Formative Evaluation of a Comprehensive Self-Management Intervention for Irritable Bowel Syndrome, Comorbid Anxiety, and Depression: Mixed Methods Study.

BACKGROUND: Irritable bowel syndrome (IBS) is a disorder of the gut-brain interaction that is associated with abdominal pain, altered bowel patterns, and reduced quality of life. Up to 50% of patients with IBS also report anxiety or depressive symptoms. Although effective self-management interventions exist for individuals with IBS, few have been effectively implemented, and most do not consider the unique needs of patients with comorbid IBS and anxiety or depression. OBJECTIVE: This study aimed to determine the anticipated acceptability, appropriateness, feasibility, and usability of a comprehensive self-management intervention using an implementation science and human-centered design approach among individuals with comorbid IBS and anxiety or depression and health care providers. METHODS: A convergent mixed methods design was used to elicit feedback on the comprehensive self-management intervention outline and content to identify refinement needs before testing. Patients with IBS and moderate to severe anxiety or depression and health care providers were purposefully sampled from primary care and gastroenterology settings. Participants completed semistructured interviews and surveys on anticipated acceptability, appropriateness, feasibility, and usability. RESULTS: Patient participants (n=12) were on average 36.8 (SD 12.2) years of age, and 42% (5/12) were currently receiving psychological therapy. Health care providers (n=14) were from primary care (n=7) and gastroenterology (n=7) settings. The mean usability scores (out of 100) were 52.5 (SD 14.5) for patients and 45.6 (SD 11.6) for providers. For patients and providers, qualitative data expanded the quantitative findings for acceptability and appropriateness. Acceptability findings were the comprehensive nature of the intervention and discussion of the gut-brain interaction. For appropriateness, participants reported that the intervention provided structure, accountability, and support. Feasibility was confirmed for patients, but there was a divergence of findings between quantitative and qualitative measures for providers. Patients focused on intervention feasibility, while providers focused on implementation feasibility in the clinic. Identified usability issues to address before implementation included the intervention delivery format, length, and lack of integration into health care settings that, if not addressed, may limit the reach of the intervention. CONCLUSIONS: Patients and health care providers found the intervention acceptable and appropriate. Several feasibility and usability issues were identified, including intervention delivery methods, length of intervention, and the best methods to implement in the clinic setting. The next steps are to refine the intervention to address the identified issues and test in a pilot study whether addressing usability issues leads to the anticipated improvements in implementation and uptake.

Factors Associated With Adherence to a Low Fermentable Carbohydrate Diet in Children With Functional Gastrointestinal Disorders.

BACKGROUND: The low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (LFD) has been associated with reduced symptomology in pediatric functional gastrointestinal disorders (FGIDs). The LFD is a complex dietary intervention that may be difficult to follow; thus, there is great interest in determining factors that contribute to adherence. OBJECTIVE: To examine whether baseline abdominal pain, emotional/behavioral problems, or quality of life predict adherence to the LFD in children with FGIDs. DESIGN: This was a single-group pre-post intervention design within a larger randomized controlled trial. PARTICIPANTS/SETTING: Thirty 7- to 12-year-old children with FGIDs were recruited from pediatric gastrointestinal and primary care settings throughout Texas from 2019 to 2021. Evaluated participants were randomized to an LFD intervention as part of a larger randomized controlled trial. INTERVENTION: Participants received dietary counseling and followed the LFD for 3 weeks. MEASURES: Emotional or behavioral problems and quality of life were obtained via parent report, and abdominal pain was measured via child report. Adherence was assessed by using diet records and computed by a decrease in consumption of overall FODMAP intake. STATISTICAL ANALYSES PERFORMED: A hierarchical generalized linear mixed regression model examined factors associated with adherence. RESULTS: Greater baseline quality of life was associated with better adherence to the LFD (beta coefficient ß = -.02, P = 0.03), and baseline emotional/behavioral problems and abdominal pain complaints were not significantly associated with adherence (all Ps > 0.28). CONCLUSIONS: Higher child quality of life as reported by parents was related to increased adherence to this complex dietary intervention.

A Comprehensive Self-Management Intervention for Inflammatory Bowel Disease (CSM-IBD): Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Despite pharmacological treatment, individuals with inflammatory bowel disease (IBD) experience a variety of symptoms, including abdominal pain, fatigue, anxiety, and depression. Few nonmedical self-management interventions are available for people with IBD. A validated comprehensive self-management (CSM) intervention is effective for patients with irritable bowel syndrome who can have symptoms similar to those of individuals with IBD. We created a modified CSM intervention tailored to individuals with IBD (CSM-IBD). The CSM-IBD is an 8-session program delivered over 8-12 weeks with check-ins with a registered nurse. OBJECTIVE: The primary objective of this pilot study is to determine the feasibility and acceptability of study procedures and the CSM-IBD intervention and to evaluate preliminary efficacy on quality of life and daily symptoms for a future randomized controlled trial. Additionally, we will examine the association of socioecological, clinical, and biological factors with symptoms at baseline and response to intervention. METHODS: We are conducting a pilot randomized controlled trial of the CSM-IBD intervention. Participants aged 18-75 years who are experiencing at least 2 symptoms are eligible for inclusion. We plan to enroll 54 participants who will be randomized (2:1) into the CSM-IBD program or usual care. Patients in the CSM-IBD program will have 8 intervention sessions. Primary study outcomes include the feasibility of recruitment, randomization, and data or sample collection, as well as the acceptability of study procedures and interventions. Preliminary efficacy outcome variables include quality of life and symptoms. Outcomes data will be assessed at baseline, immediately post intervention, and 3 months post intervention. Participants in the usual care group will have access to the intervention after study participation. RESULTS: This project is funded by the National Institutes of Nursing Research and reviewed by the University of Washington's institutional review board. Recruitment began in February 2023. As of April 2023, we have enrolled 4 participants. We expect the study to be completed by March 2025. CONCLUSIONS: This pilot study will evaluate the feasibility and efficacy of a self-management intervention (a web-based program with weekly check-ins with a registered nurse) that aims to improve symptom management in individuals with IBD. In the long term, we aim to validate a self-management intervention to improve patient quality of life, reduce direct and indirect costs related to IBD, and be culturally appropriate and accessible, particularly in rural and underserved communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT05651542; https://clinicaltrials.gov/ct2/show/NCT05651542. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46307.

Symptom management needs of patients with irritable bowel syndrome and concurrent anxiety and/or depression: A qualitative study.

AIMS: To understand the experiences and needs of symptom management among individuals with irritable bowel syndrome and concurrent symptoms of anxiety and/or depression. DESIGN: This study used a qualitative descriptive research design. METHODS: Individuals with a diagnosis of irritable bowel syndrome and concurrent symptoms of anxiety and/or depression participated were recruited through an online ResearchMatch and a listserv. Semi-structured interviews focused on symptoms and experiences with symptom management interventions conducted from June to August 2020. Interviews were transcribed and data were analysed based on thematic analysis. RESULTS: Twelve individuals participated in this study; all reported current irritable bowel syndrome and anxiety/depression symptoms. The data analysis cumulated with three themes related to symptom management: (a) irritable bowel syndrome negatively impacts physical and mental well-being; (b) a trial and error approach to symptom management; and (c) challenges with healthcare professionals supporting symptom management including negative interactions with healthcare professionals and lack of nutritional expertize and support. CONCLUSION: There is a need for individualized approaches which consider patients' current symptoms of anxiety and depression, previous experiences with the trial-and-error process and consideration for intervention delivery methods. IMPACT: There is a limited qualitative research focusing on the experiences of individuals with irritable bowel syndrome and concurrent symptoms of anxiety and/or depression. This research highlights the need for individualized approaches to enhance symptom management that acknowledges patients' psychological state and past negative experiences with providers and prior dietary regimens.

Evolution of Parent-Targeted Interventions for Pain-Predominant Disorders of Gut-Brain Interactions: Research and Clinical Practice Considerations.

Objective: Abdominal pain-related Disorders of Gut-Brain Interaction (DGBIs) in children are best understood from a biopsychosocial model, including particular attention to the child's environment. Interventions have begun to increasingly target parents as important agents of change in this population. The purpose of this manuscript is to summarize the evolution of parent-targeted interventions for pediatric pain-related DGBIs and provide recommendations for application of the model to clinical practice. Methods: A topical review of literature regarding parent-targeted interventions and related factors in the treatment of pediatric pain-related DGBIs was conducted, followed by a discussion of these findings to clinical practice settings. Results: A growing body of research has supported parent-targeted interventions in the treatment of pediatric pain-related disorders of gut-brain interactions (DGBI), although translation of these findings to practice settings is complicated by numerous factors. Strategies for obtaining physician buy-in and parental engagement are discussed, as are potential logistical considerations of multiple caregivers, child age, and billing considerations. Conclusions: There is a promising and growing evidence-base for parent-targeted interventions for pain-related DGBIs, which have not yet been widely adopted into clinical practice recommendations. Engaging all stake-holders and attending to the nuances of this approach are recommended to successfully apply parent-targeted interventions into clinical practice settings.

Children with functional abdominal pain disorders successfully decrease FODMAP food intake on a low FODMAP diet with modest improvements in nutritional intake and diet quality.

BACKGROUND: We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD). METHODS: Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined. KEY RESULTS: Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: overall median (25-75%) high FODMAP foods/day decreased from 5.7 (3.6-7.3) to 2 (0.3-3.7) (p < 0.001). A more adherent subset (n = 22/71%) of participants consumed on average ≤3 high FODMAP foods per day during the LFD. Baseline nutritional intake and quality were generally poor with several micronutrient deficiencies identified. Diet quality improved on the LFD with increased servings of vegetables and protein and decreased consumption of ultra-processed foods, trans-fatty acids, and added sugars. On the LFD, there were significant decreases in total carbohydrates and thiamin (remained within recommended intake) and significant increases in vitamin B6 (p = 0.029), vitamin C (p = 0.019), and vitamin E (p = 0.009). Children more adherent to the LFD further increased vitamin D, magnesium, potassium, and fat servings. CONCLUSIONS AND INFERENCES: The majority of children with FAPD on a dietitian-led LFD successfully decreased high FODMAP food intake. Children with FAPD on the LFD (vs. baseline) modestly improved micronutrient intake and diet quality.

Association of childhood abuse with behavioral weight-loss outcomes: Examining the mediating effect of binge eating severity.

OBJECTIVE: The study aims were to (1) document the relationship between a history of childhood abuse and weight change during behavioral obesity treatment and (2) estimate the indirect effect of childhood abuse on weight change through binge eating severity. METHODS: Participants (n = 431) were enrolled in a behavioral weight-loss intervention. Childhood physical and emotional abuse history and current binge eating severity were self-reported. Percent weight loss at 6 months was calculated using measured weight. Adjusted mediation models examined whether there was an indirect effect of childhood physical and emotional abuse on 6-month percent weight loss that operated through binge eating severity. RESULTS: After covariate adjustment, childhood physical abuse, but not emotional abuse, predicted a lower percent weight loss (B = -1.78%; 95% CI: -3.10% to -0.47%). Although childhood physical and emotional abuse were positively related to baseline binge eating severity, binge eating severity did not mediate the associations between either childhood abuse type and percent weight loss. CONCLUSIONS: Individuals with a childhood physical abuse history had a lower percent weight loss than those without such histories during behavioral obesity treatment. This effect was not explained by binge eating severity. Individuals with a history of childhood abuse may benefit from trauma-informed obesity care.

BestFIT Sequential Multiple Assignment Randomized Trial Results: A SMART Approach to Developing Individualized Weight Loss Treatment Sequences.

BACKGROUND: State-of-the-art behavioral weight loss treatment (SBT) can lead to clinically meaningful weight loss, but only 30-60% achieve this goal. Developing adaptive interventions that change based on individual progress could increase the number of people who benefit. PURPOSE: Conduct a Sequential Multiple Assignment Randomized Trial (SMART) to determine the optimal time to identify SBT suboptimal responders and whether it is better to switch to portion-controlled meals (PCM) or acceptance-based treatment (ABT). METHOD: The BestFIT trial enrolled 468 adults with obesity who started SBT and were randomized to treatment response assessment at Session 3 (Early TRA) or 7 (Late TRA). Suboptimal responders were re-randomized to PCM or ABT. Responders continued SBT. Primary outcomes were weight change at 6 and 18 months. RESULTS: PCM participants lost more weight at 6 months (-18.4 lbs, 95% CI -20.5, -16.2) than ABT participants (-15.7 lbs, 95% CI: -18.0, -13.4), but this difference was not statistically significant (-2.7 lbs, 95% CI: -5.8, 0.5, p = .09). PCM and ABT participant 18 month weight loss did not differ. Early and Late TRA participants had similar weight losses (p = .96), however, Early TRA PCM participants lost more weight than Late TRA PCM participants (p = .03). CONCLUSIONS: Results suggest adaptive intervention sequences that warrant further research (e.g., identify suboptimal responders at Session 3, use PCMs as second-stage treatment). Utilizing the SMART methodology to develop an adaptive weight loss intervention that would outperform gold standard SBT in a randomized controlled trial is an important next step, but may require additional optimization work. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov identifier; NCT02368002.

Impact of COVID-19 on Individuals With Irritable Bowel Syndrome and Comorbid Anxiety and/or Depression.

GOALS: The goal of this study was to describe the influence of the COVID-19 pandemic on ability to engage in activities and the influence on psychological distress and gastrointestinal symptoms among individuals with irritable bowel syndrome (IBS) and comorbid anxiety and/or depression. BACKGROUND: Individuals with IBS and comorbid anxiety and/or depression report increased symptoms and decreased quality of life compared with individuals with IBS alone. The current COVID-19 pandemic has the potential to further influence symptoms among individuals with IBS and comorbid anxiety and/or depression. STUDY: Individuals who met the Rome-IV IBS criteria and reported mild to severe anxiety and/or depression were included. Participants completed an online survey with questions about anxiety, depression, impact of COVID on activities and symptoms, and demographics. RESULTS: Fifty-five individuals participated in the study. The COVID-19 pandemic most commonly influenced their ability to spend time with friends and family, shop for certain types of food, and access health care. Participants also reported increased stress (92%), anxiety (81%), and depressive symptoms (67%). Finally, around half the sample reported increases in abdominal pain (48%), diarrhea (45%), or constipation (44%). CONCLUSIONS: The COVID-19 pandemic is related to self-reported increases in psychological distress and gastrointestinal symptoms among individuals with IBS and comorbid anxiety and/or depression. Additional research is needed to intervene on these symptoms.

Evaluation of a downstream process for the recovery and concentration of a Cell-Culture-Derived rVSV-Spike COVID-19 vaccine candidate.

rVSV-Spike (rVSV-S) is a recombinant viral vaccine candidate under development to control the COVID-19 pandemic and is currently in phase II clinical trials. rVSV-S induces neutralizing antibodies and protects against SARS-CoV-2 infection in animal models. Bringing rVSV-S to clinical trials required the development of a scalable downstream process for the production of rVSV-S that can meet regulatory guidelines. The objective of this study was the development of the first downstream unit operations for cell-culture-derived rVSV-S, namely, the removal of nucleic acid contamination, the clarification and concentration of viral harvested supernatant, and buffer exchange. Retaining the infectivity of the rVSV-S during the downstream process was challenged by the shear sensitivity of the enveloped rVSV-S and its membrane protruding spike protein. Through a series of screening experiments, we evaluated and established the required endonuclease treatment conditions, filter train composition, and hollow fiber-tangential flow filtration parameters to remove large particles, reduce the load of impurities, and concentrate and exchange the buffer while retaining rVSV-S infectivity. The combined effect of the first unit operations on viral recovery and the removal of critical impurities was examined during scale-up experiments. Overall, approximately 40% of viral recovery was obtained and the regulatory requirements of less than 10 ng host cell DNA per dose were met. However, while 86-97% of the host cell proteins were removed, the regulatory acceptable HCP levels were not achieved, requiring subsequent purification and polishing steps. The results we obtained during the scale-up experiments were similar to those obtained during the screening experiments, indicating the scalability of the process. The findings of this study set the foundation for the development of a complete downstream manufacturing process, requiring subsequent purification and polishing unit operations for clinical preparations of rVSV-S.

Mediation of outcomes for cognitive behavioral therapy targeted to parents of children with Functional Abdominal Pain Disorders.

OBJECTIVE: There is a large body of evidence for the efficacy of Cognitive Behavioral Therapy (CBT) in treating Functional Abdominal Pain Disorders (FAPD) in children. In most CBT interventions for FAPD, parents participate together with their children. However, only one study to date has examined targeting parents alone for treatment. The aim of the current study was to examine mediators of a parent-only CBT treatment incorporating social learning (SLCBT) for FAPD in children. METHODS: We examined mediators of child outcomes in an existing randomized controlled trial (n = 316) of parent-only social learning CBT compared to an education condition. Hypothesized mediators (parental protectiveness, perceived threat of pain, catastrophizing) were assessed at 3 months post-treatment, and outcomes (parent ratings of disability, quality of life, school absences, and health care visits) were assessed at 6 months post-treatment. Mediation analyses were performed using Hayes' PROCESS macro. RESULTS: Pain catastrophizing significantly mediated treatment effects for all outcomes (B ranged from -1.65 to 2.22). Reduction in pain threat was a significant mediator for all outcomes (B ranged from -1.84 to 3.13) except school absences and health care visits. Decrease in parental protectiveness mediated effects on disability and missed school (B ranged from -1.47 to 1.34). Mediation effects did not differ by in-person or remote delivery of SLCBT. CONCLUSION: Changes in maladaptive parental thoughts and behaviors following parent-only SLCBT intervention appeared to mediate the effects of the intervention. Parental catastrophizing appears to be a particularly important target given that decreases in that variable mediated all outcomes.

Parental Response to Only Children: Breaking the Stereotypes.

While much has been written about the relationship between only child status and parents' behavior toward children, and consequent personality and intelligence, little is known about the relationship between only child status, parental response to illness, and subsequent child illness behavior. In this study, 227 mothers of 342 children completed measures designed to assess: (a) their children's school attendance, (b) their own psychological status, and (c) their own responses to their children's expressions of stomach pain. Parents of only children were more likely to minimize their children's gastrointestinal symptoms than were parents of children with at least one sibling. In addition, only children were less likely to miss school. Parental protectiveness did not differ as a function of only child status. These findings are somewhat discrepant with commonly held beliefs about parents' patterns of responding to only children.

Passive Coping Associations With Self-Esteem and Health-Related Quality of Life in Youth With Inflammatory Bowel Disease.

Pediatric patients with inflammatory bowel disease (IBD) may experience chronic stress related to disease symptoms and treatment, with negative consequences to their health-related quality of life (HRQOL). Lower HRQOL among pediatric patients with IBD has been associated with worse disease-related symptoms and psychological functioning, while higher HRQOL has been associated with more adaptive coping with disease symptoms and treatment. In addition, patients' self-esteem may impact the selection and use of coping strategies through global cognitions about their abilities and perceived competence. The current study seeks to extend existing research on HRQOL in youth with IBD by examining cross-sectional associations among self-esteem and passive coping strategies. Youth ages 9-18 with IBD (n = 147) rated their HRQOL using a disease-specific measure, typical strategies used to cope with pain or GI symptoms, and their general self-esteem. Mediation analyses were performed using regression-based techniques and bootstrapping. Results indicated that greater self-esteem was positively associated with HRQOL but negatively associated with passive coping. Controlling for disease activity, age, and gender, significant indirect effects were found in the relation between self-esteem and HRQOL through passive coping. Multiple mediation analyses using the three passive coping subscales found that self-esteem was indirectly associated with HRQOL through its effects specifically on catastrophizing as a passive coping strategy. Results suggest that pediatric patients' general self-esteem can impact their HRQOL through passive coping and specifically, maladaptive cognitions (e.g., catastrophizing). Interventions aimed at addressing both self-esteem and catastrophizing as a passive coping strategy may offer promise for improving HRQOL in youth with IBD.

Discrepancies Between Clinician and Participant Intervention Adherence Ratings Predict Percent Weight Change During a Six-Month Behavioral Weight Loss Intervention.

BACKGROUND: Individuals receiving behavioral weight loss treatment frequently fail to adhere to prescribed dietary and self-monitoring instructions, resulting in weight loss clinicians often needing to assess and intervene in these important weight control behaviors. A significant obstacle to improving adherence is that clinicians and clients sometimes disagree on the degree to which clients are actually adherent. However, prior research has not examined how clinicians and clients differ in their perceptions of client adherence to weight control behaviors, nor the implications for treatment outcomes. PURPOSE: In the context of a 6-month weight-loss treatment, we examined differences between participants and clinicians when rating adherence to weight control behaviors (dietary self-monitoring; limiting calorie intake) and evaluated the hypothesis that rating one's own adherence more highly than one's clinician would predict less weight loss during treatment. METHODS: Using clinician and participant-reported measures of self-monitoring and calorie intake adherence, each assessed using a single item with a 7- or 8-point scale, we characterized discrepancies between participant and clinician adherence and examined associations with percent weight change over 6 months using linear mixed-effects models. RESULTS: Results indicated that ratings of adherence were higher when reported by participants and supported the hypothesis that participants who provided higher adherence ratings relative to their clinicians lost less weight during treatment (p < 0.001). CONCLUSIONS: These findings suggest that participants in weight loss treatment frequently appraise their own adherence more highly than their clinicians and that participants who do so to a greater degree tend to lose less weight.

A pilot feasibility study of an unguided, internet-delivered cognitive behavioral therapy program for irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is linked with lower health-related quality of life. Cognitive behavioral therapy (CBT) designed for IBS management can improve outcomes but further research of more accessible implementations of this treatment approach for IBS is needed. This study assessed the feasibility of a web-delivered CBT program among adults with IBS to apply to a future clinical trial. METHODS: Twenty-five participants were randomized to receive an unguided web-based, CBT program for IBS. The primary outcome was changes in IBS symptom severity (IBS Symptom Severity Scale [IBS-SSS]). Secondary outcomes included IBS-specific CBT therapeutic mechanisms of change (GI-specific anxiety, unhelpful IBS behaviors, and GI-focused cognitions) and changes in depressive (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder-7 scale [GAD-7]) symptom severity. KEY RESULTS: Among participants randomized to receive web-based CBT, the average baseline IBS-SSS score was 296.3 (SD=100.9). IBS symptom severity significantly improved at 2-month (p < 0.001) and 3-month follow-up (p < 0.0001); the within-group effect size between baseline and 3-month follow-up IBS-SSS scores was large (d = 1.14) and 63.6% experienced a clinically meaningful improvement (ie, ≥50-point IBS-SSS score reduction). GI-specific anxiety symptoms and cognitions significantly improved at 2-month follow-up, as did unhelpful IBS safety behaviors. Additionally, clinically meaningful improvement was observed in depressive and anxiety symptoms at 3-month follow-up among participants with symptoms above the clinical threshold (ie, PHQ-9 ≥ 10 and GAD-7 ≥ 10, respectively) at baseline. CONCLUSIONS & INFERENCES: These preliminary findings warrant a larger trial to investigate an unguided, web-based CBT for IBS symptom management that is powered to detect between-group treatment effects.

Sleep disturbances in children with functional gastrointestinal disorders: demographic and clinical characteristics.

STUDY OBJECTIVES: Research indicates a deleterious effect of sleep disturbances on pain and illness-related functioning across pediatric populations. Sleep problems in youth with functional gastrointestinal disorders (FGIDs) are understudied, despite studies in adult FGIDs indicating sleep disruptions increase pain and symptom severity. This study sought to better characterize sleep problems in school-age children with FGIDs and to assess relationships with demographic characteristics and gastrointestinal symptoms. METHODS: Sixty-seven children with FGIDs (pediatric Rome IV criteria) and 59 parents completed questionnaires assessing sleep problems, and children completed a 2-week pain/stooling diary. Sleep problems in this sample were compared with published normative samples, and children above and below the clinical cutoff were compared on demographics and FGID symptoms. RESULTS: Of the sample, 61% were above the clinical cutoff for sleep disturbances, with significantly greater bedtime resistance, sleep onset delay, sleep duration, and daytime sleepiness than the comparison group. Children above the clinical cutoff reported greater mean abdominal pain severity and pain interference. Relative to White participants, Black/African-American participants were more likely to be above the clinical cutoff and indicated more frequent night wakening and symptoms of sleep-disordered breathing, but lower maximum and overall mean abdominal pain severity. CONCLUSIONS: Sleep problems in children with FGIDs are common and related to greater day-to-day abdominal pain severity and pain interference. Results suggest sleep-pain relationships may differ across racial/ethnic groups. Assessing sleep in children with FGIDs is important, and further research is needed to assess underlying mechanisms and evaluate sleep as a potential treatment target in this population.

Highly Efficient Purification of Recombinant VSV-∆G-Spike Vaccine against SARS-CoV-2 by Flow-Through Chromatography.

This study reports a highly efficient, rapid one-step purification process for the production of the recombinant vesicular stomatitis virus-based vaccine, rVSV-∆G-spike (rVSV-S), recently developed by the Israel Institute for Biological Research (IIBR) for the prevention of COVID-19. Several purification strategies are evaluated using a variety of chromatography methods, including membrane adsorbers and packed-bed ion-exchange chromatography. Cell harvest is initially treated with endonuclease, clarified, and further concentrated by ultrafiltration before chromatography purification. The use of anion-exchange chromatography in all forms results in strong binding of the virus to the media, necessitating a high salt concentration for elution. The large virus and spike protein binds very strongly to the high surface area of the membrane adsorbents, resulting in poor virus recovery (<15%), while the use of packed-bed chromatography, where the surface area is smaller, achieves better recovery (up to 33%). Finally, a highly efficient chromatography purification process with CaptoTM Core 700 resin, which does not require binding and the elution of the virus, is described. rVSV-S cannot enter the inner pores of the resin and is collected in the flow-through eluent. Purification of the rVSV-S virus with CaptoTM Core 700 resulted in viral infectivity above 85% for this step, with the efficient removal of host cell proteins, consistent with regulatory requirements. Similar results were obtained without an initial ultrafiltration step.

Systematic Review: Psychosocial Correlates of Pain in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Pain is a common symptom in pediatric inflammatory bowel disease (IBD) and is associated with poor health outcomes, yet additional knowledge about the psychosocial correlates of pain is needed to optimize clinical care. The purpose of this study is to systematically review the psychosocial factors associated with pain and pain impact in youth diagnosed with IBD within a developmentally informed framework. METHODS: Manual and electronic searches yielded 2641 references. Two authors conducted screening (98% agreement), and data extraction was performed in duplicate. Average study quality was rated using the National Institutes of Health Quality Assessment Tool. RESULTS: Ten studies (N = 763 patients; N = 563 Crohn disease, N = 200 ulcerative/ indeterminate colitis) met the inclusion criteria. Findings showed consistent evidence that higher levels of child depression symptoms and child pain catastrophizing were associated with significantly greater pain and pain impact (magnitude of association ranged from small to large across studies). Greater pain and pain impact were also associated with higher levels of child anxiety symptoms, child pain threat, child pain worry, and parent pain catastrophizing. Within the included studies, female sex and disease severity were both significantly associated with pain and pain impact. Study quality was moderate on average. CONCLUSIONS: There is evidence that child psychosocial factors are associated with pain and pain impact in pediatric IBD; more studies are needed to examine parent- and family-level psychosocial factors. Youth with IBD should be routinely screened for pain severity, pain impact, and psychosocial risk factors such as anxiety/depression.

Understanding the Psychosocial and Parenting Needs of Mothers with Irritable Bowel Syndrome with Young Children.

Women of childbearing age experience the highest prevalence of irritable bowel syndrome (IBS), yet little is known about their psychosocial and parenting needs, which may influence their children's experience of future gastrointestinal or pain-related conditions. The aims of this study were to conduct qualitative interviews to understand the psychosocial and parenting needs of mothers with IBS who have young school-age children, and to assess mothers' potential interest in and acceptability of a preventive parenting intervention program. Ten mothers with IBS who have young (age 5-10), healthy children were interviewed. Interviews were coded with thematic analysis and three themes were identified: (1) Guilt about how IBS impacts children, (2) Worry that children will develop IBS, and (3) Already on high alert for children's health. All mothers expressed interest in an Internet-based preventive intervention and identified tools and strategies they would want included. Results demonstrate that mothers experience guilt about how IBS has impacted their children in their daily lives, concern that they need to pay attention to children's early signs and symptoms that could indicate gastrointestinal problems, and worry about children developing IBS in the future-suggesting that a preventive intervention may address important concerns for this population.