Bowel Movement Frequency Is Not Linked With Cognitive Function in Cirrhosis.
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ABSTRACT:
SUBMITTER: Duong N
PROVIDER: S-EPMC8589867 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Bowel Movement Frequency Is Not Linked With Cognitive Function in Cirrhosis.
Duong Nikki N Reuter Bradley B Saraireh Hamzeh H Nadhem Omar O Acharya Chathur C Fagan Andrew A Hassouneh Ramzi R Bajaj Jasmohan S JS
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20210513 4
The spectrum of hepatic encephalopathy (HE) ranges from overt HE (OHE) to cognitive impairment (ie, covert) HE (CHE).<sup>1</sup> The first-line therapy is lactulose, which is titrated to achieve ~2-3 soft/loose daily bowel movements (BM). This metric is considered dogma for practitioners despite erratic results, GI adverse events, and poor tolerance in Western countries.<sup>1</sup> There are logistic barriers for the widespread uptake of rifaximin, the second-line therapy. Moreover, although B ...[more]
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Project description:BACKGROUND:Carcinoid syndrome is associated with a reduced quality of life that can be attributed to symptoms such as diarrhea and fatigue as well as social and financial issues. This study was conducted to psychometrically assess meaningful change in bowel movement frequency among carcinoid syndrome patients using data from the TELESTAR clinical study. METHODS:An anchor-based approach for deriving meaningful change thresholds consisted of mapping change from baseline bowel movement frequency to other patient-reported assessments of change. These included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) Diarrhea Symptom responders, the EORTC Gastrointestinal NET questionnaire (GI.NET21) GI Symptom responders, and reported adequate relief at Week 12 (≥ 10-point score decrease from Day 1 to Week 12). Parameters included within-group mean change from baseline to Week 12, t-tests of the change (Wilcoxon rank sum for adequate relief), and effect size. RESULTS:There were 135 carcinoid syndrome patients with a mean baseline frequency of 5.7 bowel movements a day. A distribution-based method yielded meaningful change estimates of 0.62 bowel movements a day for overall frequency and 0.83 bowel movements a day at Week 12. Anchor-based analysis indicated a large effect size among patients who reported adequate relief at Week 12 (- 1.58; n = 18; P = 0.014), the QLQ-C30 Diarrhea domain responders (- 1.24; n = 40; P < 0.001), and the GI.NET21 GI Symptoms Domain responders (- 1.49; n = 25; P = 0.005). Exit interview data for meaningful change yielded effect size estimates of - 1.57 for overall change during the Double-blind Treatment Period and - 1.97 for change between Baseline and Week 12. CONCLUSIONS:Meaningful change derivation is critical to interpret patient outcomes for evaluating treatment efficacy. In this study, carcinoid syndrome patients experienced clinically meaningful reductions in bowel movement frequency of ≥30% over 12 weeks with telotristat ethyl treatment. TRIAL REGISTRATION:NCT01677910 .
| S-EPMC6815313 | biostudies-literature
Project description:Emerging evidence suggests a potential impact of gastrointestinal function on cardiometabolic risk. Abnormal bowel movements have been related to various cardiovascular risk factors such as dyslipidemia, hypertension, diabetes, and altered metabolism of bile acids and gut microbiota. However, little is known about whether bowel movement frequency affects risk of cardiovascular disease (CVD) and mortality. In the Nurses' Health Study, bowel movement frequency was self-reported in 1982 by 86,289 women free from CVD and cancer. During up to 30 years of follow-up, we documented 7,628 incident CVD cases and 21,084 deaths. After adjustment for dietary intake, lifestyle, medication use, and other risk factors, as compared with women with daily bowel movement, having bowel movements more than once daily was significantly associated with increased risk of CVD (hazard ratio [HR]: 1.13; 95% confidence interval [CI]: 1.05-1.21), total mortality (HR: 1.17; 95% CI: 1.12-1.22), and cardiovascular mortality (HR: 1.17; 95% CI: 1.07-1.28). With further adjustment for body mass index and diabetes status, the association with total mortality remained significant (HR: 1.10; 95% CI: 1.06-1.15), whereas the associations with incident CVD and cardiovascular mortality were no longer significant. Our results suggest increased bowel movement frequency is a potential risk factor for premature mortality.
| S-EPMC5011651 | biostudies-literature
Project description:Previous studies from case-control studies failed to draw reliable conclusions regarding the relationship between bowel movement frequency and the risk of colorectal cancer. To further examine this relationship, we collect the data from cohort studies that make a more accurate estimation. Several online data were searched from inception to February 29, 2020. Ten cohort studies involving 1,038,598 individuals were included in our study. The pooled results indicated that a bowel movement of less than once per day was not associated with the risk of colorectal cancer (relative risk (RR)= 1.00, 95% confidence interval (CI): 0.87-1.16, P = 0.950) compared with that of once per day. Compared with a bowel movement frequency of once per day, a bowel movement of more than once per day was also not related to elevated risk of colorectal cancer (RR = 1.04, 95% CI: 0.91-1.19, P = 0.570). The subgroup analyses indicated a low or high bowel movement frequency did not increase the risk of colon cancer (RR = 0.91, 95% CI: 0.80-1.03, P = 0.130). However, an increased frequency of bowel movements increased the risk of rectal cancer (RR = 1.34, 95% CI: 1.19-1.52, P < 0.001). The sensitivity analysis still supports the results. No significant publication bias existed. The data from cohort indicated that less bowel movement frequency was not associated with the risk of colorectal cancer. The frequency of bowel movement affects the risk of rectal cancer.
| S-EPMC7160378 | biostudies-literature
Project description:IntroductionThis study evaluated constipation, including reduced bowel movement frequency and difficult defecation, in patients with isolated rapid eye movement sleep behavior disorder (IRBD), which is prodromal Parkinson's disease (PD) or dementia with Lewy bodies (DLB) in middle-aged and older adults.MethodsWe used a validated Japanese version of the Constipation Assessment Scale (CAS-J) to evaluate bowel habits over 1 month in 117 men aged 50-86 years and 34 women aged 56-86 years with video-polysomnography-confirmed IRBD and 22 controls. Furthermore, we performed a longitudinal assessment of outcomes at follow-up visits.ResultsThe CAS-J score was higher in the 22 IRBD patients than in 22 age- and gender-matched paired controls. In 151 IRBD patients, the CAS-J score was higher for women than for men. At baseline, the CAS-J score was similar between patients who developed PD and DLB, but the three IRBD patients who developed multiple system atrophy had a low CAS-J score. Those with constipation (CAS-J score ≥ 2) converted to PD or DLB in a significantly shorter time duration (i.e., time frame for phenoconversion) than those with CAS-J score < 2 (log-rank test, p < 0.001). When adjusted for age and gender, Cox hazards analysis revealed that the CAS-J score significantly predicted phenoconversion to PD or DLB (hazard ratio: 5.9, 95 % confidence interval: 1.8-19.1, p = 0.003).ConclusionsConstipation, i.e., reduced bowel movement frequency and difficult defecation, was common in middle-aged and elderly patients with IRBD, and CAS-J score predicted phenoconversion to PD or DLB.
| S-EPMC11404085 | biostudies-literature
Project description:BackgroundTelotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods.MethodsFirst occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial.ResultsIn TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3-4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2-3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6-11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7-11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR.ConclusionThe time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency.Trial registrationClinicalTrials.gov Identifiers: NCT01677910, NCT02063659.
| S-EPMC7714089 | biostudies-literature
Project description:Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of gut microbial genera, blood metabolites, and variation in lifestyle factors across BMF categories. These differences relate to inflammation, heart health, liver function, and kidney function. Causal mediation analysis indicates that the association between lower BMF and reduced kidney function is partially mediated by the microbially derived toxin 3-indoxyl sulfate (3-IS). This result, in a generally healthy context, suggests that the accumulation of microbiota-derived toxins associated with abnormal BMF precede organ damage and may be drivers of chronic, aging-related diseases.
| S-EPMC11293344 | biostudies-literature
Project description:ObjectiveThe application of bowel movement frequency (BMF) in primary care is limited by the lack of solid evidence about the associations of BMF with health outcomes apart from Parkinson's disease and colorectal cancer. We examined the prospective associations of BMF with major vascular and non-vascular diseases outside the digestive system.DesignPopulation-based prospective cohort study.SettingThe China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants487 198 participants aged 30 to 79 years without cancer, heart disease or stroke at baseline were included and followed up for a median of 10 years. The usual BMF was self-reported once at baseline.Primary and secondary outcome measuresIncident events of predefined major vascular and non-vascular diseases.ResultsIn multivariable-adjusted analyses, participants having bowel movements 'more than once a day' had higher risks of ischaemic heart disease (IHD), heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus and chronic kidney disease (CKD) when compared with the reference group ('once a day'). The respective HRs (95% CIs) were 1.12 (1.09 to 1.16), 1.33 (1.22 to 1.46), 1.28 (1.22 to 1.36), 1.20 (1.15 to 1.26) and 1.15 (1.07 to 1.24). The lowest BMF ('less than three times a week') was also associated with higher risks of IHD, major coronary events, ischaemic stroke and CKD. The respective HRs were 1.07 (1.02 to 1.12), 1.22 (1.10 to 1.36), 1.11 (1.05 to 1.16) and 1.20 (1.07 to 1.35).ConclusionBMF was associated with future risks of multiple vascular and non-vascular diseases. The integration of BMF assessment and health counselling into primary care should be considered.
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Project description:Background & aimsPatients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD).MethodsWe performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups.ResultsSubjects on the GCD had more bowel movements per day (P = .04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype).ConclusionsGluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.govNCT01094041.
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Project description:Mild cognitive impairment (MCI), as a preclinical phase of dementia, provides an invaluable time window for intervention. Besides several proposed modifiable risk factors, the associations of MCI with dietary habits and bowel movement are not well clarified. We thus conducted a cross-sectional study of community-living Singapore elderly and focused on the relationship of clinically diagnosed MCI with dietary habits and bowel movement frequencies. The multiple logistic regression results showed that frequent (≥4 days per week) fruit consumption (P = 0.004), active (≥4 days per week) bowel movement within 10 minutes (P = 0.027), and years of schooling were negatively associated with MCI occurrence. In contrast, medical comorbidities including hypertension, stroke, and cataract/glaucoma were found to be risk factors. Furthermore, a Bayesian network model of causal inference detected five hypothesized causal-association paths leading to MCI, namely bowel movement, stroke, years of schooling via fruit consumption, hypertension via stroke and hypertension via cataract/glaucoma. The combination of the two direct factors (inactive bowel movement and stroke) reached a maximum conditional probability of 60.00% for MCI occurrence. Taken together, this study was the first to link bowel movement with MCI occurrence. In addition, it suggested five modifiable hypothesized causal-association paths to MCI.
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Project description:Regulation of gene transcription is a complex process controlled by many factors, including the conformation of chromatin in the nucleus. Insights into chromatin conformation on both local and global scales can be provided by the Hi-C (high-throughput chromosomes conformation capture) method. One of the drawbacks of Hi-C analysis and interpretation is the presence of systematic biases, such as different accessibility to enzymes, amplification, and mappability of DNA regions, which all result in different visibility of the regions. Iterative correction (IC) is one of the most popular techniques developed for the elimination of these systematic biases. IC is based on the assumption that all chromatin regions have an equal number of observed contacts in Hi-C. In other words, the IC procedure is equalizing the experimental visibility approximated by the cumulative contact frequency (CCF) for all genomic regions. However, the differences in experimental visibility might be explained by biological factors such as chromatin openness, which is characteristic of distinct chromatin states. Here we show that CCF is positively correlated with active transcription. It is associated with compartment organization, since compartment A demonstrates higher CCF and gene expression levels than compartment B. Notably, this observation holds for a wide range of species, including human, mouse, and Drosophila. Moreover, we track the CCF state for syntenic blocks between human and mouse and conclude that active state assessed by CCF is an intrinsic property of the DNA region, which is independent of local genomic and epigenomic context. Our findings establish a missing link between Hi-C normalization procedures removing CCF from the data and poorly investigated and possibly relevant biological factors contributing to CCF.
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