Dietary Trial Research Articles

Abstract P4-07-52: Caloric Restriction for Oncology Research (CaReFOR): Assessing dietary adherence and outcomes in African American patients during breast cancer treatment

Abstract Purpose: Epidemiologic and clinical evidence have shown an association between obesity and increased risk for breast cancer (BC) incidence and mortality. Data from human and animal studies support a potential role for weight loss in counteracting tumor-promoting properties of obesity in BC. However, dietary intervention clinical trials often show low patient adherence, especially among African American (AA) women compared to Caucasian (CC) women. They also show that AA women are disproportionately obese and lose less weight during behavior lifestyle interventions compared to CC with similar risk factors. We evaluated the efficacy and feasibility of a 10-week caloric restricted diet in patients undergoing radiation and have performed analysis to determine if adherence to dietary alterations is feasible in underrepresented patients. Methods: In an IRB approved clinical trial, we determined the feasibility and toxicity of dietary intervention during radiation in breast cancer patients 18 years and older who were undergoing breast conservation therapy with T1-2N0 cancers. The dietary intervention consisted of caloric intake reduction of 25% from baseline for a total of 10 weeks during their six-week radiation treatment which was administered to the whole breast to a dose of 50Gy with a 10Gy boost to the tumor bed. To optimize adherence to caloric restriction (CR), patients received personalized counseling, maintained food diaries, and were educated on behavioral modifications at weekly visits. To characterize the effects of CR, baseline physiologic and blood parameters were collected and compared with post intervention measurements and samples. Biometric and biological data collected during the study comparing compliant participants before and after the CaReFOR intervention was stratified by race and analyzed via two-sample paired t-test. The difference between AA and CC study participants was determined to be significant if the calculated p-value was less than < 0.05 (CI 95%). Results: A total of 32 female patients were enrolled in the CaReFOR trial, 16 were AA and 16 were CC. Participant demographics were similar across age, primary tumor size (pT), nuclear grade, and hormone receptor status. Evaluation of patients’ baseline diet demonstrated similar macronutrients across races, with AA showing less fruit/vegetable and grains. AA patients were more overweight compared to their CC counterparts. They also showed a more inflamed state compared to CC patients. The baseline inflammatory biomarker levels for ESR and cholesterol were significantly higher while adiponectin was significantly lower in AA than that of CC patients. The trends for insulin, HbA1c, and leptin were also higher for AA compared to CC. Following the 10-week diet, AA patients (87.3%) were more compliant than CC’s (81.3%). Both AA and CC patients lost weight during the trial, with AA having a significant loss in body fat and gain in muscle mass compared to CC. Similarly, after completing the CR diet, biological inflammatory markers improved in AA and CC patients. Particularly, in AA, there was a significant decrease in cholesterol levels, while insulin, leptin, and ESR serum levels trended downwards, suggesting a decreased inflammatory state. Conclusions: Contrary to published studies, we found AA patients are successful in adhering to dietary alterations and have a benefit with respect to physiologic and biologic parameters. Our dietary intervention was able to positively affect our AA patients adverse baseline factors such as obesity and inflammation. Future studies should consider dietary alterations as a possible means to decrease AA patient disparate outcomes in breast cancer. Citation Format: Siani Harding, Adeseye Adekeye, Edith P. Mitchell, Nicole Simone. Caloric Restriction for Oncology Research (CaReFOR): Assessing dietary adherence and outcomes in African American patients during breast cancer treatment. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-52.

Abstract PD12-08: PD12-08 Randomized trial of exercise and nutrition on pathological complete response among women with breast cancer receiving neoadjuvant chemotherapy: the Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study

Abstract Background: Neoadjuvant chemotherapy is available to women with locally advanced breast cancer where chemotherapy is given prior to surgery. By examining resected tissue following neoadjuvant chemotherapy pathological complete response (pCR) can be determined. pCR is a favorable prognostic factor associated with longer survival compared to residual disease after neoadjuvant chemotherapy. Physical activity and diet may improve some side effects during treatment, but less is known about their effect on chemotherapy completion and more specifically on pCR in the neoadjuvant setting. Utilizing data from a randomized trial of diet and physical activity with a primary endpoint of chemotherapy completion in women with newly diagnosed breast cancer initiating chemotherapy, we evaluated the effect of a lifestyle intervention on pCR among the subset of women in the trial who received neoadjuvant chemotherapy. Methods: The Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study enrolled 173 women with Stage I-III breast cancer who were randomized to usual care (n = 86) or a yearlong, 16-session, in-person or telephone-administered diet and physical activity intervention (n = 87) delivered by registered dietitians. Among study participants, 73 women received neoadjuvant chemotherapy and of these, 72 (98.6%) had complete follow-up pCR data (intervention = 40; usual care = 32). pCR, dates, doses and reason for dose-adjustments/delays of chemotherapy were abstracted from electronic medical records and confirmed with treating oncologists. A Chi-square test was used to examine the effect of the intervention versus usual care on pCR. Results: The 72 women receiving neoadjuvant chemotherapy with complete follow-up pCR data in LEANer were 49.4±11.6 years old, had a body mass index of 30.0+6.7 kg/m2, and 37.0% and 49.3% had stage I or II breast cancer, respectively. Just over half (52.1%) of women had ER/PR positive cancers and 32.9% of tumors were HER2 positive, with no statistically significant differences in tumor type by study arm. 92.7% of the women randomized to intervention adhered to all of the counseling sessions during their neoadjuvant chemotherapy and had statistically significant improvements in mean physical activity (161 minute increase versus 40 minute increase, p-value = < 0.001) and fiber intake (0.21 gram/day increase versus -5.17 g/day decrease, p-value = 0.020), as well as median fruit and vegetable intake (0.6 serving/day increase versus -0.5 serving/day decrease, p-value = 0.041) compared to usual care. There was a benefit of the intervention on pCR compared to usual care (52.5% with pCR in the intervention arm versus 28.1% with pCR in the usual care arm, p-value = 0.037). The intervention effect on pCR did not appear to be impacted by chemotherapy completion (relative dose intensity of 92% in intervention versus 90% in usual care) or chemotherapy dose delays as these were similar in the two study arms. In mediation analyses, results suggested that the changes in physical activity mediated, at least partially, the intervention effect on pCR. Conclusions: A primarily telephone-based diet and physical activity intervention led to improved pCR compared to usual care among the subset of women with breast cancer in the LEANer Study who received neoadjuvant chemotherapy. As pCR is an important prognostic factor for breast cancer, additional lifestyle interventions focusing on the neoadjuvant treatment setting with pCR as the primary outcome are necessary to confirm the potential benefits of lifestyle changes on pCR. Citation Format: Leah Ferrucci, Tara B. Sanft, Maura Harrigan, Brenda Cartmel, Fangyong Li, Michelle Zupa, Courtney McGowan, Leah Puklin, Thai Hien Nguyen, Anna M. Tanasijevic, Marian L. Neuhouser, Dawn Hershman, Karen Basen-Engquist, Beth Jones, Tish Knobf, Anees B. Chagpar, Andrea L.M. Silber, Jennifer A. Ligibel, Melinda L. Irwin. PD12-08 Randomized trial of exercise and nutrition on pathological complete response among women with breast cancer receiving neoadjuvant chemotherapy: the Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-08.

Differential effects of diet and physical activity interventions in pregnancy to prevent gestational diabetes mellitus and reduce gestational weight gain by level of maternal adiposity: a protocol for an individual patient data (IPD) meta-analysis of randomised controlled trials

IntroductionWomen and their infants are at increased risk of complications if gestational diabetes mellitus (GDM) or excessive gestational weight gain (GWG) occurs in pregnancy. Weight management interventions in pregnancy, consisting...

Magnesium suppresses in vivo oxidative stress and ex vivo DNA damage induced by protracted ACTH treatment in rats.

Oxidative stress, arising from disrupted balance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defences, has been implicated in the pathogenesis of stress-related disorders. There is a growing body of evidence that supports the relationship between the activity of the hypothalamic-pituitary-adrenal (HPA) stress system, oxidative stress and magnesium (Mg) homeostasis. The present study aimed to explore the gap in our current understanding of antigenotoxic and protective effects of Mg supplementation against excessive ROS production in male rats during chronic treatment with adrenocorticotropic hormone (ACTH). Our findings show that exposure to exogenous ACTH (10μg/day, s.c., for 21 days), as one of the key mediators of the HPA axis and stress response, produced an increase in superoxide anion levels and a decrease in superoxide dismutase activity in plasma. We observed that Mg supplementation, starting seven days prior to ACTH treatment and lasting 28 days (300mg/L of drinking water, per os), abolished these effects in experimental animals. Moreover, our study reveals that ACTH increased the susceptibility of peripheral blood lymphocytes to ex vivo H2O2-induced total and high-level oxidative DNA damage, while Mg completely reversed these effects. Collectively, these results highlight the promising role of Mg in stress-related conditions accompanied by increased oxidative stress in animals and support further investigation using human dietary trials.

Effects of ileocolonic delivered vitamin B2, B3 and C (ColoVit) or the Groningen anti-inflammatory diet on disease course and microbiome of patients with Crohn’s disease (VITA-GrAID study): a protocol for a randomised and partially blinded trial

BackgroundDiet plays a pivotal role in the onset and progression of Crohn’s disease (CD). Nutritional interventions revealed effects on intestinal inflammation and gut microbial composition. However, data from well-designed and...

Abstract P622: Increase From Low to Moderate Consumption of Caffeinated Coffee is Associated With Favorable Changes in Body Fat

Introduction: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies, usually with exposure assessment limited to baseline values. As BMI is a proxy for adiposity but does not capture fat tissue or its metabolically relevant distribution, precise measurements of distinct adipose tissues are needed, so the cardiometabolic impact of an anti-obesity effect can be assessed. Hypothesis: We assessed the hypothesis that an increase in coffee consumption is associated with a reduction in body fat, in particular with trunk fat and visceral adipose tissue (VAT). Methods: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome. Changes in the consumption of caffeinated and decaffeinated coffee were derived from validated food frequency questionnaires at baseline, 6 months and yearly during follow-up. Fat tissue was measured with dual x-ray absorptiometry at baseline and after 6, 12 months and three years. Linear multilevel mixed effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue over three years. Results: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤ 3 cups/ month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95 % CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95 % CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95 % CI: -0.13 to -0.01). However, changes to even higher levels (> 1 cup/day) showed no significant association. Conclusions: Moderate consumption of caffeinated coffee, but not high consumption, was associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with metabolic syndrome. Decaffeinated coffee was not linked to adiposity indicators. In conclusion, moderate consumption of caffeinated coffee may be part of a weight management strategy.

Abstract P619: DNA Methylation at SREBF1 and Long-Term Changes in Body Composition: The POUNDS Lost Trial

Introduction: A previous epigenome-wide association study has causally linked DNA methylation (DNAm) at the SREBF1 gene (cg11024682) with obesity and lipids. However, little is known about whether DNAm at SREBF1 is associated with long-term changes in body adiposity and composition. Hypothesis: We hypothesized that participants with different DNAm at SRBF1 might respond differently to dietary weight-loss interventions on changes in body adiposity and composition. Methods: The current study included 314 individuals with overweight or obese, who participated in POUNDS Lost: a 2-year randomized dietary weight-loss trial. The blood DNAm level was profiled by methylC-capture sequencing at baseline. Regional DNAm at SREBF1 was calculated as the average methylation level over CpGs within ±250 bp of cg11024682. Body composition, including total fat mass (FM), percentage of FM (FM%), total fat-free mass (FFM), percentage of FFM (FFM%), and percentage of trunk fat (TF%) were measured by dual-energy X-ray absorptiometry (DEXA) at baseline, 6 months, and 2 years. Results: Lower regional DNAm at SREBF1 was significantly associated with changes in body composition across 2 years ( Table ). At 6 months, per SD lower regional DNAm at SREBF1 was significantly associated with greater reductions in FM (β [SE] -0.23 [0.07], p=0.002), FM% (-0.30 [0.09], p<0.001), and TF% (-0.44 [0.13], p<0.001), and greater increases in FFM (0.18 [0.08], p=0.028) and FFM% (0.30 [0.09], p<0.001), regardless of dietary intervention groups and independent of concurrent weight loss. Such association remained at 2 years: FM (β [SE] -0.21 [0.10], p=0.045), FM% (-0.32 [0.11], p=0.004), TF% (-0.36 [0.16], p=0.026), FFM (0.22 [0.12], p=0.07) and FFM% (0.32 [0.11], p=0.004). Conclusions: Overweight and obese individuals with a lower regional DNAm at SREBF1 achieved greater improvement in body composition across the 2-year intervention, independent of concurrent weight loss, suggesting DNAm at SREBF1 is predictive of individuals’ response to treatment.

A bibliometric and visual analysis of low carbohydrate diet.

Numerous studies have confirmed the effects of low carbohydrate diet (LChD) on metabolism and chronic diseases. However, there were no bibliometric studies on LChD. This study was conducted through a bibliometric analysis to investigate the current status, hotspots and frontiers trends. We searched all research publications related to LChD from 2002 to 2021 on the Web of Scientific Core Collection (WoSCC). CiteSpace and VOSviewer software was used to analyze countries/regions, institutions, journals, authors, references, and keywords. A total of 6938 papers were included, with an increasing trend of annual publication. LChD categories mainly included nutrition, endocrinology, and neurosciences which reflected the interdisciplinary characteristics. USA was with the largest number and the world science center in LChD field. Universities were main research institutions and five of the top 10 institutions were from USA. Eric Heath Kossoff had 101 publications and ranked first. Nutrients was the leading journal. "A randomized trial of a low-carbohydrate diet for obesity" and "Obesity" were considered to be the most co-cited and cited reference respectively. The hotspots of LChD are four aspects, "ketogenic diet", "metabolism disease", "cardiovascular disease" and "cancer". We summarized that "oxidative stress", "gut microbiota", and "inflammation factors" are becoming frontiers trends of LChD research in the future and deserve further study. Over the past 20 years research on LChD has gained great attention. To better explore LChD field, multilevel mechanism studies will be required in the future.

Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat

Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score:-0.06; 95% CI:-0.11 to-0.02), trunk fat (Δ z-score:-0.07; 95% CI:-0.12 to-0.02), and VAT (Δ z-score:-0.07; 95% CI:-0.13 to-0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Including the child’s voice in research from a longitudinal birth cohort: insights from the ROLO young person’s advisory group

BackgroundPublic and patient involvement (PPI) through Young Person’s Advisory Groups (YPAG) enables children to provide guidance and insight into research activities. PPI is an important characteristic of research, however, to date, most collaboration has been with adults. Also, few YPAGs have been established within the Irish setting. The ROLO (Randomised cOntrol trial of a LOw glycaemic index diet in pregnancy to prevent macrosomia) YPAG was established in July 2020 to identify the research priorities of a group of healthy Irish children who are part of a longitudinal birth cohort. We aimed to describe this process and the key insights to date.MethodsThe ROLO study is a longitudinal birth cohort which has followed-up mother–child dyads at multiple timepoints over 10 years. Mothers actively involved in the study were contacted by the research team to invite their ROLO child and older sibling to participate in the YPAG. Meetings were conducted virtually between July 2020 and February 2022. Researchers encouraged free expression of views amongst the children regarding their research interests. Meetings were recorded, transcribed verbatim and analysed for themes based on the topics most frequently discussed and considered important to participants.ResultsIn all, seven ROLO children and six older siblings attended four ROLO YPAG meetings. Participants were aged between nine to fifteen years old. Four key themes were identified; study children viewed their identity as part of a longitudinal birth cohort as positive and unique; study children considered the fitness test and body measurements as fun aspects related to their participation; all children considered the impact and use of social media as an important form of communication; and all participants expressed interest in attaining new health-related information and learning opportunities. Children suggested topics such as mental health, future viruses, organ transplants, cancer, and the effect of technology and chemicals on the body were important for future research.ConclusionThe ROLO YPAG offers promising scope for continued collaboration. The themes identified from the meetings contribute to a gap in the literature which will guide future research activities, particularly with children, in view of study design, relevance, and by communication strategies.Trial Details: ISRCTN54392969 registered at www.isrctn.com.

Evaluation of dietary histories in cats presenting with chronic gastrointestinal clinical signs to a veterinary teaching hospital.

Although less frequently described than in dogs, it is also well recognised in cats that chronic gastrointestinal (GI) disease can fully respond to dietary changes only. So far, no study has assessed how much dietary information can be obtained during veterinary consultations. We retrospectively evaluated how much dietary information was available when owners presenting their cats to our gastroenterology (GE) and internal medicine (IM) service between October 2017 and January 2020 were questioned during consultations. Because of the larger IM caseload, for each week the first two cats presenting with chronic GI signs were selected for the IM group. Data from 80 cats presenting for first GE consultations were compared with data from 84 cats presenting with chronic GI signs for first IM consultations. Referrals comprised 42/80 (53%) GE cats and 53/84 (63%) IM cats. Referral documents mentioned the previously fed diet in 12/42 (29%) GE and 4/53 (8%) IM cats, and response to that previous diet trial was recorded in the referral documents of 4/12 (33%) GE and 3/4 (75%) IM cats. No cat had received more than one previous diet trial. During consultations, owners of 61/80 (76%) GE and 53/84 (63%) IM cats were asked about diet. Irrespective of referral status, previous dietary trials had been performed in 27/61 (44%) GE and 19/53 (36%) IM cats. The specific diet fed at the time of consultation could be named by 37/61 (61%) GE and 11/53 (21%) IM cat owners. Overall dietary information gained from referring veterinarians and owners was often incomplete. Although more information could be gained from owners during GE consultations vs IM consultations, awareness of the importance of diet in cats with GI disease still appears to be low among veterinarians and cat owners. Future studies need to assess if more complete dietary information can be obtained at the time of consultations with a prospective study design.

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts.

Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.

Cold-Pressed Oilseed Cakes as Alternative and Sustainable Feed Ingredients: A Review.

Due to the increasing demand for alternative protein feed ingredients, the utilization of oilseed by-products in animal nutrition has been sought as a promising solution to ensure cheap and environmentally sustainable feedstuffs. This review aimed to summarize the nutritional value of six cold-pressed cakes (rapeseed, hempseed, linseed, sunflower seed, camelina seed, and pumpkin seed) and the effects of their inclusion in diet for ruminant, pig, and poultry on nutrient digestibility, growth and productive performance, and quality of the products. The presented results indicated that these unconventional feed ingredients are a good protein and lipid source and have a balanced amino acid and fatty acid profile. However, contradictory results of animal production performances can be found in the literature depending on the cake type and chemical composition, dietary inclusion level, animal category, and trial duration. Due to the substantial amount of essential fatty acid, these cakes can be efficiently used in the production of animal products rich in n-3 and n-6 polyunsaturated fatty acids. However, the utilization of cakes in pig and poultry nutrition is limited because of the presence of antinutritive factors that can deteriorate feed intake and nutrient utilization.

Long-term outcomes of infantile spasms in children treated with ketogenic diet therapy in combination with anti-seizure medications in a resource-limited region.

Despite numerous guidelines, the overall outcome of infantile spasms is poor, with only a small number of patients being able to attend school. The purpose of this study was to investigate long-term outcomes. Patients had poor access to the recommended first-line anti-seizure medications (ASMs), such as hormones (corticotropin or prednisolone/prednisone) and vigabatrin, and their alternative treatment was other ASMs and a ketogenic diet. Patients suffering from infantile spasms who had at least 2 years of medical records in the electronic medical record system between January 2014 and August 2022 were included in this study. Patient information was retrospectively reviewed. All patients had received ketogenic diet therapy (mainly classical ketogenic diet therapy). The ketogenic diet therapy was combined with ASMs not used as first-line therapies. The primary endpoint outcome measure was the number of patients with seizure freedom. The secondary measures included the duration of ketogenic diet therapy, choice of ASMs, and patient development at the last visit. A total of 177 patients with infantile spasms were included, and 152 (86%) of them had seizure freedom. The median duration from the first to the last hospital visit was 53.27 months, and the number of visits was 47.00. The median age at the initial hospital visit was 8.00 months, and the median age at initiation of the ketogenic diet was 17.73 months. At the last visit, the proportions of patients with neurodevelopmental delay, developmental epileptic encephalopathy, drug-resistant epilepsy, and generalized seizures increased significantly. The frequently used ASMs were topiramate, valproic acid, levetiracetam, nitrazepam, and vitamin B6 injection, while the recommended first-line drugs corticotropin and vigabatrin were rarely selected. The study duration of 9.5 years was divided into three periods but the prescription of ASMs did not change significantly between these periods. Although the seizure freedom rate was high with ketogenic diet therapy combined with non-standard ASMs, the patients had a significant neurodevelopmental delay at the last visit, which was, however, similar to that of standard treatment. To improve the outcomes of infantile spasms, multicenter clinical trials of the ketogenic diet as a first-line treatment in combination with non-standard ASMs are needed.

Postmenopausal women's experiences of weight maintenance following a very low energy diet.

Very low energy diets (VLEDs) effectively induce substantial weight loss in people with obesity, yet they are rarely used as a first line treatment. There is a belief that such diets do not teach the lifestyle behavior changes needed for long-term weight maintenance. However, little is known about the lived experiences of people who have lost weight on a VLED in the long term. This study aimed to explore the behaviors and experiences of postmenopausal women who had followed a 4-month VLED (using total meal replacement products [MRPs]), followed by a food-based, moderately energy-restricted diet for an additional 8months, as part of the TEMPO Diet Trial. Qualitative in-depth semi-structured interviews were conducted with 15 participants at 12 or 24months (i.e., at 8 or 20months post diet completion). Transcribed interviews were analyzed thematically using an inductive approach. Undertaking a VLED was reported by participants to confer advantages in weight maintenance that previous weight loss attempts had not been able to do for them. Firstly, the rapid and significant weight loss, in conjunction with ease of use, was motivational and helped instill confidence in the participants. Secondly, the cessation of a normal diet during the VLED was reported by participants to break weight gain-inducing habits, allowing them to abandon unhelpful habits and to introduce in their place more appropriate attitudes toward weight maintenance. Lastly, the new identity, helpful habits and increased self-efficacy around weight loss supported participants during weight maintenance. Additionally, participants reported that ongoing occasional use of MRPs provided a useful and easy new strategy for countering weight regain and supporting their weight maintenance regimen. Among the participants in this qualitative study, most of whom had maintained a loss of over 10% of their baseline body weight at the time of interview, using a VLED in the context of a clinical weight loss trial conferred confidence, motivation and skills for weight maintenance. These findings indicate that VLEDs with clinical support could be successfully leveraged to set up behaviors that will support weight maintenance in the long term.

Lifestyle intervention in ovarian cancer enhanced survival (LIVES) study (NRG/GOG0225): Recruitment, retention and baseline characteristics of a randomized trial of diet and physical activity in ovarian cancer survivors

ObjectiveThe Lifestyle Intervention for oVarian cancer Enhanced Survival (LIVES) is a national study of a combined diet and physical activity intervention for stage II-IV ovarian cancer survival, an under-represented cancer in lifestyle behavioral intervention research. Here, we present the data on recruitment, retention, and baseline demographic, clinical and lifestyle behavior characteristics of the LIVES study participants. MethodsThe LIVES study (NRG Oncology/GOG 0225) is a Phase III diet plus physical activity intervention trial testing the hypothesis that ovarian cancer survivors in the lifestyle intervention will demonstrate better progression-free survival than those in the control condition. Study interventions were delivered via centralized telephone-based health coaching. Baseline descriptive statistics were computed for demographic, clinical, and lifestyle behavior characteristics. ResultsThe LIVES study exceeded its recruitment goals, enrolling 1205 ovarian cancer survivors from 195 NRG/NCORP-affiliated oncology practices across 49 states from 2012 to 2018. The mean age of enrollees was 59.6 years; the majority (69.4%) with stage III disease; 89% White, 5.5% Hispanic; 64% overweight/obese. Baseline self-reported diet showed a mean daily intake of 6.6 servings of fruit and vegetables, 62.7 fat grams, and 21.7 g of fiber. Physical activity averaged 13.0 MET-hours/week of moderate to vigorous physical activity; 50.9 h/week of sedentary time. Retention rates exceeded 88%. ConclusionThe LIVES study demonstrates efficiency in recruiting and retaining ovarian cancer survivors in a 24-month study of diet and physical activity intervention with a primary endpoint of progression free survival that will be reported. Trial registrationClinicalTrials.govNCT00719303.

Impact of Health Education Intervention and Intrinsic Factors on Microbiota in Overweight Individuals; A Randomized Clinical Trial

Objective The first objective was to assess the influence of a health education program that placed emphasis on improving physical activity level and diet quality on the microbiota. The second objective was to investigate the effect of extrinsic and intrinsic factors on the responses of individual microbiota taxa to the health education intervention. Design A secondary analysis of the Full Plate Diet (FPD) trial, a randomized controlled, clinical trial which included a 10-week health education program at Loma Linda, CA. Setting Drayson Center, Loma Linda University, CA. Method Fecal samples were collected at baseline (Pre) and after the termination of the health education intervention (Post). Bacterial DNA were extracted and 16S rRNA amplicon were then sequenced. Results No significant differences were observed, for any of the groups, in the α or ß diversities between baseline and post-intervention. Baseline microbiome significantly determined the shift of the individual microbial taxa; however, treatment type, gender, and baseline BMI, did not predict this shift. Conclusion A health education intervention emphasizing stress management and improvement in diet quality and physical activity did not have much influence on abundance and diversity of microbiota in a group of obese middle-aged adults. The shift in the microbiome, however, and the responsiveness to health education intervention could be predicted by the baseline microbiome level. Trial Registration Registration number is NCT03232970; July 28, 2017

Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity

BackgroundDiet, a key component of type 1 diabetes (T1D) management, modulates the intestinal microbiota and its metabolically active byproducts—including SCFA—through fermentation of dietary carbohydrates such as fiber. However, the diet–microbiome relationship remains largely unexplored in longstanding T1D. ObjectivesWe evaluated whether increased carbohydrate intake, including fiber, is associated with increased SCFA-producing gut microbes, SCFA, and intestinal microbial diversity among young adults with longstanding T1D and overweight or obesity. MethodsYoung adult men and women with T1D for ≥1 y, aged 19–30 y, and BMI of 27.0–39.9 kg/m2 at baseline provided stool samples at baseline and 3, 6, and 9 mo of a randomized dietary weight loss trial. Diet was assessed by 1–2 24-h recalls. The abundance of SCFA-producing microbes was measured using 16S rRNA gene sequencing. GC-MS measured fecal SCFA (acetate, butyrate, propionate, and total) concentrations. Adjusted and Bonferroni-corrected generalized estimating equations modeled associations of dietary fiber (total, soluble, and pectins) and carbohydrate (available carbohydrate, and fructose) with microbiome-related outcomes. Primary analyses were restricted to data collected before COVID-19 interruptions. ResultsFiber (total and soluble) and carbohydrates (available and fructose) were positively associated with total SCFA and acetate concentrations (n = 40 participants, 52 visits). Each 10 g/d of total and soluble fiber intake was associated with an additional 8.8 μmol/g (95% CI: 4.5, 12.8 μmol/g; P = 0.006) and 24.0 μmol/g (95% CI: 12.9, 35.1 μmol/g; P = 0.003) of fecal acetate, respectively. Available carbohydrate intake was positively associated with SCFA producers Roseburia and Ruminococcus gnavus. All diet variables except pectin were inversely associated with normalized abundance of Bacteroides and Alistipes. Fructose was inversely associated with Akkermansia abundance. ConclusionsIn young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.

A Randomized Trial of an Exclusive Human Milk Diet in Neonates with Single Ventricle Physiology

To determine whether weight gain velocity (g/kg/day) 30days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet. In this multicenter, randomized, single blinded, controlled trial, term neonates 7days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed. We enrolled 107 neonates (exclusive human milk=55, control=52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12g/day [IQR, 5-18g/day] vs 8g/day [IQR, 0.4-14g/day], respectively; P=.03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P=.04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups. Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation. This trial is registered with ClinicalTrials.gov (www. gov, Trial ID: NCT02860702).

Optimal designs for the development of personalized treatment rules

AbstractWe study the design of multi‐armed parallel group clinical trials to estimate personalized treatment rules that identify the best treatment for a given patient with given covariates. Assuming that the outcomes in each treatment arm are given by a homoscedastic linear model, with possibly different variances between treatment arms, and that the trial subjects form a random sample from an unselected overall population, we optimize the (possibly randomized) treatment allocation allowing the allocation rates to depend on the covariates. We find that, for the case of two treatments, the approximately optimal allocation rule does not depend on the value of the covariates but only on the variances of the responses. In contrast, for the case of three treatments or more, the optimal treatment allocation does depend on the values of the covariates as well as the true regression coefficients. The methods are illustrated with a recently published dietary clinical trial.