Introduction

Nausea and vomiting are prevalent in gastroparesis (GP) and may persist in some patients with GP (pNVGP) despite treatment with prokinetics/antiemetics. There is scarce evidence at the population level on the demographic and clinical characteristics and disease experience of patients with pNVGP.

Aims & Methods

A retrospective study was conducted using Optum Market Clarity, a large US database comprised of claims and electronic health records (EHR) that is linked at the patient level and has customised fields developed by Natural Language Processing from unstructured clinical notes (e.g., GP-specific symptoms, gastric emptying testing). The pNVGP cohort was defined as: all GP diagnoses from claims/EHR during the study period (01Jan2008–30Sep2020, 1^st documented GP Dx date in EHR/claims as the index date), with encounters for ≥5 years pre- and ≥1 year post-index in study period; received ≥14 cumulative days’ supply of prokinetics and/or antiemetics pre- and/or post-index; and still reported nausea/vomiting ≥28 days after treatment at encounters.

Results

Of 207,704 patients identified with GP (45% diabetic [DG], 45% idiopathic [IG], 10% other causes), 25,654 met the criteria for pNVGP (57% DG, 31% IG, 12% other; mean±SD age at index 51.3±16.6 years; 75% female; 80% Caucasian; mean Charlson Comorbidity Index score 2.6). Prior to index, abdominal pain (61%), nausea (50%), nausea and vomiting (42%) and vomiting (39%) were the most commonly reported symptoms for pNVGP patients. Prokinetic/antiemetic use was frequent during 1-year pre-index (71% of pNVGP patients) and increased during 1-year post-index (85%). Ondansetron (53% of pNVGP patients pre-index, 66% post-index) and metoclopramide (13% pre-index, 32% post-index) were the most frequently used.

Conclusion

In this study, a sizable subcohort of patients with GP had pNVGP despite the use of prokinetics/antiemetics. pNVGP occurs more often in diabetic GP, and often with abdominal pain. Patients with pNVGP had persistent unmet needs.

Disclosure

HF, ZH, NS and JW: Employees of Takeda and hold stock/stock options in Takeda. YJC: Employee of Takeda at the time this analysis was conducted. JT: Advisor: Adare Pharmaceuticals, Alfa Wassermann Pharma, Allergan (AbbVie), Arena Pharmaceuticals, Bayer, Chr. Hansen, Clasado Biosciences, Danone, Devintec Pharma, Dr Falk Pharma, Grünenthal, Ironwood Pharmaceuticals, Janssen, Kyowa Kirin, Menarini Group, Mylan (Viatris), Neurogastrx, NeuTec Pharma, Novartis, Noventure, Nutricia, Shanghai Tsumura Pharmaceuticals, Shionogi, Shire (Takeda), Takeda, Theravance Biopharma, Tramedico, Truvion Healthcare, Zealand Pharma and Zeria Pharmaceutical; Research support: Shanghai Tsumura Pharmaceuticals, Shire (Takeda), Sofar S.p.A and Takeda; Speaker fees: Abbott, Allergan (AbbVie), AstraZeneca, Janssen, Kyowa Kirin, Menarini Group, Mylan (Viatris), Novartis, Shire (Takeda), Takeda, Truvion Healthcare and Zeria Pharmaceutical. HPP: Consultancy fees: AEON Biopharma, Evoke Pharma, Medtronic, Renexxion and Takeda. Funding: This study was sponsored by Takeda.

Introduction

The prevalence of functional dyspepsia (FD) and gastroparesis in diabetic patients remains unknown. A high prevalence of gastroparesis has been reported in diabetic patients reaching up to 5%.¹ However, recent consensus specified the symptom pattern for gastroparesis, with nausea and/or vomiting as predominant symptoms, now defined as “gastroparesis-like symptoms” (GPLS).² The global prevalence of GPLS has been estimated to reach only 1.2% in diabetic patients, but type 1 and type 2 diabetes were not assessed separately.²

Aims & Methods

We aimed to assess the prevalence and burden of FD and GPLS in primary care patients with diabetes, comparing patients with type 1 and type 2 diabetes. An online survey was addressed to diabetic patients through general practitioners and diabetic patient associations. The survey included the Rome IV questionnaire and the Patient Assessment of Gastro-Intestinal Disorders-Symptom Severity Index (PAGI-SYM) for upper gastro-intestinal symptoms. Anxiety, depression, somatization, and quality of life were also assessed by specific questionnaires (Generalized Anxiety Disorder GAD-7, Patient Health Questionnaire PHQ-9, PHQ-15, and PAGI-QoL questionnaires respectively).

Results

A total of 216 patients completed the questionnaires, among which 146 had type 1 diabetes, and 68 had type 2 diabetes, (2 patients did not know their type of diabetes). The median age of the population was 56 (50-61) years old, with 134 female patients (61.8%). The prevalence of FD was 13.0% with no difference between the 2 groups. The prevalence of GPLS reached 4.2% and was significantly higher in patients with type 2 diabetes (8.9% vs 2.1%; p=0.03). The burden of upper gastro-intestinal symptoms and their impact on quality of life was higher in type 2 diabetes patients with higher PAGI-SYM and PAGI-QoL scores while anxiety and somatization were not different between type 1 and type 2 diabetes patients (see Table). Overall, patients with GPLS had higher anxiety (9 vs 3; p=0.003), depression (12 vs 3; p=0.001) and somatization scores (16 vs 6; p<0.001) than patients without. Compared to patients with FD without GPLS, GPLS patients had numerically higher but not statistically different scores for symptom severity (51 vs 28; p=0.46), anxiety (9 vs 7; p=0.29), depression (12 vs 7; p=0.07), somatization (16 vs 11.5; p=0.16) and quality of life scores (52 vs 24; p=0.16).

Conclusion

This study confirms that the prevalence of GPLS seems to be higher in diabetic patients compared to available population data, especially in patients with type 2 diabetes. The impact of the symptoms was similar to the impact of FD in this population. Further studies are required to assess the prevalence of delayed gastric emptying in diabetic type 1 and 2 patients with GPLS.

References

1. Choung RS, Locke GR, Schleck CD, et al. Risk of Gastroparesis in Subjects with Type 1 and 2 Diabetes in the General Population. Am J Gastroenterol 2012;107:82-88.
2. Huang I-H, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United European Gastroenterol J 2022;10:888-897.

Introduction

Gastroparesis is a severe medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain. Thus far, little is known about the underlying genetic risk factors for nausea in gastroparesis patients. We explored the association of genetic variants with nausea severity in a set of WGS data from a clinical gastroparesis study.

Aims & Methods

Blood samples were obtained from adults with a diagnosis of diabetic or idiopathic gastroparesis, having evidence of delayed gastric emptying, and moderate to severe nausea, daily average nausea score of >2.5, at least one episode of vomiting, PAGI-SYM nausea score of ≥2 at screening, and controlled blood glucose levels. WGS was conducted with 30x read depth using whole blood samples. Nausea score was assessed from a daily symptom dairy with a range from 0 mild to 5 severe. GWAS using linear model was conducted on variants with MAF ≥0.01 with adjustment of the subject’s age, sex, BMI, etiology, and the first 3 PCs.

Results

Variant clusters from multiple genes are significantly associated with baseline nausea score at p=1e-5 level. Among the top scoring variants are loci within ATF3, PP2D1, CNTN4, BMP2, ABL1, CTNNA3 and KIF6. Interestingly, upon comparing our results with a published transcriptomic analysis that included both diabetic and idiopathic gastroparesis subjects, we found that ATF3 and BMP2 were overlapping with genes differentially expressed in both diabetic and idiopathic gastroparesis when compared with controls. ABL1 was however differentially expressed in diabetic cases whereas CNTN4 was differentially expressed in idiopathic controls.
We expanded the analysis with single gene tests which shows that ATF3 is significant especially for MAF>0.05 variants (SKAT p=0.02). The top variant in ATF3 is rs79151334 (beta= 0.68, p=5.76e-6), whose minor allele associates with higher nausea score.

Conclusion

Additionally, we report new potential associations CTNNA3, PP2D1, and KIF6 as well as a cluster of variants between CDH2 and MIR302F, that associated with baseline nausea score. Among those, both CTNNA3 and CDH2 encode cadherin related proteins, suggesting this type of junction could play a role in the underlying mechanism.

Disclosure

I am an employee at Vanda Pharmaceuticals Inc.

Introduction

Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction defined by episodes of uncontrollable vomiting and retching. CVS has four phases (inter-episodic, prodrome, emetic, recovery) and affects both children and adults. There is a lack of published qualitative research on disease-related and phase-specific symptoms that impact patients with CVS.

Aims & Methods

Two qualitative, cross-sectional, observational interview studies were conducted in adults (18-65 years) and adolescents (12-17 years) with CVS. The studies aimed to explore the patient experience, identify the symptoms and understand their relevance to patients with CVS. The two studies included participants clinically diagnosed with CVS and followed at the tertiary care CVS programs at Froedtert hospital (adults) and Children’s Wisconsin (adolescents). Adolescents participated in a dyad interview with their caregiver or separately. Interviews were conducted remotely using a semi-structured interview guide and analysed with an “open coding” approach using ATLAS.ti 9.0 (adults) or 22.0 (adolescents).

Results

Semi-structured concept elicitation interviews (each up to 90 minutes long) were conducted with 13 adults (mean ± SD age 45.3 ± 13.1 years) and 15 adolescents (mean ± SD age 14.6 ± 1.8 years) by professional qualitative interviewers. Each participant described their symptoms during the prodrome and emetic phases. Most frequently reported symptoms during the prodrome were nausea (92.3%), anxiety (76.9%) and abdominal pain (69.2%) in adults; and nausea (100%), abdominal pain (73.3%), headache (73.3%) and pale skin (73.3%) in adolescents. During the emetic phase, the most frequently reported symptoms were nausea (100%), tiredness (100%), dry heaves (100%), vomiting (92.3%) and retching (92.3%) in adults; and nausea (100%), vomiting (100%), abdominal pain (93.3%), dehydration (86.7%), tiredness (86.7%) and light-headedness (86.7%) in adolescents. The patients most frequently reported nausea (5/13 adults, 6/15 adolescents) and vomiting (5/13 adults, 5/15 adolescents) as the most bothersome CVS symptom. Adults reported anxiety (associated with an impending vomiting episode; 5/13); missing work (2/13); inability to: perform daily tasks (1/13), plan their life (1/13), or parent to their full capacity (1/13); being homebound (1/13); reduced emotional well-being (1/13); and avoiding events (1/13) as the most bothersome impact of CVS symptoms. Adolescents reported impact on school (7/13 with data); missing out on sports (4/13); impacts on: social activities (4/13), sleep (1/13), friendships (1/13), or emotions (1/13); and anxiety (1/13) as the most bothersome impact of CVS symptoms (some provided >1 response). Caregivers reported the emotional impact of seeing their child suffer from CVS (5/11 with data); impact on: their child’s schooling (3/11), social activities (2/11); sports, friends/social activities, effect on their child’s future, work, daily planning, and travel planning (1/11 each) as the factor most difficult for them or their family.

Conclusion

Patients with CVS experience considerable gastrointestinal as well as extra-intestinal symptoms during both the prodrome and emetic phases. The majority suffer from nausea, vomiting and abdominal pain; the associated anxiety in adults is also notable. The study also confirmed major impact of CVS on daily life such as work/school absences, lost time with family/friends and reduced emotional well-being. CVS also markedly affects caregivers to patients with CVS.

Disclosure

Katja Kovacic reports medical advisory board from AbbVie, and is a consultant for Neurogastrx. Yaozhu J. Chen, Melody Wu, Camilla A. Richmond and James Williams are employees of the study sponsor, Takeda, and hold Takeda stock or stock options. Danielle Rodriguez is an employee of Evidera, which were contracted by Takeda for work relating to this study. Karin S. Coyne is an employee of Evidera, which were contracted by Takeda for work relating to this study, and a scientific consultant to Takeda. Thangam Venkatesan reports consultancy fees from Takeda.

Introduction

Dyspeptic patients frequently report nausea and vomiting. However, Rome IV criteria distinguish functional dyspepsia (FD) and chronic nausea and vomiting syndrome (CNVS) as separate disorders.

Aims & Methods

We aimed to assess and compare the characteristics and symptoms of patients with FD alone, with CNVS alone and those fulfilling both FD+CNVS criteria in a population of investigated dyspepsia. The retrospective study included 3,471 consecutive patients with investigated dyspepsia. Functional dyspepsia and CNVS were diagnosed according to Rome IV criteria. The severity of eight digestive symptoms during the 15 days preceding their appointment was assessed prospectively using a 5-point Likert scale. Quality of life (QoL) was quantified by the GastroIntestinal Quality of Life Index (GIQLI). Anxiety and depression were evaluated using the Hospital Anxiety and Depression scale (HADS). Sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI).

Results

Among the 2,317 patients kept for analysis, 651 had FD alone, 144 CNVS alone and 393 FD+CNVS overlap. 73.2% of patients with CNVS fulfilled the criteria for FD, whereas 37.6% of FD patients met the criteria for CNVS. Patients with FD+CNVS overlap had worse quality of life, higher depression levels, and worse sleep quality than both diagnoses alone (p < 0.05). All symptoms were at least as prevalent in patients with FD+CNVS overlap as in patients with FD alone, except early satiation.

Conclusion

Nausea and vomiting are frequently reported by patients investigated for dyspepsia. Nearly three-quarters of patients with CNVS fulfil the criteria for FD, whereas more than one-third of FD patients meet the criteria for CNVS. Patients exhibiting FD+CNVS overlap have more severe disease than those with FD or CNVS alone.

Introduction

Patients with cyclic vomiting syndrome (CVS) experience episodic severe attacks of nausea and vomiting, subsequently limiting food intake during attacks. When the attacks remit, however, patients are mostly asymptomatic. Among adults with CVS in remission, we aimed to examine differences between those with mild versus severe CVS on:
(1) eating-related quality of life (QOL) and
(2) dietary variety.

Aims & Methods

In a prospectively-maintained cohort of adults with CVS, we included all patients in remission (inter-attack phase at assessment time point) from June 2018 up to September 2022. We grouped patients into severe CVS group (4 attacks or more/year) and mild CVS group (less than 4 attacks/year). We assessed eating-related QOL on the Patient Assessment of Upper Gastrointestinal disorders- Quality of life (PAGI-QOL), using the diet and food habits subscale and diet variety on a Food Frequency Questionnaire (FFQ), capturing patient-reported outcomes (PROs) over the prior two weeks, as an approximation of long-term dietary intake.

Results

Of the 49 patients enrolled (30 [61%] females, mean age 33.5 +/- 12.6 years old), 32(65%) patients were included in the severe CVS group (>4 attacks/year), whereas 17 (35%) were enrolled in the mild CVS group. During enrollment, all patients were free of active CVS symptoms. The severe CVS group was significantly younger and experienced significantly more nausea (p<0.001), abdominal pain (p=0.003), early satiety (p=0.002), loss of appetite (p=0.012), discomfort (p=0.022) and bloating (p=0.007) compared to CVS patients with mild symptoms, during the inter-attack phase. Those with more severe CVS attacks had poorer QOL and significantly more concern about eating (p<0.001), avoidance (p=0.005) and restriction behavior, and less enjoyment of food (p=0.002), as displayed by PAGI-QoL. Despite symptom differences, there were no differences neither in food type frequencies, nor in the body mass index (BMI) between the two groups.

Conclusion

Despite the episodic nature of CVS, there are notable decreases in quality of life, specifically food-related QOL, in the inter-attack phase among those with a higher frequency of attacks. Such decrements in QOL and altered eating behaviors suggest that patients with more frequent CVS attacks may have significant inter-attack symptoms that would not typically fall into the typical CVS classification schema.

Disclosure

A.Trikola received the International training grant from American College of Gastroenterology.

Introduction

According to the ROME IV criteria, functional dyspepsia (FD) can be subdivided into PDS (postprandial distress syndrome) with meal-related symptoms such as early satiation and postprandial fullness and EPS (epigastric pain syndrome) with meal-unrelated complaints such as epigastric pain or burning. Nausea can also co-exist in FD but the literature is poor in reporting whether this symptom is mainly triggered by meal ingestion. A recent global epidemiology study of gastroparesis-like symptoms showed that the prevalence of nausea or vomiting, in combination with postprandial fullness or early satiation varies between continents.¹

Aims & Methods

This study aims to compare the difference in prevalence rates of nausea within each FD subgroup between western and eastern secondary and tertiary care centers. Adult patients with disorders of gut-brain interaction (DGBI) recruited in 9 western and 7 eastern secondary and tertiary care facilities between the ages of 18 and 70 years completed the Enhanced Asian Rome IV questionnaire (Asian European Gastrointestinal Symptoms cohort or AEGIS). The western centers were located in Belgium, Bulgaria, France, Israel, Italy (2x), Slovakia, Sweden and The United Kingdom while the eastern centers were located in Australia, China, Iran, Japan, Malaysia and Singapore (2x). FD patients were divided into PDS, EPS and PDS-EPS overlap (OVP) subgroups. Patients were furthermore classified as having nausea when this symptom was reported at least once per week. The questionnaire EARQ4 questionnaire was also used to address the relationship between nausea and food intake. Patients were asked how often they experienced nausea, whether nausea was triggered or worsened by meal intake, how often nausea occurred after a meal and if so, how soon after a meal nausea started. A comparison of the prevalence of nausea and meal-related nausea was made between eastern and western patients and among FD subgroups. Continuous variables are reported as median (IQR) and compared with a Kruskal-Wallis test. Categorical variables were compared using a Pearson Chi-square test.

Results

Of the 1074 DGBI patients that completed the survey, 483 were classified as having FD (59.4% PDS, 27.5% EPS, 13.0% PDS-EPS overlap). FD patients from eastern (N=202) and western sites (N=281) had a similar body mass index (22.5 (19.6-25.7) vs. 21.3 (19.7-25.4)kg/m²) and age (39.0 (29.0-55.0) vs. 38.0 (26.0-54.0) years). Eastern sites included significantly more female patients than western sites (43 % vs. 17.5%, p<0.001). PDS and EPS patients from eastern sites had significantly less nausea than PDS and EPS patients from western sites (17.9% vs. 46.3% and 6.8% vs. vs 40.5% respectively, both p<0.001). The majority of FD patients with nausea experienced meal-related nausea with no difference between eastern and western sites (63.9% vs. 73.7%). In PDS patients with nausea, nausea was significantly more triggered or worsened by a meal (72.4%) than in PDS-EPS overlap and EPS (48.6% and 35.3% respectively; p<0.001). All groups reported that meal-related nausea started mostly (> 85%) within 60 minutes after the meal.

Conclusion

In contrast to previous literature, we found that western PDS and EPS patients report nausea more frequently than eastern PDS and EPS patients. In both eastern and western patients nausea was mostly meal-related. Meal-related nausea is more common in PDS than in PDS-EPS overlap and EPS patients. Further research is needed to investigate the role of ethnic factors in the pathophysiology of nausea in functional dyspepsia.

References

Huang IH, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United Eur Gastroenterol J. 2022;10(8):888-897.

Disclosure

Bert Broeders received lecture fees from the Rome Foundation.