Fluconazole in Hypercalciuric Patients with Increased 1,25(OH)2D Levels: The Prospective, Randomized, Placebo-Controlled, Double Blind FLUCOLITH Trial.

BackgroundHypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)2D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.MethodsThe FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double blind trial. A total of 60 patients (10-60years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/d), increased 1,25(OH)2D levels (> 150 pmol/L) and 25-OH-D levels >20 nmol/L, will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-hour calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-hour calciuria in patients who still display at W16 a 24-hour hypercalciuria. DiscussionThe current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)2D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the “off-label” use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)2D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. Trial RegistrationClinicalTrial.gov, ID: identifier: NCT04495608. Registered on July 23rd, 2020

Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases Order to Target Them With Tailored Interventions—A Randomized Cross Over Trial

Introduction: Physical activity is associated with many physiological and psychological health benefits across the lifespan. Children with a chronic disease often have lower levels of daily physical activity, and a decreased exercise capacity compared to healthy peers. In order to learn more about limitations for physical activity, we investigate children with four different chronic diseases: children with a Fontan circulation, children with Broncho Pulmonary Dysplasia (BPD), Pompe disease and inflammatory bowel disease (IBD). Each of these diseases is likely to interfere with physical activity in a different way. Knowing the specific limitations for physical activity would make it possible to target these, and increase physical activity by a personalized intervention. The aim of this study is to first investigate limitations for physical activity in children with various chronic diseases. Secondly, to measure the effects of a tailored exercise intervention, possibly including a personalized dietary advice and/or psychological counseling, on exercise capacity, endurance, quality of life, fatigue, fear for exercise, safety, muscle strength, physical activity levels, energy balance, and body composition.Methods and Analysis: This randomized crossover trial will aim to include 72 children, aged 6–18 years, with one of the following diagnosis: a Fontan circulation, BPD, Pompe disease and IBD. Eligible patients will participate in the 12-week tailored exercise intervention and are either randomized to start with a control period or start with the intervention. The tailored 12-week exercise interventions, possibly including a personalized dietary advice and/or psychological counseling, will be designed based on the found limitations for physical activity in each disease group during baseline measurements by the Rotterdam Exercise Team. Effects of the tailored training interventions will be measured on the following endpoints: exercise capacity (measured by cardiopulmonary exercise test), endurance, physical activity levels, muscle strength, quality of life, fatigue, fear for exercise, disease activity, cardiac function (in children with a Fontan circulation), energy balance, and body composition.Ethics and Dissemination: Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval was obtained.Trial Registration Number: NL8181, https://www.trialregister.nl/trial/8181.

Reactivity thresholds in children allergic to cow's milk and egg, but tolerant of baked milk and baked egg.

Background. The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing diagnostic Oral Food Challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) are 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children. Methods. We retrospectively assessed consecutive diagnostic OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children. Results. Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 were 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 were 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are respectively 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds. Conclusions The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared to milk in the determinism of fatal anaphylactic reactions in children

Effect of a dietary intervention including minimal and unprocessed foods, high in natural saturated fats, on the lipid profile of children, pooled evidence from randomized controlled trials and a cohort study

Aim To study the possible effects of a dietary intervention with minimal and unprocessed foods, high in natural saturated fats on the lipid profile and body mass index of children. Method This study combines three intervention studies; one non-randomized retrospective cohort study and two randomized controlled trials, to a pooled analysis. The intervention group received a dietary intervention of minimal and unprocessed foods for three to six months, consisting of five times per week green vegetables, three times per week beef, daily 200–300 mL whole cow’s milk (3.4% fat) and whole dairy butter (80% fat) on each slice of bread. The control group continued their usual dietary habits. Raw data of the three intervention studies where combined into one single dataset for data analysis, using mixed effects analysis of covariance to test the effects of the dietary advice on the main study outcomes, which are measurements of the lipid profile. Results In total, 267 children aged 1 to 16 years were followed. 135 children were included in the intervention group and 139 children in the control group. Characteristics (age, gender and follow-up period) were equally distributed between the groups at baseline. In the intervention group HDL-cholesterol increased significantly from 1.22 mmol/L, 95% confidence interval (CI) 1.14–1.32 to 1.42 mmol/L 95% CI 1.30–1.65 (p = 0.007). The increase over time in HDL cholesterol in the intervention group was significantly different compared to the increase in the control group (from 1.26 mmol/L, 95% CI 1.19–1.35, to 1.30 mmol/L, 95% CI 1.26–1.37) (p = 0.04). Due to the increased HDL concentration in the intervention group, the total cholesterol/HDL cholesterol ratio decreased significantly from 3.70 mmol/L, 95% CI 3.38–3.87, to 3.25 mmol/L, 95% CI 2.96–3.31 (p = 0.05). Conclusion Consumption of minimal and unprocessed foods (high in natural saturated fats) has favourable effects on HDL cholesterol in children. Therefore, this dietary advice can safely be recommended to children.

Effect of antenatal dietary myo-inositol supplementation on the incidence of gestational diabetes mellitus and fetal outcome: protocol for a double-blind randomised controlled trial

IntroductionGestational diabetes mellitus (GDM) affects 23.6% of Qatari women and is associated with maternal and perinatal morbidity and long-term risk of developing type 2 diabetes. A number of challenges exist with current interventions, including non-compliance with dietary advice, the reluctance of mothers to ingest metformin tablets or use insulin injections. These challenges highlight the importance of pursuing evidence-based prevention strategies. Myo-inositol is readily available as an US Food and Drug Administration-approved food supplement with emerging but limited evidence suggesting it may be beneficial in reducing the incidence of GDM. Further studies, such as this one, from different ethnic contexts and with differing risk factors, are urgently needed to assess myo-inositol effects on maternal and neonatal outcomes.Methods and analysisThis study is a prospective, randomised, double-blinded, placebo controlled clinical trial to either myo-inositol supplementation or placebo.We plan to enrol 640 pregnant women attending antenatal care at Sidra Medicine, Doha, Qatar, 320 in each arm. All participants will complete at least 12 weeks of supplementation prior to undertaking the Oral Glucose Tolerance Test at 24–28 weeks. The daily use of the trial supplementation will continue until the end of pregnancy. All outcome measures will be collected from the electronic medical records.Ethics and disseminationEthical approval for the study was obtained on 12 April 2021 from Sidra Medicine (IRB number 1538656). Results of the primary trial outcome and secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration numberProspectively registered on 26 May 2021. Registration number ISRCTN16448440 (ISRCTN registry).

Sustainable eating behavior

With the growing impact of agriculture and modern food processing on the natural environment and growing concerns about all aspects of their sustainability, urgent solutions are required to promote healthy, low-impact diets. Sustainable diets are those with low environmental impact and high availability that ensure food and nutritional security. A comprehensive overview of different approaches to the analysis of sustainable eating behavior is provided. It is argued that preserving the environment is critical, including in designing programs to improve health, address inequalities in affordability, food access and availability in food system models. However, dietary advice and food policy should not be based solely on the environmental aspect of sustainability and should be carefully formulated. Economy, culture and other sociological factors should be taken into account in appropriate policies when planning ways to provide adequate nutrition to the population. It is emphasized that building sustainable food systems that support healthy communities requires a multidimensional, interdisciplinary approach. A sustainable healthy diet is based on improving the energy balance and changing the diet towards a predominantly plant-based diet, which is in line with the data on healthy eating. Updating national guidelines to reflect the latest data on healthy diets may in itself be important for improving health and reducing environmental impact, and may not only clearly define but expand the criteria for sustainability. Key principles of environmental sustainability and well-being are applied in shaping a national sustainable food strategy and are directly related to food production and consumption. To implement an integrated health and environment modeling framework, it is necessary to take different approaches to sustainable nutrition, motivating environmental, food security and public health goals. To develop a methodology for assessing indicators of sustainable nutrition, it is important to simultaneously take into account all aspects: nutritional value of products, indicators of environmental impact, availability of products, climatic, geographic and national characteristics. This methodology will allow to make competent decisions in the field of food production and consumption, will help to minimize the negative impact on the natural environment through sustainable eating behavior.

The Relationship between Addictive Eating and Dietary Intake: A Systematic Review

(1) Background: Research suggests that certain foods may have addictive effects; however, no reviews have systematically appraised studies in this area. The aims of this review were to determine the nutrients, foods and dietary patterns associated with addictive eating. (2) Methods: Published studies up to November 2020 were identified through searches of 6 electronic databases. Eligible studies included those in in children and adults that reported dietary intakes of individuals with ‘food addiction’. (3) Results: Fifteen studies (n = 12 in adults and n = 3 in children/adolescents with Yale Food Addiction Scale defined ‘food addiction’) were included. Foods commonly associated with addictive eating were those high in a combination of fat and refined carbohydrates. Generally, intakes of energy, carbohydrates and fats were significantly higher in individuals with addictive eating compared to those without. (4) Conclusions: Due to the heterogeneity in study methodologies and outcomes across included studies, it is difficult to conclude if any specific foods, nutrients or dietary patterns facilitate an addictive process. Further research is needed to elucidate potential associations. However, present addictive eating treatment approaches could incorporate individualised dietary advice targeting foods high in fat and refined carbohydrates.

Estimating Cardiovascular Health Gains From Eradicating Indoor Cold in Australia

Background Exposure to cold indoor temperature (<18 degrees Celsius) increases cardiovascular disease (CVD) risk and has been identified by the WHO as a source of unhealthy housing. While warming homes has the potential to reduce CVD risk, the reduction in disease burden is not known. We simulated the population health gains from reduced CVD burden if all homes in Australia were adequately warm. Methods The health effect of eradicating cold housing through reductions in CVD was simulated using proportional multistate lifetable model. The model sourced CVD burden and epidemiological data from Australian and Global Burden of Disease studies. The prevalence of cold housing in Australia was estimated from the Australian Housing Conditions Survey. The effect of cold indoor temperature on blood pressure (and in turn stroke and coronary heart disease) was estimated from published research. Results Eradication of exposure to indoor cold could achieve a gain of undiscounted one and a half weeks of additional health life per person alive in 2016 (baseyear) in cold housing through CVD alone. This equates to 0.447 (uncertainty interval: 0.064, 1.34; 3% discount rate) HALYs per 1,000 persons over remainder of their lives through CVD reduction. One-fifth of the total health gains are achievable between 2016 and 2035. Although seemingly modest, the gains outperform currently recommended CVD interventions including dietary advice for adults (0.017 per 1000 people, UI: 0.01, 0.027), lifestyle program for adults (0.024, UI: 0.01, 0.027) and Community Heart Health Program (0.141, UI: 0.071, 0.221). Conclusion Cardiovascular health gains achievable through eradication of cold housing are comparable with lifestyle and dietary interventions. The benefits of housing improvement are also substantial in other social domains (comfort, heating bills and energy efficiency).

Perceptions of Tailored Dietary Advice to Improve the Nutrient Adequacy of the Diet in French Pregnant Women

Tailored dietary counseling could be specifically efficient during pregnancy, a period accompanied by a rise in nutrition awareness, but little is known about the expectations of pregnant women in this regard. We studied these expectations regarding tailored dietary advice in French women during their pregnancy, as well as their motivations and the perceived barriers and enablers. In French pregnant women, we evaluated the perceptions of tailored dietary advice provided by stepwise dietary counseling based on three types of dietary changes, consisting of: (1) a modification of the amounts consumed, (2) substitutions within the food subgroups, and (3) substitutions between food subgroups. A sequential explanatory mixed-method approach was designed. Using qualitative data from a focus group study (n = 40), we intended to explore in depth the women’s expectations regarding dietary advice and adherence to a tailored approach. These were combined with quantitative and qualitative data from a 6-week online longitudinal study (n = 115), using questionnaires designed to assess the modifications of dietary habits during pregnancy and to evaluate each type of dietary change. Both studies confirmed that most women in our samples did indeed intend to institute changes regarding healthier dietary practices during pregnancy. The principal motivation behind changes to their habits was to ensure the health and well-being of both their babies and themselves. The proposal of dietary advice that is tailored to both the current diet and the specific needs of pregnant women, but that is also positive and credible, was perceived as enabling implementing healthier dietary practices during pregnancy. Regarding the implementation of the dietary changes proposed, the enablers and barriers identified differed between modifications of the amounts consumed and substitutions. The women displayed interest in all types of dietary changes. This gave relevance to combining different types of changes in order to propose dietary counseling during pregnancy. Tailored dietary counseling was identified by French pregnant women in our samples as enabling them to adopt a healthier diet. However, perceived barriers might limit the implementation of dietary changes, especially when they involved marked modifications to their usual diet.