Assessment of a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy'Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT).

BACKGROUND: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage. METHODS: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. DISCUSSION: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845.

A blinded study assessment of the efficacy of an original formula with retinol in combination with sonophoresis.

An appropriately designed cosmetic product and regimen of treatment can improve facial skin appearance and provide good tolerability. The aim of the study was to evaluate the effect of 0.3 and 0.5% retinol in liquid crystal formula, applied with sonophoresis, on mature skin. Serum with various concentrations of retinol was applied to the left and right sides of the face and treated with ultrasound. The treatments were performed once a week for a period of 7 weeks. The skin condition before and after treatment was compared using the Fotomedicus system. The Visual Analogue Scale method enabled the results to be assessed by three independent specialists. The Multi Probe Adapter system was used to evaluate the efficacy of a series of treatments. Subjective assessment of volunteers identified perceived improvement of skin conditions. In addition, treatment was associated with greater skin moisture level, reduced wrinkling and decreased skin discoloration. Mild side effects appeared mainly after the first treatment and on the left side of the face with 0.5% retinol. More significant results may be obtained by extending the treatment duration in longer-term studies. Nonetheless, the findings confirmed the effectiveness of the procedures.

Is it time for South Africa to end the routine high-dose vitamin A supplementation programme?

In accordance with World Health Organization guidelines, South Africa (SA) introduced routine periodic high-dose vitamin A supplementation (VAS) in 2002. These guidelines were developed after research in the 1980s and 1990s showed the efficacy of VAS in reducing childhood mortality. However, two recent studies in low- to middle-income countries (2013 and 2014) have shown no effect of high-dose VAS on mortality. Additionally, there is no clear research evidence that 6-monthly doses of vitamin A result in a sustained shift in serum retinol levels or reduce subclinical vitamin A deficiency. These two points should encourage SA to re-examine the validity of these guidelines. A long-term view of what is in the best interests of the majority of the people is needed. The short-term intervention of administering vitamin A capsules not only fails to improve serum retinol levels but may create dependence on a 'technical fix' to address the fundamental problem of poor nutrition, which is ultimately underpinned by poverty. It may also cause harm. Although there are those, some with vested interests, who will argue for continuation of the routine high-dose VAS programmes, SA policymakers and scientists need to evaluate the facts and be prepared to rethink this policy. There is cause for optimism: SA's health policymakers have previously taken bold stands on the basis of evidence. The examples of regulation of tobacco products and taxation of sugar-sweetened beverages, ending the free distribution of formula milk for HIV-positive mothers and legislating against the marketing of breastmilk substitutes provide precedents. Here is a time yet again for decision-makers to make bold choices in the interests of the people of SA. While the cleanest choice would be national discontinuation of the routine VAS programme, there may be other possibilities, such as first stopping the programme in Northern Cape Province (where there is clear evidence of hypervitaminosis A), followed by the other provinces in time.

Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing.

BACKGROUND: Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects. OBJECTIVES: To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing. METHODS: This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness. RESULTS: Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging. CONCLUSIONS: Our study demonstrates that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol. Bakuchiol is promising as a more tolerable alternative to retinol.

In vivo assessment of iron bioavailability from fortified pearl millet based weaning food.

BACKGROUND: Iron is an essential micronutrient required for normal growth and development of the body. Infants are more vulnerable to develop iron-deficiency anaemia due to inadequate iron supply in early stages. The objective of the study was in vivo assessment of iron bioavailability from pearl millet based weaning food fortified with iron and vitamin A, and to investigate the role of vitamin A in iron absorption in animal models. RESULTS: Results revealed that anaemic group showed significantly (P < 0.05) higher bioavailability than that of normal rat models. Animals fed vitamin A supplemented pearl-millet diet exhibited comparable results with a sub-group provided commercially available weaning diet in both normal and anaemic groups, but significantly (P < 0.05) higher values for studied biological indices than that of a sub-group provided iron fortified pearl-millet or synthetic diet. When the anaemic rats were provided iron + vitamin A fortified diet, iron bioavailability increased and liver iron stores returned to the normal levels after 30 days, indicating a promoter role of vitamin A in intestinal iron absorption. CONCLUSIONS: Overall, bioavailability of electrolytic iron could be improved by supplementation of vitamin A, and this mixture can be considered as a useful fortificant for pearl millet based complementary foods fortification designed to prevent iron deficiency. © 2016 Society of Chemical Industry.

Heterologous and sex differential effects of administering vitamin A supplementation with vaccines.

WHO recommends high-dose vitamin A supplementation (VAS) to children from 6 months to 5 years of age in low-income countries, in order to prevent and treat vitamin A deficiency-associated morbidity and mortality. The current policy does not discriminate this recommendation either by sex or vaccination status of the child. There is accumulating evidence that the effects of VAS on morbidity, mortality and immunological parameters depend on concomitant vaccination status. Moreover, these interactions may manifest differently in males and females. Certain vaccines administered through the Expanded Program on Immunization have been shown to alter all-cause mortality from infections other than the vaccine-targeted disease. This review summarizes the evidence from observational studies and randomized-controlled trials of the effects of VAS on these so-called heterologous or non-specific effects of vaccines, with a focus on sex differences. In general, VAS seems to enhance the heterologous effects of vaccines, particularly for diphtheria-tetanus-pertussis and live measles vaccines, where some studies, although not unanimously, show a stronger interaction between VAS and vaccination in females. We suggest that vaccination status and sex should be considered when evaluating the effects of VAS in early life.

Combination of retinyl palmitate and UV-filters: phototoxic risk assessment based on photostability and in vitro and in vivo phototoxicity assays.

This study aimed to assess the phototoxic potential of combined UV-filters and retinyl palmitate (RP) in the presence or not of bemotrizinol (BMTZ), employing photostability and in vitro and in vivo phototoxicity assays. The formulations tested contained octocrylene (OCT), octyl methoxycinnamate (OMC), benzophenone-3 (BZP-3) and RP (photostable) or octocrylene (OCT), octyl methoxycinnamate (OMC), avobenzone (AVO) and RP (less photostable). Both formulations were supplemented with bemotrizinol. Photostability was evaluated by exposing, or not, formulations spread on a glass plate to UVA/UVB irradiation. The resulting products were quantified by HPLC analysis. In vitro phototoxicity of UV-filters and combinations were evaluated using 3T3 viable monolayer fibroblast cultures submitted, or not, to irradiation according to OECD TG 432. In vivo photoallergy and photoxicity were assessed by clinical studies (photopatch test). Photostability assays showed that UV-filter bemotrizinol was a better photostabilizer for RP/benzophenone-3 than for RP/avobenzone. The in vitro phototoxicity of the combination RP/avobenzone was reduced by bemotrizinol. Clinical studies did not indicate phototoxic or photoallergenic potentials in all formulations tested. It is concluded that the 3T3 NRU phototoxicity test may be considered a supplementary assay in formulation developments, since it can detect chemically unstable and potentially phototoxic combinations. However, extrapolation of in vitro positive results to human photopatch tests may be performed only to a limited extent.

Vitamin A fortification of wheat flour: considerations and current recommendations.

BACKGROUND: Vitamin A deficiency is a major public health nutrition problem, affecting an estimated 190 million preschool-aged children and 19 million pregnant and lactating women globally, and 83 million adolescents in Southeast Asia alone. Its consequences (disorders) include xerophthalmia (the leading cause of early childhood blindness), increased severity of infection, anemia, and death. Because vitamin A deficiency is largely due to chronic dietary insufficiency of preformed vitamin A and proactive carotenoids, food fortification can offer an effective approach to prevention. OBJECTIVE: To provide guidance on fortifying wheat and maize flour milled in industrial rollers for national fortification programs in countries where vitamin A deficiency is considered a public health problem. METHODS: Critical review of the literature on the dietary gap in vitamin A intake and levels of wheat flour intake among risk groups as a basis for determining vitamin A fortificant levels. Additional review of efficacy evidence, safety and cost considerations, and country experiences related to wheat-flour fortification with vitamin A. RESULTS: Mill-rolled wheat flour is a technically fortifiable, centrally processed food vehicle that, where routinely and adequately consumed by target groups, should be considered a candidate for fortification. Vitamin A can be stable in flour under typical, ambient conditions, with processing losses estimated at approximately 30%, depending on source and premix conditions. CONCLUSIONS: Factors to guide a decision to fortify flour with vitamin A include the extent of deficiency, availability of other food vehicle options, the centrality of milling, market reach and population intake distributions of the flour products, the dietary vitamin A intake required, and associated costs. Large gaps persist in knowledge of these factors, which are needed to enable evidence-based fortification in most countries, leaving most decisions to fortify guided by assumptions. Where flour can and should be fortified, guidelines are given for providing nearly 25% of the Recommended Dietary Allowance for vitamin A to vulnerable groups consuming varying ranges of flour products. The costs will vary according to the level of fortification.

Risk assessment and risk management of vitamins and minerals.

OBJECTIVE OF WORKSHOP: The EANS workshop held in 1998 examined the various approaches to determine requirements and safety of vitamins and minerals. The methodology used and approaches taken on both sides of the Atlantic provided the focus of the event. Over three years later, and with risk assessment much advanced, the progress made was reviewed and inadequacies as well as limitations were defined. In addition, this workshop looked beyond assessment to the broader context in which nutrition science operates. What are the particular problems facing risk managers in the light of risk assessment conclusions? To what extent can nutrition research provide the answers that risk managers require and should the nutrition research agenda be shaped by the needs of the policymaker?

Using cost-effectiveness analysis to evaluate targeting strategies: the case of vitamin A supplementation.

Given the demonstrated efficacy of vitamin A supplements in reducing childhood mortality, health officials now have to decide whether it would be efficient to target the supplements to high risk children. Decisions about targeting are complex because they depend on a number of factors; the degree of clustering of preventable deaths, the cost of the intervention, the side-effects of the intervention, the cost of identifying the high risk group, and the accuracy of the 'diagnosis' of risk. A cost-effectiveness analysis was used in the Philippines to examine whether vitamin A supplements should be given universally to all children 6-59 months, targeted broadly to children suffering from mild, moderate, or severe malnutrition, or targeted narrowly to pre-schoolers with moderate and severe malnutrition. The first year average cost of the universal approach was US$67.21 per death averted compared to $144.12 and $257.20 for the broad and narrow targeting approaches respectively. When subjected to sensitivity analysis the conclusion about the most cost-effective strategy was robust to changes in underlying assumptions such as the efficacy of supplements, clustering of deaths, and toxicity. Targeting vitamin A supplements to high risk children is not an efficient use of resources. Based on the results of this cost-effectiveness analysis and a consideration of alternate strategies, it is apparent that vitamin A, like immunization, should be provided to all pre-schoolers in the developing world. Issues about targeting public health interventions can usefully be addressed by cost-effectiveness analysis.

PIP: It has been established that vitamin A supplementation can help reduce levels of child mortality. Findings are reported from a cost-effectiveness study in the Philippines undertaken to determine whether vitamin A supplements should be given universally to all children age 6-59 months; targeted broadly to children with mild, moderate, or severe malnutrition; or targeted narrowly to preschoolers with moderate and severe malnutrition. Whether to target supplementation depends upon the degree of clustering of preventable deaths, the cost of the intervention, the side effects of the intervention, the cost of identifying the high risk group, and the accuracy of the diagnosis of risk. The first year average cost of the universal approach would be US$67.21 per death averted, $144.12 for the broad targeting approach, and $257.20 for the narrow approach. Targeting vitamin A supplements to high-risk children is therefore not an efficient use of resources. Vitamin A, like immunization, should be provided to all preschoolers in the developing world.

Comparative assessment of the toxicology of vitamin A and retinoids in man.

As the title implies, any assessment of the toxic effects of vitamin A derivatives must distinguish between vitamin A in the truest sense, i.e. retinol, and retinoic acid and its synthetic derivatives. Just as no single description is universally applicable to the mode of action of vitamin A derivatives, so too do their toxic effects defy generalization. The recommendation made in 1982 by IUPAC [Eur. J. Biochem., 129 (1989) 1] to designate all derivatives with the typical structure of the vitamin as being retinoids may be chemically logical and correct but, when it comes to describing the effects and side-effects of vitamin A derivatives, it leads to misunderstandings. Retinol, which is frequently used as synonym for vitamin A, can eliminate all symptoms of vitamin A deficiency if it is taken in sufficient quantity with the diet. The term retinol will therefore be used here as a synonym for vitamin A whereas retinoic acid and its derivatives--including the synthetic ones--will be referred to as retinoids because they do not cover the whole spectrum of effects exerted by retinol and because they also vary markedly in their side-effects. In contrast to the nomenclature proposed by IUPAC, this system provides a clear and logical distinction for describing biological processes. Other authors have favoured it in recent times [Chytil, F., J. Am. Acad. Dermatol., 15 (1986) 741; Olson, J.A., Semin. Oncol., x (3) (1983) 290; Olson, J.A., Am. J. Clin. Nutr., 45 (1987) 704; Zbinden, G., Acta Dermatovener., 74 (1975) 36]. By vitamin A, therefore, is meant all derivatives that can possibly originate from retinol in the organism. This also covers the small quantities of retinoic acid formed from retinol. On the other hand, by retinoids is meant the natural retinoic acid derivatives and their synthetic forms in their special modes of action. Since retinoic acid cannot be reduced to retinol in the organism, this nomenclature provides a clear demarcation within the biological system. Vitamin A is essential to the growth and development of higher life forms and functions in many different ways within the organism. Although vitamin A was one of the first vitamins to be described, even today there is still some uncertainty as to its mode of action, with the exception of that of retinal (vitamin A aldehyde) in vision.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of cost-effectiveness analysis in planning cancer chemoprophylaxis trials.

We present a conceptual framework for the use of cost-effectiveness analysis in planning cancer chemoprophylaxis trials and evaluating such choices as sample size, study design, diagnostic evaluation, and duration of follow-up. The approach is illustrated by cost-effectiveness calculations for a trial of synthetic retinoids as cancer prophylaxis agents. Our work emphasizes the need for studies large enough to have a reasonable power of detecting 10%-20% reductions in mortality. Conversely, we note that rare but serious idiosyncratic side effects such as those seen the the "swine-flu" vaccination program are likely to escape detection even in trials involving tens of thousands of subjects.