Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies.

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.

Exploring the psychometric properties of the Intellectual Disability versions of the Short Warwick-Edinburgh Mental Wellbeing Scale and Kidscreen10, self-reported by adolescents with intellectual disability.

BACKGROUND: There are no validated self-report measures that can be used to assess health and wellbeing in adolescents with intellectual disability (ID). METHOD: The aim of this study was to explore the psychometric properties of two newly adapted self-report health-related quality of life (HRQoL) and mental wellbeing measures: the Intellectual Disability versions of the Short Warwick-Edinburgh Mental Wellbeing Scale (ID-SWEMWBS) and Kidscreen10 (ID-Kidscreen10). For this, we used data from a sample of 427 adolescents (aged 11-19) with ID recruited from special school settings. RESULTS: Confirmatory factor analysis (CFA) was conducted to validate the factor structure of both measures. Internal consistency was assessed using Cronbach's alpha and test-retest reliability was analysed using intra-class correlation coefficients. The internal consistency measured using Cronbach's alpha was found to be in the range of 0.70-0.78, test-retest reliabilities were expressed using intra-class correlation coefficients that were found to be high for both measures (ID-SWEMWBS, 0.758; ID-Kidscreen10, 0.723), and the CFA supported the unidimensional structure of both measures. CONCLUSIONS: The results of this study indicate that the ID-SWEMWBS and ID-Kidscreen10 have very good psychometric properties and can be used as self-report measures to assess HRQoL and mental wellbeing in adolescents with ID.

Process evaluation of an intervention to improve HIV treatment outcomes among children and adolescents.

SETTING: Children and adolescents with HIV encounter challenges in initiation and adherence to antiretroviral therapy (ART). A community-based support intervention of structured home visits, aimed at improving initiation, adherence and treatment, was delivered by community health workers (CHWs) to children and adolescents newly diagnosed with HIV. OBJECTIVES: To 1) describe intervention delivery, 2) explore CHW, caregiver and adolescents' perceptions of the intervention, 3) identify barriers and facilitators to implementation, and 4) ascertain treatment outcomes at 12 months' post-HIV diagnosis. DESIGN: We drew upon: 1) semi-structured interviews (n = 22) with 5 adolescents, 11 caregivers and 6 CHWs, 2) 28 CHW field manuals, and 3) quantitative data for study participants (demographic information and HIV clinical outcomes). RESULTS: Forty-one children received at least a part of the intervention. Of those whose viral load was tested, 26 (n = 32, 81.3%) were virally suppressed. Interviewees felt that the intervention supported ART adherence and strengthened mental health. Facilitators to intervention delivery were convenience and rapport between CHWs and families. Stigma, challenges in locating participants and inadequate resources for CHWs were barriers. CONCLUSION: This intervention was helpful in supporting HIV treatment adherence among adolescents and children. Facilitators and barriers may be useful in developing future interventions.

CONTEXTE: Les enfants et les adolescents séropositifs rencontrent des difficultés dans l'initiation et l'adhésion à la thérapie antirétrovirale (TAR). Des agents de santé communautaires (CHW) ont mis en place une intervention de soutien communautaire sous forme de visites structurées à domicile visant à améliorer l'initiation, l'adhésion et le traitement, auprès d'enfants et d'adolescents nouvellement diagnostiqués séropositifs. OBJECTIFS: 1) Décrire la mise en œuvre de l'intervention, 2) explorer les perceptions de l'intervention par les CHW, les soignants et les adolescents, 3) identifier les obstacles et les facilitateurs de la mise en œuvre, et 4) vérifier les résultats du traitement 12 mois après le diagnostic du VIH. METHODES: Nous nous sommes appuyés sur 1) des entretiens semi-structurés (n = 22) avec 5 adolescents, 11 soignants et 6 CHW, 2) 28 manuels de terrain des CHW, et 3) des données quantitatives sur les participants à l'étude (informations démographiques et résultats cliniques du VIH). RÉSULTATS: Quarante et un enfants ont reçu au moins une partie de l'intervention. Parmi ceux dont la charge virale a été testée, 26 (n = 32 ; 81,3%) étaient sous suppression virale. Les personnes interrogées ont estimé que l'intervention soutenait l'adhésion au TAR et renforçait la santé mentale. Les facilitateurs de la mise en œuvre de l'intervention étaient la commodité et les rapports entre les CHW et les familles. La stigmatisation, les difficultés à trouver des participants et les ressources inadéquates pour les CHW étaient des obstacles. CONCLUSION: Cette intervention a été utile pour soutenir l'adhésion au traitement du VIH chez les adolescents et les enfants. Les facilitateurs et les obstacles peuvent être utiles pour développer de futures interventions.

Involving adolescents with intellectual disability in the adaptation of self-reported subjective well-being measures: participatory research and methodological considerations.

BACKGROUND: The measurement of subjective well-being is challenging with samples of adolescents with intellectual disability (ID) given the cognitive and linguistic difficulties they face in comprehending standardised measures, and as such is primarily based on proxy reports. The lack of appropriate tools needs to be addressed so that adolescents with ID can self-report on their own well-being. The current study reports on the use of participatory research methods to adapt and modify two standardised self-report measures of subjective well-being suitable for completion by adolescents with ID. METHOD: Two special schools were recruited for this study. At each school, staff (n = 15) and pupils aged 11-17 years (n = 35) participated. A series of co-design workshops were conducted to adapt two standardised subjective well-being measures: Kidscreen-10 and short-form Warwick-Edinburgh Mental Well-being Scale. RESULTS: Specific aspects for measure adaption were identified: simplifying the item wording and phrasing; inclusion of pictorial communication symbols and visual prompts to represent the meaning of items; changing of tense of questions from past to present; asking questions rather than statements; reducing 5-point Likert scales to 3-point or dichotomous; presenting one item at a time during administration; and developing alternate formats of the survey to ensure inclusivity. CONCLUSIONS: This paper illustrates the value of using participatory research methods when working alongside adolescents with ID and offers methodological, as well as practical, guidance in the context of adapting subjective self-report measures for this target group, serving as a guide to fellow researchers and clinicians interested in modifying or developing self-report measures for adolescents with ID.

Effects of Maternal Suicidal Ideation on Child Cognitive Development: A Longitudinal Analysis.

This study aimed to assess the association between suicidal ideation among mothers living with HIV in Zimbabwe and the cognitive development of their children. Participants were mother-child dyads recruited from two rural districts in Zimbabwe. Data were collected at baseline and 12 months follow-up. Suicidal ideation was assessed using item-10 from the Edinburgh postnatal depression scale. Mixed-effects linear regression was used to assess the association of child cognitive outcomes at follow-up (using the Mullen scales of early learning) with maternal suicidal ideation. Mothers with suicidal ideation at baseline (n = 171) tended to be younger, unmarried, experienced moderate to severe hunger, had elevated parental stress and depression symptoms compared with non-suicidal mothers (n = 391). At follow-up, emerging maternal suicidal ideation was associated with poorer child cognitive outcomes (adjusted mean difference - 6.1; 95% CI - 10.3 to - 1.8; p = 0.03). Suicidal ideation affects child cognitive development and should be addressed, particularly in HIV positive mothers.

Understanding Number Line Estimation in Williams Syndrome and Down Syndrome.

Previous studies suggest that tasks dependent on the mental number line may be difficult for Williams Syndrome (WS) and Down Syndrome (DS) groups. However, few have directly assessed number line estimation in these groups. The current study assessed 28 WS, 25 DS and 25 typically developing (TD) participants in non-verbal intelligence, number familiarity, visuo-spatial skills and number line estimation. Group comparisons indicated no differences in number line estimation. However, the WS group displayed difficulties with visuo-spatial skills and the DS group displayed difficulties with number familiarity. Differential relationships between number line estimation and visuo-spatial/number familiarity skills were observed across groups. Data is discussed in the context of assessment of skills in neurodevelopmental disorders.

Evaluating the effectiveness of a multi-component intervention on early childhood development in paediatric HIV care and treatment programmes: a randomised controlled trial.

BACKGROUND: HIV infection in a family may affect optimum child development. Our hypothesis is that child development outcomes among HIV-exposed infants will be improved through a complex early childhood stimulation (ECS) programme, and income and loans saving programme for HIV positive parents. METHODS: The study was a cluster-randomized controlled trial in 30 clinic sites in two districts in Zimbabwe. Clinics were randomised in a 1:1 allocation ratio to the Child Health Intervention for Development Outcomes (CHIDO) intervention or Ministry of Health standard care. The CHIDO intervention comprises three elements: a group ECS parenting programme, an internal savings and lending scheme (ISALS) and case-management home visits by village health workers. The intervention was aimed at caregiver-child dyads (child aged 0-24 months) where the infant was HIV exposed or infected. The primary outcomes were cognitive development (assessed by the Mullen Scales of Early Learning) and retention of the child in HIV care, at 12 months after enrolment. A comprehensive process evaluation was conducted. DISCUSSION: The results of this cluster-randomised trial will provide important information regarding the effects of multi-component interventions in mitigating developmental delays in HIV-exposed infants living in resource-limited environments. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry ( www.pactr.org ), registration number PACTR201701001387209; the trial was registered on 16th January 2017 (retrospectively registered).

If you had less than a year to live, would you want to know? A seven-country European population survey of public preferences for disclosure of poor prognosis.

OBJECTIVE: With increasing European cancer deaths, clinicians must manage information regarding poor prognosis. This study aimed to determine European citizens' preferences, within a scenario of serious illness such as cancer with less than a year to live, for information disclosure regarding poor prognosis, the likely symptoms and problems, and the care options available, to measure variations between countries and to identify factors associated with preferences. METHODS: A population-based cross-national telephone survey using random digit dialling in seven countries was conducted. RESULTS: Among 9344 respondents, data revealed an international preference (73.9%) to always be informed in the scenario of having a serious illness such as cancer with less than a year to live. This varied from 67.6% in Italy to 80.7% in Flanders. A minority (21.1%) did not want such information unless they ask, or at all. People younger than 70 years (OR 0.72, 95% CI 0.62-0.83, p < 0.001), men (OR 1.23, 95% CI 1.10-1.37, p < 0.001), those with experience of illness (OR = 1.20. 95% CI 1.01-1.43, p < 0.05) and with more education (OR = 1.20, 95% CI 1.09-1.32, p < 0.001) were more likely to want to know of limited time left. CONCLUSIONS: The models confirmed the influence of four factors in more than one country (age, gender, education and most concerning problem) and added 11 country-specific factors to which national policies and clinical practice should respond. These findings confirm a majority public preference to be informed in a scenario of poor prognosis. Policy clinical practice should facilitate elucidation and delivery of preferences. Evidence for effective communication skills-building interventions for clinicians is required.

A mixed-methods evaluation of complementary therapy services in palliative care: yoga and dance therapy.

To inform service provision and future research, we evaluated two complementary therapy services: yoga classes and dance therapy [The Lebed Method (TLM)]. Both were run as 6-week group courses. Patients completed the Measure Yourself Concerns and Wellbeing questionnaire pre- and post-course. Mean change over time was calculated for patient-nominated concern and well-being scores. Qualitative data regarding factors affecting health other than the therapy and benefits of the service were analysed using content analysis. Eighteen patients participated (mean age 63.8 years; 16 female; 14 cancer diagnoses); 10 were doing yoga, five TLM, and three both yoga and TLM; 14 completed more than one assessed course. Patients' most prevalent concerns were: mobility/fitness (n= 20), breathing problems (n= 20), arm, shoulder and neck problems (n= 18), difficulty relaxing (n= 8), back/postural problems (n= 8), fear/anxiety (n= 5). Factors affecting patients' health other than the therapy were prevalent and predominantly negative (e.g. treatment side effects). Patients reported psycho-spiritual, physical and social benefits. Concern scores improved significantly (P < 0.001) for both therapies; improved well-being was clinically significant for yoga. Evaluations of group complementary therapy services are feasible, can be conducted effectively and have implications for future research. Yoga and TLM may be of benefit in this population.

Hurricane Isabel-related mortality--virginia, 2003.

BACKGROUND: Hurricane Isabel had a massive negative environmental, public health, and economic impact; Virginia bore the highest death toll (32) among nine states affected by this storm. A descriptive mortality analysis was conducted to identify modifiable risk factors and corresponding injury prevention measures that might mitigate future natural disaster-related morbidity and mortality in Virginia. METHODS: Information for the decedents, including demographic data, health status, and injury circumstances, was collected from the records of the Virginia Office of the Chief Medical Examiner and Office of Vital Records/Health Statistics. Criteria from the National Hurricane Center were used to classify deaths as direct or indirect. Storm assessments and emergency-response reports were also reviewed. RESULTS: A total of 32 deaths associated with Hurricane Isabel occurred in several densely populated localities in southeastern and central Virginia. The median age of decedents was 48 years (range: 7-85 years). A disproportionately higher mortality (21 [66%] of 32) occurred among persons older than 45 years (Virginia 2000 Census data). Twelve deaths were directly caused by environmental factors related to the storm (eg, seven drowning deaths and five traumatic head injuries from falling trees). Twenty deaths were indirectly associated with the storm and its effects: six fatal motor vehicle crashes, five related to clean-up operations, seven associated with power outages, and two stress-related (ie, myocardial infarction and suicide). The presence of alcohol or drugs was observed in 9 (28%) of 32 deaths. CONCLUSIONS: Classifying deaths as direct or indirect facilitates better target interventions on the basis of the identification of modifiable risk factors underlying hurricane-associated fatal injuries. Public education messages that reinforce avoidance of use of alcohol and drugs during natural disaster situations might reduce risk for injury.