scholarly journals Thiamine Status of Supplemented, Lactating Mothers in Rural Cambodia: A Randomized Controlled Trial

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 830-830
Author(s):  
Kyly Whitfield ◽  
Rem Ngik ◽  
Jelisa Gallant ◽  
Kathleen Chan ◽  
Lisa N Yelland ◽  
...  
Keyword(s):  
New York ◽  
Human Milk ◽  
Controlled Trial ◽  
York Academy ◽  
Blood Biomarkers ◽  
Double Blind ◽  
Randomized Controlled ◽  
Lactating Mothers ◽  
Gates Foundation ◽  
The Impact

Abstract Objectives Thiamine deficiency is a cause of infant morbidity and mortality throughout Southeast and South Asia. Maternal intake influences human milk thiamine concentrations, thus mother's intake must be improved to combat infant deficiency. However, the dose of supplemental thiamine required by lactating mothers is unknown. We aimed to estimate the maternal oral thiamine dose required to optimize milk thiamine concentrations, and to investigate the impact of various doses on thiamine status biomarkers. Methods This was a double-blind, four-parallel arm randomized controlled dose-response trial. At 2 weeks postpartum, healthy mothers were randomized to consume one capsule daily for 22 weeks, containing either 0 mg (placebo, n = 83), 1.2 mg (estimated average requirement, n = 86), 2.4 mg (n = 81), or 10 mg (n = 85) thiamine. Human milk total thiamine, whole blood thiamine diphosphate, and erythrocyte transketolase activity coefficient (ETKac) were assessed. An Emax curve, estimated using a non-linear least squares model, was plotted for human milk. Linear mixed-effects models were used to test for differences between treatment groups for milk and blood biomarkers. Results A maternal supplemental dose of 2.35 (95% CI 0.58, 7.01) mg/d was estimated to reach 90% of the maximum average human milk total thiamine concentration of 191 µg/L. The mean (SD) milk thiamine concentration was significantly higher in all intervention groups (183 (91), 190 (105), and 206 (89) µg/L, for 1.2, 2.4, and 10 mg, respectively) compared to placebo (153 (85) µg/L; p < 0.0001), and did not differ from each other. Blood biomarkers followed similar group trends, except for infant ETKac, where only the 10 mg (mean [SD]: 1.18 [0.10]) and placebo (1.12 [0.06]) groups differed significantly (p = 0.003). Conclusions While an estimated maternal dose of 2.35 (0.58, 7.01) mg/d was required to reach a milk thiamine concentration of 191 µg/L in Emax dose analyses, group comparisons suggest a daily dose of 1.2 mg/d is sufficient to improve maternal biomarkers to levels similar to higher doses (2.4 and 10 mg/d) and consistent with thiamine-replete populations. However, a higher maternal dose of 10 mg/d was required to improve infant ETKac status compared to other dose groups. Funding Sources Bill & Melinda Gates Foundation, The New York Academy of Sciences.

scholarly journals Maternal Thiamine Supplementation Promotes Infants’ Language Processing at 24 Weeks

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 892-892
Author(s):  
Dare A Baldwin ◽  
Jeffrey Measelle ◽  
Lauren Gallivan ◽  
Anna Sanchirico ◽  
Netanel Weinstein ◽  
...  
Keyword(s):  
New York ◽  
Language Processing ◽  
Motor Development ◽  
Controlled Trial ◽  
Vitamin B1 ◽  
York Academy ◽  
Double Blind ◽  
Lactating Mothers ◽  
Preference Task ◽  
Gates Foundation

Abstract Objectives In 2005, researchers observed a link between infants’ access to thiamine (vitamin B1) and their subsequent language functioning: infants fed formula that inadvertently lacked thiamine later displayed significant delays in language and motor development. In the context of a double-blind, randomized, controlled trial, the present research provided the first experimental test of a relationship between early life thiamine exposure and infants’ early language processing. Methods 335 lactating mothers were randomly assigned to receive capsules containing either 0, 1.2, 2.4, or 10 mg of thiamine daily, from 2 weeks postpartum until infants were 24 weeks. We assessed the integrity of 24-week-old infants’ developing system for language processing by measuring the extent to which they displayed attentional enhancement in response to infant-directed speech (IDS) relative to adult-directed speech (ADS). Such IDS-related attentional enhancement implies that infants can differentiate IDS from ADS, which requires underlying skills for analysis of the complex stream of sound that human speech embodies. Of the 335 infants in the study, analyzable data for the IDS preference task were available for 251. Results As predicted, a greater-than-chance percentage of all infants displayed enhanced attention to IDS relative to ADS, replicating prior research (one-sample t(250) = 3.06, P = 0.002). The magnitude of the IDS-elicited attentional-enhancement increased significantly in relation to the thiamine dose that lactating mothers received (beta-weight 0.007, t = 2.57, P = 0.011). Notably, however, when supplementation groups were examined separately, only infants whose mothers received the 10 mg daily supplement displayed a statistically significant IDS-related attentional enhancement (10 mg group: one-sample t(63) = 4.14, P = 0.000; all other groups t’s < 1.41, P’s > 0.16). Conclusions Taken together, these findings confirm a link between infants’ post-natal access to thiamine and their language processing facility at 24 weeks. The findings both showcase the value of the IDS preference task for monitoring the integrity of infants’ language processing, and underscore the importance of adequate thiamine for ensuring infants’ optimal language development. Funding Sources Bill & Melinda Gates Foundation and the New York Academy of Sciences.

scholarly journals 2226. Impact of Prior and Concomitant Antibacterial Therapy on Outcomes in the ASPECT-NP Randomized, Controlled Trial of Ceftolozane/Tazobactam (C/T) vs. Meropenem (MEM) in Patients with Ventilated Nosocomial Pneumonia (NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S760
Author(s):  
Richard G Wunderink ◽  
Christopher Bruno ◽  
Ignacio Martin-Loeches ◽  
Marin Kollef ◽  
Jean-Francois Timsit ◽  
...  
Keyword(s):  
Antibacterial Therapy ◽  
Controlled Trial ◽  
Treatment Options ◽  
Study Drug ◽  
Drug Susceptibility ◽  
Double Blind ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background NP is a frequent healthcare-acquired infection associated with high mortality; rising resistance rates among causative Gram-negative pathogens require new treatment options. In the randomized, controlled, double-blind, phase 3 ASPECT-NP trial, C/T (at double the initially approved dose) was noninferior to MEM for ventilated NP in both primary and key secondary endpoints. Here we evaluate the impact of prior and concomitant Gram-negative antibacterial therapy on outcomes in that trial. Methods Mechanically ventilated patients with ventilator-associated or hospital-acquired pneumonia were randomized 1:1 to 3 g C/T or 1 g MEM, both by 1-h IV infusion every 8 hours for 8–14 days. Patients could receive ≤24 hours of active antibacterial therapy within ≤72 hours prior to first dose; longer durations were permitted in case of prior treatment failure (i.e., signs and/or symptoms of the current episode of ventilated NP persisted/worsened despite ≥48 hours of treatment). At sites with MEM-resistant Pseudomonas aeruginosa rates ≥15%, patients could optionally receive up to 72 h of adjunctive empiric aminoglycoside (amikacin was recommended) until study drug susceptibility was confirmed. Primary and key secondary endpoints, respectively, were 28-d all-cause mortality and clinical response at test of cure (TOC; 7–14 days after the end of therapy) in the intent to treat (ITT) population (all randomized patients). Results In the C/T arm, 285/362 (79%) ITT patients received prior systemic Gram-negative therapy and 103/362 (28%) received adjunctive aminoglycoside, compared with 288/364 (79%) and 112/364 (31%) patients, respectively, in the MEM arm. In the microbiologic ITT population, causative pathogens in patients failing prior therapy at the time of enrollment (C/T 15%, MEM 11%) were mainly Klebsiella spp (33%), P. aeruginosa (17%), Escherichia coli (14%), and Acinetobacter baumannii (8%). Mortality and cure rates were comparable between C/T and MEM regardless of receipt of prior systemic or adjunctive Gram-negative therapy (table). Conclusion Prior and adjunctive Gram-negative antibacterial therapy did not affect the relative efficacy of C/T (at the 3-g dose) vs. MEM in these high-risk patients with Gram-negative ventilated NP. Disclosures All authors: No reported disclosures.

scholarly journals Protocol for an app-based affective control training for adolescents: proof-of-principle double-blind randomized controlled trial

2019 ◽  
Vol 4 ◽  
pp. 91
Author(s):  
Susanne Schweizer ◽  
Jovita T. Leung ◽  
Rogier Kievit ◽  
Maarten Speekenbrink ◽  
William Trender ◽  
...  
Keyword(s):  
Mental Health ◽  
Randomized Controlled Trial ◽  
Mental Health Problems ◽  
Controlled Trial ◽  
Health Problems ◽  
Matching Task ◽  
Double Blind ◽  
Randomized Controlled ◽  
The Impact ◽  
Proof Of Principle

Background: 75% of all mental health problems have their onset before the end of adolescence. Therefore, adolescence may be a particularly sensitive time period for preventing mental health problems. Affective control, the capacity to engage with goal relevant and inhibit distracting information in affective contexts, has been proposed as a potential target for prevention. In this study, we will explore the impact of improving adolescents’ affective control capacity on their mental health. Methods: The proof-of-principle double-blind randomized controlled trial will compare the effectiveness of an app-based affective control training (AC-Training) to a placebo training (P-Training) app. In total, 200 (~50% females) adolescents (11-19 years) will train for 14 days on their training app. The AC-Training will include three different n-back tasks: visuospatial, auditory and dual (i.e., including both modalities). These tasks require participants to flexibly engage and disengage with affective and neutral stimuli (i.e., faces and words). The P-Training will present participants with a perceptual matching task. The three versions of the P-Training tasks vary in the stimuli included (i.e., shapes, words and faces). The two training groups will be compared on gains in affective control, mental health, emotion regulation and self-regulation, immediately after training, one month and one year after training. Discussion: If, as predicted, the proposed study finds that AC-Training successfully improves affective control in adolescents, there would be significant potential benefits to adolescent mental health. As a free app, the training would also be scalable and easy to disseminate across a wide range of settings. Trial registration: The trial was registered on December 10th 2018 with the International Standard Randomised Controlled Trial Number (Registration number: ISRCTN17213032).

scholarly journals Protocol for an app-based affective control training for adolescents: proof-of-principle double-blind randomized controlled trial

2019 ◽  
Vol 4 ◽  
pp. 91 ◽  
Author(s):  
Susanne Schweizer ◽  
Jovita T. Leung ◽  
Rogier Kievit ◽  
Maarten Speekenbrink ◽  
William Trender ◽  
...  
Keyword(s):  
Mental Health ◽  
Randomized Controlled Trial ◽  
Mental Health Problems ◽  
Controlled Trial ◽  
Health Problems ◽  
Matching Task ◽  
Double Blind ◽  
Randomized Controlled ◽  
The Impact ◽  
Proof Of Principle

Background: 75% of all mental health problems have their onset before the end of adolescence. Therefore, adolescence may be a particularly sensitive time period for preventing mental health problems. Affective control, the capacity to engage with goal relevant and inhibit distracting information in affective contexts, has been proposed as a potential target for prevention. In this study, we will explore the impact of improving adolescents’ affective control capacity on their mental health. Methods: The proof-of-principle double-blind randomized controlled trial will compare the effectiveness of an app-based affective control training (AffeCT) to a placebo training (P-Training) app. In total, 200 (~50% females) adolescents (11-19 years) will train for 14 days on their training app. The AffeCT will include three different n-back tasks: visuospatial, auditory and dual (i.e., including both modalities). These tasks require participants to flexibly engage and disengage with affective and neutral stimuli (i.e., faces and words). The P-Training will present participants with a perceptual matching task. The three versions of the P-Training tasks vary in the stimuli included (i.e., shapes, words and faces). The two training groups will be compared on gains in affective control, mental health, emotion regulation and self-regulation, immediately after training, one month and one year after training. Discussion: If, as predicted, the proposed study finds that AffeCT successfully improves affective control in adolescents, there would be significant potential benefits to adolescent mental health. As a free app, the training would also be scalable and easy to disseminate across a wide range of settings. Trial registration: The trial was registered on December 10th 2018 with the International Standard Randomised Controlled Trial Number (Registration number: ISRCTN17213032).

scholarly journals Neurocognitive Benefits of Maternal Thiamine Supplementation for Breastfed Cambodian Infants

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 931-931
Author(s):  
Kyly Whitfield ◽  
Dare A Baldwin ◽  
Mary Chea ◽  
Tim Green ◽  
Frank Wieringa ◽  
...  
Keyword(s):  
At Risk ◽  
Language Development ◽  
Thiamine Deficiency ◽  
Controlled Trial ◽  
Newborn Infants ◽  
Cognitive Test ◽  
York Academy ◽  
Double Blind ◽  
Significant Drop ◽  
The Impact

Abstract Objectives Women reliant on rice-heavy diets can have inadequate thiamine intakes, placing breastfed infants at risk of thiamine deficiency and, in turn, neurocognitive impairments. We investigated the impact of maternal thiamine supplementation doses on infants’ cognitive, motor, and language development across the first year. Methods In this double-blind, four-parallel arm, randomized controlled trial, healthy mothers of exclusively breastfed newborn infants were recruited in Kampong Thom, Cambodia. At 2-weeks postnatal, women (n = 335) were randomized to one of four treatment groups to consume one capsule/day with varying amounts of thiamine for 22 weeks: 0 mg, 1.2 mg, 2.4 mg, and 10 mg. At 2-, 12-, 24- and 52-weeks of age, infants were assessed with the Mullen Scales of Early Learning (MSEL). Results Mixed effects modeling suggest that by 6 months of age, the highest maternal thiamine dose (10 mg/day) held significant benefits for infants’ language development, F's (3,659) > 33.2, P's < 0.001, but generally not for motor or visual reception development. Despite having achieved standardized scores on the MSEL that approximated US norms by 6 months, infants showed a significant drop in all cognitive domains following trial completion, indicating that nutritional interventions beyond 6 months may be necessary. Conclusions Findings provide the first experimental evidence that thiamine supplementation among lactating mothers at risk of thiamine deficiency protects their infants’ neurocognitive development, with particular benefit to developing language capacities. Results are consistent with studies that report a widening gap in cognitive test scores over time between children from high vs. low-risk contexts. Important questions remain, particularly with respect to the appropriate duration of thiamine supplementation and/or alternate interventions such as mandatory fortification, with potential to build protective stores of thiamine in preconception or pregnancy. Funding Sources Bill & Melinda Gates Foundation and the New York Academy of Sciences (Opportunity ID OPP1176128).

Sign in / Sign up

Export Citation Format

Share Document