An adapted algorithm for patient engagement in care for young people living with perinatal HIV in England

BACKGROUND: Evidence suggests that engagement in care (EIC) may be worse in young people living with perinatal HIV (YPLPHIV) compared to adults or children living with HIV. We took a published EIC algorithm for adults with HIV, which takes patients’ clinical scenarios into account, and adapted it for use in YPLPHIV in England, to measure their EIC. METHODS: The adult algorithm predicts when in the next 6 months the next clinic visit should be scheduled, based on routinely collected clinical indicators at the current visit. We updated the algorithm based on the latest adult guidelines at the time, and modified it for young people in paediatric care using the latest European paediatric guidelines. Paediatric/adolescent HIV consultants from the UK reviewed and adapted the resulting flowcharts. The adapted algorithm was applied to the Adolescent and Adults Living with Perinatal HIV (AALPHI) cohort in England. Data for 12 months following entry into AALPHI were used to predicted visits which were then compared to appointment attendances, to measure whether young people were in care in each month. Proxy markers (e.g. dates of CD4 counts, viral loads (VL)) were used to indicate appointment attendance. RESULTS: Three hundred sixteen patients were in AALPHI, of whom 41% were male, 82% of black African ethnicity and 58% born abroad. At baseline (time of AALPHI interview) median [IQR] age was 17 [15–18] years, median CD4 was 597 [427, 791] cells/µL and 69% had VL ≤50c/mL. 10 patients were dropped due to missing data. 306 YPLPHIV contributed 3,585 person months of follow up across the 12 month study in which a clinic visit was recorded for 1,204 months (38/1204 dropped due to missing data). The remaining 1,166 months were classified into 3 groups: Group-A: on ART, VL ≤ 50c/mL—63%(734/1,166) visit months, Group-B: on ART, VL > 50c/mL—27%(320/1,166) Group-C: not on ART-10%(112/1,166). Most patients were engaged in care with 87% (3,126/3,585) of months fulfilling the definition of engaged in care. CONCLUSIONS: The adapted algorithm allowed the varying clinical scenarios of YPLPHIV to be taken into account when measuring EIC. However availability of good quality surveillance data is crucial to ensure that EIC can be measured well

Evolution of CD4 T-Cell count with age in a cohort of young people growing up with perinatally acquired HIV

Background: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired HIV (PHIV). We examine changes and predictors of CD4 over time in PHIV in the UK and compare to published CD4 data in the general population.// Methods: PHIV followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onwards were included. Follow-up data from the UK Collaborative HIV Cohort Study were also used. Changes in CD4 count over time from age 10 to 20 years were analysed using mixed effects models. Potential predictors included demographics, age at ART start, nadir CD4 z-score (age-adjusted) in childhood and time-updated viral load.// Results: Of 1,258 PHIV included, 669 (53%) were female, median [IQR] age at ART initiation was 8.3 years [3.5, 12.1] and nadir CD4 z-score was -4.0 [-5.9, -2.5]. In multivariable analysis, mean CD4 count was higher in PHIV who started ART before age 10 and had a nadir CD4 z-score ≥-4 in childhood; these PHIV had a decline in CD4 count after age 10 which was comparable to the general population. Mean CD4 count was lower in PHIV who had started ART before age 10 and had a nadir CD4 z-score <-4 in childhood; for this group the decline in CD4 count after age 10 was steeper over time.// Conclusions: In children, as well as starting ART at an early age, optimising ART to maintain a higher CD4 z-score during childhood may be important to maximize immune reconstitution later in life

A qualitative understanding of the effects of reusable sanitary pads and puberty education: Implications for future research and practice

BACKGROUND: The management of menstruation has come to the fore as a barrier to girls’ education attainment in low income contexts. Interventions have been proposed and piloted, but the emerging nature of the field means limited evidence is available to understand their pathways of effect. // METHODS: This study describes and compares schoolgirls’ experiences of menstruation in rural Uganda at the conclusion of a controlled trial of puberty education and sanitary pad provision to elucidate pathways of effect in the interventions. Semi-structured interviews were undertaken with schoolgirls who participated in the Menstruation and the Cycle of Poverty trial concurrent with the final set of quantitative surveys. A framework approach and cross-case analysis were employed to describe and compare the experiences of 27 menstruating girls across the four intervention conditions; education (n = 8), reusable sanitary pads (n = 8), education with reusable sanitary pads (n = 6), and control (n = 5). // RESULTS: Themes included: menstrual hygiene, soiling, irritation and infection, physical experience, knowledge of menstruation, psychological, social and cultural factors, and support from others. Those receiving reusable pads experienced improvements in comfort and reliability. This translated into reduced fears around garment soiling and related school absenteeism. Other menstrual hygiene challenges of washing, drying and privacy remained prominent. Puberty education improved girls’ confidence to discuss menstruation and prompted additional support from teachers and peers. // CONCLUSIONS: Findings have important implications for the development and evaluation of future interventions. Results suggest the provision of menstrual absorbents addresses one core barrier to menstrual health, but that interventions addressing broader needs such as privacy may improve effectiveness. Puberty education sessions should increase attention to body awareness and include strategies to address a wider range of practical menstrual challenges, including pain management. Interviews revealed possibilities for improving quantitative surveys in future research

CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

Objectives: The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). Methods: Data from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression. Results: In 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long-term CD4% was highest in those with a TI lasting 1 to <3 months, those with r-ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%. Conclusions: After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Menstruation and the cycle of poverty: a cluster quasi-randomised control trial of sanitary pad and puberty education provision in Uganda

BACKGROUND: Poor menstrual knowledge and access to sanitary products have been proposed as barriers to menstrual health and school attendance. In response, interventions targeting these needs have seen increasing implementation in public and private sectors. However, there has been limited assessment of their effectiveness. // OBJECTIVES: Assess the impact of providing reusable sanitary pads and puberty education on girls’ school attendance and psychosocial wellbeing outcomes. // METHODS: A cluster quasi-randomised controlled trial was conducted across 8 schools, including 1124 girls, in rural Uganda. Schools were allocated to one of four conditions: the provision of puberty education alone; reusable sanitary pads alone; puberty education and reusable sanitary pads; and a control (no intervention). The primary outcome was school attendance. Secondary outcomes reflected psychosocial wellbeing. // RESULTS: At follow-up, school attendance had worsened for girls across all conditions. Per-protocol analysis revealed that this decline was significantly greater for those in the control condition d = 0.52 (95%CI 0.26–0.77), with those in control schools having a 17.1% (95%CI: 8.7–25.5) greater drop in attendance than those in any intervention school. There were no differences between the intervention conditions. High rates of school drop-out and transfer meant the trial suffered from substantial participant drop-out. Intention-to-treat analyses using two different imputation strategies were consistent with the main results, with mean differences of 5.2% attendance in best-case and 24.5% in worst-case imputations. Results were robust to adjustments for clustering. There was no impact of the interventions on girls’ self-reported shame or insecurity during menstruation. // CONCLUSION: Results of the trial support the hypothesised positive impact of providing sanitary pads or puberty education for girls’ school attendance in a developing country context. Findings must be interpreted with caution in light of poor participant retention, intervention fidelity, and the attendance measures used

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

INTRODUCTION Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood

The Simons Observatory: Science goals and forecasts

The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes (SATs) and one large-aperture 6-m telescope (LAT), with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The SATs will target the largest angular scales observable from Chile, mapping ~10% of the sky to a white noise level of 2 $\mu$K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, $r$, at a target level of $\sigma(r)=0.003$. The LAT will map ~40% of the sky at arcminute angular resolution to an expected white noise level of 6 $\mu$K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the LSST sky region and partially with DESI. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources

Cognition and bimanual performance in children with unilateral cerebral palsy: Protocol for a multicentre, cross-sectional study

© 2018 The Author(s). Background: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. Methods/Design: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. Discussion: This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy

Children living with HIV in Europe: do migrants have worse treatment outcomes?

OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. RESULTS: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96-2.38, p = 0.072). CONCLUSIONS: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring