Antiretroviral treatment for children

No Abstract. South African Medical Journal Vol. 96(9) (Part 2) 2006: 988-99

Antiretroviral treatment for children

Objective: To describe the response of children during their first year on highly active antiretroviral therapy (HAART). Design: Retrospective, descriptive. Setting. Tertiary, referral hospital. Subjects: All HIV-infected children commenced on HAART from 1 August 2002 until 31 December 2004. Outcome measures: Children were retrospectively restaged using the WHO 4-stage clinical classification and CDC immunological staging system. After commencing HAART, patients were assessed at monthly intervals for the first 6 months and thereafter mostly 3-monthly. Baseline and 6- monthly CD4 counts and viral loads were performed. Results. Of 409 children commenced on HAART, 50.6% were < 2 years old, 62.7% had severe clinical disease and 76.6% had severe immune suppression. After 1 year, 65.8% were alive and continued HAART at the hospital, 11.2% had been transferred to another antiretroviral site, 15.4% had died, 4.6% were lost to follow-up and treatment had been discontinued in 2.9%. Kaplan-Meier survival estimate for 407 children at 1 year was 84% (95% confidence interval (CI) 80 - 87%). On multivariate analysis, survival was adversely affected in children with WHO stage 4 v. stage 2 and 3 disease (adjusted hazard ratio (HR): 5.26 (95% CI 2.25 - 12.32), p = 0.000), age < 12 months (adjusted HR: 2.46 (95% CI 1.48 - 4.09), p = 0.001) and CD4 absolute count (per 100 cell increase) (adjusted HR: 0.93 (95% CI 0.88 - 0.98), p = 0.013). In a separate multivariate model including only children with an initial viral load (N = 367), viral load r 1 million copies/ml (adjusted HR: 1.84 (95% CI 1.03 - 3.29)) and taking a protease inhibitor (PI)-based regimen (adjusted HR: 2.25 (95% CI 1.10 - 4.61)) were additionally independently associated with poorer survival; however, young age was not a significant predictor of mortality, after adjusting for viral load (p = 0.119). After 1 year of HAART 184/264 (69.7%) of children had a viral load < 400 copies/ml. Comparative analysis showed significant improvements in growth, immunological status and virological control. Conclusion: HAART can improve the health of many HIVinfected children with advanced disease, including those aged less than 2 years in resource-limited settings

Transcriptional response of ovine lung to infection with jaagsiekte sheep retrovirus

Jaagsiekte sheep retrovirus (JSRV) is the etiologic agent of ovine pulmonary adenocarcinoma (OPA), a neoplastic lung disease of sheep. OPA is an important economic and welfare issue for sheep farmers and a valuable naturally-occurring animal model for human lung adenocarcinoma. Here, we used RNA sequencing to study the transcriptional response of ovine lung tissue to infection by JSRV. We identified 1,971 ovine genes differentially-expressed in JSRV-infected lung compared to non-infected lung, including many genes with roles in carcinogenesis and immunomodulation. The differential expression of selected genes was confirmed using immunohistochemistry and RT-qPCR. A key finding was the activation of anterior-gradient-2, yes-associated protein-1 and amphiregulin in OPA tumor cells, indicating a role for this oncogenic pathway in OPA. In addition, there was differential expression of genes related to innate immunity including genes encoding cytokines, chemokines and complement system proteins. In contrast, there was little evidence for upregulation of genes involved in T-cell immunity. Many genes related to macrophage function were also differentially expressed, reflecting the increased abundance of these cells in OPA-affected lung tissue. Comparison of the genes differentially regulated in OPA with transcriptional changes occurring in human lung cancer revealed important similarities and differences between OPA and human lung adenocarcinoma. This study provides valuable new information on the pathogenesis of OPA and strengthens the use of this naturally occurring animal model for human lung adenocarcinoma

Enhancing diversity of clinical trial populations in multiple sclerosis

BACKGROUND: Demographic characteristics, social determinants of health (SDoH), health inequities, and health disparities substantially influence the general and disease-specific health outcomes of people with multiple sclerosis (MS). Participants in clinical trials do not represent all people with MS treated in practice. Objective: To provide recommendations for enhancing diversity and inclusion in clinical trials in MS. METHODS: We held an international workshop under the Auspices of the International Advisory Committee on Clinical Trials in MS (the “Committee”) to develop recommendations regarding diversity and inclusivity of participants of clinical trials in MS. Workshop attendees included members of the Committee as well as external participants. External participants were selected based on expertise in trials, SDoH, health equity and regulatory science, and diversity with respect to gender, race, ethnicity, and geography. RESULTS: Recommendations include use of diversity plans, community engagement and education, cultural competency training, biologically justified rather than templated eligibility criteria, adaptive designs that allow broadening of eligibility criteria over the course of a trial, and logistical and practical adjustments to reduce study participant burden. Investigators should report demographic and SDoH characteristics of participants. CONCLUSION: These recommendations provide sponsors and investigators with methods of improving diversity and inclusivity of clinical trial populations in MS

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport

Funding: LF acknowledges financial support from the UK Research and Innovation (UKRI) Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in Applied Photonics (Grant No. EP/S022821/1) and the Laser Research and Therapy Fund (Grant No. SC030850).Significance Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photo- dynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT’s impact on brain tissue temperature.  Results The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J∕cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 μM. Increases in treatment time and light power (light fluence = 400 J∕cm2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 μM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer.  Conclusions With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.Peer reviewe

Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community

BACKGROUND AND OBJECTIVES: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. METHODS: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. RESULTS: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. CONCLUSION: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles

Priority setting: women’s health topics in multiple sclerosis

BackgroundA scoping review found that most studies on women’s health in multiple sclerosis (MS) focused on pregnancy, fetal/neonatal outcomes and sexual dysfunction. Few studies addressed menopause, contraception, gynecologic cancers/cancer screening. However, the perceived relative importance of these knowledge gaps to people living with MS and other partners is unknown. We engaged a range of partners, including people living with MS, health care providers, researchers, and patient advocacy groups, to set priorities for future research in women’s health in MS.MethodsWe employed a three-step global engagement process. First, we identified which broad research topics relevant to women’s health in MS were of highest priority using two surveys. Second, we developed specific research questions within these topics using focus groups. Finally, we prioritized the research questions with a third survey.ResultsOverall, 5,266 individuals responded to the initial surveys [n = 1,430 global survey, mean (SD) age 50.0 (12.6), all continents; n = 3,836 North American Research Committee on Multiple Sclerosis survey, mean (SD) age 64.8 (9.6), United States]. Menopause, sexual dysfunction, pregnancy, gynecologic cancer/cancer screening, hormones and parenthood were identified as the most important topics. Focus groups generated 80 potential research questions related to these topics. In the final survey 712 individuals prioritized these questions. The highest priority questions in each research topic were: (i) How do perimenopause and menopause affect disease activity, course, response to disease-modifying treatment and quality of life in MS; (ii) What are the most effective strategies for managing issues around sexual intimacy, including related to low sexual desire, changes in physical function, and MS symptoms; (iii) Are there long-term effects of disease-modifying therapies on the children of persons with MS; (iv) What are the short and long-term effects of disease-modifying drugs on gynecologic cancer risk, particularly for high efficacy disease-modifying drugs and hematopoietic stem cell transplantation; (v) Are there hormone related treatments that can stabilize fluctuations in MS symptoms; and (vi) How does MS fatigue impact parenting strategies.ConclusionPriorities for research relating to women’s health issues for persons with MS have been delineated using a collaborative process with key partners. Alignment of future research with these priorities should be monitored

Healthcare Comics

This comic, and the series of workshops that produced it, emerged from a partnership between the Comics Studies team in the School of Humanities, Social Sciences and Law, and the School of Dentistry, both at the University of Dundee in Scotland. In recent years we have produced many comics about oral health and homelessness, oral health and public engagement, and several other themes. This led to a series of workshops as part of the postgraduate student-learning Forum for Public Engagement, Inclusion, and Impact. This forum aims to raise awareness of health/oral health inequalities in culturally diverse groups. Over the course of three intensive workshops, ten students who were undertaking Masters programmes in Dental Public Health (MDPH) and Public Health (MPH) worked together to produce three stories, which are presented here. In each case, the aim was to think about ways to use comics to communicate an important health message, but also to show the impact health professionals can make on the experience of patients and the public more generally.Working in Dundee Comics Creative Space, and with help from Dr Damon Herd and Thushani Indumani Devi Wijesiri, the students worked in groups to produce scripts and sketches, which comics artist Clio Ding, who joined the workshops online from Singapore, then used to produce the final comics. The students did a fantastic job and responded with huge enthusiasm and creativity, and we are all very grateful to Clio for bringing these stories to life

Healthcare Comics

This comic, and the series of workshops that produced it, emerged from a partnership between the Comics Studies team in the School of Humanities, Social Sciences and Law, and the School of Dentistry, both at the University of Dundee in Scotland. In recent years we have produced many comics about oral health and homelessness, oral health and public engagement, and several other themes. This led to a series of workshops as part of the postgraduate student-learning Forum for Public Engagement, Inclusion, and Impact. This forum aims to raise awareness of health/oral health inequalities in culturally diverse groups. Over the course of three intensive workshops, ten students who were undertaking Masters programmes in Dental Public Health (MDPH) and Public Health (MPH) worked together to produce three stories, which are presented here. In each case, the aim was to think about ways to use comics to communicate an important health message, but also to show the impact health professionals can make on the experience of patients and the public more generally.Working in Dundee Comics Creative Space, and with help from Dr Damon Herd and Thushani Indumani Devi Wijesiri, the students worked in groups to produce scripts and sketches, which comics artist Clio Ding, who joined the workshops online from Singapore, then used to produce the final comics. The students did a fantastic job and responded with huge enthusiasm and creativity, and we are all very grateful to Clio for bringing these stories to life

The AEDUCATE Collaboration. Comprehensive antenatal education birth preparation programmes to reduce the rates of caesarean section in nulliparous women. Protocol for an individual participant data prospective meta-analysis

Introduction: Rates of medical interventions in normal labour and birth are increasing. This prospective meta-analysis (PMA) proposes to assess whether the addition of a comprehensive multicomponent birth preparation programme reduces caesarean section (CS) in nulliparous women compared with standard hospital care. Additionally, do participant characteristics, intervention components or hospital characteristics modify the effectiveness of the programme? Methods and analysis: Population: women with singleton vertex pregnancies, no planned caesarean section (CS) or epidural. Intervention: in addition to hospital-based standard care, a comprehensive antenatal education programme that includes multiple components for birth preparation, addressing the three objectives: preparing women and their birth partner/support person for childbirth through education on physiological/hormonal birth (knowledge and understanding); building women’s confidence through psychological preparation (positive mindset) and support their ability to birth without pain relief using evidence-based tools (tools and techniques). The intervention could occur in a hospital-based or community setting. Comparator: standard care alone in hospital-based maternity units. Outcomes: Primary: CS. Secondary: epidural analgesia, mode of birth, perineal trauma, postpartum haemorrhage, newborn resuscitation, psychosocial well-being. Subgroup analysis: parity, model of care, maternal risk status, maternal education, maternal socio-economic status, intervention components. Study design: An individual participant data (IPD) prospective meta-analysis (PMA) of randomised controlled trials, including cluster design. Each trial is conducted independently but share core protocol elements to contribute data to the PMA. Participating trials are deemed eligible for the PMA if their results are not yet known outside their Data Monitoring Committees. Ethics and dissemination: Participants in the individual trials will consent to participation, with respective trials receiving ethical approval by their local Human Research Ethics Committees. Individual datasets remain the property of trialists, and can be published prior to the publication of final PMA results. The overall data for meta-analysis will be held, analysed and published by the collaborative group, led by the Cochrane PMA group. Trial registration number: CRD42020103857