Creating a data collection and management platform to support measurement of adolescent HIV care transition processes within low- and middle-income countries: The GRADUATE project.

Few national programs and research cohorts within low- and middle-income countries (LMICs) document transition-related processes and outcomes for adolescents and young adults living with HIV (AYLH) transitioning to adulthood. Between 2017-2020, The Global fRAmework of Data collection Used for Adolescent HIV Transition Evaluation (GRADUATE) project convened a collaborative advisory group to identify key variables and definitions capturing the process, predictors, and outcomes across the transition period. In total, 114 variables identified as essential to measuring AYLH transition-related data were identified and formatted into a GRADUATE Data Exchange Standard (DES), which was added to and harmonized with the existing International epidemiology Databases to Evaluate AIDS (IeDEA) DES.

ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013-2019): a retrospective cohort study.

Introduction: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception.

Methods: We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019.

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

Aims: The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa.

The IeDEA harmonist data toolkit: A data quality and data sharing solution for a global HIV research consortium.

We describe the design, implementation, and impact of a data harmonization, data quality checking, and dynamic report generation application in an international observational HIV research network. The IeDEA Harmonist Data Toolkit is a web-based application written in the open source programming language R, employs the R/Shiny and RMarkdown packages, and leverages the REDCap data collection platform for data model definition and user authentication. The Toolkit performs data quality checks on uploaded datasets, checks for conformance with the network's common data model, displays the results both interactively and in downloadable reports, and stores approved datasets in secure cloud storage for retrieval by the requesting investigator.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

Objective: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa.

Study Design And Setting: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption.

Improving Methods to Classify Perinatal versus Nonperinatal HIV Acquisition in Young Adolescents 10-14 Years of Age.

Mode of HIV acquisition for adolescents with HIV is often not recorded within routine healthcare databases. Hence, age at enrollment in HIV care is often used as a proxy for perinatal versus nonperinatal infection. Using routine cohort data from adolescents presenting for HIV care 10-14 years of age, we developed logistic regression models to predict likely mode of infection.

Mental health, substance use and viral suppression in adolescents receiving ART at a paediatric HIV clinic in South Africa.

Introduction: Mental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders.

Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.

Introduction: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa.

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis.

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia.

Isolation of Separate Ureaplasma Species From Endotracheal Secretions of Twin Patients.

Isolation of Ureaplasma spp. from preterm neonates and the association with development of bronchopulmonary dysplasia has been previously investigated. However, few studies have contrasted the nature of infection in twins.

Growth of HIV-Exposed Uninfected Infants in the First 6 Months of Life in South Africa: The IeDEA-SA Collaboration.

Background: HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life.

Methods: This is a retrospective cohort based on routine clinical data from two South African PMTCT programmes.

Incidence of AIDS-defining and Other Cancers in HIV-positive Children in South Africa: Record Linkage Study.

Background: Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa.

Methods: We linked the records of 5 ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers.

Antibiotic Resistance among Clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013.

Ureaplasma spp. are associated with numerous clinical sequelae with treatment options being limited due to patient and pathogen factors. This report examines the prevalence and mechanisms of antibiotic resistance among clinical strains isolated from 95 neonates, 32 women attending a sexual health clinic, and 3 patients under investigation for immunological disorders, between 2007 and 2013 in England and Wales.

Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

Background: The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.

Objectives: To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.

Temporal trends in the characteristics of children at antiretroviral therapy initiation in southern Africa: the IeDEA-SA Collaboration.

Background: Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration.

Methodology/principal Findings: Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed.

Short-term risk of anaemia following initiation of combination antiretroviral treatment in HIV-infected patients in countries in sub-Saharan Africa, Asia-Pacific, and central and South America.

Background: The objective was to examine the short-term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV-infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration.

Methods: Anaemia was defined as haemoglobin of < 10 g/dL. Patients were included if they started cART with three or more drugs, had prior haemoglobin of > = 10 g/dL, and had one or more follow-up haemoglobin tests.

Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa.

Objectives: To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts.

Methods: We included 18,706 adult patients starting ART in South Africa and 80,937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months.

Relationship of proteinases and proteinase inhibitors with microbial presence in chronic lung disease of prematurity.

Background: A proteolytic imbalance has been implicated in the development of "classical" chronic lung disease of prematurity (CLD). However, in "new" CLD this pattern has changed. This study examines the longitudinal relationship between neutrophil proteinases and their inhibitors in ventilated preterm infants and their relationship to microbial colonisation.

Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

Objectives: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007.

Design And Setting: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal.

Subjects: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008.

Concurrent titration and determination of antibiotic resistance in ureaplasma species with identification of novel point mutations in genes associated with resistance.

Antibiotic resistance determination of Ureaplasma spp. (Ureaplasma parvum and Ureaplasma urealyticum) usually requires predetermination of bacterial titer, followed by antibiotic interrogation using a set bacterial input. This 96-well method allows simultaneous quantification of bacteria in the presence and absence of antibiotics.

Does Ureaplasma spp. cause chronic lung disease of prematurity: ask the audience?

Ureaplasma has long been implicated in the pathogenesis of both preterm labour and neonatal morbidity, particularly chronic lung disease of prematurity (CLD), but despite numerous studies, reviews and meta-analyses, its exact role remains unclear. Many papers call for a definitive randomised control trial to determine if eradication of pulmonary Ureaplasma decreases the rates of CLD but few address in detail the obstacles to an adequately powered clinical trial. We review the evidence for Ureaplasma as a causative agent in CLD, asking why a randomised control trial has not been performed.

Monoclonal anti-neutrophil elastase antibody characterisation: ability to block function, detect free versus serpin-complexed enzyme and stain intracellular granules.

Four commercially available monoclonal antibodies (clones NP57, 256-3K1, 39A and 203) were characterised for their ability to block human neutrophil elastase (HNE) activity; capture free purified HNE or neutralised HNE in complex with alpha-1-antitrypsin (AAT); detect HNE and HNE-AAT by Western blot analysis; and detect intracellular HNE by flow cytometry. The ability to block small substrate cleavage by HNE ranged from 0% (265-3K1) to 15-18% (39A and 203) to 100% (NP57). All antibodies had the ability to capture free HNE with varying degrees of sensitivity, but HNE neutralisation by AAT resulted in complete loss of detection (NP57) to 2-4-fold decreased detection (39A and 203) to a 8-fold increase in detection (265-3K1).

The role of inflammation and infection in the development of chronic lung disease of prematurity.

CLD is a significant cause of infant morbidity and mortality. The lung injury is multifactorial in origin with supplemental oxygen and ventilatory damage being only part of the picture. Antenatal and postnatal infection and inflammation are also important in the development of CLD, although their precise role has still to be fully ascertained.

Cytomegalovirus: a cause of colonic stricture in a premature infant.

A 27-week-old infant developed symptoms of bowel obstruction when full enteral feeds were started. Laparotomy revealed strictures in the ascending and proximal transverse colon. Right hemicolectomy was performed.

Antenatal infection and inflammation: what's new?

Purpose Of Review: Recently antenatal infection and inflammation have received significant attention because of their potential role in promoting premature labour and in causing morbidity in preterm infants including the development of chronic lung disease of prematurity and cerebral white matter changes. This review highlights recent developments in this field.

Recent Findings: Recent reports have improved our understanding of the inflammatory responses to antenatal infection although questions remain about the exact relationship between antenatal infection and inflammation.