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Aim: Microsampling has the advantage of smaller blood sampling volume and suitability in vulnerable populations compared to venous sampling in clinical pharmacokinetics studies. Current regulatory guidance requires correlative studies to enable microsampling as a technique. A post hoc population pharmacokinetic (POPPK) approach was utilized to investigate blood capillary microsampling as an alternative to venous sampling. Methods: Pharmacokinetic data from microsampling and venous sampling techniques during a paediatric study evaluating tafenoquine, a single‐dose antimalarial for P. vivax, were used. Separate POPPK models were developed and validated based on goodness of fit and visual predictive checks, with pharmacokinetic data obtained via each sampling technique. Results: Each POPPK model adequately described tafenoquine pharmacokinetics using a two‐compartment model with body weight based on allometric scaling of clearance and volume of distribution. Tafenoquine pharmacokinetic parameter estimates including clearance (3.4 vs 3.7 L/h) were comparable across models with slightly higher interindividual variability (38.3% vs 27%) in capillary microsampling‐based data. A bioavailability/bioequivalence comparison demonstrated that the point estimate (90% CI) of capillary microsample versus venous sample model‐based individual post hoc estimates for area under the concentration‐time curve from time zero to infinity (AUC0‐inf) (100.7%, 98.0‐103.5%) and Cmax (79.7%, 76.9‐82.5%) met the 80‐125% and 70‐143% criteria, respectively. Overall, both POPPK models led to the same dose regimen recommendations across weight bins based on achieving target AUC. Conclusions: This analysis demonstrated that a POPPK approach can be employed to assess the performance of alternative pharmacokinetic sampling techniques. This approach provides a robust solution in scenarios where variability in pharmacokinetic data collected via venous sampling and microsampling may not result in a strong linear relationship. The findings also established that microsampling techniques may replace conventional venous sampling methods. [ABSTRACT FROM AUTHOR]

Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18-65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200 mg versus placebo (ΔΔQTcF) was <10 milliseconds for all pre-defined time points. The maximum ΔΔQTcF with tafenoquine 1200 mg (n = 50) was 6.39 milliseconds (90% CI 2.85, 9.94) at 72 hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300 mg (n = 48) or 600 mg (n = 52) had no effect on ΔΔQTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine-QTcF concentration-effect relationship demonstrated a shallow slope (0.5 ms/μg mL-1) over a wide concentration range. For moxifloxacin (n = 51), maximum ΔΔQTcF was 8.52 milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization. [ABSTRACT FROM AUTHOR]

Examines the linear manifestation of discoid lupus erythematosus. Diagnosis of the skin disease; Treatment and management of the disease; Signs and symptoms of the disease.

Primary cutaneous extranodal NK/T-cell lymphoma (PC-ENKTL) is a rare, aggressive malignancy which typically presents on the extremities as erythematous plaques and ulcerated, subcutaneous nodules.[1] It is often misdiagnosed due to its similar presentation to other cutaneous lymphomas. PC-ENKTL is often misdiagnosed as other cutaneous T-cell lymphomas due to its similar presentation;[1] however, correctly identifying PC-ENKTL is essential as treatment regimens differ. Primary cutaneous extranodal natural killer/T-cell lymphoma misdiagnosed as peripheral T-cell lymphoma: the importance of EBV in situ hybridization for diagnosis. [Extracted from the article]

We report a rare case of a nocardial adrenal abscess in an HIV patient that underwent the first drainage of adrenal abscess by laparoscopy. Adrenal abscesses are exceedingly rare in adults and prove to be a diagnostic challenge. Laparoscopic adrenal exploration is both a diagnostic and therapeutic modality with low perioperative morbidity that should be considered in the management of indeterminate adrenal masses and abscesses. [ABSTRACT FROM AUTHOR]

Background: Serious injury, including burn trauma, induces a hyper metabolic response and insulin resistance are still not well understood. Mitochondrial proteins and genes are damaged after burn injury in animals. However, mitochondrial function has not previously been assessed in human burn patients. Methods: Muscle biopsies were taken from 40 children sustaining burns >40% of their body surface area and from 13 healthy children controls requiring non-emergent open abdominal surgery. The rates of maximal muscle mitochondrial oxidative capacity or ATP production and uncoupled oxidation or heat production for both palmitate and pyruvate were measured. Results: Maximal mitochondrial oxidation of both pyruvate and palmitate were significantly reduced in burn patients compared to healthy controls (4.0¡Ó 0.2 vs. 1.9¡Ó0.1 fÝmolO2/citrate synthase activity/mg protein/ min pyruvate; CON vs. BURN; P<0.001 and 3.0¡Ó0.1 vs. 0.9¡Ó0.03 fÝmolO2/citrate synthase activity/mg protein/min palmatyl CoA; CON vs. BURN; P=0.003). However, the rates of uncoupled oxidation were the same between the two groups. Thus the respiratory quotient index, or ratio of coupled to uncoupled oxidation was significantly higher in control subjects (4.9¡Ó0.2 vs. 1.9¡Ó0.1 pyruvate; P<0.001 CON vs. BURN and 3.9¡Ó0.2 vs. 1.4¡Ó0.1 palmitate; P<0.001 CON vs. BURN)Conclusions: The maximal coupled mitochondrial oxidative capacity is severely impaired after burn injury, although there are no alterations in the rate of uncoupled oxidative capacity. It may be that the ratio of these indicates that a larger portion of energy production in trauma patients is wasted through uncoupling, rather than used for healing. [ABSTRACT FROM AUTHOR]