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Setting: Reducing pain from intramuscular injection of kanamycin (KM) could improve the tolerability of multidrug-resistant tuberculosis (MDR-TB) treatment. Lidocaine has been shown to be an effective anaesthetic diluent for some intramuscular injections, but has not been investigated with KM in the treatment of adult patients with MDR-TB., Objective and Design: We performed a randomised single-blinded crossover study to determine if lidocaine reduces KM injection-site pain. We recruited patients aged 18 years on MDR-TB treatment at two TB hospitals in Cape Town, South Africa. KM pharmacokinetic parameters and a validated numeric pain scale were used at intervals over 10 h following the injection of KM with and without lidocaine on two separate occasions., Results: Twenty participants completed the study: 11 were males, the median age was 36 years, 11 were HIV-infected, and the median body mass index was 17.5 kg/m2. The highest pain scores occurred early, and the median pain score was 0 by 30 min. The use of lidocaine with KM significantly reduced pain at the time of injection and 15 min post-dose. On multiple regression analysis, lidocaine halved pain scores (adjusted OR 0.5, 95%CI 0.3-0.9). The area under the curve at 0-10 h of KM with and without lidocaine was respectively 147.7 and 143.6 μg·h/ml., Conclusion: Lidocaine significantly reduces early injection-site pain and has no effect on KM pharmacokinetics.

Background: Psoriasis and psoriatic arthritis (PsA) are inflammatory associated autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164), aberrantly alters its gene expression and linked with the pathogenesis of several disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are extremely rare in the indigenous African population and most common in both the Indian and Caucasian population. The aim of this study was to investigate whether the miR-146a rs2910164 contributes towards psoriasis and PsA development in South African Indian and Caucasian patients., Methods: South African Indian (n = 84) and Caucasian (n = 32) PsA patients (total n = 116) and healthy control subjects (Indian: n = 62 and Caucasian: n = 38; total n = 100) were recruited in the study. DNA was extracted from whole blood taken from all subjects, and genotyped for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from pathology reports. The consulting rheumatologist collected all other clinical data., Results: Unstratified data (Caucasians + Indians): A significant decrease in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at inclusion vs. after 6 months of treatment) (18.95 ± 2.81 mg/L vs. 9.68 ± 1.32 mg/L, p = 0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA patients was significantly higher vs. healthy controls (35.78% vs. 26% respectively, p = 0.0295, OR = 1.59 95% CI 1.05-2.40). Stratified data (Indians): The variant C-allele frequency in Indian PsA patients was significantly higher vs. healthy Indian controls (35.71% vs. 22.58%, p = 0.0200, OR = 1.91 95% CI 1.13-3.22). Stratified data (Caucasians): The variant C-allele frequency distribution between Caucasian PsA patients and healthy Caucasian controls was similar., Conclusion: The rs2910164 variant C-allele may play a role in the progression of PsA in the South African Indian population. The main limitation in this study was the small sample size in the case-control cohorts, with a low overall statistical power (post-hoc power analysis = 19%).

Setting: Terizidone/cycloserine (TRD/CS) is included in standard treatment regimens for multidrug-resistant tuberculosis (MDR-TB) in many countries. The steady state pharmacokinetics (PKs) of CS after TRD administration are not known., Objectives and Design: We recruited in-patients treated with 250-750 mg oral TRD daily as part of standard treatment regimens for pulmonary MDR-TB in Cape Town, South Africa. Plasma CS assays were performed in samples taken pre-dose and at 2, 4, 6, 8 and 10 h post-dose. CS concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. Non-compartmental PK analyses were performed., Results: Of 35 participants enrolled, 22 were males, and 20 (57%) were infected with the human immunodeficiency virus; the median age was 37 years. The median duration on TRD at the time of sampling was 33 days (interquartile range [IQR] 28-39). The area under the concentration-time curve at 0-10 h (AUC0-10) was 319 μg.h/ml (IQR 267.5-378.7), and peak concentration was 38.1 μg/ml (IQR 32.6-47.2). On multiple regression, dose (mg/kg) was the only factor independently associated with AUC0-10., Conclusion: Steady state concentrations of CS in patients treated with TRD for MDR-TB were higher than those reported with CS formulations. Our findings support once-daily dosing.