A systematic review of economic evaluations of CHW interventions aimed at improving child health outcomes.

Evidence of the cost-effectiveness of community health worker interventions is pertinent for decision-makers and programme planners who are turning to community services in order to strengthen health systems in the context of the momentum generated by strategies to support universal health care, the post-2015 Sustainable Development Goal agenda.We conducted a systematic review of published economic evaluation studies of community health worker interventions aimed at improving child health outcomes. Four public health and economic evaluation databases were searched for studies that met the inclusion criteria: National Health Service Economic Evaluation Database (NHS EED), Cochrane, Paediatric Economic Evaluation Database (PEED), and PubMed. The search strategy was tailored to each database.The 19 studies that met the inclusion criteria were conducted in either high income countries (HIC), low- income countries (LIC) and/or middle-income countries (MIC). The economic evaluations covered a wide range of interventions. Studies were grouped together by intended outcome or objective of each study. The data varied in quality. We found evidence of cost-effectiveness of community health worker (CHW) interventions in reducing malaria and asthma, decreasing mortality of neonates and children, improving maternal health, increasing exclusive breastfeeding and improving malnutrition, and positively impacting physical health and psychomotor development amongst children.Studies measured varied outcomes, due to the heterogeneous nature of studies included; a meta-analysis was not conducted. Outcomes included disease- or condition -specific outcomes, morbidity, mortality, and generic measures (e.g. disability-adjusted life years (DALYs)). Nonetheless, all 19 interventions were found to be either cost-effective or highly cost-effective at a threshold specific to their respective countries.There is a growing body of economic evaluation literature on cost-effectiveness of CHW interventions. However, this is largely for small scale and vertical programmes. There is a need for economic evaluations of larger and integrated CHW programmes in order to achieve the post-2015 Sustainable Development Goal agenda so that appropriate resources can be allocated to this subset of human resources for health. This is the first systematic review to assess the cost-effectiveness of community health workers in delivering child health interventions.

Costs of a school-based dental mobile service in South Africa.

BACKGROUND: The burden of untreated tooth decay remains high and oral healthcare utilisation is low for the majority of children in South Africa. There is need for alternative methods of improving access to low cost oral healthcare. The mobile dental unit of the University of the Witwatersrand (Wits) has been operational for over 25 years, providing alternative oral healthcare to children and adults who otherwise would not have access. The aim of this study was to conduct a cost-analysis of a school based oral healthcare program in the Wits mobile dental unit. The objectives were to estimate the general costs of the school based program, costs of oral healthcare per patient and the economic implications of providing services at scale. METHODS: In 2012, the Wits mobile dental unit embarked on a 5 month project to provide oral healthcare in four schools located around Johannesburg. Cost and service use data were retrospectively collected from the program records for the cost analysis, which was undertaken from a provider perspective. The costs considered included both financial and economic costs. Capital costs were annualised and discounted at 6 %. One way sensitivity tests were conducted for uncertain parameters. RESULTS: The total economic costs were R813.701 (US$76,048). The cost of screening and treatment per patient were R331 (US$31) and R743 (US$69) respectively. Furthermore, fissure sealants cost the least out of the treatments provided. The sensitivity analysis indicated that the Wits mobile dental unit was cost efficient at 25 % allocation of staff time and that a Dental Therapy led service could save costs by 9.1 %. CONCLUSIONS: Expanding the services to a wider population of children and utilising Dental Therapists as key personnel could improve the efficiency of mobile dental healthcare provision.

Identifying high-risk areas for sporadic measles outbreaks: lessons from South Africa.

OBJECTIVE: To develop a model for identifying areas at high risk for sporadic measles outbreaks based on an analysis of factors associated with a national outbreak in South Africa between 2009 and 2011. METHODS: Data on cases occurring before and during the national outbreak were obtained from the South African measles surveillance programme, and data on measles immunization and population size, from the District Health Information System. A Bayesian hierarchical Poisson model was used to investigate the association between the risk of measles in infants in a district and first-dose vaccination coverage, population density, background prevalence of human immunodeficiency virus (HIV) infection and expected failure of seroconversion. Model projections were used to identify emerging high-risk areas in 2012. FINDINGS: A clear spatial pattern of high-risk areas was noted, with many interconnected (i.e. neighbouring) areas. An increased risk of measles outbreak was significantly associated with both the preceding build-up of a susceptible population and population density. The risk was also elevated when more than 20% of infants in a populous area had missed a first vaccine dose. The model was able to identify areas at high risk of experiencing a measles outbreak in 2012 and where additional preventive measures could be undertaken. CONCLUSION: The South African measles outbreak was associated with the build-up of a susceptible population (owing to poor vaccine coverage), high prevalence of HIV infection and high population density. The predictive model developed could be applied to other settings susceptible to sporadic outbreaks of measles and other vaccine-preventable diseases.

Introducing an Ethics Framework for health priority-setting in South Africa on the path to universal health coverage.

BACKGROUND: South Africa (SA) has embarked on a process to implement universal health coverage (UHC) funded by National Health Insurance (NHI). The 2019 NHI Bill proposes creation of a health technology assessment (HTA) body to inform decisions about which interventions NHI funds will cover under UHC. In practice, HTA often relies mainly on economic evaluations of cost-effectiveness and budget impact, with less attention to the systematic, specific consideration of important social, organisational and ethical impacts of the health technology in question. In this context, the South African Values and Ethics for Universal Health Coverage (SAVE-UHC) research project recognised an opportunity to help shape the health priority-setting process by providing a way to take account of multiple, ethically relevant considerations that reflect SA values. The SAVE-UHC Research Team developed and tested an SA-specific Ethics Framework for HTA assessment and analysis. OBJECTIVES: To develop and test an Ethics Framework for use in the SA context for health priority-setting. METHODS: The Framework was developed iteratively by the authors and a multidisciplinary panel (18 participants) over a period of 18 months, using the principles outlined in the 2015 NHI White Paper as a starting point. The provisional Ethics Framework was then tested with multi-stakeholder simulated appraisal committees (SACs) in three provinces. The membership of each SAC roughly reflected the composition of a potential SA HTA committee. The deliberations and dedicated focus group discussions after each SAC meeting were recorded, analysed and used to refine the Framework, which was presented to the Working Group for review, comment and final approval. RESULTS: This article describes the 12 domains of the Framework. The first four (Burden of the Health Condition, Expected Health Benefits and Harms, Cost-Effectiveness Analysis, and Budget Impact) are commonly used in HTA assessments, and a further eight cover the other ethical domains. These are Equity, Respect and Dignity, Impacts on Personal Financial Situation, Forming and Maintaining Important Personal Relationships, Ease of Suffering, Impact on Safety and Security, Solidarity and Social Cohesion, and Systems Factors and Constraints. In each domain are questions and prompts to enable use of the Framework by both analysts and assessors. Issues that arose, such as weighting of the domains and the availability of SA evidence, were discussed by the SACs. CONCLUSIONS: The Ethics Framework is intended for use in priority-setting within an HTA process. The Framework was well accepted by a diverse group of stakeholders. The final version will be a useful tool not only for HTA and other priority-setting processes in SA, but also for future efforts to create HTA methods in SA and elsewhere.

Evidence for high sugar content of baby foods in South Africa.

BACKGROUND: Early-life exposure to excess sugar affects eating behaviour and creates a predisposition to non-communicable diseases (NCDs). While reducing sugar consumption has been high on the public health agenda, little is known about the sugar content of baby foods. OBJECTIVES: To describe and analyse the sugar content of baby foods in South Africa (SA). METHODS: A cross-sectional study was conducted to analyse the sugar content of baby foods. The study sample included commercially available baby foods targeted at children aged <12 months, sold in supermarkets and by other major retailers in SA. Primary data were obtained from the packaging, and sugar content was compared with recommended intake guidelines. Bivariate analyses were conducted to determine whether there were any associations between the sugar content, added sugar and the characteristics of foods. RESULTS: Over 70% of products were sweet in taste, with one in four containing added sugars. Sugar content was high in 78% of the foods sampled. Over 80% of cereals and pureed desserts contained added sugar. Fewer than 10% of pureed composite meal and pureed fruit and vege-table categories contained added sugar. Most products adhered to SA labelling standards, but none had front-of-pack nutritional information. CONCLUSIONS: The SA baby food market is characterised by products with a high sugar content, promoting an environment that encourages development of sweet-taste preferences and in the long term contributing to the rising burden of NCDs. There is an urgent need for mandatory regulation of sugar in baby foods.

Projecting the fiscal impact of South Africa's contraceptive needs: Scaling up family planning post 2020.

BACKGROUND: Evidence-informed priority setting is vital to improved investment in public health interventions. This is particularly important as South Africa (SA) makes the shift to universal health coverage and institution of National Health Insurance. OBJECTIVES: To measure the financial impact of increasing the demand for modern contraceptive methods in the SA public health sector. We estimated the total cost of providing contraceptives, and specifically the budgetary impact of premature removals of long-acting reversible contraceptives. METHODS: We created a deterministic model in Microsoft Excel to estimate the costs of contraception provision over a 5-year time horizon (2018 - 2023) from a healthcare provider perspective. Only direct costs of service provision were considered, including drugs, supplies and personnel time. Costs were not discounted owing to the short time horizon. Scenario analyses were conducted to test uncertainty. RESULTS: The base-case cost of current contraceptive use in 2018 was estimated to be ZAR1.64 billion (ZAR29 per capita). Injectable contraceptives accounted for ~47% of total costs. To meet the total demand for family planning, SA would have to spend ~30% more than the estimate for current contraceptive use. In the year 2023, the 'current use' of modern contraceptives would increase to ZAR2.2 billion, and fulfilling the total demand for family planning would require ZAR2.9 billion. The base-case cost of implantable contraceptives was estimated at ZAR54 million. Assuming a normal removal rate, the use of implants is projected to increase by 20% during the 5-year period between 2019 and 2023, with an estimated 46% increase in costs. The cost of early removal of Implanon NXT is estimated at ZAR75 million, with total contraception costs estimated at ZAR102 million in 2019, compared with ZAR56 million when a normal removal rate is applied. CONCLUSIONS: The costs of scaling up modern contraceptives in SA are substantial. Early and premature removals of implantable contraceptives are costly to the nation and must be minimised. The government should consider conducting appropriate health technology assessments to inform the introduction of new public health interventions as SA makes the shift to universal health coverage by means of National Health Insurance.

Rapidly increasing body mass index among children, adolescents and young adults in a transitioning population, South Africa, 2008-15.

Background: There is a global epidemic of overweight and obesity; however, this rate of increase is even greater in some low- and middle-income countries (LMIC). South Africa (SA) is undergoing rapid socioeconomic and demographic changes that have triggered a rapid nutrition transition. The paper focuses on the recent rate of change of body mass index (BMI) among children, adolescents and young adults, further stratified by key sociodemographic factors. Methods: We analysed mean BMI of 28 247 individuals (including children) from 7301 households by age and year, from anthropometric data from four national cross-sectional (repeated panel) surveys using non-linear fitted curves and associated 95% confidence intervals. Results: From 2008 to 2015, there was rapid rise in mean BMI in the 6-25 age band, with the highest risk (3-4+ BMI unit increase) among children aged 8-10 years. The increase was largely among females in urban areas and of middle-high socioeconomic standing. Prominent gains were also observed in certain rural areas, with extensive geographical heterogeneity across the country. Conclusions: We have demonstrated a major deviation from the current understanding of patterns of BMI increase, with a rate of increase substantially greater in the developing world context compared with the global pattern. This population-wide effect will have major consequences for national development as the epidemic of related non-communicable disease unfolds, and will overtax the national health care budget. Our refined understanding highlights that risks are further compounded for certain groups/places, and emphasizes that urgent geographical and population-targeted interventions are necessary. These interventions could include a sugar tax, clearer food labelling, revised school feeding programmes and mandatory bans on unhealthy food marketing to children.The scenario unfolding in South Africa will likely be followed in other LMICs.

'Best buys' for surgery in South Africa.

Improving access to basic surgical interventions has great potential to improve the length and quality of life of many people in low- and middle-income countries (LMICs). However, research has shown that current access to surgical interventions is limited, and initiatives such as the Lancet Commission on Global Surgery 2030 advocate for improved access to basic surgical interventions for all. As the needs, health system context and available budgets in each country will be different, a critical component of effective local scale-up of surgical interventions will be to use tools and processes of health technology assessment (HTA). HTA has traditionally been used in high-income countries to make decisions about which medicines and devices should be available in a health system, but its central concepts, such as assessing clinical effectiveness, cost-effectiveness and feasibility, appraising all available evidence, and incorporating wider health systems objectives in decision-making, can be applied to decisons about how LMICs can best utilise basic surgical interventions from within available resources - in essence, to focus spending on the 'best buys'. As South Africa (SA) moves towards National Health Insurance (NHI), HTA functions will be strengthened. There is potential for SA to lead the practice of application of HTA to decisions about how basic surgical interventions are chosen and implemented, contributing to the success and sustainability of NHI in SA and the health of people in LMICs worldwide.

Available data sources for monitoring non-communicable diseases and their risk factors in South Africa.

BACKGROUND: Health information systems for monitoring chronic non-communicable diseases (NCDs) in South Africa (SA) are relatively less advanced than those for infectious diseases (particularly tuberculosis and HIV) and for maternal and child health. NCDs are now the largest cause of premature mortality owing to exposure to risk factors arising from obesity that include physical inactivity and accessible, cheap but unhealthy diets. The National Strategic Plan for the Prevention and Control of Non-Communicable Diseases 2013 - 17 developed by the SA National Department of Health outlines targets and monitoring priorities. OBJECTIVES: To assess data sources relevant for monitoring NCDs and their risk factors by identifying the strengths and weaknesses, including usability and availability, of surveys and routine systems focusing at national and certain sub-national levels. METHODS: Publicly available survey and routine data sources were assessed for variables collected, their characteristics, frequency of data collection, geographical coverage and data availability. RESULTS: Survey data sources were found to be quite different in the way data variables are collected, their geographical coverage and also availability, while the main weakness of routine data sources was poor quality of data. CONCLUSIONS: To provide a sound basis for monitoring progress of NCDs and related risk factors, we recommend harmonising and strengthening available SA data sources in terms of data quality, definitions, categories used, timeliness, disease coverage and biomarker measurement.

South African clinical practice guidelines: A landscape analysis.

BACKGROUND: South Africa (SA) is in the process of implementing National Health Insurance (NHI), which will require co-ordination of health provision across sectors and levels of care. Clinical practice guidelines (CPGs) are tools for standardising and implementing care, and are intended to influence clinical decision-making with consequences for patient outcomes, health system costs and resource use. Under NHI, CPGs will be used to guide the provision of healthcare for South Africans. It is therefore important to explore the current landscape of CPG developers and development. OBJECTIVE: To identify and describe all CPGs available in the public domain produced by SA developers for the SA context. METHODS: We conducted a cross-sectional evaluation using a two-part search process: an iterative, electronic search of grey literature and relevant websites (161 websites searched), and a systematic search for peer-reviewed literature (PubMed) after publication year 2000. CPGs were identified, and data were extracted and categorised by two independent reviewers. Any discrepancies were referred to a third reviewer. Data extracted included a description of the developer, condition, and reporting of items associated with CPG quality. RESULTS: A search conducted in May 2017 identified 285 CPGs published after January 2000. Of those, 171 had been developed in the past 5 years. Developers included the national and provincial departments of health (DoH), professional societies and associations, ad hoc collaborations of clinicians, and the Council for Medical Schemes. Topics varied by developer; DoH CPGs focused on high-burden conditions (HIV/AIDS, tuberculosis and malaria), and other developers focused on non-communicable diseases. A conflict of interest statement was included in 23% of CPGs developed by societies or clinicians, compared with 4% of DoH CPGs. CONCLUSION: Accessing CPGs was challenging and required extensive searching. SA has many contributors to CPG development from the public and private sectors and across disciplines, but there is no formal co-ordination or prioritisation of topics for CPG development. Different versions of the CPGs were identified and key quality items were poorly reported, potentially affecting the usability and credibility of those available. There was substantial variation in CPG comprehensiveness and methodological approach. Establishing a national CPG co-ordinating unit responsible for developing standards for CPG development along with clinical quality standards, and supporting high-quality CPG development, is one essential step for moving forward with NHI.

Thyroid hormone and carrier protein interrelationships in children recovering from kwashiorkor.

We have studied 15 infants with severe protein energy malnutrition (PEM) as a model of nutritional nonthyroidal illness. Changes in circulating thyroid hormones, binding proteins, and their interrelationships were assessed before and during recovery. Serum concentrations of total thyroxine and triiodothyronine and of thyroxine-binding proteins were extremely reduced, and increased progressively during 3 wk of refeeding. The T4:TBG molar ratio was initially 0.180 +/- 0.020, and increased progressively, parallel to the increases in TT4, to 0.344 +/- 0.038 after 21 days (p less than 0.025). The changes in free T4 estimates varied according to the methods used--FTI and analogue FT4 increased, dialysis FT4 fraction decreased. Serum TSH levels increased transiently during recovery. It is concluded 1) there is reduced binding of T4 and T3 to TBG in untreated PEM which takes 2-3 wk to recover; 2) there are methodological differences in evaluating free T4 levels in PEM; 3) increased TSH secretion appears to be an integral part of the recovery from PEM.

The retinoblastoma protein-associated transcription repressor RBaK interacts with the androgen receptor and enhances its transcriptional activity.

In search of potential androgen receptor coregulators we performed a yeast two-hybrid screening using the androgen receptor ligand-binding domain as bait and a human prostate cDNA library as prey and found that the carboxy-terminal domain of retinoblastoma-associated Krüppel protein (RbaK), a member of the Krüppel zinc finger protein family, interacts in a ligand-dependent way with the ligand-binding domain of the androgen receptor. RBaK was recently identified as a transcriptional regulator that interacts with the retinoblastoma protein and thereby influences E2F regulated transcription. The interaction of RBaK with the androgen receptor was further documented using mammalian two-hybrid experiments, in vitro binding studies and coimmunoprecipitation. Finally, we demonstrated that both RBaK and the retinoblastoma protein coactivate androgen receptor-mediated transcription in cotransfection experiments. In conclusion, our data show that RBaK interacts with the androgen receptor and increases its transcriptional activity. Moreover, the double interaction of RBaK with the retinoblastoma protein and with the androgen receptor provides a novel link between the androgen receptor and the regulation of the cell cycle.

Apparent coactivation due to interference of expression constructs with nuclear receptor expression.

Transient cotransfection in COS-7 cells, a standard approach to demonstrate coactivation, was used to study the coactivation properties of NuRIP183, a new nuclear receptor interacting protein of 183 kDa, isolated by a yeast two-hybrid screening. Transfection with a NuRIP183 expression construct strongly increased the ligand-dependent response of reporter constructs for several nuclear receptors when compared to transfection with the empty expression vector. A more detailed study, however, revealed major changes in the expression level of the nuclear receptors in cotransfection experiments, indicating that the observed changes in receptor activity were not due to coactivation but to differences in receptor concentration caused by interference from the cotransfected expression constructs with the expression of the receptor. Such interference, which is inversely related to the length of the insert, was observed, not only in COS-7 cells but also in CV-1 and MCF-7 cells, using different transfection techniques (FuGENE-6 and calcium phosphate) and different expression vectors (pSG5, pcDNA1.1 and pIRESneo). These data cast some doubt on coactivation of nuclear receptors based on similar cotransfection experiments without measurement of receptor concentration. Moreover, it is recommended to limit the amounts of (co)transfected expression plasmid and to avoid the use of empty expression plasmid as a control. Finally, one should be aware of similar misleading results in other experimental set-ups based on cotransfection.

Diffusion of information about neurofibromatosis type 1 DNA testing.

There is little information available as to how individuals with genetic disorders receive information about the availability of DNA tests and what effect this has on their utilization. The purpose of this study was to survey centers where some individuals with neurofibromatosis type 1 (NF 1) are cared for, to establish how this type of information was disseminated. In 1990 announcement of the availability of testing for familial NF 1 was published in a newsletter of the National Neurofibromatosis Foundation (NNFF) and sent to individuals with NF 1 or NF 2 and their families, professionals, and NF centers in North America. Two years later these centers were surveyed to determine whether they had notified their patients of test availability. Of the 46 responding centers, 65% indicated they had attempted to notify their patients. The majority (80%) notified patients on an individual basis in clinic. The rest did so either on an individual basis in the clinic or by telephone or by letter or by a combination of these. Based on a survey response rate of 56% and approximately 1,000 enquiries received by the NNFF from families and physicians, it is concluded that 1) factors other than knowledge of test availability determined whether DNA testing for NF 1 was utilized; 2) some centers used testing more frequently than others; 100% of the referrals came from 40% of the centers, with 15% of referrals coming from a single center; 3) a significant percentage (35%) of NF centers did not inform their patients that DNA testing was available.

Familial systematized epidermal nevus syndrome.

Epidermal nevi are typically congenital but rarely familial. We report on a family in which 3 relatives have systematized epidermal nevi. The propositus also has evidence of a hemangioma and a hemangioendothelioma. Peripheral blood and skin fibroblast karyotypes of the propositus did not show evidence of mosaicism. Epidermal nevi have been associated with nondermatologic pathology, involving the nervous, vascular, and skeletal systems in sporadic cases. This report demonstrates that nondermatologic pathology can be also be associated with systematized epidermal nevi in a familial setting. The apparent skipping of generations may be explained by autosomal dominant inheritance with decreased penetrance.

Smith-Lemli-Opitz syndrome: prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid.

Until recently, the diagnosis of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive malformation/mental retardation syndrome, was made on the basis of clinical criteria alone. As a result, prenatal diagnosis has been possible only if sonography disclosed distinct fetal malformations in a subsequent pregnancy. However, the recent description of increased levels of 7-dehydrocholesterol (cholesta-5,7-dien-3 beta-ol) in patients with SLOS, most likely caused by a deficiency of 3 beta-hydroxysteroid-delta 7-reductase, has provided an apparently reliable biochemical marker for diagnosis of SLOS. To determine if this abnormality of sterol metabolism has utility for prenatal diagnosis of SLOS, we measured the levels of neutral sterols in stored amniotic fluid samples from two SLOS pregnancies. In both cases, the diagnosis of SLOS was made in the neonatal period by clinical criteria and the finding of markedly increased levels of 7-dehydrocholesterol in plasma. Quantitative analysis by gas chromatography of sterols extracted from the amniotic fluid of both pregnancies revealed similar, markedly increased levels of 7-dehydrocholesterol and its precursor, lathosterol (cholest-7-en-3 beta-ol), both of which were undetectable in reference amniotic fluids. These findings suggest that abnormalities of cholesterol biosynthesis in SLOS may be sufficiently expressed in fetal life to permit prenatal diagnosis of this disorder by measurement of 7-dehydrocholesterol in amniotic fluid.