Browsing by Subject "Longitudinal Studies"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Open Access
    The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
    (2017) Sharma, Shilpee; Aralaguppe, Shambhu G; Abrahams, Melissa-Rose; Williamson, Carolyn; Gray, Clive; Balakrishnan, Pachamuthu; Saravanan, Shanmugam; Murugavel, Kailapuri G; Solomon, Suniti; Ranga, Udaykumar
    Abstract Background HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study. Methods In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C. Results In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24–36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years. Conclusion We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1.
  • Thumbnail Image
    Item
    Open Access
    The use of the EQ-5D-Y health related quality of life outcome measure in children in the Western Cape, South Africa: psychometric properties, feasibility and usefulness - a longitudinal, analytical study
    (2017) Scott, Des; Ferguson, Gillian D; Jelsma, Jennifer
    Abstract Background The EQ-5D-Y, an outcome measure of Health Related Quality of Life (HRQoL) in children, was developed by an international task team in 2010. The multinational feasibility, reliability and validity study which followed was undertaken with mainly healthy children. The aim of this study was to investigate the psychometric properties of the EQ-5D-Y when used to assess the HRQoL of children with different health states. Method A sample of 224 children between eight and twelve years were grouped according to their health state. The groups included 52 acutely ill children, 67 children with either a chronic health condition or disability and 105 mostly healthy, mainstream school children as a comparator. They were assessed at baseline, at three months and at six months. An analysis of the psychometric properties was performed to assess the reliability, validity and responsiveness of the EQ-5D-Y in the different groups of children. Cohen’s kappa, the intraclass correlation coefficient, Pearson Chi-square, Kruskal-Wallis ANOVA and effect size of Wilcoxon Signed-rank test were used to determine the reliability, validity and responsiveness of the instrument. Results The EQ-5D-Y dimensions were found to be reliable on test-retest (kappa varying from 0.365 to 0.653), except for the Usual Activities dimension (kappa 0.199). The Visual Analogue Scale (VAS) was also reliable (ICC = 0.77). Post-hoc analysis indicated that dimensions were able to discriminate between acutely ill and healthy children (all differences p < 0.001). The acutely ill children had the lowest ranked VAS (median 50, range 0–100), indicating worst HRQoL and was the only group significantly different from the other three groups (p < 0.001 in all cases). Convergent validity between all similar EQ-5D-Y and PedsQL, WeeFIM and Faces Pain Scale dimensions was only evident in the acutely ill children. As expected the largest treatment effect was also observed in these children (Wilcoxon Signed-rank test for VAS was 0.43). Six of the nine therapists who took part in the study, found the measure quick and easy to apply, used the information in the management of the child and would continue to use it in future. Conclusions The EQ-5D-Y could be used with confidence as an outcome measure for acutely-ill children, but demonstrated poorer psychometric properties in children with no health condition or chronic conditions. It appears to be feasible and useful to include the EQ-5D-Y in routine assessments of children.
  • Thumbnail Image
    Item
    Open Access
    Validation of a guideline-based composite outcome assessment tool for asthma control
    (2007) Spencer, Sally; Mayer, Bhabita; Bendall, Kate L; Bateman, Eric D
    BackgroundA global definition of asthma control does not currently exist. The purpose of this study was to validate two new guideline-based composite measures of asthma control, defined as totally controlled (TC) asthma and well controlled (WC) asthma.MethodsWe used data from 3416 patients randomised and treated in the multi-centre Gaining Optimal Asthma controL (GOAL) study. The criteria comprising the asthma control measures were based on Global Initiative for Asthma/National Institutes of Health guidelines. This validation study examined the measurement properties of the asthma control measures using data from run-in, baseline, 12 and 52 weeks. Forced expiratory volume in 1 second (FEV1) and the Asthma Quality of Life Questionnaire (AQLQ) were used as the reference criteria in the validation analysis.ResultsBoth measures had good discriminative ability showing significant differences in FEV1 and AQLQ scores between control classification both cross-sectionally and longitudinally (p < 0.001). Overall both of the composite measures accounted for more of the variance in FEV1 after 52 weeks than the individual components of each asthma control measure. Both of the reference criteria were independently related to each asthma control measure (p < 0.0001). The measures also had good predictive validity showing significant differences in FEV1 and AQLQ scores at 52 weeks by control classification at 12 weeks (p < 0.0001).ConclusionThe guideline-based composite asthma control measures of WC asthma and TC asthma have good psychometric properties and are both valid functional indices of disease control in asthma.