Browsing by Author "Innes, Steve"
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- ItemAccurate arterial path length estimation for pulse wave velocity calculation in growing children and adolescents(Gates Open Research, 2021-05) Witbooi, Lee-Roy C.; Page, Ben; Pitcher, Richard D.; Innes, SteveBackground: Most adult cardiovascular disease begins in childhood. Given the burgeoning obesity pandemic in children worldwide, there is a need for precise and scalable surveillance methods to detect subclinical cardiovascular disease in children and adolescents. Early detection allows early intervention and intensified primary prevention strategies in affected individuals. Carotid-femoral pulse wave velocity (PWV) directly measures arterial wall stiffness, an early feature of atherosclerosis. Calculation of PWV in growing children requires an accurate estimation of the true distance travelled by the aorto-femoral pressure wave, using surface anatomy landmarks. However, a variety of methods are used to estimate this distance, and these have not previously been investigated in growing children and adolescents. We sought to investigate this by comparing true arterial path length measured on computerized tomography (CT) scans, with a variety of estimations based on surface anatomy landmarks. Methods: Arterial path lengths were measured using multi-planar reformation (MPR) imaging software. These measurements were then compared with the surface anatomy measurements obtained using the same MPR imaging software. The fidelity of a variety of arterial path length estimation methods was tested. Results: The surface anatomy distance between the suprasternal notch and the angle of the mandible (PWV recording site in the neck), should be adjusted using the formula y=4.791+(1.0534*x). This value subtracted from the unadjusted distance from the suprasternal notch to the umbilicus, through the mid-inguinal crease to the femoral PWV recording site, provides the simplest reliable approximation of true intraluminal distance travelled. Conclusions: There is high correlation between the surface anatomy distances and the arterial path lengths they represent; however, these are not equal. Most surface anatomy measurements require adjustment using the formulae that we have provided, to accurately estimate the true distance travelled by the pulse wave.
- ItemComparative study of different brands of stavudine capsules for the off-label 'opened capsule' dosing method recommended for HIV-infected infants and children in resource-limited settings(Health and Medical Publishing Group, 2009) Innes, Steve; Smuts, Marlize; Cotton, Mark F.; Seifart, Heiner; Rosenkranz, BerndIntroduction. If a caregiver does not have access to a refrigerator, the South African National Department of Health advises that stavudine adult capsule formulations be employed using the off-label 'opened capsule' dosing method. The accuracy of this dosing method has not previously been validated. Aim. To assess the accuracy of the off-label opened capsule method for stavudine dosing in infants and children. In addition, we assessed the relative ease of dispersion of generic and original capsule preparations in water to determine which preparations, if any, are suitable for the off-label opened capsule dosing method. Method. We evaluated 10 Zerit (Bristol-Myers Squibb), 5 Stavudine (Aspen), and 5 Stavir (Cipla) capsules. Each capsule was dispersed in 30 ml water, creating 20 separate solutions. Timed dispersion of each generic was compared with that of the original (Zerit). Each solution was then centrifuged to remove sediment, and the concentration of active drug (mg/ml) was analysed by high-performance liquid chromatography. Results. The ease of dispersion of the contents of Aspen Stavudine capsules was equivalent to that of Zerit, and resulted in a mean recovery of active drug from solution of over 97%, confirming the accuracy of this dosing method. The contents of Stavir capsules, however, were extremely difficult to disperse in water despite prolonged agitation; consequently, the recovery of active drug from the solution was reduced. Conclusion. The accuracy of the off-label opened capsule dosing method for stavudine is acceptable. There is no need to instruct caregivers to include sediment in the aliquot given to the infant. However, studies that confirm adequate bioavailability and efficacy are needed. In addition, it is important to avoid supplying generic capsules the contents of which do not disperse easily in water, as this may lead to a significant reduction in the amount of active drug that a child receives.
- ItemEarly severe HIV disease precedes early antiretroviral therapy in infants : are we too late?(International AIDS Society, 2014-06) Innes, Steve; Lazarus, Erica; Otwombe, Kennedy; Afaaf Liberty, Afaaf; Germanus, Ramona; Janse van Rensburg, Anita; Grobbelaar, Nelis; Hurter, Theunis; Eley, Brian; Violari, Avy; Cotton, Mark F.Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral therapy (ART) by three months of age in a programmatic setting in South Africa. Design: This was a programmatic cohort study. Methods: Electronic and manual data extraction from databases and antiretroviral registers in 20 public clinics in Cape Town and electronic data extraction from a large ART service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of all infants initiated on ART by three months of age between June 2007 and September 2010 were extracted. Demographics, immunological and clinical stage at ART initiation were analyzed descriptively by chi-square, two-sample t-test and Kaplan Meier methods. Results: A total of 403 records were identified: 88 in Cape Town and 315 in Soweto. Median age at ART initiation was 8.4 [interquartile range (IQR): 7.2 9.7] weeks. At ART initiation, 250 infants (62%) had advanced HIV disease (CD4% B25% or absolute CD4B1500 cells/mm3 or WHO clinical Stage 3 or 4). Median age at ART initiation by site was 10.3 (IQR: 8.2 11.9) weeks in Cape Town and 8.6 (IQR: 7.7 10.0) weeks in Soweto infants (pB0.0001). In Cape Town, 73 infants (83%) had advanced HIV disease at ART initiation, compared to 177 infants (56%) in Soweto (pB0.0001). On logistic regression, each month increase in age at ART initiation lowered the odds of initiating ART in an optimal state (OR: 0.56, CI: 0.36 0.94) and increased the odds of advanced HIV disease at ART initiation (OR: 1.69, CI: 1.05 2.71). Conclusions: ART initiation by three months of age may not adequately prevent disease progression. New emphasis on early diagnosis and rapid initiation of ART in the first weeks of life are essential to further reduce infant mortality.
- ItemHigh prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy : a cross-sectional study(BioMed Central, 2012-11) Innes, Steve; Cotton, Mark F.; Haubrich, Richard; Conradie, Maria M.; Van Niekerk, Margaret; Edson, Clair; Rabie, Helena; Jain, Sonia; Sun, Xiaoying; Zollner, Ekkehard W.; Hough, Stephen; Browne, Sara H.Background: Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. Methods: In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants. Results: Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%–45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008). Conclusions: The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resourcelimited settings where specialized skills and equipment are not available.
- ItemLipoatrophy/lipohypertrophy outcomes after antiretroviral therapy switch in children in the UK/Ireland(Public Library of Science, 2017) Innes, Steve; Harvey, Justin; Collins, Intira Jeannie; Cotton, Mark F.; Judd, AliBackground: Following widespread use of stavudine, a thymidine analogue, in antiretroviral therapy (ART) over the past three decades, up to a third of children developed lipoatrophy (LA) and/or lipohypertrophy (LH). Following phasing-out of stavudine, incidence of newly-diagnosed LA and LH declined dramatically. However, the natural history of existing cases should be explored, particularly with prolonged protease inhibitor exposure. Methods: The Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort study of most HIV-infected children in the United Kingdom and Ireland. Those on ART with a LA/LH assessment recorded in 2003–2011 were included. Assessments were completed annually by consultant physicians. Using the 0–3 grading system, LA or LH was defined as grade 2 or 3. Resolution was defined as return to grade 1 or 0 in all body regions. Results: Of 1345 children followed for median (IQR) 5.5 (2.9, 8.2) years after ART initiation, 30 developed LA and 27 developed LH, all at least 2 years after ART initiation. Median age at LA diagnosis was 11 (10, 13) years and at LH diagnosis was 13 (11, 15) years. Children with LA were more likely white (p<0.0001); lower height-for-age z-score at ART initiation (p = 0.02); initiated ART earlier (p = 0.04), with longer ART exposure (p = 0.04). Children with LH were similar to those without. Analysis of individual drugs revealed that LA was associated with greater duration of exposure to stavudine and didanosine; while LH was associated with greater duration of exposure to stavudine and ritonavir (given alone or in combination with another protease inhibitor). Median time in follow-up following ART switch was 2.8 (1.9, 4.9) and 2.5 (1.6, 4.7) years respectively. Resolution occurred in 10 (30%) of LA cases (median time to resolution 2.3 [1.8, 3.6] years) and 3 (11%) of LH cases (median time to resolution 2.0 [1.7, 2.1] years). Conclusions: Prevalence of LA and LH were low, with some resolution noted, especially for LA. More long-term data are needed.
- ItemLow-dose stavudine trials: a public health priority for developing countries(AOSIS Publishing, 2012-03-13) Venter, W. D. Francois; Innes, Steve; Cotton, MarkThe debate around relooking at stavudine dosing, both in terms of the adult low-dose stavudine study and more broadly, is welcome. The study being proposed to evaluate low-dose stavudine v. tenofovir is a fairly standard placebo-controlled non-inferiority study. The study design is not controversial; however, the choice of study drug has attracted critical attention.