Citations

Abstract Study Objectives Narcolepsy is a chronic condition affecting the sleep/wake cycle that is challenging to diagnose. Epidemiological data from large US-focused studies remain limited, with no validated claims-based case selection definitions for narcolepsy. We estimated the prevalence/incidence of diagnosed narcolepsy (type 1 [NT1], type 2 [NT2], overall) in an insured US population using validated, claims-based narcolepsy case definitions. Materials and Methods This observational study used HealthVerity administrative claims-linked electronic medical records to develop case definitions identifying individuals with NT1, NT2, and overall narcolepsy from diagnosis, medication, and procedure codes. Claims-based case definition performance (NT1, NT2, overall narcolepsy) was assessed using positive predictive values (PPVs). Prevalence (per 100 000 persons, on December 31, 2023) and annual incidence (per 100 000 person-years [PY], 2020 − 2023) were calculated/adjusted using PPVs for each case definition. Results Unadjusted point prevalence among individuals with ≥12 months of continuous enrollment were 15.5/100 000 (NT1), 51.1/100 000 (NT2), and 67.0/100 000 (overall narcolepsy). Unadjusted incidence rates were stable from 2020 − 2023 for NT1 (range, 2.0 − 2.3/100 000 PY) but declined across years for NT2 (9.1 − 7.6/100 000 PY) and overall narcolepsy (11.3 − 9.6/100 000 PY). PPVs (95% confidence interval) of NT1, NT2, and overall narcolepsy were 0.81 (0.72 − 0.88), 0.84 (0.75 − 0.91), and 0.80 (0.71 − 0.87), contributing to epidemiologic estimates being reduced by ~20% after PPV adjustment. Prevalence and incidence were higher in females than males. Individuals with NT1 were ~ 4 years younger versus NT2. Conclusions Validated definitions for narcolepsy can reduce potential misclassification. Our findings highlight a relatively low NT1 prevalence in the US. In contrast, NT2 prevalence estimates were > 3 times higher than NT1.

ABSTRACT Background Patients with gastric dysmotility exhibit abnormal transit and reduced contractility, for which quantification is limited with current methodologies. The Atmo Capsule is a wireless motility capsule that measures regional gastrointestinal transit. We tested its technical capabilities to evaluate gastric contractility by detecting changes in capsule acceleration during transit. Methods Data from 91 healthy controls and 182 patients with suspected dysmotility who ingested the Atmo Capsule following a standardized protocol were included. Gastric emptying times (GET) ≥ 5 h were considered delayed. Contraction frequencies (cycles per minute [cpm]) and amplitudes (as arbitrary units [au]) were identified following Fast Fourier Transformation of accelerometer data using 5‐min windows and were assessed in 30‐min windows post‐ingestion (early gastric phase) and before gastric emptying (late gastric phase). Data were compared via ANOVA, using Bonferroni corrections, between healthy controls, patients with normal gastric emptying, and patients with delayed gastric emptying. Key Results Gastric emptying was delayed in 53/182 (29%) patients. Three cpm contraction frequencies were identified across both gastric phases in controls and patients. Contraction amplitudes did not differ between groups in the early gastric phase. In the late phase, mean amplitudes were lower in patients with delayed gastric emptying (6.4 au) compared with subjects with normal gastric emptying (controls, 9.7 au, p < 0.0001; patients, 8.6 au, p < 0.0001). Conclusions & Inference The Atmo Capsule enables precise quantification of gastric contraction profiles, permitting differentiation of normal from pathological motor patterns. Findings of this technical assessment support its potential for evaluating gastric physiology and detecting pathophysiological patterns of gastric dysmotility.

ABSTRACTBackground and AimsBowel diaries are used to characterize the severity of fecal incontinence (FI) but have not been adequately validated for this purpose. Our aims were to validate a new bowel diary and to compare the characteristics of FI as assessed with a bowel diary and a validated questionnaire.MethodsIn this four‐center prospective study, patients with a history of FI and asymptomatic controls completed a 28‐day bowel diary and validated questionnaires to evaluate bowel habits and FI, quality of life related to FI (FIQoL), and PROMIS scales for anxiety, depression, and self‐efficacy.ResultsAmong 59 participants with FI and 29 asymptomatic controls, the bowel diary was 97% sensitive and 93% specific for distinguishing between FI participants and controls. Over 28 days, FI participants experienced an average [SD] of 31.1 [50.7] FI episodes, consisting of staining (12.6 [14.9]), some stool (12.5 [20.3]), or a full bowel movement (4.4 [8.5]). Correlations between the questionnaire and diary were statistically significant for frequency (Spearman ρ = 0.5, p < 0.001), amount (ρ = 0.4, p < 0.001), and awareness of FI (ρ = 0.3, p = 0.04). In 71% of participants, there was agreement between the consistency of FI as reported in the questionnaire and the diary. More severe FI was associated with poorer FIQoL (p = 0.002). Anxiety, depression, and self‐efficacy scores did not significantly affect the agreement between the frequency of FI reported in the diary and questionnaire.ConclusionThis bowel diary effectively discriminates between healthy participants and those with FI. There is significant, albeit modest, agreement between the characteristics of FI recorded with a diary and a questionnaire.

ABSTRACTIntroductionStudies demonstrate an overlap of constipation with gastroparesis and functional dyspepsia, but the impact of treatments that target constipation on improving upper gastrointestinal (UGI) symptoms is unexplored. We quantified the effects of constipation medication therapies on UGI and constipation symptom severity in subjects presenting with symptoms of gastroparesis.MethodsFifty‐six subjects with symptoms of gastroparesis underwent concurrent wireless motility capsule and gastric emptying scintigraphy and were recommended to receive either a new medication therapy for constipation or a change in constipation therapy based on investigator interpretation of test results. Gastroparesis Cardinal Symptom Index (GCSI), upper abdominal pain, and constipation scores were compared between baseline and 6 months. Data were compared between delayed or non‐delayed gastric emptying and the presence or absence of slow colonic transit.Key ResultsSubjects with slow colonic transit had improvements in GCSI (p = 0.007) and constipation scores (p = 0.004) after treatment with a new or changed constipation medication, with the delayed emptying subgroup driving GCSI improvements (p = 0.004). Reductions in nausea/vomiting (p = 0.02) and early satiety/fullness subscores (p = 0.002) with trends to improved bloating/distention subscores (p = 0.06) were observed in this subgroup, but upper abdominal pain was unchanged. Subjects with normal colonic transit showed no improvement in GCSI scores regardless of gastric emptying status (p > 0.05).Conclusions and InferencesIdentifying and treating delayed colonic transit in gastroparetic (delayed gastric emptying) subjects improves global UGI symptoms as well as selected individual symptoms. Evaluation of whole gut motility as well as recognizing and managing extragastric delay may promote improved outcomes in these patients.Trial RegistrationClinicalTrials.gov: NCT02022826

INTRODUCTION: Pharmacologic therapies for symptoms of gastroparesis (GP) have limited efficacy, and it is difficult to predict which patients will respond. In this study, we implemented a machine learning model to predict the response to prokinetics and/or neuromodulators in patients with GP-like symptoms. METHODS: Subjects with suspected GP underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their GP Cardinal Symptom Index at 6 months decreased by ≥1 from baseline. A machine learning model was trained using lasso regression, ridge regression, or random forest. Five-fold cross-validation was used to train the models, and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set. RESULTS: Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were nonresponders. A ridge regression model with the variables, such as body mass index, infectious prodrome, delayed gastric emptying scintigraphy, no diabetes, had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with gastric emptying time, duodenal motility index, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). DISCUSSION: This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with GP-like symptoms.

AbstractBackgroundProkinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high‐quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects.PurposeHere, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications.

Constipation is a common problem, affects 15% of the population, and is often self-diagnosed and self-managed. Over the past 3 decades, there have been significant advances in our understanding and management of chronic constipation, with the emerging recognition that occasional constipation (OC) is another subtype that falls outside current classifications. The purpose of this review was to describe the process of developing and proposing a new definition for OC based on expert consensus and taking into consideration the multifactorial nature of the problem such as alterations in bowel habit that include stool frequency and difficulty with stool passage, perception of the sufferer, duration of symptoms, and potential responsiveness to treatment. Leading gastroenterologists from 5 countries met virtually on multiple occasions through an online digital platform to discuss the problem of OC and recommended a practical, user-friendly definition: “OC can be defined as intermittent or occasional symptomatic alteration(s) in bowel habit. This includes a bothersome reduction in the frequency of bowel movements and/or difficulty with passage of stools but without alarming features. Bowel symptoms may last for a few days or a few weeks, and episodes may require modification of lifestyle, dietary habits and/or use of over-the-counter laxatives or bulking agents to restore a satisfactory bowel habit.” Prospective studies are required to validate this definition and determine OC prevalence in the community. This review highlights current knowledge gaps and could provide impetus for future research to facilitate an improved understanding of OC and development of evidence-based management guidelines.