comparison of bootstrap approaches for estimating uncertainty of parameters in linear mixed-effects models.

A version of the nonparametric bootstrap, which resamples the entire subjects from original data, called the case bootstrap, has been increasingly used for estimating uncertainty of parameters in mixed-effects models. It is usually applied to obtain more robust estimates of the parameters and more realistic confidence intervals (CIs). Alternative bootstrap methods, such as residual bootstrap and parametric bootstrap that resample both random effects and residuals, have been proposed to better take into account the hierarchical structure of multi-level and longitudinal data.

Safe and effective variability-a criterion for dose individualization.

Background: A primary goal of clinical pharmacology is to understand the factors that determine the dose-effect relationship and to use this knowledge to individualize drug dose.

Methods: A principle-based criterion is proposed for deciding among alternative individualization methods.

Results: Safe and effective variability defines the maximum acceptable population variability in drug concentration around the population average.

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease.

Aim: To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables.

Methods: Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest.

Progression of motor and nonmotor features of Parkinson's disease and their response to treatment.

Aims: (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments.

Methods: Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D).

The influence of tuberculosis treatment on efavirenz clearance in patients co-infected with HIV and tuberculosis.

Purpose: Drug interactions are of concern when treating patients co-infected with human immunodeficiency virus (HIV) and tuberculosis. Concomitant use of efavirenz (EFV) with the enzyme inducer rifampicin might be expected to increase EFV clearance. We investigated the influence of concomitant tuberculosis treatment on the plasma clearance of EFV.

The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications.

Among patients with tuberculosis, rifampin plasma concentrations and sputum conversion rates have been reported to be lower in Africans. Rifampin is a substrate of P-glycoprotein (coded for by the ABCB1 gene) and organic anion-transporting polypeptide 1B1 (coded for by SLCO1B1). The objectives were to identify genetic polymorphisms of drug transporters and the transcriptional regulators pregnane X receptor (PXR) and constitutive androstane receptor (CAR) with an impact on rifampin pharmacokinetics in South Africans.

Nonlinear pharmacokinetics of piperacillin in healthy volunteers--implications for optimal dosage regimens.

Aims: (i) To describe the first-order and mixed-order elimination pathways of piperacillin, (ii) to determine the between occasion variability (BOV) of pharmacokinetic parameters and (iii) to propose optimized dosage regimens.

Methods: We performed a five-period replicate dose study in four healthy volunteers. Each subject received 4g piperacillin as a single 5min intravenous infusion in each study period.

A combined pharmacokinetic model for the hypoxia-targeted prodrug PR-104A in humans, dogs, rats and mice predicts species differences in clearance and toxicity.

Background: PR-104 is a phosphate ester that is systemically converted to the corresponding alcohol PR-104A. The latter is activated by nitroreduction in tumours to cytotoxic DNA cross-linking metabolites. Here, we report a population pharmacokinetic (PK) model for PR-104 and PR-104A in non-human species and in humans.

Dyskinesia and the antiparkinsonian response always temporally coincide: a retrospective study.

Objective: To clinically characterize the temporal relationship between dyskinesia and the antiparkinsonian response when dyskinesia first emerges during long-term levodopa therapy and to determine if it is consistent with the hypothesized mechanism by which dyskinesia develops.

Methods: Dyskinesia and the antiparkinsonian response to levodopa during 2-hour levodopa infusions were monitored at intervals through the first 4 years of long-term levodopa therapy in 20 subjects with idiopathic Parkinson disease (PD) and previously untreated with levodopa. The onset and offset of the antiparkinsonian response and dyskinesia were compared when dyskinesia first appeared during the 4 years.

Washout and delayed start designs for identifying disease modifying effects in slowly progressive diseases using disease progression analysis.

Treatment of a slowly progressive disease, such as Parkinson's and Alzheimer's disease should slow down or even reverse progression of the disease. For estimating the actual treatment effect a clinical trial should allow the time course of treatment effects to be distinguished from those due to natural disease progression. A symptomatic treatment effect has a rapid onset, which will disappear after treatment cessation, whereas disease modifying effects are slow and persistent.