Homogenization of the long-term global ozonesonde records

Póster presentado en: WMO Technical Conference on Meteorological and Environmental Instruments and Methods of Observation celebrada del 10 al 13 de octubre de 2022 en París

Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Low-grade extraskeletal osteosarcomas (ESOS) are extremely rare.</p> <p>Case presentation</p> <p>We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter) calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of <it>MDM2 </it>and <it>CDK4 </it>oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms.</p> <p>Conclusion</p> <p>We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases.</p

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

Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks gestation, at the onset of labour and the rapid testing of infants

<p>Abstract</p> <p>Background</p> <p>Preventing HIV transmission is a worldwide public health issue. Vertical transmission of HIV from a mother can be prevented with diagnosis and treatment, but screening incurs cost. The U.S. Virgin Islands follows the mainland policy on antenatal screening for HIV even though HIV prevalence is higher and rates of antenatal care are lower. This leads to many cases of vertically transmitted HIV. A better policy is required for the U.S. Virgin Islands.</p> <p>Methods</p> <p>The objective of this research was to estimate the cost-effectiveness of relevant HIV screening strategies for the antenatal population in the U.S. Virgin Islands. An economic model was used to evaluate the incremental costs and incremental health benefits of nine different combinations of perinatal HIV screening strategies as compared to existing practice from a societal perspective. Three opportunities for screening were considered in isolation and in combination: by 14 weeks gestation, at the onset of labor, or of the infant after birth. The main outcome measure was the cost per life year gained (LYG).</p> <p>Results</p> <p>Results indicate that all strategies would produce benefits and save costs. Universal screening by 14 weeks gestation and screening the infant after birth is the recommended strategy, with cost savings of $1,122,787 and health benefits of 310 LYG. Limitations include the limited research on the variations in screening acceptance of screening based on specimen sample, race and economic status. The benefits of screening after 14 weeks gestation but before the onset of labor were also not addressed.</p> <p>Conclusion</p> <p>This study highlights the benefits of offering screening at different opportunities and repeat screening and raises the question of generalizing these results to other countries with similar characteristics.</p

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies

Background: Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children. Results: Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW&lt;2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months. Conclusion: Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates