Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy.

BACKGROUND: Delamanid and bedaquiline are two of the most recently developed antituberculosis (TB) drugs that have been extensively studied in patients with multidrug-resistant TB. There is currently a need for more potent, less-toxic drugs with novel mechanisms of action that can be used in combination with these newer agents to shorten the duration of treatment as well as prevent the development of drug resistance. Quabodepistat (QBS) is a newly discovered inhibitor of decaprenylphosphoryl-ß-D-ribose-2'-oxidase, an essential enzyme for Mycobacterium tuberculosis to synthesize key components of its cell wall. The objective of this study is to evaluate the safety, efficacy, and appropriate dosing of a 4-month regimen of QBS in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary TB in comparison with the 6-month standard treatment (i.e., rifampicin, isoniazid, ethambutol, and pyrazinamide). METHODS: This phase 2b/c, open-label, randomized, parallel group, dose-finding trial will enroll approximately 120 participants (including no more than 15% with human immunodeficiency virus [HIV] coinfection) aged ≥ 18 to ≤ 65 years at screening with newly diagnosed pulmonary drug-sensitive TB from ~8 sites in South Africa. Following a screening period of up to 14 days, eligible participants will be randomized in a ratio of 1:2:2:1 to one of four arms. Randomization will be stratified by HIV status and the presence of bilateral cavitation on a screening chest x-ray. After the end of the treatment period, participants will be followed until 12 months post randomization. The primary efficacy endpoint is the proportion of participants achieving sputum culture conversion in Mycobacteria Growth Indicator Tube by the end of the treatment period. The safety endpoints consist of adverse events, clinical laboratory tests, vital signs, physical examination findings, and electrocardiographic changes. DISCUSSION: QBS's potent bactericidal activity and distinct mechanism of action (compared with other TB drugs currently available for human use) may make it an ideal candidate for inclusion in a novel treatment regimen to improve efficacy and potentially prevent resistance to concomitant TB drugs. This trial will assess the effectiveness, safety, and dosing of a new, shorter, QBS-based, combination anti-TB treatment regimen. TRIAL STATUS: ClinicalTrials.gov NCT05221502. Registered on February 3, 2022.

Average portions of foods commonly eaten by infants and toddlers in the United States.

OBJECTIVES: To examine average portion sizes consumed per eating occasion by infants and toddlers. Average portions reported for toddlers were compared to average portions for comparably aged children reported in the 1994 to 1996 and 1998 Continuing Survey of Food Intakes by Individuals. In addition, reported average portions were compared with minimum required portion sizes for meals served to infants and toddlers in the Child and Adult Care Food Program (CACFP). DESIGN: Data from 24-hour recalls collected in the 2002 Feeding Infants and Toddlers Study (FITS) were analyzed. Average portion sizes were determined for major food groups and individual foods that were reported by at least 5% of the population. Most foods were reported separately; however, sandwiches were disaggregated into their components. Gram weights of portions consumed were converted, on a food-by-food basis, to household units so that foods with different volume-to-weight ratios could be analyzed together. SUBJECTS/SETTING: A national random sample of 3,022 US infants and toddlers 4 to 24 months of age. STATISTICAL ANALYSES PERFORMED: For each food and food group, average portion sizes per eating occasion were computed for up to six age groups. An average per-eating occasion portion was determined for each child who consumed a given food by summing the total amount of food consumed over the day and dividing by the number of eating occasions. These estimates were then summed across all children who consumed the food and divided by the total number of consumers. The number of eating occasions was defined as the total number of times a child had anything to eat or drink during the day, excluding eating occasions that included only water and/or supplements. RESULTS: For most foods, there was a gradual increase in the average portion as age increased. Average portions reported for FITS toddlers were consistent with those reported for comparably aged children in the most recent Continuing Survey of Food Intakes by Individuals. The average portions reported for FITS infants and toddlers were consistent with CACFP-recommended portion sizes for formula, juice, meats, and cheese. For milk (toddlers only), cereal, breads, fruits, and vegetables, average portions reported in FITS were consistently larger than CACFP portion sizes. Distributions showed that, in many cases, the per-eating occasion portion sizes of 50% to 90% of FITS infants and toddlers exceeded the CACFP portion sizes. CONCLUSIONS: Dietitians, pediatricians, and health educators can use the data presented in this article to provide guidance to parents and caregivers about reasonable portion sizes for infants and toddlers. The data should also be useful to those who plan meals for infants and toddlers in child care settings and to researchers studying dietary intakes of infants and toddlers. Advice about reasonable portion sizes should always be tempered with appropriate cautions about avoiding coercive "clean your plate" feeding practices. Parents and caregivers should be encouraged to offer infants and toddlers appropriate portions of healthful foods from the basic food groups, with a special emphasis on fruits, vegetables, and whole grains, and allow them to eat until they are satiated.

Nutrient intakes of infants and toddlers.

OBJECTIVES: To assess the nutrient adequacy of the diets of US infants and toddlers 4 to 24 months of age. DESIGN: Descriptive analysis of the usual nutrient intakes of infants and toddlers using 24-hour recall data from the 2002 Feeding Infants and Toddlers Study. SUBJECTS: A national random sample of 3,022 infants and toddlers, with 2 days of recall available for 703 sample members. Sample sizes by age were: infants 4 to 6 months (n=862), infants 7 to 11 months (n=1,162), and toddlers 12 to 24 months (n=998). STATISTICAL ANALYSES PERFORMED: Using the personal computer version of the Software for Intake Distribution Estimation, we estimated (where applicable) the percentage of infants and toddlers with usual intakes below the estimated average requirement, compared the means of usual nutrient intake distributions with adequate intake levels, and compared the 99th percentile of usual intake distributions with tolerable upper intake levels. RESULTS: For infants under 12 months of age, mean usual intakes exceeded the adequate intake for all nutrients. For toddlers 12 to 24 months of age, the estimated prevalence of inadequacy was low for most nutrients; however, 58% of toddlers had usual vitamin E intakes less than the estimated average requirement. Mean energy intake exceeded the estimated energy requirement by 10% for infants 4 to 6 months, 23% for infants 7 to 12 months, and 31% for toddlers 12 to 24 months of age. The discrepancy between mean energy intake and the estimated energy requirement for infants 4 to 6 months of age was larger for infants fed solids than for infants consuming only breast milk or formula. Fiber intakes of toddlers were below the adequate intake. APPLICATIONS: Studies should examine whether parents overreport foods consumed by infants and toddlers, and whether infants and toddlers are consuming more energy than required. Additional research is indicated to substantiate some of the new Dietary Reference Intakes for infants and children 1 to 3 years of age.

Feeding infants and toddlers study: Improvements needed in meeting infant feeding recommendations.

OBJECTIVE: To assess adherence to infant feeding recommendations among a sample of infants and toddlers four to 24 months of age in the United States. DESIGN: Descriptive analysis of data collected in the 2002 Feeding Infants and Toddlers Study (FITS) based on telephone interviews and 24-hour dietary recalls collected with the Nutrition Data System for Research of the University of Minnesota. SUBJECTS: A national random sample of 3,022 infants and toddlers age four to 24 months, including 2,024 infants age four to 11 months. MAIN OUTCOME MEASURES: Breastfeeding, timing of introduction of complementary foods, and adherence to infant feeding recommendations. STATISTICAL ANALYSES: Means and standard errors, percentile distributions, and percentages by age group (four to six months, seven to eight months, and nine to 11 months). RESULTS: About 76% of infants and toddlers were fully or partly breastfed at birth. This percentage declined to 30% at six months and 16% at 12 months-short of Healthy People 2010 goals of 50% and 25%, respectively. The average duration of breastfeeding was 5.5 months for all who initiated breastfeeding. About two-thirds of infants had been introduced to complementary foods between four and six months-the period recommended by the American Academy of Pediatrics (AAP); 17% consumed juice before the AAP recommended age of six months or later. Twenty-two percent of infants nine to 11 months consumed cow's milk on a daily basis before the recommended age of 12 months or later, and one in 10 consumed french fries and/or sweetened beverages on any given day. APPLICATIONS/CONCLUSIONS: More parents and caregivers can benefit from guidance about the introduction of developmentally appropriate, micronutrient-rich first solid foods such as iron-rich infant cereals, iron-fortified grain products, meats, soft fruits, and cooked vegetables and the importance of breastfeeding through the first year of life. A smaller proportion of parents and caregivers require guidance on delaying the introduction of juices until six months of age and cow's milk other than formula until one year of age.

Toddlers' transition to table foods: Impact on nutrient intakes and food patterns.

OBJECTIVE: To describe the differential changes in average intakes of nutrients and food groups among higher versus lower table food consumers during the transition from baby foods to table foods. DESIGN: A comparative analysis of food and nutrient intakes in the lowest versus highest quartile of energy from table foods based on 24-hour dietary recall data. SUBJECTS: A national random sample of 1,677 US infants and toddlers 9 to 24 months in the 2002 Feeding Infants and Toddlers Study (FITS). STATISTICAL ANALYSES: Mean and percentiles of energy intake from table foods; comparisons of mean daily nutrient intake and the percentages consuming various foods and beverages in the lowest versus highest quartile of energy from table foods, by age. RESULTS: The mean percentage of energy from table foods increased from 25% at 9 to 11 months to 63% at 19 to 24 months. Mean intakes of energy, macronutrients, sodium, folate, and fiber were significantly higher for children 9 to 11, 12 to 14, and 15 to 18 months in the highest table food energy quartiles compared to the lowest. Mean calcium intakes were significantly lower among toddlers 15 to 24 months consuming high table food energy, and associated with lower milk consumption. A higher percentage of children in the lowest quartiles of energy from table food were consuming deep yellow vegetables among ages 9 through 14 months. The percentage of children consuming popular items such as pizza, carbonated sodas, French fries, candy and other sweets was higher among those who consumed more energy from table foods in every age group. APPLICATIONS: The epidemic of overweight children mandates helping parents teach healthy eating habits early. Messages that educate parents and caregivers about toddler feeding include: (1) offer a wide variety of nutritious foods, particularly fruits and vegetables, in forms that are developmentally appropriate, (2) continue to feed foods that are good sources of iron, such as iron-fortified infant cereals, ready-to-eat cereals that are high in iron, and meats, (3) to ensure adequate calcium intake, build the habit of drinking milk, and (4) teach children to recognize and honor their hunger and satiety cues.