Risk, double effect and the social benefit requirement.

Many ethicists maintain that medical research on human subjects that presents no prospect of direct medical benefit must have a prospect of social benefit to be ethical. Payment is not the sort of benefit that justifies exposing subjects to risk. Alan Wertheimer has raised a serious challenge to this view, pointing out that in industry, social value is not considered necessary to make dangerous jobs ethical. This article argues that Wertheimer was correct to think that the ethics of hazard pay should be the same in medical research and in business. Nevertheless, a qualified social benefit requirement should apply in both fields. For a study or a job with significant net physical risk to be ethical, it must have social value beyond the satisfaction of ordinary preferences, including the preference for money. The requirement derives from a non-absolutist version of the doctrine of double effect. If a risky study or a dangerous job has no distinctive social value, and hazard pay is subjects' or workers' only reason to undergo risks, the very fact that they undergo risk is intended as a means to a financial end. Inviting people to enrol in such a study or to take such a job wrongfully treats people as mere means. By contrast, if a study or a job has social value, people can participate with a primary end other than money, even if they accept compensation. Researchers or employers do not intend but merely foresee risks to subjects or workers.

Two-year impact of community-based health screening and parenting groups on child development in Zambia: Follow-up to a cluster-randomized controlled trial.

BACKGROUND: Early childhood interventions have potential to offset the negative impact of early adversity. We evaluated the impact of a community-based parenting group intervention on child development in Zambia. METHODS AND FINDINGS: We conducted a non-masked cluster-randomized controlled trial in Southern Province, Zambia. Thirty clusters of villages were matched based on population density and distance from the nearest health center, and randomly assigned to intervention (15 clusters, 268 caregiver-child dyads) or control (15 clusters, 258 caregiver-child dyads). Caregivers were eligible if they had a child 6 to 12 months old at baseline. In intervention clusters, caregivers were visited twice per month during the first year of the study by child development agents (CDAs) and were invited to attend fortnightly parenting group meetings. Parenting groups selected "head mothers" from their communities who were trained by CDAs to facilitate meetings and deliver a diverse parenting curriculum. The parenting group intervention, originally designed to run for 1 year, was extended, and households were visited for a follow-up assessment at the end of year 2. The control group did not receive any intervention. Intention-to-treat analysis was performed for primary outcomes measured at the year 2 follow-up: stunting and 5 domains of neurocognitive development measured using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). In order to show Cohen's d estimates, BSID-III composite scores were converted to z-scores by standardizing within the study population. In all, 195/268 children (73%) in the intervention group and 182/258 children (71%) in the control group were assessed at endline after 2 years. The intervention significantly reduced stunting (56/195 versus 72/182; adjusted odds ratio 0.45, 95% CI 0.22 to 0.92; p = 0.028) and had a significant positive impact on language (ß 0.14, 95% CI 0.01 to 0.27; p = 0.039). The intervention did not significantly impact cognition (ß 0.11, 95% CI -0.06 to 0.29; p = 0.196), motor skills (ß -0.01, 95% CI -0.25 to 0.24; p = 0.964), adaptive behavior (ß 0.21, 95% CI -0.03 to 0.44; p = 0.088), or social-emotional development (ß 0.20, 95% CI -0.04 to 0.44; p = 0.098). Observed impacts may have been due in part to home visits by CDAs during the first year of the intervention. CONCLUSIONS: The results of this trial suggest that parenting groups hold promise for improving child development, particularly physical growth, in low-resource settings like Zambia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02234726.

Justifying community benefit requirements in international research.

It is widely agreed that foreign sponsors of research in low- and middle-income countries (LMICs) are morally required to ensure that their research benefits the broader host community. There is no agreement, however, about how much benefit or what type of benefit research sponsors must provide, nor is there agreement about what group of people is entitled to benefit. To settle these questions, it is necessary to examine why research sponsors have an obligation to benefit the broader host community, not only their subjects. Justifying this claim is not straightforward. There are three justifications for an obligation to benefit host communities that each apply to some research, but not to all. Each requires a different amount of benefit, and each requires benefit to be directed toward a different group. If research involves significant net risk to LMIC subjects, research must provide adequate benefit to people in LMICs to avoid an unjustified appeal to subjects' altruism. If research places significant burdens on public resources, research must provide fair compensation to the community whose public resources are burdened. If research is for profit, research sponsors must contribute adequately to the upkeep of public goods from which they benefit in order to avoid the wrong of free-riding, even if their use of these public goods is not burdensome.

Cost sharing in managed care and the ethical question of business purpose.

For-profit managed care organizations face decisions about cost sharing that can involve a tradeoff between the interests of investors and the interests of patients. No successful business can ignore the interests of its investors, but moral philosophy points to ethical reasons for managed care organizations to make patients' health, rather than investors' profit, their primary goal. One reason is the ethical obligation of all businesses to avoid wrongful exploitation of vulnerable customers. An insurance company's cost-sharing policy can exploit customers either by collecting an unfairly large amount of money from them or by unfairly deterring them from making claims for resources they medically need. Another reason stems from the fact that managed care organizations' profits derive in part from the existence of artificial barriers to access to medicine, notably including patents. Putting a fence around a water well in the desert is legitimate only if doing so facilitates a financial arrangement that maximizes people's access to water they need. Likewise, patents and other artificial barriers to access to medically necessary drugs are legitimate only if they are used to help finance access to medical resources people need. For these reasons, managed care organizations should make cost-sharing decisions that maximize the sustainable availability of effective drugs to patients who need them. DISCLOSURES: The thoughts and opinions expressed in this article are those of the author only and are not the thoughts and opinions of any current or former employer of the author. Nor is this publication made by, on behalf of, or endorsed or approved by any current or former employer of the author.

Parental experiences of childcare in an informal urban settlement: qualitative interview findings from the Nairobi Early Childcare in Slums (NECS) project.

OBJECTIVES: To gain an in-depth understanding of parent/carers' perspectives on, and decision-making about, early childhood care in general, and paid childcare specifically, in informal settlements in Nairobi. DESIGN: In-depth telephone interviews, conducted using a topic guide, were analysed through a combination of deductive and inductive thematic analysis and regular reflexivity meetings. We explored parents' childcare needs and experiences over time, and their perspectives on the provision of paid childcare in the slums. SETTING: Three informal settlements or slums in Nairobi: Kibera; Kawangware; and Mukuru-Viwandani. PARTICIPANTS: A purposively selected sample of 21 parental and non-parental carers of children aged under 5 years who were currently living in three Nairobi slums, including men and women, and users and non-users of paid childcare. RESULTS: Childcare is complex, with a plurality of approaches being used. Common strategies include family member provided care (often but not exclusively by mothers, at home or at a place of work), paid childcare and informal or ad hoc arrangements with neighbours. Childcare decision-making in these settings is constrained by economics and the broader context of living in the slum. Paid childcare is frequently used, but is widely understood to be lacking in quality, especially for the poorest. Quality of childcare is understood to comprise a combination of structural factors, such as the physical space, play and learning resources and processes such as interactions between the care provider and children or parents. CONCLUSIONS: These findings suggest a need, and opportunity, to improve early childhood care in slums. Understanding parental perspectives on both the deficiencies and valued features of childcare is likely to be vital to informing efforts to improve childcare in these settings.

Let's just ask them. Perspectives on urban dwelling and air quality: A cross-sectional survey of 3,222 children, young people and parents.

This research aimed to capture and synthesise the views of children, young people, parents and expectant parents (CYPP) about the cities where they live, with a specific focus on air pollution (AP), in order to support the generation of evidence-informed policy that reflects CYPP's perspectives, ultimately contributing to the development of child-centered, healthier, sustainable cities. The Children, Cities and Climate (CCC) project used targeted social media adverts to recruit CYPP to complete an online survey with a combination of open and closed questions in order to collect perceptions about air quality in their home cities, the main sources of AP, and how they would improve their cities. The survey was completed by 3,222 CYPP in 59 of the most polluted cities in 14 countries. Nearly two in five (39%) CYPP cited AP as one of the worst things about their city, with motor transport perceived as the main contributor. CYPP reported differing views on whether their cities were becoming better (43%) or worse (34%) places to live (33% reported it was 'staying the same'). Numerous specific ideas to improve cities and urban air quality emerged, alongside an emphasis on also addressing structural barriers to change. A clear set of principles that should guide how city leaders act was also described, including the need to engage with young people meaningfully. CYPPs articulated good and bad experiences of urban living and perceived AP and traffic as pressing concerns. They provided a clear set of suggestions for improving their cities. Further efforts to engage young people on these issues are warranted.

Parental experiences of the impacts of Covid-19 on the care of young children; qualitative interview findings from the Nairobi Early Childcare in Slums (NECS) project.

INTRODUCTION: The Covid-19 pandemic, and societal attempts to control it, have touched almost every aspect of people's lives around the world, albeit in unequal ways. In particular, there is considerable concern about the way that stringent 'lockdowns', as implemented in Kenya and many other countries, affected young children, especially those living in informal settlements. However, to date, there has been little research attempting to unpack and understand how the pandemic has impacted on the care of young children. METHODS: In-depth telephone interviews were conducted with 21 parents/carers of children aged under five years living in three Nairobi slums between May and September 2021 exploring the ways in which Covid-19, and policies to control the pandemic, impacted on their household and the care of their child/children. RESULTS: The impacts of Covid-19 control measures on the care of children have been widely felt, deep and multiple. The impact of economic hardship has been significant, reportedly undermining food security and access to services including healthcare and childcare. Respondents reported an associated increase in domestic and community violence. Many people relied on help from others; this was most commonly reported to be in the form of variable levels of flexibility from landlords and help from other community members. No direct harms from Covid-19 disease were reported by respondents. CONCLUSION: The impacts of Covid-19 control measures on the care of young children in informal settlements have been indirect but dramatic. Given the breadth and depth of these reported impacts, and the particular vulnerability of young children, deeper consideration ought to inform decisions about approaches to implementation of stringent disease control measures in future. In addition, these findings imply a need for both short- and long-term policy responses to ameliorate the impacts described.

Individual risk and community benefit in international research.

It is widely agreed that medical researchers who conduct studies in low- and middle-income countries (LMICs) are morally required to ensure that their research benefits the broader host community, not only the subjects. The justification for this moral requirement has not been adequately examined. Most attempts to justify this requirement focus on researchers' interaction with the community as a whole, not on their relationship with their subjects. This paper argues that in some cases, research must benefit the broader host community for researchers to treat subjects and prospective subjects ethically. If research presents substantial net risks to subjects, researchers can ethically ask LMIC citizens to participate only if people in LMICs, normally including people in the host community, stand to benefit.

Illness Characteristics of COVID-19 in Children Infected with the SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. METHODS: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (≥28 day) illness, and calculated odds ratios for symptoms presenting within the first 28 days of illness. RESULTS: 694 (276 younger (5-11 years), 418 older (12-17 years)) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2-9.75) with Alpha, 5 days (IQR 2-9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2-5) symptoms with Alpha, 4 (IQR 2-7) with Delta; in older children, 5 (IQR 3-8) symptoms with Alpha, 6 (IQR 3-9) with Delta infection ). The odds of presenting several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. CONCLUSIONS: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

Post-vaccination infection rates and modification of COVID-19 symptoms in vaccinated UK school-aged children and adolescents: A prospective longitudinal cohort study.

Background: We aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and adolescents (CA) in the UK during periods of Delta and Omicron variant predominance. Methods: In this prospective longitudinal cohort study, we analysed data from 115,775 CA aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CA with post-vaccination SARS-CoV-2 infection, compared to unvaccinated CA, and post-vaccination side-effects. Findings: Between August 5, 2021 and February 14, 2022, 25,971 UK CA aged 12-17 years received one dose of BNT162b2 vaccine. The probability of testing positive for infection diverged soon after vaccination, and was lower in CA with prior SARS-CoV-2 infection. Vaccination reduced proxy-reported infection risk (-80·4% (95% CI -0·82 -0·78) and -53·7% (95% CI -0·62 -0·43) at 14-30 days with Delta and Omicron variants respectively, and -61·5% (95% CI -0·74 -0·44) and -63·7% (95% CI -0·68 -0.59) after 61-90 days). Vaccinated CA who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CA; during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CA. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved within few days (3 days in most cases). Interpretation: One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CA aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CA also had generally mild disease. Overall, vaccination was well-tolerated. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimer's Society, and ZOE Limited.

Making pre-school children wear masks is bad public health.

Children are not small adults. This is a critical point that many pediatricians and other child health professionals get bored of saying, yet it does seem to need repeating. While children have the lowest risk from COVID-19 directly, they risk suffering the indirect impacts of policy decisions, many of which appear to have been made with next to no explicit consideration of their interests. Public health interventions should not only be about infectious disease control, they should consider a broad set of outcomes. In addition, they ought to consider vulnerability, including that in early childhood - a time when young children's brains are developing rapidly and are most susceptible to adversity. We believe that mandating masking of pre-school children is not in line with public health principles, and needs to be urgently re-considered.

Who actually cares for children in slums? Why we need to think, and do, more about paid childcare in urbanizing sub-Saharan Africa.

The early years are critical and inform the developmental trajectory of children. This is justifiably attracting growing policy attention. Much of this attention is focused on interventions and policies directed at parents, especially mothers. Yet emerging evidence suggests that increasing numbers of children in rapidly urbanizing low- and middle-income countries are now spending much of their day with other formal and informal childcare providers, including largely unregulated paid childcare providers. This paper summarizes the limited literature about the use of such paid childcare in low- and middle-income countries in sub-Saharan Africa, before considering possible reasons behind the lack of research evidence. Finally, key research gaps and their implications for public health practice are explored, with reference to the ongoing British Academy funded Nairobi Early Childcare in Slums research programme in Nairobi, Kenya. We argue that improving childcare may be an under-explored strategy to help some of the world's most disadvantaged children in the most important period of their lives, and that interventions in this largely informal market should be built on a rigorous research base. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'.

Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2.

BACKGROUND: In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. METHODS: In this prospective cohort study, data from UK school-aged children (age 5-17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5-11 years) and older (age 12-17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. FINDINGS: 258 790 children aged 5-17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3-11) versus 3 days (2-7) in children testing negative, and was positively associated with age (Spearman's rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3-12) than younger children (5 days, 2-9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1-4) compared with the first week of illness (median 6 symptoms, 4-8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7-11·0 vs 8, 6-9) and after day 28 (5 symptoms, IQR 1·5-6·5 vs 2, 1-4) than did children who tested positive for SARS-CoV-2. INTERPRETATION: Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. FUNDING: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society.

Nairobi Early Childcare in Slums (NECS) Study Protocol: a mixed-methods exploration of paid early childcare in Mukuru slum, Nairobi.

INTRODUCTION: The early years are critical. Early nurturing care can lay the foundation for human capital accumulation with lifelong benefits. Conversely, early adversity undermines brain development, learning and future earning.Slums are among the most challenging places to spend those early years and are difficult places to care for a child. Shifting family and work structures mean that paid, largely informal, childcare seems to be becoming the 'new normal' for many preschool children growing up in rapidly urbanising Africa. However, little is known about the quality of this childcare. AIMS: To build a rigorous understanding what childcare strategies are used and why in a typical Nairobi slum, with a particular focus on provision and quality of paid childcare. Through this, to inform evaluation of quality and design and implementation of interventions with the potential to reach some of the most vulnerable children at the most critical time in the life course. METHODS AND ANALYSIS: Mixed methods will be employed. Qualitative research (in-depth interviews and focus group discussions) with parents/carers will explore need for and decision-making about childcare. A household survey (of 480 households) will estimate the use of different childcare strategies by parents/carers and associated parent/carer characteristics. Subsequently, childcare providers will be mapped and surveyed to document and assess quality of current paid childcare. Semistructured observations will augment self-reported quality with observable characteristics/practices. Finally, in-depth interviews and focus group discussions with childcare providers will explore their behaviours and motivations. Qualitative data will be analysed through thematic analysis and triangulation across methods. Quantitative and spatial data will be analysed through epidemiological methods (random effects regression modelling and spatial statistics). ETHICS AND DISSEMINATION: Ethical approval has been granted in the UK and Kenya. Findings will be disseminated through journal publications, community and government stakeholder workshops, policy briefs and social media content.