Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial.

INTRODUCTION: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development. METHODS AND ANALYSIS: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period. ETHICS AND DISSEMINATION: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12620000386932.

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Non-pharmacological interventions for sleep disturbances in people with dementia.

BACKGROUND: Sleep disturbances occur frequently in people with dementia with a reported prevalence of up to 40%. Common problems are increased number and duration of awakenings and increased percentage of light sleep. Sleep disturbances are associated with a number of problems for people with dementia, their relatives, and carers. In people with dementia, they may lead to worsening of cognitive symptoms, challenging behaviours such as restlessness or wandering, and further harms, such as accidental falls. Sleep disturbances are also associated with significant carer distress and have been reported as a factor contributing to institutionalisation of people with dementia. As pharmacological approaches have shown unsatisfactory results, there is a need to synthesise the research evidence on non-pharmacological strategies to improve sleep in people with dementia. As interventions are often complex, consisting of more than one active component, and implemented in complex contexts, it may not be easy to identify effective intervention components. OBJECTIVES: To evaluate the benefits and harms of non-pharmacological interventions on sleep disturbances in people with dementia compared to usual care, no treatment, any other non-pharmacological intervention, or any drug treatment intended to improve sleep, and to describe the components and processes of any complex intervention included. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 13 January 2022. SELECTION CRITERIA: We included individually or cluster-randomised controlled trials in people with dementia comparing non-pharmacological interventions to improve sleep compared to usual care or to other interventions of any type. Eligible studies had to have a sleep-related primary outcome. We included people with a diagnosis of dementia and sleep problems at baseline irrespective of age, type of dementia, severity of cognitive impairment, or setting. Studies reporting results on a mixed sample (e.g. in a nursing home) were only considered for inclusion if at least 80% of participants had dementia. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. objective sleep-related outcomes (e.g. total nocturnal sleep time, consolidated sleep time at night, sleep efficiency, total wake time at night (or time spent awake after sleep onset), number of nocturnal awakenings, sleep onset latency, daytime/night-time sleep ratio, night-time/total sleep ratio over 24 hours) and 2. ADVERSE EVENTS: Our secondary outcomes were 3. subjective sleep-related outcomes, 4. behavioural and psychological symptoms of dementia, 5. quality of life, 6. functional status, 7. institutionalisation, 8. compliance with the intervention, and 9. attrition rates. We used GRADE to assess the certainty of evidence and chose key outcomes to be included in summary of findings tables. MAIN RESULTS: We included 19 randomised controlled trials with 1335 participants allocated to treatment or control groups. Fourteen studies were conducted in nursing homes, three included community residents, one included 'inpatients', one included people from a mental health centre, and one included people from district community centres for older people. Fourteen studies were conducted in the US. We also identified nine ongoing studies. All studies applied one or more non-pharmacological intervention aiming to improve physiological sleep in people with dementia and sleep problems. The most frequently examined single intervention was some form of light therapy (six studies), five studies included physical or social activities, three carer interventions, one daytime sleep restriction, one slow-stroke back massage, and one transcranial electrostimulation. Seven studies examined multimodal complex interventions. Risk of bias of included studies was frequently unclear due to incomplete reporting. Therefore, we rated no study at low risk of bias. We are uncertain whether light therapy has any effect on sleep-related outcomes (very low-certainty evidence). Physical activities may slightly increase the total nocturnal sleep time and sleep efficiency, and may reduce the total time awake at night and slightly reduce the number of awakenings at night (low-certainty evidence). Social activities may slightly increase total nocturnal sleep time and sleep efficiency (low-certainty evidence). Carer interventions may modestly increase total nocturnal sleep time, may slightly increase sleep efficiency, and may modestly decrease the total awake time during the night (low-certainty evidence from one study). Multimodal interventions may modestly increase total nocturnal sleep time and may modestly reduce the total wake time at night, but may result in little to no difference in number of awakenings (low-certainty evidence). We are uncertain about the effects of multimodal interventions on sleep efficiency (very low-certainty evidence). We found low-certainty evidence that daytime sleep restrictions, slow-stroke back massage, and transcranial electrostimulation may result in little to no difference in sleep-related outcomes. Only two studies reported information about adverse events, detecting only few such events in the intervention groups. AUTHORS' CONCLUSIONS: Despite the inclusion of 19 randomised controlled trials, there is a lack of conclusive evidence concerning non-pharmacological interventions for sleep problems in people with dementia. Although neither single nor multimodal interventions consistently improved sleep with sufficient certainty, we found some positive effects on physical and social activities as well as carer interventions. Future studies should use rigorous methods to develop and evaluate the effectiveness of multimodal interventions using current guidelines on the development and evaluation of complex interventions. At present, no single or multimodal intervention can be clearly identified as suitable for widespread implementation.

Protocol and statistical analysis plan for a randomized controlled trial of the effect of intravenous iron on anemia in Malawian pregnant women in their third trimester (REVAMP - TT).

Background: Anemia affects 40% of pregnant women globally, leading to maternal mortality, premature birth, low birth weight, and poor baby development. Iron deficiency causes over 40% of anemia cases in Africa. Oral iron supplementation is insufficient for Low-and-Middle-Income-Countries (LMICs) to meet current WHO targets. We hypothesized that a single intravenous dose of Ferric Carboxymaltose (FCM) may be more effective than oral iron treatment for anemia recovery, particularly in these settings where women present late for antenatal care. Methods: This is a two-arm parallel open-label individual-randomized controlled trial in third trimester, in malaria Rapid Diagnostic Test-negative pregnant women with moderate or severe anemia - capillary hemoglobin <10 g/dL - who are randomized to receive either parenteral iron - with FCM - or standard-of-care oral iron for the remainder of pregnancy. This is the sister trial to the second-trimester REVAMP trial, funded by the Bill and Melinda Gates Foundation (trial registration ACTRN12618001268235, Gates Grant number INV-010612). In REVAMP-TT, recruitment and treatment are performed within primary health centers. The trial will recruit 590 women across Zomba district, Malawi. The primary outcome is the proportion of anemic women - venous hemoglobin <11 g/dL - at 36 weeks' gestation or delivery (whichever occurs first). Other pre-specified key secondary clinical and safety outcomes include maternal iron-status and hypophosphatemia, neonate birth weight, infant growth and infant iron and hematological parameters. Discussion: This study will determine whether FCM, delivered within primary health centers, is effective, safe and feasible for treating moderate to severe anemia in third-trimester pregnant Malawian women. This intervention could have long-term benefits for maternal and child health, resulting in improved survival and child development.

Absorption of iron from edible house crickets: a randomized crossover stable-isotope study in humans.

BACKGROUND: Edible insects are a novel source of animal protein. Moreover, edible insects contain iron concentrations similar to meat, potentially making them a valuable iron source for human consumers. Yet, it is unknown to what extent iron from insects is absorbed in humans. OBJECTIVES: In this exploratory study, we assessed fractional iron absorption from house crickets (Acheta domesticus) consumed with refined (low-phytate, noninhibiting) or nonrefined (high-phytate, inhibiting) meals. METHODS: Intrinsically [57Fe]-labeled and control crickets were reared. Six iron-balanced experimental meals were randomly administered crossover to 20 iron-depleted females (serum ferritin <25 µg/L; 18-30 y old), in 2 time-blocks of 3 consecutive days, 2 wk apart. Three meals consisted of refined maize flour porridge with either [57Fe]-labeled crickets, [58Fe]SO4 (reference meal), or unlabeled crickets plus [54Fe]SO4. The other 3 meals consisted of nonrefined maize flour porridge with the same respective additions. Blood samples were drawn to assess the 14-d isotope enrichment in erythrocytes, and meal-specific fractional iron absorption was calculated. In vitro digestion was used to explore possible explanations for unexpected findings. RESULTS: Mean fractional iron absorption from 57Fe-labeled house crickets with refined maize porridge (3.06%) and from refined maize porridge with unlabeled crickets (4.92%) was lower than from the reference meal (14.2%), with respective mean differences of -11.1% (95% CI: -12.6%, -9.68%) and -9.29% (95% CI: -10.8%, -7.77%). Iron absorption from all meals based on unrefined maize porridge was low (<3%), and did not differ for the 2 meals with crickets compared with the reference meal. In vitro digestion showed that chitin, chitosan, and calcium limited iron bioaccessibility to a large extent. CONCLUSIONS: Iron absorption from house crickets and fortified maize porridge with crickets is low, which may be explained by the presence of chitin and other inhibitors in the cricket biomass.This trial was registered at https://www.trialregister.nl as NL6821.

Effect of postpartum anaemia on maternal health-related quality of life: a systematic review and meta-analysis.

BACKGROUND: Postpartum anaemia remains a persistent and severe public health issue in many parts of the world. Studies have reported mixed findings on the effects of anaemia during the postpartum period on maternal health-related quality of life (HRQoL). We conducted this systematic review to summarise available evidence to inform public health practitioners on whether 1) anaemia negatively impact maternal health-related quality of life and 2) whether iron supplementation in anaemic women can improve maternal HRQoL during the postpartum period. METHODS: This review's protocol was registered online with PROSPERO (CRD42020206618). We extensively searched Embase, PubMed, Cochrane and Scopus through the HINARI website to identify studies that reported either association or effect of postpartum anaemia on fatigue, depression and mother-child interaction. We restricted our search to studies of human females published in English language from databases inception until August 2020. We followed a Cochrane guideline for reporting systematic reviews and meta-analysis to synthesise data. RESULTS: Twenty-seven studies were included in this systematic review, with some reporting all three domains (fatigue, depression and mother-child interaction) of HRQoL. Seven observational studies with pooled dichotomous outcomes showed that iron deficient or anaemic women were 1.66 times more likely to experience symptoms of depression than non-anaemic or iron-replete women [RR = 1.66 (95% CI: 1.28; 2.16), I2 = 67.0%, P < 0.01]. In three randomized controlled trials (RCTs), pooled continuous data showed statistically significant reduction in fatigue scores in women who received iron supplementation than the control group [MD: -1.85 (95% CI: -3.04; -0.67), I2 = 65.0%, p < 0.06]. Two of the four included studies showed that anaemic mothers were less responsive and had negative feelings towards their children than non-anaemic mothers. CONCLUSION: Evidence from this review suggests that postpartum anaemia negatively affects health-related quality of life and that iron replenishment improves both symptoms of fatigue and depression. Nevertheless, it remains unclear whether postpartum anaemia affects mother-child interaction.

Regulation of membrane phospholipids during the adult life of worker honey bee.

Two female castes that are genetically identical are found in honey bees: workers and queens. Adult female honey bees differ in their morphology and behaviors, but the most intriguing difference between the castes is the difference in their longevity. Queens live for years while workers live generally for weeks. The mechanisms that mediate this extraordinary difference in lifespan remain mostly unknown. Both castes share similar developmental stages and are fed liquid food (i.e. a jelly) during development. However, after emergence, workers begin to feed on pollen while queens are fed the same larval food for their entire life. Pollen has a high content of polyunsaturated fatty acids (PUFA) while royal jelly has negligible amounts. The difference in food during adult life leads to drastic changes in membrane phospholipids of female honey bees, and those changes have been proposed as mechanisms that could explain the difference in lifespan. To provide further details on those mechanisms, we characterized the membrane phospholipids of adult workers at seven different ages covering all life-history stages. Our results suggest that the majority of changes in worker membranes occur in the first four days of adult life. Shortly after emergence, workers increase their level of total phospholipids by producing phospholipids that contained saturated (SFA) and monounsaturated fatty acids (MUFA). From the second day, workers start replacing fatty acid chains from those pre-synthesized molecules with PUFA acquired from pollen. After four days, worker membranes are set and appear to be maintained for the rest of adult life, suggesting that damaged PUFA are replaced effectively. Plasmalogen phospholipids increase continuously throughout worker adult life, suggesting that plasmalogen might help to reduce lipid peroxidation in worker membranes. We postulate that the diet-induced increase in PUFA in worker membranes makes them far more prone to lipid-based oxidative damage compared to queens.

Iron Bioavailability from Infant Cereals Containing Whole Grains and Pulses: A Stable Isotope Study in Malawian Children.

BACKGROUND: Compared with infant cereals based on refined grains, an infant cereal containing whole grains (WGs) and pulses with adequate amounts of ascorbic acid to protect against absorption inhibitors could be a healthier source of well-absorbed iron. However, iron absorption from such cereals is uncertain. OBJECTIVE: We measured iron bioavailability from ferrous fumarate (Fefum) added to commercial infant cereals containing 1) refined wheat flour (reference meal), 2) WG wheat and lentil flour (WG-wheat-lentil), 3) WG wheat and chickpea flour (WG-wheat-chickpeas), and 4) WG oat flour (WG-oat) and from ferrous bisglycinate (FeBG) added to the same oat-based cereal (WG-oat-FeBG). METHODS: In a prospective, single-blinded randomized crossover study, 6- to 14-mo-old Malawian children (n = 30) consumed 25-g servings of all 5 test meals containing 2.25 mg stable isotope-labeled iron and 13.5 mg ascorbic acid. Fractional iron absorption (FIA) was assessed by erythrocyte incorporation of isotopes after 14 d. Comparisons were made using linear mixed models. RESULTS: Seventy percent of the children were anemic and 67% were iron deficient. Geometric mean FIA percentages (-SD, +SD) from the cereals were as follows: 1) refined wheat, 12.1 (4.8, 30.6); 2) WG-wheat-lentil, 15.8 (6.6, 37.6); 3) WG-wheat-chickpeas, 12.8 (5.5, 29.8); and 4) WG-oat, 9.2 (3.9, 21.5) and 7.4 (2.9, 18.9) from WG-oat-FeBG. Meal predicted FIA (P ≤ 0.001), whereas in pairwise comparisons, only WG-oat-FeBG was significantly different compared with the refined wheat meal (P = 0.02). In addition, FIAs from WG-wheat-lentil and WG-wheat-chickpeas were significantly higher than from WG-oat (P = 0.002 and P = 0.04, respectively) and WG-oat-FeBG (P < 0.001 and P = 0.004, respectively). CONCLUSION: In Malawian children, when given with ascorbic acid at a molar ratio of 2:1, iron bioavailability from Fefum-fortified infant cereals containing WG wheat and pulses is ≈13-15%, whereas that from FeBG- and Fefum-fortified infant cereals based on WG oats is ≈7-9%.

Iron deficiency anaemia in sub-Saharan Africa: a review of current evidence and primary care recommendations for high-risk groups.

The epidemiology of iron deficiency anaemia in sub-Saharan Africa differs from that in other parts of the world. The low-quality diets prevalent in this region are a poor source of iron, the population is frequently exposed to infection, and demographic characteristics result in a greater prevalence of people at high risk of iron deficiency anaemia than in other parts of the world. We herein review the causes, disease burden, and consequences of iron deficiency anaemia in the general population in this region, and current policies and interventions for its control. The current debate is dominated by concerns about the safety of iron interventions, namely regarding its effects on malaria and other infectious diseases. However, universal antenatal iron supplementation and delayed cord clamping are safe interventions and stand out for their potential to improve maternal and infant health. Effective infection control is a precondition to safe and efficacious iron interventions in children. Greater emphasis should be given to approaches aiming to reduce iron loss due to helminth infections and menstruation, alongside interventions to increase iron intake. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

The adult lifespan of the female honey bee (Apis mellifera): Metabolic rate, AGE pigment and the effect of dietary fatty acids.

Female honey bees can be queens or workers and although genetically identical, workers have an adult lifespan of weeks while queens can live for years. The mechanisms underlying this extraordinary difference remain unknown. This study examines three potential explanations of the queen-worker lifespan difference. Metabolic rates were similar in age-matched queens and workers and thus are not an explanation. The accumulation of fluorescent AGE pigment has been successfully used as a good measure of cellular senescence in many species. Unlike other animals, AGE pigment level reduced during adult life of queens and workers. This unusual finding suggests female honey bees can either modify, or remove from their body, AGE pigment. Another queen-worker difference is that, as adults, workers eat pollen but queens do not. Pollen is a source of polyunsaturated fatty acids. Its consumption explains the queen-worker difference in membrane fat composition of female adult honey bees which has previously been suggested as a cause of the lifespan difference. We were able to produce "queen-worker" membrane differences in workers by manipulation of diet that did not change worker lifespan and we can, thus, also rule out pollen consumption by workers as an explanation of the dramatic queen-worker lifespan difference.

Defining and describing treatment heterogeneity in new-onset idiopathic lower back and extremity pain through reconstruction of longitudinal care sequences.

BACKGROUND CONTEXT: Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices. PURPOSE: To describe treatment heterogeneity in surgically-managed LBP and LEP. STUDY DESIGN/SETTING: Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016). PATIENT SAMPLE: A population-based sample of opioid-naïve adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up. EXPOSURE: Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion). OUTCOME MEASURES: Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage. METHODS: Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance. RESULTS: A total of 2,496,908 opioid-naïve adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs. 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs. 63.8%, p<.001). Non-outlier sequences were more frequently characterized by early conservative interventions (31.9% vs. 7.4%, p<.001). CONCLUSIONS: Surgically-managed LBP and LEP care sequences demonstrate high heterogeneity despite established practice guidelines. Outlier sequences associated with high opioid usage and costs can be identified and are characterized by increased early imaging and decreased early conservative management. Elements that may portend suboptimal longitudinal management could provide opportunities for standardization of patient care.

Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial.

BACKGROUND: Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring. OBJECTIVES: We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation. METHODS: We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23). RESULTS: Analysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L). CONCLUSIONS: Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.

The contribution of provitamin A biofortified cassava to vitamin A intake in Nigerian pre-schoolchildren.

Biofortified yellow cassava has been developed to alleviate vitamin A deficiency. We examined the potential contribution of yellow cassava to total retinol activity equivalent (RAE) intake if replacing white by yellow cassava among pre-school Nigerian children. Dietary intake was assessed as part of a randomised controlled trial. Pre-schoolchildren (n 176) were randomly assigned to receive either white cassava (WC) or yellow cassava (YC) for 17 weeks. Dietary intake assessments were conducted during the intervention and 1 month after, when children had resumed their habitual diet. Differences in RAE intake between groups and time points were compared using a linear mixed model regression analysis. During intervention, median RAE intake was 536 µg/d in the YC group and 301 µg/d in the WC group (P < 0·0001). YC contributed approximately 40 % to total RAE intake. Of the children, 9 % in the YC group and 29 % in the WC group had RAE intake below the Estimated Average Requirement. After intervention, median RAE intake was 300 µg/d and did not differ between intervention groups (P = 0·5). The interaction effect of group and time showed a 37 % decrease in RAE intake in the YC group after the intervention (Exp(ß) = 0·63; 95 % CI 0·56, 0·72). If WC was replaced by YC after intervention, the potential contribution of YC to total RAE intake was estimated to be approximately 32 %. YC increased total RAE intake and showed a substantially lower inadequacy of intake. It is therefore recommended as a good source of provitamin A in cassava-consuming regions.

Sociocultural determinants and patterns of healthcare utilization for epilepsy care in Uganda.

OBJECTIVE: Epilepsy is a global public health concern, with the majority of cases occurring in lower- and middle-income countries where the treatment gap remains formidable. In this study, we simultaneously explore how beliefs about epilepsy causation, perceived barriers to care, seizure disorder characteristics, and demographics influence the initial choice of healthcare for epilepsy and its impact on attaining biomedical care (BMC). METHODS: This study utilized the baseline sample (n = 626) from a prospective cohort study of people with epilepsy (PWE) attending three public hospitals in Uganda (Mulago National Referral Hospital, Butabika National Referral Mental Hospital, and Mbarara Regional Referral Hospital) for epilepsy care. Patient and household demographics, clinical seizure disorder characteristics, and sociocultural questionnaires were administered. Logistic regression and principal component analyses (PCA) were conducted to examine associations with the choice of primary seizure treatment. RESULTS: The sample was 49% female, and 24% lived in rural settings. A biomedical health facility was the first point of care for 355 (56.7%) participants, while 229 (36.6%) first sought care from a traditional healer and 42 (6.7%) from a pastoral healer. Preliminary inspection of candidate predictors using relaxed criteria for significance (p < 0.20) identified several factors potentially associated with a greater odds of seeking BMC first. Demographic predictors included older caredriver (decision-maker for the participant) age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: [0.99, 1.02], p-value: 0.09), greater caredriver education level (OR = 1.21, 95% CI: [1.07, 1.37], p-value = 0.003), and lower ratio of sick to healthy family members (OR = 0.77 [0.56, 1.05], P = 0.097). For clinical predictors, none of the proposed predictors associated significantly with seeking BMC first. Self-report causation predictors associated with a greater odds of seeking BMC first included higher belief in biological causes of epilepsy (OR = 1.31 [0.92, 1.88], P = 0.133) and lower belief in socio-spiritual causes of epilepsy (OR = 0.68 [0.56, 0.84], P < 0.001). In the multivariate model, only higher caredriver education (OR = 1.19 [1.04, 1.36], P = 0.009) and lower belief in socio-spiritual causes of epilepsy (OR = 0.69 [0.56, 0.86], P < 0.01) remained as predictors of seeking BMC first. Additionally, PCA revealed a pattern which included high income with low beliefs in nonbiological causes of epilepsy as being associated with seeking BMC first (OR = 1.32 [1.12, 1.55], p = 0.001). Despite reaching some form of care faster, individuals seeking care from traditional or pastoral healers experienced a significant delay to eventual BMC (P < 0.001), with an average delay of more than two years (traditional healer: 2.53 years [1.98, 3.24]; pastoral care: 2.18 [1.21, 3.91]). CONCLUSIONS: Coupled with low economic and educational status, belief in spiritual causation of epilepsy is a dominant determinant of opting for traditional or pastoral healing over BMC, regardless of concurrent belief in biological etiologies. There is a prolonged delay to eventual BMC for PWE who begin their treatment seeking with nonallopathic providers, and although nonallopathic healers provide PWE with benefits not provided by BMC, this notable delay likely prevents earlier administration of evidence-based care with known efficacy. Based on these findings, initiatives to increase public awareness of neurobiological causes of epilepsy and effectiveness of biomedical drug treatments may be effective in preventing delays to care, as would programs designed to facilitate cooperation and referral among traditional, faith-based, and biomedical providers. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Iron Absorption from Iron-Biofortified Sweetpotato Is Higher Than Regular Sweetpotato in Malawian Women while Iron Absorption from Regular and Iron-Biofortified Potatoes Is High in Peruvian Women.

BACKGROUND: Sweetpotato and potato are fast-maturing staple crops and widely consumed in low- and middle-income countries. Conventional breeding to biofortify these crops with iron could improve iron intakes. To our knowledge, iron absorption from sweetpotato and potato has not been assessed. OBJECTIVE: The aim was to assess iron absorption from regular and iron-biofortified orange-fleshed sweetpotato in Malawi and yellow-fleshed potato and iron-biofortified purple-fleshed potato in Peru. METHODS: We conducted 2 randomized, multiple-meal studies in generally healthy, iron-depleted women of reproductive age. Malawian women (n = 24) received 400 g regular or biofortified sweetpotato test meals and Peruvian women (n = 35) received 500 g regular or biofortified potato test meals. Women consumed the meals at breakfast for 2 wk and were then crossed over to the other variety. We labeled the test meals with 57Fe or 58Fe and measured cumulative erythrocyte incorporation of the labels 14 d after completion of each test-meal sequence to calculate iron absorption. Iron absorption was compared by paired-sample t tests. RESULTS: The regular and biofortified orange-fleshed sweetpotato test meals contained 0.55 and 0.97 mg Fe/100 g. Geometric mean (95% CI) fractional iron absorption (FIA) was 5.82% (3.79%, 8.95%) and 6.02% (4.51%, 8.05%), respectively (P = 0.81), resulting in 1.9-fold higher total iron absorption (TIA) from biofortified sweetpotato (P < 0.001). The regular and biofortified potato test meals contained 0.33 and 0.69 mg Fe/100 g. FIA was 28.4% (23.5%, 34.2%) from the regular yellow-fleshed and 13.3% (10.6%, 16.6%) from the biofortified purple-fleshed potato meals, respectively (P < 0.001), resulting in no significant difference in TIA (P = 0.88). CONCLUSIONS: FIA from regular yellow-fleshed potato was remarkably high, at 28%. Iron absorbed from both potato test meals covered 33% of the daily absorbed iron requirement for women of reproductive age, while the biofortified orange-fleshed sweetpotato test meal covered 18% of this requirement. High polyphenol concentrations were likely the major inhibitors of iron absorption. These trials were registered at www.clinicaltrials.gov as NCT03840031 (Malawi) and NCT04216030 (Peru).

Antenatal iron supplementation and birth weight in conditions of high exposure to infectious diseases.

BACKGROUND: A recent cohort study among Papua New Guinean women surprisingly showed iron deficiency during pregnancy to be associated with increased birth weight. These findings seemingly contradict previous trial evidence that iron supplementation leads to increased birth weight, particularly in iron-deficient women, and hence require explanation. MAIN TEXT: We have re-analysed data from a previous trial in Kenya and demonstrated that, because women who were initially iron deficient respond better to iron supplementation, they show an increase in birthweight. There is evidence that this benefit is decreased in iron-replete women, possibly due to the adverse effects of haemoconcentration that can impair oxygen and nutrient transfer across the placenta. The Papua New Guinean results might be explained by a similar differential response to the iron supplements that they all received. CONCLUSIONS: Antenatal iron supplementation should ideally be administered in conjunction with measures to prevent, diagnose and treat malaria given the propensity of pathogenic microorganisms to proliferate in iron-supplemented individuals. However, even where services to prevent and treat malaria are poor, current evidence supports the conclusion that the benefits of universal iron supplementation outweigh its risks. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1146-z. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1376-8.

A model species for agricultural pest genomics: the genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae).

The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain why Leptinotarsa decemlineata has high sensitivity to dsRNA. The L. decemlineata genome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.

Paciente con EPOC grave, insuficiencia respiratoria crónica y agudización cardiorrespiratoria tratado con la asociación CDB-SWEETraining / Patient with severe COPD, chronic respiratory failure and cardiopulmonary exacerbation treated with a combination of CDB-SWEETraining

Objetivo: Evaluar el tratamiento combinado del comprehensive directed breathing con el programa de entrenamiento Square Wave Endurance Exercise Test en cicloergómetro con oxigenoterapia en el ejercicio en un paciente con EPOC grave, insuficiencia respiratoria crónica y agudización cardiorrespiratoria. Metodología: Se evalúa clínica y funcionalmente tras el alta médica a un paciente de 61 años con EPOC grave. Inicia entrenamiento tipo Square Wave Endurance Exercise Test combinado con ventilación dirigida contrastada (Comprehensive Directed Breathing) y oxigenoterapia en el ejercicio. Tras 40 sesiones de 90min se analizan parámetros físicos (frecuencia cardiaca, respiratoria y SaO2) en reposo y tras el ejercicio, funcionales (disnea de reposo y esfuerzo) y espirométricos. Resultados: Tras 8 semanas de entrenamiento se objetivan mejoras en la frecuencia cardiorrespiratoria, la SaO2, la disnea de reposo y esfuerzo, la gasometría y la espirometría (PEF 4,8L/s [+98%] y PIF 3,9L/s [+48%]), manteniéndose a los 6 meses, uno y 3 años. Conclusión: El tratamiento combinado comprehensive directed breathing -Square Wave Endurance Exercise Test con oxigenoterapia durante el ejercicio supervisado mejora la frecuencia cardiorrespiratoria, la SaO2, la disnea, la gasometría y la espirometría, manteniéndose a los 6 meses, uno y 3 años

Objective: To evaluate the effect of combined treatment with comprehensive directed breathing and Square Wave Endurance Exercise Test in cycle ergometer associated with oxygen therapy on exercise in a patient with severe COPD, chronic respiratory failure and cardiopulmonary exacerbation. Methods: Treatment with Square Wave Endurance Exercise Test, comprehensive directed breathing, and oxygen therapy during exercise was implemented in a 61-year-old patient with severe COPD. After 40 sessions of 90min, an analysis was performed on the physical parameters, including heart and respiratory rate, oxygen saturation, gasometry, and spirometry. Results: After 8 weeks of training, improvement were obtained in heart and respiratory rates, oxygen saturation, dyspnoea, gasometry, and spirometry (PEF 4.8L/s [+98%] and PIF 3.9L/s [+48%]) at 6 month and one and 3 years. Conclusion: Comprehensive directed breathing -Square Wave Endurance Exercise Test and oxygen therapy during exercise improved clinical and functional parameters at 6 months, and one and 3 years

Influence of Dietary Salt Knowledge, Perceptions, and Beliefs on Consumption Choices after Stroke in Uganda.

BACKGROUND: Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices. PURPOSE: Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda. METHODS: Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships between healthy dietary salt compliance, dietary salt knowledge, and participant characteristics were assessed using logistic regression analyses. RESULTS: Healthy dietary salt consumption behaviors were associated with basic salt knowledge (P < .0001), but no association was found between compliance and salt disease-related knowledge (P = .314). Only 20% and 7% obtained health-related salt knowledge from their health facility and educational sources, respectively, whereas 44% obtained this information from media personalities; 92% of participants had no understanding of nutrition labels, and only 25% of the study population consumed potash-an inexpensive salt substitute that is both rich in potassium and low in sodium. CONCLUSION: One barrier to healthy dietary consumption choices among Uganda's stroke survivors is a lack of credible disease-related information. Improving health-care provider stroke-related dietary knowledge in Uganda and encouraging the use of potash as a salt substitute would help reduce hypertension and thereby lower the risk of stroke.

Iron for Africa-Report of an Expert Workshop.

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue.