RESUMEN
BACKGROUND & AIMS: The estimated prevalence of irritable bowel syndrome (IBS) using Rome IV criteria in the United States (US) ranges from 4.7% to 5.3%, although these estimates arise from studies with relatively small sample sizes. This study assessed the prevalence of IBS and its associated burden of illness using a nationally representative data set with nearly 89,000 people in the US. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults aged ≥18 years old as a "national health survey." We recruited a representative sample of people in the US to complete the survey, which included the Rome IV IBS questionnaire, National Institutes of Health Patient-Reported Outcome Measurement Information System (PROMIS) gastrointestinal scales, and questions on health care-seeking behavior. RESULTS: Overall, 88,607 people completed the survey, of whom 5414 (6.1%) met Rome IV IBS criteria: mixed IBS (n = 1838 [33.9%]), constipation-predominant IBS (n = 1819 [33.6%]), diarrhea-predominant IBS (n = 1521 [28.1%]), and unsubtyped IBS (n = 236 [4.4%]). Women had higher odds for IBS compared with men, whereas racial/ethnic minorities had lower odds for IBS vs non-Hispanic Whites. Across the 3 main subtypes, 68.2% to 73.2% of people reported ever seeking care for their IBS symptoms, whereas 53.8% to 58.9% did so in the past 12 months. CONCLUSIONS: In this nationwide US survey, we found that Rome IV IBS is slightly more prevalent (6.1%) vs prior estimates (4.7%-5.3%). Additional research is needed to determine whether this higher prevalence is in part due to the coronavirus disease 2019 pandemic during which this study was conducted.
Asunto(s)
Síndrome del Colon Irritable , Estados Unidos/epidemiología , Adulto , Masculino , Humanos , Femenino , Adolescente , Estudios Transversales , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/epidemiología , Prevalencia , Ciudad de Roma , Costo de EnfermedadRESUMEN
INTRODUCTION: Chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) are disorders that negatively affect quality of life. We sought to assess the prevalence, symptom severity, and medication use among people with Rome IV CIC, OIC, and opioid-exacerbated constipation (OEC) using a nationally representative data set with nearly 89,000 people in the United States. METHODS: From May 3, 2020, to June 24, 2020, we recruited a representative sample of people in the United States ≥ 18 years to complete an online national health survey. The survey guided participants through the Rome IV CIC and OIC questionnaires, Patient-Reported Outcome Measurement Information System gastrointestinal scales (percentile 0-100; higher = more severe), and medication questions. Individuals with OEC were identified by asking those with OIC whether they experienced constipation before starting an opioid and whether their symptoms worsened afterward. RESULTS: Among the 88,607 participants, 5,334 (6.0%) had Rome IV CIC, and 1,548 (1.7%) and 335 (0.4%) had Rome IV OIC and OEC, respectively. When compared with people with CIC (Patient-Reported Outcome Measurement Information System score, 53.9 ± 26.5; reference), those with OIC (62.7 ± 28.0; adjusted P < 0.001) and OEC (61.1 ± 25.8, adjusted P = 0.048) had more severe constipation symptoms. People with OIC (odds ratio 2.72, 95% confidence interval 2.04-3.62) and OEC (odds ratio 3.52, 95% confidence interval 2.22-5.59) were also more likely to be taking a prescription medication for their constipation vs those with CIC. DISCUSSION: In this nationwide US survey, we found that Rome IV CIC is common (6.0%) while Rome IV OIC (1.7%) and OEC (0.4%) are less prevalent. Individuals with OIC and OEC have a higher burden of illness with respect to symptom severity and prescription constipation medication use.
Asunto(s)
Estreñimiento , Estreñimiento Inducido por Opioides , Humanos , Estados Unidos/epidemiología , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Estreñimiento/epidemiología , Analgésicos Opioides/efectos adversos , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Calidad de Vida , Prevalencia , Ciudad de Roma , Costo de EnfermedadRESUMEN
Linaclotide, a potent guanylate cyclase C agonist, is a therapeutic peptide approved in the United States for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. We present for the first time the metabolism, degradation, and disposition of linaclotide in animals and humans. We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide. Systemic exposure to these active peptides is low in rats and humans, and the low systemic and portal vein concentrations of linaclotide and MM-419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration. Linaclotide is stable in the acidic environment of the stomach and is converted to MM-419447 in the small intestine. The disulfide bonds of both peptides are reduced in the small intestine, where they are subsequently proteolyzed and degraded. After oral administration of linaclotide, <1% of the dose was excreted as active peptide in rat feces and a mean of 3-5% in human feces; in both cases MM-419447 was the predominant peptide recovered. MM-419447 exhibits high-affinity binding in vitro to T84 cells, resulting in a significant, concentration-dependent accumulation of intracellular cyclic guanosine-3',5'-monophosphate (cGMP). In rat models of gastrointestinal function, orally dosed MM-419447 significantly increased fluid secretion into small intestinal loops, increased intraluminal cGMP, and caused a dose-dependent acceleration in gastrointestinal transit. These results demonstrate the importance of the active metabolite in contributing to linaclotide's pharmacology.