Efficacy of mindfulness and goal setting interventions for increasing resilience and reducing smoking in lower socio-economic groups: randomised controlled trial protocol.

BACKGROUND: Smoking and resulting health problems disproportionately impact low socioeconomic status (SES) individuals. Building resilience presents an approach to 'closing the gap'. Mindfulness-based interventions and setting realistic goals are preferred in low socioeconomic communities. We aim to test if these interventions, delivered online and consolidated with peer support offered via ex-smokers, are successful in promoting smoking cessation and resilience. Our conceptualisation of resilience encompasses the inner capacity/skills and external resources (e.g., social support) which smokers utilise to bounce back from adversity. We include a process evaluation of barriers/facilitators to interventions and cost-effectiveness analysis (from health system perspective). METHODS: We plan a four-arm parallel 12-month RCT with a 6-month follow-up to test the efficacy of three group-based interventions each followed by peer support. Arm 1: mindfulness-integrated cognitive behavioural therapy; Arm 2: mindfulness training; Arm 3: setting realistic goals; Arm 4: active control group directed to quit services. All interventions will be administered online. Participants are adult smokers in Australia (N = 812) who have an average weekly household income less than $457AUD or receive welfare benefits. Group-based interventions will occur over 6 months, followed by 6 months of forum-based peer support. PRIMARY OUTCOME: self-reported 14-day period prevalence of smoking abstinence at 6 months, with remote biochemical verification of saliva cotinine (< 30 ng/mL). Secondary outcomes include: internal resilience (Connor-Davidson Resilience Scale-25); external resilience (ENRICHD social support tool); quality adjusted life years (EQ-5D-5L); self-efficacy for smoking abstinence (Smoking-Abstinence Self-Efficacy Questionnaire); motivation to quit smoking (Biener and Abrams Contemplation Ladder); nicotine dependence (Fagerstrom Test for Nicotine Dependency); equanimity (Equanimity Scale-16); stress (Perceived Stress Scale-10); goal assessment/attainment (Problems and Goals Assessment Scale). DISCUSSION: This study is the first to compare resilience interventions for low SES smokers which have been identified by them as acceptable. Our various repeated measures and process evaluation will facilitate exploration of mechanisms of impact. We intervene within the novel framework of the Psychosocial Model of Resilience, applying a promising paradigm to address a critical and inequitable public health problem. Trial registration Australian New Zealand Clinical Trials Registry ID: ACTRN12621000445875, registered 19 April 2021 ( https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381007&isReview=true ). The Universal Trial Number is U1111-1261-8951.

Effect of Native and Acetylated Dietary Resistant Starches on Intestinal Fermentative Capacity of Normal and Stunted Children in Southern India.

The health benefits of dietary amylase resistant starch (RS) arise from intestinal microbial fermentation and generation of short chain fatty acids (SCFA). We compared the intestinal fermentative capability of stunted and nonstunted ('healthy') children in southern India using two types of RS: high amylose maize starch (HAMS) and acetylated HAMS (HAMSA). Twenty children (10 stunted and 10 healthy) aged 2 to 5 years were fed biscuits containing HAMS (10 g/day) for two weeks followed by a 2-week washout and then HAMSA biscuits (10 g/day) for 2 weeks. Fecal samples were collected at 3-4 day intervals and pH and SCFA analyzed. At entry, stunted children had lower SCFA concentrations compared to healthy children. Both types of RS led to a significant decrease in fecal pH and increase in fecal acetate and propionate in both healthy and stunted children. However, while HAMS increased fecal butyrate in both groups of children, HAMSA increased butyrate in healthy but not stunted children. Furthermore, healthy children showed a significantly greater increase than stunted children in both acetate and butyrate when fed either RS. No adverse effects were reported with either RS. Stunted children have impaired capacity to ferment certain types of RS which has implications for choice of RS in formulations aimed at improving microbial function in stunted children.

The Capacity of the Fecal Microbiota From Malawian Infants to Ferment Resistant Starch.

In Low and Middle-Income Countries (LMIC), weaning is associated with environmentally acquired and inflammation-associated enteric disorders. Dietary intake of high amylose maize starch (HAMS) can promote commensal fermentative bacteria and drive the production of short chain fatty acids (SCFAs). By stabilizing commensal gut microbiology, and stimulating the production of anti-inflammatory metabolites, HAMS supplementation might therefore influence enteric health. However, the extent to which the gut microbiota of LMIC infants are capable of fermenting HAMS is unclear. We assessed the capacity of the fecal microbiota from pre-weaning and weaning Malawian infants to ferment HAMS and produce SCFAs using an in vitro fermentation model. Fecal microbiota from both pre-weaning and weaning infants were able to ferment HAMS, as indicated by an increase in bacterial load and total SCFA concentration, and a reduction in pH. All of these changes were more substantial in the weaning group. Acetate production was observed with both pre-weaning and weaning groups, while propionate production was only observed in the weaning group. HAMS fermentation resulted in significant alterations to the fecal microbial community in the weaning group, with significant increases in levels of Prevotella, Veillonella, and Collinsella associated with propionate production. In conclusion, fecal microbiota from Malawian infants before and during weaning has the capacity to produce acetate through HAMS fermentation, with propionate biosynthetic capability appearing only at weaning. Our results suggest that HAMS supplementation might provide benefit to infants during weaning.

Resistant Starch is Actively Fermented by Infant Faecal Microbiota and Increases Microbial Diversity.

In adults, fermentation of high amylose maize starch (HAMS), a resistant starch (RS), has a prebiotic effect. Were such a capacity to exist in infants, intake of RS might programme the gut microbiota during a critical developmental period. This study aimed to determine if infant faecal inocula possess the capacity to ferment HAMS or acetylated-HAMS (HAMSA) and characterise associated changes to microbial composition. Faecal samples were collected from 17 healthy infants at two timepoints: Preweaning and within 10 weeks of first solids. Fermentation was assessed using in vitro batch fermentation. Following 24 h incubation, pH, short-chain fatty acid (SCFA) production and microbial composition were compared to parallel control incubations. In preweaning infants, there was a significant decrease at 24 h in pH between control and HAMS incubations and a significant increase in the production of total SCFAs, indicating fermentation. Fermentation of HAMS increased further following commencement of solids. Fermentation of RS with weaning faecal inocula increased Shannon's diversity index (H) and was associated with increased abundance of Bifidobacterium and Bacteroides. In conclusion, the faecal inocula from infants is capable of RS fermentation, independent of stage of weaning, but introduction of solids increases this fermentation capacity. RS may thus function as a novel infant prebiotic.

Drug-development concepts as guides for optimizing clinical trials of supplemental zinc for populations at risk of deficiency or diarrhea.

Studies on the efficacy of zinc supplementation for treatment or prevention of diarrhea have shown an inconsistent effect in populations at risk for zinc deficiency. Unlike drugs, which have no preexisting presence in the body, endogenous zinc must be assessed pharmacokinetically by isotope tracer studies. Although such methods have produced much data, very few studies have estimated the dose and the timing of dosing of zinc supplementation. This review examines drug kinetics used to establish the best dose, the timing of such doses, and the mechanism of action through pharmacodynamic markers and applies them, where possible, to zinc supplements. The findings reveal that little is known, especially in children at highest risk of zinc deficiency. Key data missing to inform proper dosing, whether for treatment of disease or for preventive nutrient supplementation, are noted. Addressing these uncertainties could improve study design, leading to future studies of zinc supplements that might be of greater benefit.

The effect of dietary resistant starch type 2 on the microbiota and markers of gut inflammation in rural Malawi children.

BACKGROUND: Resistant starch (RS) decreases intestinal inflammation in some settings. We tested the hypothesis that gut inflammation will be reduced with dietary supplementation with RS in rural Malawian children. Eighteen stunted 3-5-year-old children were supplemented with 8.5 g/day of RS type 2 for 4 weeks. The fecal samples were analyzed for the microbiota, the microbiome, short chain fatty acids, metabolome, and proteins indicative of inflammation before and after the intervention. Subjects served as their own controls. RESULTS: The consumption of RS changed the composition of the microbiota; at the phylum level Actinobacteria increased, while Firmicutes decreased. Among the most prevalent genera, Lactobacillus was increased and Roseburia, Blautia, and Lachnospiracea incertae sedis were decreased. The Shannon H index at the genus level decreased from 2.02 on the habitual diet and 1.76 after the introduction of RS (P < 0.01). Fecal acetate concentration decreased, and fecal propionate concentration increased after RS administration (-5.2 and 2.0 µmol/g, respectively). Fecal calprotectin increased from 29 ± 69 to 89 ± 49 µg/g (P = 0.003) after RS was given. The lipopolysaccharide biosynthesis pathway was upregulated. CONCLUSIONS: Our findings do not support the hypothesis that RS reduces gut inflammation in rural Malawian children.

The potential for zinc stable isotope techniques and modelling to determine optimal zinc supplementation.

It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease.

Resistant starch does not affect zinc homeostasis in rural Malawian children.

OBJECTIVE: This study tested the hypothesis that Malawian children at risk for zinc deficiency will have reduced endogenous fecal zinc (EFZ) and increased net absorbed zinc (NAZ) following the addition of high amylose maize resistant starch (RS) to their diet. METHODS: This was a small controlled clinical trial to determine the effects of added dietary RS on zinc homeostasis among 17 stunted children, aged 3-5 years consuming a plant-based diet and at risk for perturbed zinc homeostasis. Dual zinc stable isotope studies were performed before and after 28 d of intervention with RS, so that each child served as their own control. The RS was incorporated into fried wheat flour dough and given under direct observation twice daily for 28 d. Changes in zinc homeostatic measures were compared using paired Student's t-tests and linear regression analysis. RESULTS: Children had a mean height-for-age Z-score of -3.3, and consumed animal source foods ≤twice per month. Their habitual diet contained a phytate:zinc molar ratio of 34:1. Children avidly consumed the RS without complaints. EFZ was 0.8±0.4mg/d (mean±SD) both before and after the intervention. Fractional absorption of zinc was 0.38±0.08 and 0.35±0.06 before and after the RS intervention respectively. NAZ was 1.1±0.5 and 0.6±0.7 before and after the RS intervention. This reduction of NAZ corresponded with diminished dietary zinc intake on the study day following intervention with RS. Regression analysis indicated no change in zinc absorption relative to dietary intake as a result of the RS intervention. CONCLUSION: Consumption of RS did not improve zinc homeostasis in rural African children without zinc deficiency. RS was well tolerated in this setting.

The relevance of the colon to zinc nutrition.

Globally, zinc deficiency is widespread, despite decades of research highlighting its negative effects on health, and in particular upon child health in low-income countries. Apart from inadequate dietary intake of bioavailable zinc, other significant contributors to zinc deficiency include the excessive intestinal loss of endogenously secreted zinc and impairment in small intestinal absorptive function. Such changes are likely to occur in children suffering from environmental (or tropical) enteropathy (EE)-an almost universal condition among inhabitants of developing countries characterized by morphologic and functional changes in the small intestine. Changes to the proximal gut in environmental enteropathy will likely influence the nature and amount of zinc delivered into the large intestine. Consequently, we reviewed the current literature to determine if colonic absorption of endogenous or exogenous (dietary) zinc could contribute to overall zinc nutriture. Whilst we found evidence that significant zinc absorption occurs in the rodent colon, and is favoured when microbially-fermentable carbohydrates (specifically resistant starch) are consumed, it is unclear whether this process occur in humans and/or to what degree. Constraints in study design in the few available studies may well have masked a possible colonic contribution to zinc nutrition. Furthermore these few available human studies have failed to include the actual target population that would benefit, namely infants affected by EE where zinc delivery to the colon may be increased and who are also at risk of zinc deficiency. In conducting this review we have not been able to confirm a colonic contribution to zinc absorption in humans. However, given the observations in rodents and that feeding resistant starch to children is feasible, definitive studies utilising the dual stable isotope method in children with EE should be undertaken.

Zinc deficiency in children with environmental enteropathy-development of new strategies: report from an expert workshop.

Zinc deficiency is a major cause of childhood morbidity and mortality. The WHO/UNICEF strategy for zinc supplementation as adjunctive therapy for diarrhea is poorly implemented. A conference of experts in zinc nutrition and gastrointestinal disorders was convened to consider approaches that might complement the current recommendation and what research was needed to develop these approaches. Several key points were identified. The design of novel zinc interventions would be facilitated by a better understanding of how disturbed gut function, such as environmental (or tropical) enteropathy, affects zinc absorption, losses, and homeostasis. Because only 10% of zinc stores are able to be rapidly turned over, and appear to be rapidly depleted by acute intestinal illness, they are probably best maintained by complementary regular supplementation in a primary prevention strategy rather than secondary prevention triggered by acute diarrhea. The assessment of zinc status is challenging and complex without simple, validated measures to facilitate field testing of novel interventions. Zinc bioavailability may be a crucial factor in the success of primary prevention strategies, and a range of options, all still inadequately explored, might be valuable in improving zinc nutrition. Some therapeutic actions of zinc on diarrhea seem attributable to pharmacologic effects, whereas others are related to the reversal of deficiency (ie, nutritional). The distinction between these 2 mechanisms cannot be clarified given the insensitivity of serum zinc to identify subclinical deficiency states. Why zinc seems to be less effective than expected at all ages, and ineffective for secondary prevention of diarrhea in children <12 mo of age, remains unclear. It was concluded that a reframing of the current recommendation is warranted with consideration of how to better optimize and deliver zinc and whether to provide a complementary public health primary prevention zinc strategy. This requires careful consideration of the zinc product to be used as well as strategies for its delivery.

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia.

BACKGROUND: As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. METHODS: Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. RESULTS: It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0-42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17860 per infection averted (median, $13651-24287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. CONCLUSIONS: The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.