Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee.

Functional gastrointestinal disorders (FGID), such as infant regurgitation, infant colic, and functional constipation, are common and typically physiological phenomena during the early months of an infant's life and account for frequent consultations with pediatricians. Various infant formulas are marketed for their management and are frequently given by parents to infants before a medical consultation. However, the evidence supporting their effectiveness is limited and some have altered nutritional compositions when compared to standard formulas. Thus, these products should only be used under medical supervision and upon medical advice. Marketing and over-the-counter sales do not ensure proper medical guidance and supervision. The aim of this position paper is to review the current evidence regarding the safety and efficacy of formulas specifically formulated for addressing regurgitation, colic, and constipation, recognized as FGID. The objective is to provide guidance for clinical management based on the highest quality of available evidence. A wide search using Pubmed, MEDLINE, EMBASE and Cochrane Database of Systematic Reviews was performed including the MESH terms infant formula, colic, constipation, regurgitation, reflux, palmitate, lactase, lactose, magnesium, hydrolyzed protein, prebiotics or probiotics. 752 papers were identified and screened. Finally, 72 papers were included in the paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained by multiple e-mail exchange and meetings of the Nutrition Committee. (1) For breastfed infants experiencing FGID such as regurgitation, colic, or constipation, transitioning from breastfeeding to commercial formulas is not recommended. (2) In general, whether an infant is breastfed or formula-fed, it's crucial to reassure parents that FGIDs are normal and typically do not necessitate treatment or change to a special formula. (3) Thickened formulas, often termed anti-reflux formulas, may be considered in specific cases of regurgitation. (4) The usage of specialized formulas for infants with colic is not advised due to a lack of clinical evidence. (5) In the case of constipation in infants, the use of formulas enriched with high ß-palmitate and increased magnesium content may be considered to soften the stool. Generally, there is limited evidence supporting the use of specialized formulas for FGID. Breastfeeding should never be discontinued in favor of formula feeding.

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network.

BACKGROUND: Researchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PURPOSE: MDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. STUDY DESIGN: Acute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. METHODS/RESULTS: Here, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. CONCLUSION: Brain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

Designing, Developing, and Validating a Set of Standardized Pictograms to Support Pediatric-Reported Gastroduodenal Symptoms.

OBJECTIVE: To develop and validate a set of static and animated gastroduodenal symptom pictograms for children. STUDY DESIGN: There were 3 study phases: 1: cocreation using experience design methods to develop pediatric gastroduodenal symptom pictograms (static and animated); 2: an online survey to assess acceptability, as well as face and content validity; and 3: a preference study. Phases 2 and 3 compared the novel pediatric pictograms with existing pictograms used with adult patients. RESULTS: Eight children aged 6-15 years (5 female) participated in phase 1, and 69 children in phase 2 (median age 13 years: IQR 9-15); an additional 49 participants were included in phase 3 (median age 15: IQR 12-17). Face and content validity were higher for the pediatric static and animated pictogram sets compared with pre-existing adult pictograms (78% vs 78% vs 61%). Participants with worse gastric symptoms had superior comprehension of the pediatric pictograms (χ2 [8, N = 118] P < .001). All participants preferred the pediatric static pictogram set was over both the animated and adult sets (χ2 [2, N = 118] P < .001). CONCLUSIONS: The cocreation phase resulted in the symptom concept confirmation and design of 10 acceptable static and animated gastroduodenal pictograms with high face and content validity when evaluated with children aged 6-18. Validity was superior when children reported more problematic symptoms. Therefore, these pictograms could be used in clinical and research practice to enable standardized symptom reporting for children with gastroduodenal disorders.

Quality of Life and Bidirectional Gut-Brain Interactions in Irritable Bowel Syndrome From Adolescence to Adulthood.

BACKGROUNDS AND AIMS: Reports on cross-sectional and longitudinal associations between health-related quality of life (HRQoL), psychological distress, and irritable bowel syndrome (IBS) in the adolescent and young adult general population are few. We aimed to describe cross-sectional associations between HRQoL and IBS in adolescence and young adulthood, and examine bidirectional gut-brain interactions in the transition from childhood to adulthood. METHODS: We included 3391 subjects from a prospective birth cohort study, with data on IBS at 16 years of age and 24 years of age. IBS was assessed using the pediatric Rome III (16 years of age) and the adult Rome IV (24 years of age) diagnostic questionnaires. HRQoL and psychological distress were assessed through EQ-5D. Sex-adjusted logistic regression models were used to examine associations between overall HRQoL/psychological distress at 16 years of age and new-onset IBS at 24 years of age (brain-gut) and between IBS at 16 years of age and new-onset psychological distress at 24 years of age (gut-brain). RESULTS: In subjects with vs without IBS at 16 and 24 years of age, overall HRQoL (EQ visual analog scale, EQ-5D index value) was lower, and it was more common reporting problems in 4 of 5 EQ-5D dimensions (all P < .05). EQ-5D index value at 16 years of age was inversely associated (odds ratio [OR], 0.1, 95% confidence interval [CI], 0.01-0.6), and psychological distress at 16 years of age was positively associated (OR, 1.6; 95% CI, 1.2-2.3), with new-onset IBS at 24 years of age. Having any abdominal pain-related disorder of gut-brain interaction at 16 years of age was associated with new-onset psychological distress at 24 years of age (OR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS: Adolescents and young adults with IBS in the general population have impaired HRQoL. Bidirectional gut-brain interactions are relevant for symptom generation in abdominal pain-related disorders of gut-brain interaction, and for HRQoL impairment and psychological distress in the transition from childhood to adulthood.

The Impact of Nutritional Therapy on Gastrointestinal Motility in Older Adults.

Japan is becoming a superaged society, and nutrition therapy for the elderly population is very important. Elderly individuals often have multiple diseases and are prone to malnutrition. Furthermore, functional constipation, diarrhoea, faecal incontinence, etc., may occur despite no organic abnormality of digestive tract function. Due to these disabilities, the resulting malnutrition, and the slow recovery, it is often difficult for elderly individuals to reintegrate into society. Secondary or incorrect nutritional management increases complications, decreases physical function and worsens the prognosis. Previous statistical research suggests that in-hospital mortality is significantly higher among hospitalised patients aged ≥65 years who ingest less than half of their caloric needs. Therefore, appropriate nutritional management from an early stage is essential for elderly individuals. Moreover, functional excretion disorders, dementia, and sarcopenia (muscle-wasting disease) are attracting attention as pathological conditions unique to elderly individuals, and it is essential to undergo rehabilitation early with nutritional management. Being elderly does not preclude nutritional management, and it is necessary to reconsider appropriate nutritional therapy even in the terminal stage and in advanced physical and mental illnesses. This review explores the relationship between dietary intake and FGIDs, with a focus on elderly adults.

Gastrointestinal functioning and menstrual cycle phase in emerging young adult women: a cross-sectional study.

BACKGROUND: Women experience more severe gastrointestinal (GI) symptoms compared to men. The onset of puberty and the menstrual cycle may influence these differences. Additionally, health anxiety is an important construct that has been shown to play a role in increased symptomatology across many medical conditions. Using standardized clinical measures often employed to assess disorders of gut-brain interaction (DGBI) we aimed to identify differences of GI functioning across menstrual cycle phases and to evaluate the role of health anxiety in this relationship. METHODS: Six hundred three participants completed a survey including functional GI assessment scales (PROMIS-GI®), an abdominal pain scale and map, and a health anxiety measure. They were grouped by menstrual cycle phases (Menses, Follicular, Early-Luteal, and Premenstrual) based on self-reported start date of most recent period. Multivariate analyses of covariance were conducted to identify differences between menstrual cycle phase and scores on the symptom scales. Heath anxiety was included as a covariate in all analyses. RESULTS: No significant differences were found between menstrual cycle group and PROMIS-GI scores. Higher GI-symptom and pain levels were found as health anxiety increased. Pain in the hypogastric region of the abdomen was significantly higher during the Menses phase when compared to Early-Luteal and Premenstrual phases. A subset of participants with DGBI diagnoses demonstrated significantly higher GI-symptom severity on several PROMIS-GI scales when compared to matched controls who did not have those diagnoses. In addition, participants with DGBI diagnoses reported significantly greater pain across multiple abdominal regions than their non-diagnosed counterparts. CONCLUSIONS: GI symptom levels as measured by the PROMIS-GI scales in otherwise healthy women were not dependent on menstrual cycle phase. Yet, the PROMIS-GI scales were sensitive to symptom differences in women with DGBI diagnoses. Overall, this study demonstrated that the PROMIS-GI measures are unlikely to be affected by gynecological functioning in healthy young women. We argue that the abdominal pain map is an essential addition to classification and diagnosis.

Gastrointestinal Symptoms in Pediatric Patients with Anxiety Disorders and Their Relationship to Selective Serotonin Reuptake Inhibitor Treatment or Placebo.

Gastrointestinal symptoms are commonly reported as adverse effects of selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacologic treatment for pediatric anxiety disorders; however, the temporal course of these symptoms during treatment, although believed to be transient, has never been prospectively evaluated. Additionally, rates of gastrointestinal symptoms and functional gastrointestinal syndromes in anxious youth are poorly understood. We examined gastrointestinal symptoms in youth with anxiety disorders during a double-blind, placebo-controlled trial of escitalopram (n = 51). Then, in a separate sample of prospectively treated children and adolescents with generalized, social and/or separation anxiety disorders (n = 56), we examined the frequency of gastrointestinal symptoms based on the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) and ROME III criteria and the association of these symptoms with clinical and demographic characteristics using logistic regression. The frequency/severity of abdominal pain, diarrhea, bloating constipation or total gastrointestinal symptoms did not differ between patients receiving placebo (n = 25) or escitalopram (n = 26). However, escitalopram-treated youth had transient changes in nausea/vomiting and total upper gastrointestinal symptoms during the first two weeks of treatment. ROME III criteria for functional gastrointestinal syndromes were present in 12/56 patients (21.4%). QPGS-related functional gastrointestinal syndromes and symptoms were unrelated to treatment, treatment type, or clinical or demographic variables. Gastrointestinal symptoms are common in youth with anxiety and SSRIs produce transient-rather than sustained-gastrointestinal symptoms. Assessing gastrointestinal symptoms prior to pharmacotherapy and discussing factors that increase (or decrease) the likelihood of transient SSRI-related symptoms in youth may decrease patient uncertainty related to side effects and decrease medication-related anxiety.

Re-investigation of functional gastrointestinal disorders utilizing a machine learning approach.

BACKGROUND: Functional gastrointestinal disorders (FGIDs), as a group of syndromes with no identified structural or pathophysiological biomarkers, are currently classified by Rome criteria based on gastrointestinal symptoms (GI). However, the high overlap among FGIDs in patients makes treatment and identifying underlying mechanisms challenging. Furthermore, disregarding psychological factors in the current classification, despite their approved relationship with GI symptoms, underlines the necessity of more investigation into grouping FGID patients. We aimed to provide more homogenous and well-separated clusters based on both GI and psychological characteristics for patients with FGIDs using an unsupervised machine learning algorithm. METHODS: Based on a cross-sectional study, 3765 (79%) patients with at least one FGID were included in the current study. In the first step, the clustering utilizing a machine learning algorithm was merely executed based on GI symptoms. In the second step, considering the previous step's results and focusing on the clusters with a diverse combination of GI symptoms, the clustering was re-conducted based on both GI symptoms and psychological factors. RESULTS: The first phase clustering of all participants based on GI symptoms resulted in the formation of pure and non-pure clusters. Pure clusters exactly illustrated the properties of most pure Rome syndromes. Re-clustering the members of the non-pure clusters based on GI and psychological factors (i.e., the second clustering step) resulted in eight new clusters, indicating the dominance of multiple factors but well-discriminated from other clusters. The results of the second step especially highlight the impact of psychological factors in grouping FGIDs. CONCLUSIONS: In the current study, the existence of Rome disorders, which were previously defined by expert opinion-based consensus, was approved, and, eight new clusters with multiple dominant symptoms based on GI and psychological factors were also introduced. The more homogeneous clusters of patients could lead to the design of more precise clinical experiments and further targeted patient care.

Possible role of the gut microbiome in mediating the beneficial effects of the six-herbal formulation STW 5-II on digestive health.

BACKGROUND: STW 5-II is a combination of six herbal extracts with clinically proven efficacy in functional dyspepsia (FD) and irritable bowel syndrome (IBS). STW 5-II contains a wide variety of secondary plant constituents that may interact with the human gut microbiome. In addition to complex carbohydrates, secondary plant metabolites, such as polyphenols, are known to exert prebiotic-like effects. PURPOSE: This study aimed to assess the bidirectional interactions between STW 5-II and the human gut microbiome. METHODS: STW 5-II was incubated with human fecal microbiota in a short-term colonic model. In the samples, the impact of STW 5-II on microbial fermentation capacity (pH, gas production), short chain fatty acid (SCFA) production, and microbial composition (Illumina 16S rRNA gene sequencing) was analyzed. In addition, the biotransformation of STW 5-II constituents by the fecal microbiota was assessed by UHPLCHRMS-based metabolite profiling. Furthermore, Caco-2/THP1 co-culture assay was used to explore the effect on gut barrier integrity and inflammatory markers. RESULTS: Fermentation of STW 5-II by fecal microbiota led to consistent changes in pH and gas production and increased production of SCFAs (acetate, propionate, and butyrate). STW 5-II promoted the enrichment of Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Eggerthellaceae and suppressed the growth of pathogenic species from the Enterobacteriaceae family. In Caco2/THP1 culture, treatment with STW 5-II-incubated samples resulted in significantly increased transepithelial electrical resistance, indicating enhanced barrier function. Among inflammatory markers, STW 5-II-incubated samples increased LPS-induced secretion of the anti-inflammatory cytokine IL-10, as well as NF-κB activity, and significantly decreased the secretion of the pro-inflammatory chemokine MCP-1. UHPLCHRMS analysis identified 110 constituents of STW 5-II with changed levels during incubation with fecal microbiota: 63 constituents that were metabolized, 22 intermittently increased metabolites, and 25 final metabolites, including compounds with established anti-inflammatory activity, such as 18ß-glycyrrhetinic acid. CONCLUSION: These findings indicate a microbiome-mediated digestive health-promoting effect of STW 5-II via three different routes, namely enhanced microbial SCFA production, microbial production of potentially bioactive metabolites from STW 5-II constituents, and prebiotic-like action by promoting the proliferation/growth of beneficial bacteria.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: a prospective follow-up cohort study.

BACKGROUND: Acute gastrointestinal infections can lead to post-infectious irritable bowel syndrome (PI-IBS). Moreover, coronavirus disease (COVID-19) is related to long-term gastrointestinal sequelae. In this study, the frequency, disease spectrum, and risk factors for post-infection functional gastrointestinal disease (PI-FGID) in COVID-19 patients and healthy controls were prospectively examined. METHODS: Validated Rome III and Rome IV questionnaires and limited objective assessment were used to assess the incidence of PI-FGID in 190 COVID-19 patients, and 160 healthy controls prospectively followed for 1, 3, and 6 months. RESULTS: Six(3.2%), 1(0.5%), 3(1.6%), 5(2.6%), 6(3.2%)COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at 1 month, respectively, while 4(2.1%), 1(0.5%), 4(2.1%), 4(2.1%), and 6(3.2%)COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at three months, respectively. Furthermore, 2(1.3%), 4(2.5%), and 3(1.9%)healthy controls developed constipation, dyspepsia, and their overlap at one month, respectively (P = 0.193), while 2(1.3%), 4(2.5%), and 2(1.3%)healthy controls developed constipation, dyspepsia and their overlap at three months, respectively (P = 0.286). FGIDs incidence was higher among COVID-19 patients(8.9%) than in healthy controls(3.1%) at 6-month follow-up (P = 0.025). Moreover, 7 (3.7%), 5 (2.6%), 3 (1.6%), and 2 (1.1%) COVID-19 patients developed IBS, functional dyspepsia(FD), functional diarrhea(FDr), functional constipation(FC)at six months, respectively, while only 2 (1.3%) and 3 (1.9%) healthy controls developed IBS and FD at six months, respectively. Notably, gastrointestinal(GI)symptoms at onset were the independent risk factors for post-COVID-19 FGIDs at six months. CONCLUSIONS: COVID-19 increases new-onset PI-FGID at six months compared with healthy controls. GI symptom at the onset of COVID-19 is an independent risk factor for post-COVID-19 FGIDs.

Clinical outcome of disorders of gut-brain interaction in secondary care: A longitudinal study.

BACKGROUND: Real-world data on the outcome of routine treatment for disorders of gut-brain interaction (DGBI) in secondary care are lacking. METHOD: A longitudinal study of consecutive adult patients with various DGBI attending this institution's gastroenterology clinic was conducted. Following 2 years of treatment, the proportion of patients with symptom improvement, details of clinical therapy, factors associated with and the impact of 'no symptom improvement' were determined. RESULTS: A total of 289 patients (median age 68 years; 64.7% females; 28.4% irritable bowel syndrome (IBS), 20.1% functional dyspepsia (FD), 8.7% functional constipation (FC), 42.9% overlap syndrome) were recruited. After 2 years, 66.1% patients reported symptom improvement. Patients with overlap syndrome were less likely to have symptomatic improvement compared to those with a single DGBI (Overlap 55.6% vs IBS 74.4% vs FD 72.4% vs FC 76.0%, p = 0.014). Reassurance was associated with symptom improvement (p < 0.001). On multivariate analysis, overlap syndrome remained significantly associated with a poorer outcome (OR 2.27, 95% CI 1.22-4.25, p = 0.010), while providing reassurance was associated with a positive outcome (OR 0.30, 95% CI 0.16-0.56, p < 0.001). Only 25.6% and 14.9% of patients were referred for a low FODMAP diet and psychiatric intervention respectively. DGBI patients who had 'no improvement' were more likely to seek further GI consultations and had more work absenteeism. CONCLUSION: Two-thirds of DGBI patients in secondary care showed symptom improvement. Patients who were reassured had better symptom improvement, while those with an overlap syndrome were associated with a poorer outcome, resulting in greater healthcare consultation and work absenteeism.

Oral exploration and food selectivity: A case-control study conducted in a multidisciplinary outpatient setting.

Background: Pediatric feeding disorders (PFDs) are common, and their great phenotypic variability reflects the breadth of the associated nosological profiles. PFDs should be assessed and managed by multidisciplinary teams. Our study aimed to describe clinical signs of feeding difficulties in a group of PFD patients assessed by such a team, and to compare them with children in a control group. Methods: In this case-control study, case group patients 1 to 6 years old were consecutively recruited through the multidisciplinary unit for the treatment of pediatric feeding difficulties based at Robert Debré Teaching Hospital in Paris, France. Children with an encephalopathy, severe neurometabolic disorder, or genetic syndrome (suspected or confirmed) were excluded. Members of the control group, consisting of children with no feeding difficulties (i.e., Montreal Children's Hospital Feeding Scale scores below 60) or severe chronic diseases, were recruited from a day care center and 2 kindergartens. Data from medical histories and clinical examination related to mealtime practices, oral motor skills, neurodevelopment, sensory processing, and any functional gastrointestinal disorders (FGIDs) were recorded and compared between groups. Results: In all, 244 PFD cases were compared with 109 controls (mean ages: cases, 3.42 [±1.47]; controls, 3.32 [±1.17]; P = 0.55). Use of distractions during meals was much more among PFD children (cases, 77.46%; controls, 5.5%; P < 0.001), as was conflict during meals. While the groups did not differ in their members' hand-mouth coordination or ability to grab objects, cases began exploring their environments later; mouthing, especially, was less common in the case group (cases, n = 80 [32.92%]; controls, n = 102 [94.44%]; P < 0.001). FGIDs and signs of visual, olfactory, tactile, and oral hypersensitivity were significantly more frequent among cases. Conclusion: Initial clinical assessments showed that, in the children with PFDs, normal stages of environmental exploration were altered, and that this was often associated with signs of sensory hypersensitivity and digestive discomfort.

Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19. METHODS: Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI. RESULTS: Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01). CONCLUSIONS: COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.

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.

Disorders of gut-brain interaction: Highly prevalent and burdensome yet under-taught within medical education.

BACKGROUND AND OBJECTIVE: To determine the population prevalence and associated health impairment of disorders of gut-brain interaction (DGBI) across Great Britain, and the emphasis placed upon them within medical education. METHODS: An Internet-based cross-sectional health survey was completed by 1906 general population adults across Great Britain without self-reported organic GI disease. The survey enquired for demographics, symptom-based criteria for Rome IV DGBI, healthcare use, non-GI somatic symptoms, and quality of life. As a separate analysis, we evaluated which DGBI are considered core knowledge at undergraduate medical school level and post-graduate specialization level for Gastroenterologists and General Practitioners. RESULTS: The overall prevalence of DGBI across Great Britain was 37%, being similar for England (37%), Scotland (33%), and Wales (36%); p = 0.66. There was no difference between English regions (range 33%-43%, p = 0.26). The prevalence of DGBI was highest in those aged 18-40 years (40%), then 40-64 years (37%), and least amongst those ≥65 years (29%); p < 0.001. The most common DGBI were bowel disorders (30%), followed by gastroduodenal (10.5%), anorectal (8.1%) and oesophageal disorders (6.2%). Individuals with DGBI were significantly more likely than those without DGBI to have increased GI-related healthcare visits, medication use, surgical interventions, non-GI somatic symptoms, and reduced quality of life. One-in-three people with DGBI had multiple GI organ regions involved and this correlated with increased health impairment (p < 0.001). The only DGBI mentioned across all medical training curricula is irritable bowel syndrome, while the General Practitioner and Gastroenterology Curricula also recognise the outdated term non-ulcer dyspepsia (as opposed to functional dyspepsia). The 2010 Gastroenterology Curriculum also includes functional constipation and disordered defecation, with the incoming 2022 iteration adding in functional upper GI syndromes, functional abdominal pain, and opioid-induced GI disturbances. CONCLUSION: Disorders of gut-brain interaction are common across Great Britain and incur substantial health impairment. However, they are generally under-taught within the British medical education system. Increasing awareness and education of disorders of gut-brain interaction might improve patient outcomes.

Understanding and modifying Fabry disease: Rationale and design of a pivotal Phase 3 study and results from a patient-reported outcome validation study.

The use of available treatments for Fabry disease (FD) (including enzyme replacement therapy [ERT]) may be restricted by their limited symptom improvement and mode of administration. Lucerastat is currently being investigated in the MODIFY study as oral substrate reduction therapy for the treatment of FD. By reducing the net globotriaosylceramide (Gb3) load in tissues, lucerastat has disease-modifying potential to improve symptoms and delay disease progression. MODIFY is a multicenter, double-blind, randomized, placebo-controlled, parallel-group Phase 3 study (ClinicalTrial.gov: NCT03425539); here we present the rationale and design of this study. Eligible adults with a genetically confirmed diagnosis of FD and FD-specific neuropathic pain entered screening. Patients were randomized (2:1) to receive either oral lucerastat twice daily or placebo for 6 months; treatment allocation was stratified according to sex and ERT treatment status. The main objectives of MODIFY are to assess the effects of lucerastat on neuropathic pain, gastrointestinal (GI) symptoms, FD biomarkers, and determine its safety and tolerability. Neuropathic pain and GI symptoms are key features of FD that have a significant impact on quality of life. Despite various tools available to assess pain and GI symptoms, there are currently limited tools available to assess neuropathic and GI symptoms in FD, validated according to health authority guidelines. Based on FDA recommendations, we undertook a patient-reported outcome (PRO) validation study, using a novel eDiary-based PRO tool to assess the validity of evaluating neuropathic pain as a primary efficacy endpoint in MODIFY. Results from the PRO validation study are included. To date, MODIFY is the largest Phase 3 clinical study conducted in patients with FD. Enrollment to MODIFY is now complete, with 118 patients randomized. Results will be presented in a separate publication. Long-term effects of lucerastat are being assessed in the ongoing open-label extension study (NCT03737214).

Diet, fibers, and probiotics for irritable bowel syndrome.

Many aspects make irritable bowel syndrome (IBS) challenging for both patients and physicians. The unclear pathogenesis with many pathways to be explored, bothering symptoms that affect the quality of life, and many subtypes of the condition are only a few reasons that make IBS difficult to control and obtain satisfactory results. Treatment options start with general advice for lifestyle, continue with non-pharmaceutical treatments, and finally touch classic treatments. In this review, pharmaceutical treatment options are not accounted for. Consensus groups and meta-analyses have concluded guidelines that overall are the same, with variations in the strength of recommendations and some cultural and geographical particularities. Dietary interventions, probiotics, and fibers can be seen as non-pharmaceutical treatments that coexist in various protocols because of the relevant evidence regarding their efficacy in treating IBS symptoms.

Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: Prevalence, temporal stability, and associated comorbidities.

BACKGROUND: Co-occurring (overlapping) irritable bowel syndrome (IBS), functional dyspepsia (FD), and heartburn has been observed. However, whether it is a distinct entity has not been established, nor what clinical, demographic, lifestyle, and psychological traits are associated with it. This study sought to estimate the prevalence and temporal stability of this overlap and to identify features specific to it in order to gain some insights into the potential etiopathogenesis. METHODS: Two waves of a survey to a population-representative sample were conducted 3 years apart, recruiting 1312 individuals for this study. The chance-expected probability of complete overlap (CO) was calculated and compared with the observed CO. A range of demographic, lifestyle factors, medical diagnoses, sleep quality, and psychological distress were tested to identify predictors of overlap using logistic regression. KEY RESULTS: CO was observed in 2.1% (95% confidence interval 1.9, 3.7) of the sample and was closely replicated in wave 2 at 2.0%. The observed CO was greater than expected by chance (0.2%) to a statistically significant extent (p < 0.001). Overlap between IBS subtypes, FD subtypes, and heartburn was also elevated above chance expectation. Individuals with CO were separately differentiated from others with respect to elevated rates of self-reported medically diagnosed asthma, elevated psychological distress score, and elevated impact on sleep quality. The discrimination provided by these factors was further independent of age and sex. CONCLUSIONS AND INFERENCES: Overlap between IBS, FD, and heartburn (GERD) appears to be a distinct entity that has a profile including psychological morbidity, sleep disturbance, and elevated rates of atopy.