A Likelihood-Based Approach to Early Stopping in Single Arm Phase II Clinical Trials

Phase II studies in oncology have evolved over the previous several decades. Currently, the number of drugs in phase II development has increased, and patient eligibility has narrowed due to targeted agents, competing trials and curative therapies in the first-line setting. As a result of these changes, more attention needs to be focused toward conducting more efficient phase II trials. Given the increased difficulty in accruing patients to phase II studies and the ethical concern of treating patients with agents that are ineffective, there is significant motivation to stop a single arm trial early when the investigational agent shows evidence of a low response rate

Measuring the Impact of Biostatistical Methods on General Medical Research

Background: Novel statistical methods are constantly being developed within the context of biomedical research; however, the rate of diffusion of this knowledge into the field of general / internal medicine is unclear. This study highlights the statistical journal articles, the statistical journals, and the statistical methods that appear to be having the most direct impact on research in the field of general / internal medicine. Methods: Descriptive techniques, including analyses of articles’ keywords and controlled vocabulary terms, were used to characterize the articles published in statistics and probability journals that were subsequently referenced within general / internal medicine journal articles during a recent 10-year period (2000-2009). Results: From the 45 statistics and probability journals of interest, a total of 597 unique articles were identified as being cited by 900 (out of a total of about 10,501) unique general / internal medicine journal articles. The most frequently cited statistical topics included general/other statistical methods, followed by epidemiologic methods, randomized trials, generalized linear models, meta-analysis, and missing data. Conclusion: As statisticians continue to develop and refine techniques, the promotion and adoption of these methods should also be addressed so that their efforts spent in developing the methods are not done in vain

The Fecal Fermentation Profile of Infants with Different Feeding Modalities

Introduction/Background Research indicates nutrition and environment in the first year of a child\u27s life are crucial in their development and growth and can contribute to lower chances of developing obesity and other health concerns. Key factors that can determine these outcomes include the bacteria and resulting short chain fatty acids (SCFAs) present in the gut. This composition may be affected by feeding modality (formula feeding vs breastfeeding), exposure to the mother’s microbiota, weight status of the child, and type of delivery. This research aims to identify the impact of infant feeding modality on toddlers\u27 fecal fermentation profile, and if there are associations between weight status and microbiome, fecal fermentation profile. Methods/ Procedures Participants (n=40) were recruited during well-child pediatric appointments at ETSU’s Pediatric primary care clinic. Researchers explained the requirements of the study and participants were provided with a 90-question food frequency questionnaire (FFQ) for children ages 2-7, including 90 questions and asks about a child\u27s typical intake over the previous 6-month period. The food list was developed from NHANES III dietary recall data. The child’s history was obtained, including current age, birth length and weight, delivery type (C-section or vaginal), feeding method (breast, bottle fed, or both) and duration. The child’s weight and height were obtained, and body mass index (BMI) calculated. Participant-provided stool samples were freeze-dried and ground, and SCFAs were extracted using a procedure developed by Schwiertz et al. that was modified. One mL of the SCFA extraction solution, containing Oxalic acid (0.1 mol/L), Sodium Azide (40 mmol/L), and Caproic acid (0.1 mmol/L) (internal standard) was added to 80 mg of a freeze-dried stool sample in a 16 x 100 mm disposable culture tube, and analyzed using a Shimadzu GC2010 gas chromatograph with SigmaAldrich ZB-Wax Plus capillary column. Samples were run in duplicate, and values for each participant were averaged. Data analysis was generated using SAS software, Version 9.4 of the SAS System, Copyright © 2013 SAS Institute Inc. Results Initial findings showed no significant differences in the SCFA composition of obese vs non-obese toddlers in the sample. However, there were significant differences in the amount of specific SCFAs (isobutyrate, isovaleric acid, and octanoic acid) in toddlers who were formula fed as infants versus toddlers who were breastfed, and those fed a combination of breastmilk, and formula (p \u3c 0.05). Further analysis will determine if these initial results may be contributed to overall dietary intake, and more specifically fiber intake

Comparison of Short Chain Volatile Fatty Acids in the Breastmilk of Normal and Overweight/Obese Mothers

INTRODUCTION: Health professionals emphasize the importance of breastfeeding in the development of children up to 6-months of age. It is known that short chain volatile fatty acids (SCVFAs) are a byproduct of nutrient fermentation by gut microbiome. These SCVFAs interact with the gut/brain axis and are known to influence infant development. Therefore, a reflection of maternal gut microbiome could likely be found in breastmilk (BM) due to diffusion of SCVFAs across the gut wall into the blood. Previous research in our laboratory has shown differences in the SCVFA fecal fermentation profile between individuals with normal (N) versus overweight/obese (OWOB) body mass index (BMI). Therefore, our research question is: Is there a difference in the relative amount and diversity of SCVFAs in the BM of N compared to OWOB women? We hypothesized that women of N will have a more diverse SCVFA profile than OWOB women in their BM. BM samples (200 ml) were collected from 44 women (22 N (BMI 22.0) and 22 OWOB (BMI 33.7) p2 while OWOB participants had a pre-gravid BMI of greater than 25.0 kg/m2. To our knowledge, this is the first time that SCVFAs have been quantified in the milk of lactating women using GC with an FID detector. This data supports the argument that the pre-gravid BMI of a mother can correlate to the SCVFA profile of her BM. It is unknown if the concentration observed in the mother’s BM in this study has an influence on the neonate’s gut/brain axis and neurological signals, however, we have demonstrated that the SCVFA profile is more diverse in the N BMI mother. Further research is warranted on the influence of maternal BM SCVFA composition on the growth and neurological development of her infant

Maternal body composition and its impact on short chain fatty acid and microbiome profiles of breast milk in Caucasian women of Northeast Tennessee

Objectives- The purpose of this study was to determine if differences in breast milk (BM) short chain fatty acid (SCFA) and microbiome profiles are correlated to maternal BMI. Our hypothesis is that BM SCFA are a reflection of colonic SCFA distribution and concentration and may reflect microbiome diversity in the maternal gut. Methods- Study design-This was a cohort study in which forty-six Caucasian participants were recruited from BABE Breastfeeding Coalition of Tri-Cities, divided into two groups, one group with normal pre-gravid BMI between 18.5 and 24.9 kg/m2 (n=23) and the other group with overweight or obese pre-gravid BMI greater than 25.0 kg/m2 (n=23). Each participant completed a demographic and health survey and provided 4 ounces of expressed BM. This study was approved by the ETSU IRB (0915.8s-ETSU). 16s rRNA Isolation & Quantification- Microbiome analysis was performed on thirty-four samples (n=13 for overweight/obese, and n=21 for normal weight). Qiagen QIAmp PowerFecal Pro DNA Kit was utilized for isolation of microbiome DNA; Amplicon sequencing of the 16S rRNA region was performed at the University of Tennessee Genomics Core Laboratory utilizing a modified Klindworth et al method. Microbiome Analysis- Operational Taxonomic Unit (OUT) clustering and taxonomic analysis were performed using CLC Genomics Workbench. Alpha diversity indexes were calculated using the Abundance Analysis tool, and the weighted Unifrac metric was used to calculate Beta diversity. Fatty Acid Profile- BM samples were subjected to SCFA extraction and analysis using a modified Schwiertz et al. method. The resulting SCFA profiles were then utilized to determine if there were any significant differences between groups. Results- No significance was observed in BM microbiome between the normal weight and overweight/obese groups for alpha or beta diversity. Significance was detected between the groups for valeric (p=0.02) and isocaproic acids (p=0.05) with the normal weight group higher than the overweight/obese group. No significance was observed for any of the other SCFAs. Conclusions- Although these results are not significant due to low sample size and lack of diversity, they potentially offer insights into the impact of maternal BMI on microbiome and SCFA profiles, which can have implications for infant health and development. Funding Sources- ETSU Small RDC Gran

The Fecal Fermentation Profile of Infants with Different Feeding Modalities

Introduction/Background Research indicates nutrition and environment in the first year of a child\u27s life is crucial in their development and growth, and can contribute to lower chances of developing obesity and other health concerns. Key factors that can determine these outcomes include the bacteria, and resulting short chain fatty acids (SCFAs) present in the gut. This composition may be affected by feeding modality (formula feeding vs breastfeeding), exposure to the mother’s microbiota, weight status of the child, and type of delivery. This research aims to identify the impact of infant feeding modality on toddlers\u27 fecal fermentation profile, and if there are associations between weight status and microbiome, fecal fermentation profile. Methods/ Procedures Participants (n=40) were recruited during well-child pediatric appointments at ETSU’s Pediatric primary care clinic. Researchers explained the requirements of the study and participants were provided with a 90-question food frequency questionnaire (FFQ) for children ages 2-7, including 90 questions and asks about a child\u27s typical intake over the previous 6-month period. The food list was developed from NHANES III dietary recall data. The child’s history was obtained, including current age, birth length and weight, delivery type (C-section or vaginal), feeding method (breast, bottle-fed, or both), and duration. The child’s weight and height were obtained, and body mass index (BMI) was calculated. Participant-provided stool samples were freeze-dried and ground, and SCFAs were extracted using a procedure developed by Schwiertz et al. that was modified. One mL of the SCFA extraction solution, containing Oxalic acid (0.1 mol/L), Sodium Azide (40 mmol/L), and Caproic acid (0.1 mmol/L)(internal standard) was added to 80 mg of a freeze-dried stool sample in a 16 x 100 mm disposable culture tube, and analyzed using a Shimadzu GC2010 gas chromatograph with SigmaAldrich ZB-Wax Plus capillary column. Samples were run in duplicate, and values for each participant were averaged. Data analysis was generated using SAS software, Version 9.4 of the SAS System, Copyright © 2013 SAS Institute Inc. Results Initial findings showed no significant differences in the SCFA composition of obese vs non-obese toddlers in the sample. However, there were significant differences in the amount of specific SCFAs (isobutyrate, isovaleric acid, and octanoic acid) in toddlers who were formula-fed as infants versus toddlers who were breastfed, and those fed a combination of breastmilk, and formula (p \u3c 0.05). Further analysis will determine if these initial results may be contributed to overall dietary intake, and more specifically fiber intake

Motivating Students to Engage in Preparation for Flipped Classrooms by Using Embedded Quizzes in Pre-class Videos

BACKGROUND: The success of flipped classrooms is dependent upon students\u27 preparation prior to class, the lack of which is the most common challenge associated with this teaching methodology. To mitigate this limitation, it is important to develop and assess methods of engaging learners during pre-class activities. OBJECTIVE: To determine if quiz delivery method (embedded throughout versus after pre-class videos) affects students\u27 knowledge retention, grades, and video viewing behavior. METHODS: Participating students were randomized to take quizzes, either during pre-class videos via Panopto (EQV) or after pre-class videos in the traditional manner via Moodle (TMM). Outcomes assessed included students\u27 knowledge retention, scores on pre- and post-class quizzes, and pre-class video viewing behavior (total views and minutes viewed per student) during a three-week period. Having experienced both quizzing modalities during the semester, the perceptions from students in the EQV group were surveyed. RESULTS: Baseline assessment results of both groups (n = 27 per group) were comparable with a median score of 33% (IQR: 17, 50) in both groups. Performance was also similar on knowledge retention [TMM: 67% (50, 83) vs. EQV: 83% (50, 83)], pre-class quiz scores [TMM: 90% (87, 97) vs. EQV: 93% (90, 95)], and post-class quiz scores [TMM: 93% (80, 100) vs. EQV: 87% (80, 100)], while students in the EQV group had more total views [10 (8, 12)] vs. [5 (2, 11)] and minutes viewed [71 (36, 108) vs. 35 (15, 81)]. Results from the perception survey administered to students in the EQV group (74.1% response rate) indicated a preference for embedded quizzes overall (58%) and for class preparation (75%) when compared with post-video quizzes. CONCLUSION: Students\u27 knowledge retention and performance were similar in both EQV and TMM groups, though students in the EQV group were more engaged with videos and most of them preferred this quiz delivery. Using embedded quizzes for formative rather than summative assessment might be an appropriate mechanism to encourage students\u27 viewing of pre-class videos and their preparation for flipped classes

The Association Between Grandparents as Caregivers and Overdose Mortality in Appalachia vs. Non-Appalachia

Substance use is a serious and growing problem in the U.S. The impact of substance use disorders is vast and can affect more than the person with the disorder. Drug overdose deaths and related hospitalizations are positively associated with a rise in foster care case nationwide. When a child is removed from a home, social workers see first if there are biological family members who could provide a suitable home for the child as to make the transition less disruptive for the child. The average age of a kin caregiver was 59 years old in 2018, so this likely means grandparents are stepping in the caregiver role. Appalachia specifically has been hit hard by the opioid epidemic, and its rates of both overdose deaths and foster care cases have greatly increased. However, no research has analyzed the association between rates of grandparents as primary caregivers of children and county-level drug overdose mortality rates in Appalachia specifically and then compared that to the same association for non-Appalachian areas. Thus, this study decided to examine the association between those variables with a national dataset made from county-level data from multiple sources, mainly the CDC National Center for Health Statistics and the U.S. Census Bureau American Communities Survey (ACS). A cross-sectional analysis of 5-year estimates for drug overdose mortality on a county-level associated with the ACS data on grandparents acting as primary caregivers of grandchildren under the age of 18 was performed. There were three hypotheses: 1) counties with higher rates of drug overdose mortality will have higher rates of grandparents acting as primary caregivers of children under 18 years old, 2) the rate of grandparents serving as primary guardians of children under 18 years old will be higher in Appalachian counties than in non-Appalachian counties, 3) the correlation between grandparents serving as primary caregivers of children under 18 years old and drug overdose mortality will be stronger in Appalachian counties as opposed to non. For each hypothesis, a bivariate analysis was run independently, and by using multivariate modeling, the association between grandparents as primary caregivers and overdose mortality was evaluated. Running these analyses determined some statistically significant results: as overdose rates increase, rates of grandparent guardians increase; the rate of grandparent caregivers is higher in Appalachian counties than non-Appalachian counties; and there is a stronger correlation between overdose mortality rate increases and grandparents as caregivers increases in Appalachian counties as opposed to non-Appalachian counties. This is useful as there is a lack of research discussing this specific relationship, especially in rural areas such as in Appalachia. Furthermore, these results could help inform policies and programs to support grandparent guardians and help lessen the impacts of parental substance use for children