The objective of this study was to compare the effect of virtual reality to passive distraction and standard care on burn treatment pain in adolescents.This single-blinded, randomized controlled study enrolled 30 adolescents who were 10 to 17 years of age from the burn clinic of a large children's hospital. After providing informed consent/assent, these participants were randomly assigned to one of three groups during wound care: standard care, passive distraction watching a movie, or virtual reality (VR) using a tripod-arm device rather than an immersive helmet. Before wound care, participants completed the Spielberger's State-Trait Anxiety Inventory for Children and Pre-Procedure Questionnaire while blinded to group assignment. A total of 28 participants completed the study and rated treatment pain after wound care by using the Adolescent Pediatric Pain Tool and completed a Post-Procedure Questionnaire. The VR group reported less pain during wound care than either the passive distraction or standard care group as determined by multivariable linear regression adjusted for age, sex, preprocedure pain, state anxiety, opiate use, and treatment length. The VR group was the only group to have an estimated decrease in pain perception from baseline preprocedure pain to procedural pain reported. Adolescents pretreated with opiate analgesics and female adolescents reported more pain during wound care.This between-subjects clinical study provides further support for VR, even without requiring wearing of an immersive helmet, in lessening burn wound care pain in adolescents. Passive distraction by watching a movie may be less effective in reducing treatment pain. Additional between-subjects randomized controlled trials with larger samples of children and during other healthcare treatments may further support VR's effectiveness in pediatric procedural pain management.
Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml.
While studies of HIV-infected adults on antiretroviral treatment (ART) report no sex differences in immune recovery and virologic response but more ART-associated complications in women, sex differences in disease progression and response to ART among children have not been well assessed. The objective of this study was to evaluate for sex differences in response to ART in South African HIV-infected children who were randomized to continue ritonavir-boosted lopinavir (LPV/r)-based ART or switch to nevirapine-based ART.
A sensitive and selective liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of ofloxacin in 20 ?l human plasma over the concentration range of 0.078-20 ?g/ml. Sample preparation was achieved by protein precipitation with acetonitrile and methanol containing the internal standard (Gatifloxacin). Chromatographic separation was achieved on a Luna 5 ?m PFP (110 A, 50 × 2 mm) column with acetonitrile and water containing 0.1% formic acid (50:50, v/v) as the mobile phase, at a flow rate of 400 ?l/ml. The within-day and between-day precision determinations for ofloxacin, expressed as the percentage coefficient of variation, were lower than 7% at all test concentrations. Recovery of ofloxacin was greater than 70% and reproducible at the low, medium and high end of the dynamic range. No significant matrix effects were observed for the analyte or internal standard. The assay was successfully used to examine the pharmacokinetics of ofloxacin as part of a study to characterize the pharmacokinetics of a number of anti-tuberculosis drugs utilized in the treatment of multi-drug resistant tuberculosis (MDR-TB).
The aim of this study was to synthesize a series of ethylene glycol ether derivatives of the antimalarial drug artemisinin, determine their values for selected physicochemical properties and evaluate their antimalarial activity in vitro against Plasmodium falciparum strains.
A solvent extraction method was developed and validated for the determination of the antimalarial drug, artemether and its active metabolite dihydroartemisinin (DHA) in malaria patient plasma samples. An AB Sciex 4000 triple quadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode was used for detection in the positive ionisation mode. Liquid-liquid extraction was followed by PFP liquid chromatography and tandem mass spectrometry. Stable isotope labelled artemether and DHA was used as internal standards. The calibration range was between 2.00 and 500 ng/ml for both artemether and DHA during the original validation and the upper limit was lowered to 200 ng/ml during a re-instatement validation, prior to sample analysis. The assay was used to measure artemether and DHA in human plasma samples, which were generated from a safety and efficacy clinical trial in Mbarara, Uganda; as well as for a pharmacokinetic interaction study between the antimalarial combination artemether/lumefantrine and combination antiretroviral therapy including nevirapine in HIV-infected adults.
The ongoing global spread of Tomato yellow leaf curl virus (TYLCV; Genus Begomovirus, Family Geminiviridae) represents a serious looming threat to tomato production in all temperate parts of the world. Whereas determining where and when TYLCV movements have occurred could help curtail its spread and prevent future movements of related viruses, determining the consequences of past TYLCV movements could reveal the ecological and economic risks associated with similar viral invasions. Towards this end we applied Bayesian phylogeographic inference and recombination analyses to available TYLCV sequences (including those of 15 new Iranian full TYLCV genomes) and reconstructed a plausible history of TYLCVs diversification and movements throughout the world. In agreement with historical accounts, our results suggest that the first TYLCVs most probably arose somewhere in the Middle East between the 1930s and 1950s (with 95% highest probability density intervals 1905-1972) and that the global spread of TYLCV only began in the 1980s after the evolution of the TYLCV-Mld and -IL strains. Despite the global distribution of TYLCV we found no convincing evidence anywhere other than the Middle East and the Western Mediterranean of epidemiologically relevant TYLCV variants arising through recombination. Although the region around Iran is both the center of present day TYLCV diversity and the site of the most intensive ongoing TYLCV evolution, the evidence indicates that the region is epidemiologically isolated, which suggests that novel TYLCV variants found there are probably not direct global threats. We instead identify the Mediterranean basin as the main launch-pad of global TYLCV movements.
Tomato leaf curl disease (TLCD) and and tomato yellow leaf curl (TYLCD) is caused by a number of begomovirus species that collectively threaten tomato production worldwide. We report here that an ongoing TLCD and TYLCD epidemic in Iran is caused by variants of tomato leaf curl Palampur virus (ToLCPMV), a newly proposed begomovirus species previously only detected in India. Besides infecting tomatoes, we identified ToLCPMV as the causal agent of a cucurbit disease that has devastated greenhouse cucumber and melon farms in Jiroft, southeastern Iran. We found no convincing evidence that the ToLCPMV DNA-B sequences have been derived through inter-species recombination, however, all of the currently sampled ToLCPMV DNA-A sequences are descendents of a sequence that probably arose through recombination between a ToLCNDV isolate and a currently unsampled geminivirus species that falls outside the ToLCNDV-ToLCPMV cluster. The increasing incidence of ToLCPMV in different cultivated species throughout Iran may signal the emergence of a serious new threat to agricultural production throughout the Middle East.
We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure.
Despite the important role of fluoroquinolones and the predominant use of ofloxacin for treating multidrug-resistant tuberculosis in South Africa, there are limited data on ofloxacin pharmacokinetics in patients with multidrug-resistant tuberculosis, no ofloxacin pharmacokinetic data from South African patients, and no direct assessment of the relationship between ofloxacin pharmacokinetics and the MIC of ofloxacin of patient isolates. Our objectives are to describe ofloxacin pharmacokinetics in South African patients being treated for multidrug-resistant tuberculosis and assess the adequacy of ofloxacin drug exposure with respect to the probability of pharmacodynamic target attainment (area under the time curve/MIC ratio of at least 100). Sixty-five patients with multidrug-resistant tuberculosis were recruited from 2 hospitals in South Africa. We determined the ofloxacin MICs for the Mycobacterium tuberculosis isolates from baseline sputum specimens. Patients received daily doses of 800 mg ofloxacin, in addition to other antitubercular drugs. Patients underwent pharmacokinetic sampling at steady state. NONMEM was used for data analysis. The population pharmacokinetics of ofloxacin in this study has been adequately described. The probability of target attainment expectation in the study population was 0.45. Doubling the dose to 1,600 mg could increase this to only 0.77. The currently recommended ofloxacin dose appeared inadequate for the majority of this study population. Studies to assess the tolerability of higher doses are warranted. Alternatively, ofloxacin should be replaced with more potent fluoroquinolones.
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