TOpCLASS Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort.

BACKGROUND AND AIMS: Perianal fistulizing Crohn's disease (PFCD) is an aggressive phenotype of Crohn's disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. METHODS: We identified all patients with PFCD and at least one baseline and one follow-up pelvic (pMRI). TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. RESULTS: We identified 100 patients with PFCD of which 96 were assigned TOpCLASS Classes 1 - 2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved class. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. CONCLUSION: The TOpCLASS classification highlights the dynamic nature of PFCD over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.

Geldof Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort.

Background and Aims: Perianal fistulizing Crohn's disease (CD-PAF) is an aggressive phenotype of Crohn's disease (CD) defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by Geldof et al. that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. Methods: We identified all patients with CD-PAF and at least one baseline and one follow-up pelvic (pMRI). Geldof Classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. Results: We identified 100 patients with CD-PAF of which 96 were assigned Geldof Classes 1 - 2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. Conclusion: Geldof classification highlights the dynamic nature of CD-PAF over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower Geldof classification.

Loneliness in older primary care patients and its relationship to physical and mental health-related quality of life.

BACKGROUND: Loneliness is a significant public health challenge in the United States, especially among older adults. The epidemiology of loneliness among older adults in primary care is lacking, and specific research is needed on how loneliness impacts older primary patients' physical, mental, and cognitive health. A large sample of older primary care patients were recruited for a trial during the COVID-19 pandemic to measure the relationship between loneliness and physical and mental quality of life (QOL). METHODS: Baseline data come from the Caregiver Outcomes of Alzheimer's Disease Screening (COADS) study, an ongoing randomized controlled trial evaluating benefits and risks of Alzheimer's disease and related dementias screening among primary care patients ages 65 and older, collected April 2020 to September 2021. Loneliness was measured with the 5-item, Loneliness Fixed Form Ages 18+ from The NIH Toolbox Emotion Battery, physical and mental health-related QOL was measured with the SF-36v2, and depression and anxiety severity were measured with the PHQ-9 and GAD-7, respectively. RESULTS: Spearman correlation analyses revealed that loneliness was moderately correlated with mental health QOL (r[601] = -0.43, p < 0.001), anxiety severity (r[601] = 0.44, p < 0.001), and depression severity (r[601] = 0.42, p < 0.001), while weakly correlated with physical health QOL (r[601] = -0.15, p < 0.001). After conducting unadjusted and adjusted linear regression models, we found that loneliness was significantly associated with both lower mental (p < 0.001) and physical (p < 0.001) QOL. Furthermore, loneliness remained significantly associated with worse mental QOL after adjusting for age, gender, race, ethnicity, educational level, perceived income status, neighborhood disadvantage, severity of comorbidities, and comorbid depression and anxiety. CONCLUSION: Primary care providers should discuss loneliness with their older adult patients and provide resources to help patients develop and maintain meaningful social relationships.

Association Between Subjective Cognitive Decline and Twice-Weekly Muscle-Strengthening Activities in Middle-Aged and Older US Adults: An Analysis of the 2019 Behavioral Risk Factor Surveillance System.

PURPOSE: Adults with subjective cognitive decline (SCD), the self-reported concern of reduced cognitive function, are recommended to do physical activity for its brain health benefits. US adults aged ≥45 with SCD are less likely to meet the American College of Sports Medicine (ACSM) aerobic activity recommendations. Their engagement in muscle-strengthening activities is unknown. We aimed to identify if US adults aged ≥45 with SCD are less likely to do twice-weekly muscle-strengthening activities compared to those without SCD. DESIGN: Secondary analysis of the 2019 Behavioral Risk Factor Surveillance System (BRFSS) data. SAMPLE: 114 164 respondents, representing approximately 59 million US adults aged ≥45. MEASURES: SCD was indicated if the respondent reported confusion or memory loss during the past 12 months (yes/no). Respondents reported the frequency of muscle-strengthening activities, which we categorized as meeting the ACSM's recommendations (2+ times per week) or not (<2 times per week). ANALYSIS: Crude and adjusted logistic regression models controlling for variables associated with SCD and muscle-strengthening activities. The models used sample weights to represent US adults in the included 31 states and Washington D.C. RESULTS: US adults aged ≥45 with SCD were less likely to do twice-weekly muscle-strengthening activities than those without SCD (28.6% [SE: .8%] vs 33.5% [SE: .3%], adjusted OR, .9; 95% CI: .9-1.0). CONCLUSION: Primary care providers should encourage middle-aged and older patients to engage in muscle-strengthening and aerobic activities.

Relationship of Decisional Conflict About Driving Habits Between Older Adult Drivers and Their Family Members and Close Friends.

This study examines the relationship of decisional conflict about driving habits between older adult drivers (≥70 years old) and their family members and close friends. This secondary analysis utilizes data originating from a multi-site randomized controlled trial assessing the effect of a driving decision aid (DDA) intervention. Decisional conflict about stopping or changing driving habits for drivers was measured with the Decisional Conflict Scale (DCS). Dyadic associations between drivers' and study partners' (SPs') DCS scores were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, Dyadic DCS was correlated at baseline (r = .18, p < .01), and pre-intervention DCS was associated with post-intervention DCS (p < .001 for SPs [ß = .73] and drivers [ß = .73]). Drivers' baseline DCS and SPs' post-intervention DCS were slighly correlated (ß = .10; p = .036). Higher decisional conflict about driving among older drivers is frequently shared by their SPs. Shared decisional conflict may persist beyond intervening to support decision-making about driving cessation.

Relationship between health-related quality of life, depression, and anxiety in older primary care patients and their family members.

OBJECTIVES: Patient-family member dyads experience transitions through illness as an interdependent team. This study measures the association of depression, anxiety, and health-related quality of life (HRQOL) of older adult primary care patient-family member dyads. METHODS: Baseline data from 1,808 patient-family member dyads enrolled in a trial testing early detection of Alzheimer's disease and related dementias in primary care. Actor-Partner Independence Model was used to analyze dyadic relationships between patients' and family members' depression (PHQ-9), anxiety (GAD-7), and HRQOL (SF-36 Physical Component Summary score and Mental Component Summary score). RESULTS: Family member mean (SD) age is 64.2 (13) years; 32.2% male; 84.6% White; and 64.8% being the patient's spouse/partner. Patient mean (SD) age is 73.7 (5.7) years; 47% male; and 85.1% White. For HRQOL, there were significant actor effects for patient and family member depression alone and depression and anxiety together on their own HRQOL (p < 0.001). There were significant partner effects where family member depression combined with anxiety was associated with the patient's physical component summary score of the SF-36 (p = 0.010), and where the family member's anxiety alone was associated with the patient's mental component summary score of the SF-36 (p = 0.031). CONCLUSION: Results from this study reveal that many dyads experience covarying health status (e.g. depression, anxiety) even prior to entering a caregiving situation.

Older adults' exposure to and posting of health-related messages on Facebook by chronic health condition status.

Objective: Older adults may be particularly interested in health-related content on Facebook, especially those who have chronic health conditions. The purpose of this study was to compare older adult Facebook users with and without a chronic health condition on their frequency of posting and exposure to health-related content. Methods: Participants, recruited via Qualtrics, were regular Facebook users aged 50 + years. Participants were asked separately if they had seen, posted, and shared: Health-related information; about others'/their own health behaviors (e.g., exercise); and about others'/their own medical condition. Six logistic regression models, controlling for demographics and Facebook login frequency, were run to assess whether viewing and/or posting health-related messages differed by chronic health condition status. Results: Respondents (N = 697; 77.9% female) were on average 61.2 (SD = 7.9) years old and (n = 625; 89.7%) were White. One-half reported a chronic health condition (n = 351; 50.4%). In adjusted models, those with a chronic health condition had a higher likelihood of seeing posts containing health information (OR = 1.41; 95% CI: 1.04, 1.93) and about others' medical conditions (OR = 1.67; 95% CI: 1.22, 2.27) at least once a month compared to those with no chronic health conditions. People with and without chronic health conditions did not differ in terms of how often they see others' post about health behaviors. Those with a chronic health condition had a higher likelihood of posting or sharing health information (OR = 1.67; 95% CI: 1.22, 2.27), posting about their own health behaviors (OR = 1.55; 95% CI: 1.00, 2.44; p = 0.048), and about their health condition (OR = 1.96; 95% CI: 1.17, 3.27) at least once a month. Conclusion: Most older adults on Facebook are exposed to and post multiple forms of health-related content. Therefore, Facebook may be an appropriate channel for conducting health-related communication targeting older adults.

An Evaluation of a Personalized Multicomponent Commercial Digital Weight Management Program: Single-Arm Behavioral Trial.

BACKGROUND: Digital behavioral weight loss programs are scalable and effective, and they provide an opportunity to personalize intervention components. However, more research is needed to test the acceptability and efficacy of personalized digital behavioral weight loss interventions. OBJECTIVE: In a 6-month single-arm trial, we examined weight loss, acceptability, and secondary outcomes of a digital commercial weight loss program (WeightWatchers). This digital program included a personalized weight loss program based on sex, age, height, weight, and personal food preferences, as well as synchronous (eg, virtual workshops and individual weekly check-ins) and asynchronous (eg, mobile app and virtual group) elements. In addition to a personalized daily and weekly PersonalPoints target, the program provided users with personalized lists of ≥300 ZeroPoint foods, which are foods that do not need to be weighed, measured, or tracked. METHODS: We conducted a pre-post evaluation of this 6-month, digitally delivered, and personalized WeightWatchers weight management program on weight loss at 3 and 6 months in adults with overweight and obesity. The secondary outcomes included participation, satisfaction, fruit and vegetable intake, physical activity, sleep quality, hunger, food cravings, quality of life, self-compassion, well-being, and behavioral automaticity. RESULTS: Of the 153 participants, 107 (69.9%) were female, and 65 (42.5%) identified as being from a minoritized racial or ethnic group. Participants' mean age was 41.09 (SD 13.78) years, and their mean BMI was 31.8 (SD 5.0) kg/m2. Participants had an average weight change of -4.25% (SD 3.93%) from baseline to 3 months and -5.05% (SD 5.59%) from baseline to 6 months. At 6 months, the percentages of participants who experienced ≥3%, ≥5%, and ≥10% weight loss were 63.4% (97/153), 51% (78/153), and 14.4% (22/153), respectively. The mean percentage of weeks in which participants engaged in ≥1 aspects of the program was 87.53% (SD 23.40%) at 3 months and 77.67% (SD 28.69%) at 6 months. Retention was high (132/153, 86.3%), and more than two-thirds (94/140, 67.1%) of the participants reported that the program helped them lose weight. Significant improvements were observed in fruit and vegetable intake, physical activity, sleep quality, hunger, food cravings, quality of life, and well-being (all P values <.01). CONCLUSIONS: This personalized, digital, and scalable behavioral weight management program resulted in clinically significant weight loss in half (78/153, 51%) of the participants as well as improvements in behavioral and psychosocial outcomes. Future research should compare personalized digital weight loss programs with generic programs on weight loss, participation, and acceptability.

Outcomes following liver transplant for alcohol-associated liver disease: comparing alcohol-associated hepatitis and cirrhosis.

BACKGROUND: Liver transplant (LT) is a highly effective therapy for refractory severe alcohol-associated hepatitis (SAH), but optimal selection criteria remain unknown. We aim to evaluate the outcomes of patients who received LT for alcohol-associated liver disease at our center following the introduction of updated selection criteria, including the removal of the minimum sobriety requirement. METHODS: Data were collected on all patients who underwent LT for alcohol-associated liver disease from January 1, 2018, to September 30, 2020. Patients were divided into SAH and cirrhosis cohorts based on disease phenotype. RESULTS: One hundred twenty-three patients underwent LT for alcohol-associated liver disease, including 89 (72.4%) for cirrhosis and 34 (27.6%) for SAH. There was no difference in 1- (97.1 ± 2.9% vs. 97.7 ± 1.6%, p = 0.97) and 3-year (97.1 ± 2.9% vs. 92.4 ± 3.4%, p = 0.97) survival between SAH and cirrhosis cohorts. Return to alcohol use was more frequent in the SAH cohort at 1 year (29.4 ± 7.8% vs. 11.4 ± 3.4%, p = 0.005) and 3 years (45.1 ± 8.7% vs. 21.0 ± 6.2%, p = 0.005) including higher frequencies of both slips and problematic drinking. Unsuccessful alcohol use counseling (HR 3.42, 95% CI 1.12-10.5) and prior alcohol support meetings (HR 3.01, 95% CI 1.03-8.83) predicted a return to harmful alcohol use patterns in early LT recipients. Both duration of sobriety (c-statistic 0.32 (95% CI 0.34-0.43) and SALT score (c-statistic 0.47, 95% CI 0.34-0.60) were independently poor predictors of return to harmful drinking. CONCLUSION: Survival following LT was excellent in both SAH and cirrhosis cohorts. Higher rates of return to alcohol use highlight the importance of further individualized refinement of selection criteria and improved support following LT.

Automated Clinical Pathway Utilizing Custom Risk Stratification Identifies Substantial Rates of Overdue Follow-up Among Patients With Inflammatory Bowel Disease and Facilitates Population Health Interventions.

We describe the development and implementation of a dynamic clinical pathway, the IBD CarePath, integrated into the electronic health record that applies custom risk stratification to identify patients with IBD who are overdue for clinical follow-up.

The Impact of the COVID-19 Pandemic on the Mental Health of Older Primary Care Patients and Their Family Members.

The COVID-19 pandemic introduced mandatory stay-at-home orders and concerns about contracting a virus that impacted the physical and mental health of much of the world's population. This study compared the rates of depression and anxiety in a sample of older primary care patients (aged ≥65 years old) and their family members recruited for a clinical trial before and during the COVID-19 pandemic. Participants were dyads enrolled in the Caregiver Outcomes of Alzheimer's Disease Screening (COADS) trial, which included 1,809 dyads of older primary care patients and one of their family members. Mean scores on the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder Scale-7 (GAD-7) were measured and compared before and during the pandemic. We found no difference in depression and anxiety among dyads of older primary care patients and their family members recruited before and during COVID-19. Additionally, we found that older primary care patients and family members who reported their income as comfortable had significantly lower depression and anxiety compared to those who reported having not enough to make ends meet. Along with this, older primary care patients with a high school education or less were more likely to have anxiety compared to those with a postgraduate degree. Moreover, our findings support the notion that certain demographics of older primary care patients and family members are at a higher risk for depression and anxiety, indicating who should be targeted for psychological health interventions that can be adapted during COVID-19. Future research should continue monitoring older primary care patients and their family members through the remainder of the COVID-19 pandemic.

Predicting Participant Engagement in a Social Media-Delivered Lifestyle Intervention Using Microlevel Conversational Data: Secondary Analysis of Data From a Pilot Randomized Controlled Trial.

BACKGROUND: Social media-delivered lifestyle interventions have shown promising outcomes, often generating modest but significant weight loss. Participant engagement appears to be an important predictor of weight loss outcomes; however, engagement generally declines over time and is highly variable both within and across studies. Research on factors that influence participant engagement remains scant in the context of social media-delivered lifestyle interventions. OBJECTIVE: This study aimed to identify predictors of participant engagement from the content generated during a social media-delivered lifestyle intervention, including characteristics of the posts, the conversation that followed the post, and participants' previous engagement patterns. METHODS: We performed secondary analyses using data from a pilot randomized trial that delivered 2 lifestyle interventions via Facebook. We analyzed 80 participants' engagement data over a 16-week intervention period and linked them to predictors, including characteristics of the posts, conversations that followed the post, and participants' previous engagement, using a mixed-effects model. We also performed machine learning-based classification to confirm the importance of the significant predictors previously identified and explore how well these measures can predict whether participants will engage with a specific post. RESULTS: The probability of participants' engagement with each post decreased by 0.28% each week (P<.001; 95% CI 0.16%-0.4%). The probability of participants engaging with posts generated by interventionists was 6.3% (P<.001; 95% CI 5.1%-7.5%) higher than posts generated by other participants. Participants also had a 6.5% (P<.001; 95% CI 4.9%-8.1%) and 6.1% (P<.001; 95% CI 4.1%-8.1%) higher probability of engaging with posts that directly mentioned weight and goals, respectively, than other types of posts. Participants were 44.8% (P<.001; 95% CI 42.8%-46.9%) and 46% (P<.001; 95% CI 44.1%-48.0%) more likely to engage with a post when they were replied to by other participants and by interventionists, respectively. A 1 SD decrease in the sentiment of the conversation on a specific post was associated with a 5.4% (P<.001; 95% CI 4.9%-5.9%) increase in the probability of participants' subsequent engagement with the post. Participants' engagement in previous posts was also a predictor of engagement in subsequent posts (P<.001; 95% CI 0.74%-0.79%). Moreover, using a machine learning approach, we confirmed the importance of the predictors previously identified and achieved an accuracy of 90.9% in terms of predicting participants' engagement using a balanced testing sample with 1600 observations. CONCLUSIONS: Findings revealed several predictors of engagement derived from the content generated by interventionists and other participants. Results have implications for increasing engagement in asynchronous, remotely delivered lifestyle interventions, which could improve outcomes. Our results also point to the potential of data science and natural language processing to analyze microlevel conversational data and identify factors influencing participant engagement. Future studies should validate these results in larger trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02656680; https://clinicaltrials.gov/ct2/show/NCT02656680.

A Facebook-Delivered Weight Loss Intervention Using Open Enrollment: Randomized Pilot Feasibility Trial.

BACKGROUND: Behavioral weight loss programs typically enroll 12-40 people into groups that then suffer from declining engagement over time. Web-based patient communities, on the other hand, typically offer no limits on capacity and membership is fluid. This model may be useful for boosting engagement in behavioral weight loss interventions, which could lead to better outcomes. OBJECTIVE: In this study, we aimed to examine the feasibility and acceptability of continuously enrolling participants into a Facebook-delivered weight loss intervention for the first 8 of 16 weeks relative to the same intervention where no new participants were enrolled after randomization. METHODS: We conducted a randomized pilot trial to compare a Facebook weight loss group that used open enrollment with a group that used closed enrollment on feasibility and acceptability in adults with BMI 27-45 kg/m2. The feasibility outcomes included retention, engagement, and diet tracking adherence. We described the percentage loss of ≥5% weight in both groups as an exploratory outcome. We also explored the relationship between total volume of activity in the group and weight loss. The participants provided feedback via web-based surveys and focus groups. RESULTS: Randomized participants (68/80, 85% women) were on average, aged 40.2 (SD 11.2) years with a mean BMI of 34.4 (SD 4.98) kg/m2. We enrolled an additional 54 participants (50/54, 93% female) in the open enrollment condition between weeks 1 and 8, resulting in a total group size of 94. Retention was 88% and 98% under the open and closed conditions, respectively. Randomized participants across conditions did not differ in engagement (P=.72), or diet tracking adherence (P=.42). Participant feedback in both conditions revealed that sense of community was what they liked most about the program and not enough individualized feedback was what they liked the least. Weight loss of ≥5% was achieved by 30% (12/40) of the participants randomized to the open enrollment condition and 18% (7/40) of the participants in the closed enrollment condition. Exploratory analyses revealed that the open condition (median 385, IQR 228-536.5) had a greater volume of engagement than the closed condition (median 215, IQR 145.5-292; P=.007). Furthermore, an increase of 100 in the total volume of engagement in the Facebook group each week was associated with an additional 0.1% weekly weight loss among the randomized participants (P=.02), which was independent of time, individual participant engagement, and sociodemographic characteristics. CONCLUSIONS: Open enrollment was as feasible and acceptable as closed enrollment. A greater volume of engagement in the Facebook group was associated with weight loss, suggesting that larger groups that produce more engagement overall may be beneficial. Future research should examine the efficacy of the open enrollment approach for weight loss in a fully powered randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02656680; https://clinicaltrials.gov/ct2/show/NCT02656680.

Development of Written Materials for Participants in an Alzheimer's Disease and Related Dementias Screening Trial.

Given that participants' experiences in clinical trials include a variety of communication touchpoints with clinical trial staff, these communications should be designed in a way that enhances the participant experience by paying attention to the self-determination theoretical concepts of competence, autonomy, and relatedness. In this feature, we argue that clinical trial teams need to consider the importance of how they design their written participant communication materials, and we explain in detail the process our multidisciplinary team took to design written materials for the patient and family caregiver participants in our Alzheimer's disease and related dementias (ADRD) screening trial. This article concludes with suggested guidance and steps for other clinical trial teams.

Proof-of-Concept Feasibility Trial of a Dissonance-Based Sun Safety Intervention for Young Adult Tanners.

BACKGROUND: Melanoma is the second most common cancer in young adults. Social media may be a means to conduct interventions to increase sun safety in young adults. PURPOSE: We conducted a randomized proof-of-concept pilot trial to evaluate the feasibility and acceptability of a dissonance-based social media intervention designed to promote sun safety in young adult tanners. METHODS: Young adult tanners (N = 66) were randomized into two 4-week interventions in which participants were incentivized to create content for a social media campaign on healthy skin or healthy lifestyle. Feasibility outcomes included retention, participation, acceptability, and contamination. We also examined the impact of participation on motivation to engage in the target health behaviors and outdoor tanning intentions. RESULTS: Retention was 100%. Most Healthy Skin (88%) and Healthy Lifestyle participants (91%) created ≥1 post. Acceptability was high with 94% and 97% of participants in Healthy Skin and Healthy Lifestyle conditions, respectively, agreeing they would recommend the campaign to a friend. At 4 weeks, Healthy Skin participants reported greater declines in motivation to tan indoors (p = .0017) and outdoors (p = .0003), and greater increases in motivation to wear sunscreen (p = .0009) and protective clothing (p = .0342). Healthy Skin participants reported greater declines in intentions to tan outdoors in the next year (p = .0286). CONCLUSIONS: A dissonance-based, social media sun safety intervention was feasible and acceptable. Future research should examine the efficacy and longer-term effects of this intervention in young adults at elevated risk for skin cancer. TRIAL REGISTRATION: Clinicaltrials.gov NCT03834974 https://clinicaltrials.gov/ct2/show/NCT03834974.

Effects of 0.5% and 2.0% Sodium Lauryl Sulfate in Male CD-1 Mice From a 3-Month Oral Gavage Toxicity Study.

The tolerability of single daily gavage doses of 0.5% or 2.0% (wt/vol) sodium lauryl sulfate (SLS) in 11- to 12-week-old male CD-1 mice was evaluated in a study of 3 months in duration. Live-phase, gross necropsy, and histopathologic parameters were evaluated. Mortality of 14% occurred in mice administered formulations containing SLS. Clinical observations in mice administered SLS included abnormal respiration (audible, irregular, and/or labored), swollen abdomen, rough haircoat, hunched appearance, and hypoactivity. Necropsy findings in mice administered SLS consisted of enlarged intestines containing abnormal contents with gas. There were no instances of mechanical gavage-related injury. Histologic evaluation of the respiratory tract revealed injury to the nasal passages and nasopharynx, including, but not limited to, inflammation, exudate, apoptosis/necrosis of epithelium, and atrophy of epithelium or olfactory nerves. Collectively, the data indicated that under the experimental conditions of our 3-month study in male CD-1 mice, once-daily gavage administration of vehicle formulations containing SLS at 0.5% or 2.0% resulted in nasal injury and 14% mortality supportive of gastroesophageal reflux. Sponsors utilizing formulations containing SLS in toxicity studies in CD-1 mice should exclude gastroesophageal reflux as a confounding factor in studies with morbidity or mortality associated with respiratory distress or evidence of aerophagia.

Slip Buddy App for Weight Management: Randomized Feasibility Trial of a Dietary Lapse Tracking App.

BACKGROUND: Although calorie tracking is one of the strongest predictors of weight loss in behavioral weight loss interventions, low rates of adherence are common. OBJECTIVE: This study aims to examine the feasibility and acceptability of using the Slip Buddy app during a 12-week web-based weight loss program. METHODS: We conducted a randomized pilot trial to evaluate the feasibility and acceptability of using the Slip Buddy app compared with a popular commercial calorie tracking app during a counselor-led, web-based behavioral weight loss intervention. Adults who were overweight or obese were recruited on the web and randomized into a 12-week web-based weight loss intervention that included either the Slip Buddy app or a commercial calorie tracking app. Feasibility outcomes included retention, app use, usability, slips reported, and contextual factors reported at slips. Acceptability outcomes included ratings of how helpful, tedious, taxing, time consuming, and burdensome using the assigned app was. We described weight change from baseline to 12 weeks in both groups as an exploratory outcome. Participants using the Slip Buddy app provided feedback on how to improve it during the postintervention focus groups. RESULTS: A total of 75% (48/64) of the participants were female and, on average, 39.8 (SD 11.0) years old with a mean BMI of 34.2 (SD 4.9) kg/m2. Retention was high in both conditions, with 97% (31/32) retained in the Slip Buddy condition and 94% (30/32) retained in the calorie tracking condition. On average, participants used the Slip Buddy app on 53.8% (SD 31.3%) of days, which was not significantly different from those using the calorie tracking app (mean 57.5%, SD 28.4% of days), and participants who recorded slips (30/32, 94%) logged on average 17.9 (SD 14.4) slips in 12 weeks. The most common slips occurred during snack times (220/538, 40.9%). Slips most often occurred at home (297/538, 55.2%), while working (153/538, 28.4%), while socializing (130/538, 24.2%), or during screen time (123/538, 22.9%). The conditions did not differ in participants' ratings of how their assigned app was tedious, taxing, or time consuming (all values of P>.05), but the calorie tracking condition gave their app higher helpfulness and usability ratings (all values of P<.05). Technical issues were the most common type of negative feedback, whereas simplicity was the most common type of positive feedback. Weight losses of ≥5% of baseline weight were achieved by 31% (10/32) of Slip Buddy participants and 34% (11/32) of calorie tracking participants. CONCLUSIONS: Self-monitoring of dietary lapses and the contextual factors associated with them may be an alternative for people who do not prefer calorie tracking. Future research should examine patient characteristics associated with adherence to different forms of dietary self-monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT02615171; https://clinicaltrials.gov/ct2/show/NCT02615171.

Standardizing Outcome Assessment in Parkinson Disease: A Knowledge Translation Project.

BACKGROUND AND PURPOSE: Rehabilitation therapists do not consistently utilize standardized outcome measures. The purpose of this study was to develop and implement a tailored knowledge translation (KT) intervention to facilitate application of standardized outcome measures used in patients with Parkinson disease (PD) receiving outpatient rehabilitation. METHODS: Four clinics within a hospital-based outpatient system including physical therapists (n = 7) and occupational therapists (n = 2) collaborated with researcher clinicians. A mixed-methods study, using the knowledge to action (KTA) framework, was executed to standardize the assessment battery completed on patients with PD. The project was titled iKNOW-PD (integrating KNOWledge translation for Parkinson Disease). RESULTS: Four measures were selected for iKNOW-PD (9-Hole Peg Test, miniBESTest, 10-m walk test, and 5 times sit-to-stand). A multimodal intervention that overcame specific identified barriers (equipment, time) was implemented to ensure successful uptake. Consistency of utilizing iKNOW-PD measures on initial evaluation and discharge, across therapists and clinics, was evaluated. Therapists significantly increased the use of iKNOW-PD measures from 1.9 to 3.1 on initial evaluation (P < 0.001). The 10-meter walk test demonstrated the greatest uptake (>50%) from pre-iKNOW-PD to post-iKNOW-PD. DISCUSSION AND CONCLUSIONS: Standardizing outcome assessment for persons with PD in an outpatient setting can be successfully implemented. Overcoming identified barriers and capitalizing on facilitators promoted the uptake of standardized outcomes. Following the 6-month intervention period, therapists endorsed an improvement in their application of standardized measures and labeled iKNOW-PD as a positive experience that allowed them to minimize variability in practice.Video Abstract available for more insights from the authors (see the Video, Supplemental Content 1, available at: http://links.lww.com/JNPT/A329).

Impaired Notch Signaling Leads to a Decrease in p53 Activity and Mitotic Catastrophe in Aged Muscle Stem Cells.

The decline of tissue regenerative potential with age correlates with impaired stem cell function. However, limited strategies are available for therapeutic modulation of stem cell function during aging. Using skeletal muscle stem cells (MuSCs) as a model system, we identify cell death by mitotic catastrophe as a cause of impaired stem cell proliferative expansion in aged animals. The mitotic cell death is caused by a deficiency in Notch activators in the microenvironment. We discover that ligand-dependent stimulation of Notch activates p53 in MuSCs via inhibition of Mdm2 expression through Hey transcription factors during normal muscle regeneration and that this pathway is impaired in aged animals. Pharmacologic activation of p53 promotes the expansion of aged MuSCs in vivo. Altogether, these findings illuminate a Notch-p53 signaling axis that plays an important role in MuSC survival during activation and is dysregulated during aging, contributing to the age-related decline in muscle regenerative potential.

Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy.

Nearly three out of four survivors experience Cancer-Related Cognitive Impairment (CRCI) for months or years following treatment. Both clinical and animal studies point to the hippocampus as a likely brain region affected in CRCI, however no previous study has investigated the functional connectivity of the hippocampus in CRCI. We compared hippocampal connectivity in cancer survivors and healthy controls and tested the relationship between functional connectivity differences and measures of objective and subjective cognition. Exploratory analysis of inflammatory markers was conducted in a small subset of participants as well. FMRI data were acquired during a memory task from 16 breast cancer survivors and 17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro-QoL was used to measure self-reported cognitive concerns. Whole-brain group-level comparisons identified clusters with different connectivity to the hippocampus in survivors versus controls during task. Average connectivity was extracted from clusters of significant difference between the groups and correlated with cognitive performance and subjective report. Survivors performed worse on a test of episodic memory and reported greater cognitive concern than controls. Exploratory analysis found higher IL6 in cancer survivors compared to controls. Cancer survivors demonstrated higher connectivity of hippocampus with left cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared with controls. In survivors, higher task-related hippocampal-cortical connectivity was related to worse subjective measures of cognitive concern. Of the four significant clusters, higher connectivity of the precuneus with hippocampus was significantly associated with worse cognitive concern in survivors. The observed greater hippocampal-cortical connectivity in survivors compared to controls is the first reported fMRI biomarker of subjective concern, and may represent a compensatory response to cancer and its treatments. This compensation could explain, in part, the subjective feelings of cognitive impairment that were reported by survivors.