Instruções em bulas destinadas ao uso de medicamentos para dispepsia e constipação durante a lactação / Instructions in package inserts intended for the use of medicines for dyspepsia and constipation during lactation / Instrucciones en prospectos destinados al uso de medicamentos para la dispepsia y el estreñimiento durante la lactancia

Introdução: A segurança e eficácia do uso de medicamentos durante a lactação são preocupações para mães e profissionais de saúde. Esta pesquisa analisa as orientações das bulas de medicamentos comumente prescritos para dispepsia e constipação, que visa fornecer informações essenciais para orientar as decisões terapêuticas durante esse período crucial da maternidade. Objetivos: Analisar as informações das bulas sobre contraindicações de medicamentos para dispepsia e constipação durante a amamentação, verificando se estão de acordo com as evidências científicas. Métodos: Medicamentos para dispepsia e constipação foram selecionados de acordo com a classificação da Anatomical Therapeutic Chemical (ATC) e o registro ativo no Brasil. A presença de contraindicações para o uso de medicamentos nas bulas do profissional de saúde e do paciente foi comparada com as informações contidas no manual técnico do Ministério da Saúde, Medicamentos e Leite Materno, LactMed, UptoDate, Micromedex, Documento Científico da Sociedade Brasileira de Pediatria e Reprotox. Resultados: Nenhuma informação sobre o uso durante a amamentação foi encontrada em 20,0 e 24,3% das bulas para dispepsia e constipação, respectivamente. A concordância entre as bulas dos medicamentos para dispepsia e as fontes consultadas foi baixa (27,2% das bulas contraindicavam o medicamento na lactação, enquanto nas fontes o percentual de contraindicação variou de 0 a 8,3%). Com relação a medicamentos para constipação, 26,3% das bulas os contraindicavam, enquanto nas fontes o percentual variou de 0 a 4,8%. Conclusões: O estudo mostrou que pelo menos duas em cada dez bulas para dispepsia e constipação não fornecem informações adequadas sobre o uso desses medicamentos em lactentes, e também que houve baixa concordância entre o texto das bulas e as fontes de referência quanto à compatibilidade do medicamento com a amamentação.

Introduction: The safety and effectiveness of medication use during lactation are concerns for mothers and healthcare professionals. This research analyzes the instructions on the leaflets of medications commonly prescribed for dyspepsia and constipation, which aims to provide essential information to guide therapeutic decisions during this crucial period of motherhood. Objectives: To analyze the information in package inserts about contraindications of drugs for dyspepsia and constipation during breastfeeding, verifying whether these are consistent with scientific evidence. Methods: Drugs for dyspepsia and constipation were selected according to the Anatomical Therapeutic Chemical (ATC) classification and active registry in Brazil. The presence of contraindications for the use of medications in the health professional's and patient's package inserts was compared with the information in the technical manual of the Ministry of Health, Medications and Mothers' Milk, LactMed, UptoDate, Micromedex, Documento Científico da Sociedade Brasileira de Pediatria and Reprotox. Results: No information about use during breastfeeding was found in 20.0 and 24.3% of leaflets for dyspepsia and constipation, respectively. The agreement between the leaflets of medications for dyspepsia and the sources consulted was low (27.2% of the leaflets contraindicated the medication during lactation, while in the sources the percentage of contraindication varied from 0 to 8.3%). In relation to medicines for constipation, 26.3% of the leaflets contraindicated them, while in the sources the percentage ranged from 0 to 4.8%. Conclusions: The study pointed out that at least two out of every ten package inserts for dyspepsia and constipation do not provide adequate information on the use of these drugs in infants, and also shows low concordance between the text of the package inserts and the reference sources regarding compatibility of the drug with breastfeeding.

Introducción: La seguridad y eficacia del uso de medicamentos durante la lactancia son preocupaciones para las madres y los profesionales de la salud. Esta investigación analiza las instrucciones contenidas en los prospectos de medicamentos comúnmente recetados para la dispepsia y el estreñimiento, con el objetivo de proporcionar información esencial para guiar las decisiones terapéuticas durante este período crucial de la maternidad. Objetivos: Analizar la información contenida en los prospectos sobre las contraindicaciones de los medicamentos para la dispepsia y el estreñimiento durante la lactancia, verificando si estas son consistentes con la evidencia científica. Métodos: Se seleccionaron medicamentos para la dispepsia y el estreñimiento de acuerdo con la clasificación ATC y el registro activo en Brasil. Se comparó la presencia de contraindicaciones para el uso de medicamentos en los prospectos del profesional de la salud y del paciente con la información del manual técnico del Ministerio de Salud, Medicamentos y Leche Materna, LactMed, UptoDate, Micromedex, Documento Científico da Sociedade Brasileira de Pediatria y Reprotox. Resultados: No se encontró información sobre su uso durante la lactancia en el 20% y el 24,3% de los prospectos para dispepsia y estreñimiento, respectivamente. La concordancia entre los prospectos de los medicamentos para la dispepsia y las fuentes consultadas fue baja (el 27,2% de los prospectos contraindicaba el medicamento durante la lactancia, mientras que en las fuentes el porcentaje de contraindicación variaba del 0% al 8,3%). Con relación a los medicamentos para el estreñimiento, el 26,3% de los prospectos los contraindicaba, mientras que en las fuentes el porcentaje osciló entre el 0% y el 4,8%. Conclusiones: El estudio señaló que al menos dos de cada diez prospectos para dispepsia y estreñimiento no brindan información adecuada sobre el uso de estos medicamentos en lactantes, y también muestra la baja concordancia entre el texto de los prospectos y la referencia. fuentes sobre la compatibilidad del fármaco con la lactancia.

Association between bowel movement disorders and depressive symptoms: a cross-sectional study.

Objectives: This study aimed to explore the association between bowel movement disorders and depression in adults. Method: A cross-sectional study was conducted using data from the National Health and Nutritional Examination Survey (NHANES), 2005-2010. Depression, constipation, diarrhea, and fecal incontinence were self-reported via questionnaires. Weighted logistic regression and subgroup analyses were performed to explore the association between bowel movement disorders and the risk of depression. Restricted cubic spline (RCS) was also conducted to investigate the association between bowel movements disorder and depression. Results: A total of 13,820 participants were collected. Compared to the participants with normal bowel movements, the full-adjusted depression model ORs for constipation and diarrhea were 2.28 (95%CI,1.78-2.92), 1.75 (95%CI,1.31-2.31), respectively. Any kind of bowel leakage were associated with depression. The RCS showed the possible nonlinear association between bowel movement frequency/stool shape and depression. Conclusions: Constipation, diarrhea, and bowel leakage are associated with an increased risk of depression.

What Happens Post-Malone? An Investigation of Long-Term Postoperative Management of Antegrade Continence Enemas.

BACKGROUND: An option for medically refractory fecal incontinence and/or constipation is the antegrade continence enema (ACE). We investigated ACE usage and its perceptions, including whether patients were able to discontinue use of the appendicostomy/cecostomy tube. METHODS: Patients who underwent appendicostomy creation or cecostomy tube placement at two institutions between 2012 and 2021 were reviewed. Patients or parents/guardians were contacted for completion of a survey. Summary statistics for clinical data were tabulated and associations were evaluated with chi-square analysis. RESULTS: A total of 165 patients were included, including 92 (55.8%) males. Eighty-two (49.7%) surveys were completed. Most patients (51.5%) presented with fecal incontinence; 38 (23.3%) presented with constipation. More patients had a primary underlying diagnosis of anorectal malformation (39.4%), followed by functional constipation (21.2%), Hirschsprung disease (18.8%), and spinal malformation (17.6%). Thirty-six (21.8%) patients discontinued flushes by time of contact, with switch to laxatives being the most common reason (19%), followed by appendicostomy stricture/obstruction/closure (17%), switch to ileostomy/colostomy (17%), and patient preference (14%). There was no difference in patients' ability to stop using flushes based on underlying diagnosis (p = 0.31). The majority (84.1%) of respondents were "very likely" to recommend antegrade enemas to other children with similar diagnosis and 76.8% reported being "very satisfied" that the operation was done. CONCLUSIONS: There remains a high degree of satisfaction with antegrade continence enemas for children with constipation and fecal incontinence; some children may be able to stop using antegrade enemas with varied mechanisms including patient/family weaning versus with assistance and laxative trials. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Economic Impact of Daily Bowel Management Regimens.

BACKGROUND: Chronic constipation and fecal incontinence are devastating problems for patients with anorectal malformations, Hirschsprung's disease, idiopathic constipation, and spina bifida/spinal cord injuries. Finding the proper regimen allows these patients to be out of diapers and free of stool accidents. A typical bowel management regimen consists of daily laxatives or enemas; because these products are sold over the counter, insurance companies do not cover them. This study reviews the cost of bowel regimens and analyzes their economic impact on the families we treat. METHODS: A retrospective review of patients undergoing bowel management between January 2016 and September 2023 was done. The mean annual income of families was calculated using their zip codes. RESULTS: Upon review, 430 patients met inclusion criteria; 167 were on laxatives, and 263 were using enemas. There was significant variation in the cost of medications based on the distributors they were bought from and the dose of the medication in their regimen. The cost of laxatives ranged from $15.70 to $2938.10 annually. The cost of enemas containing glycerin ranged from $29.20 to $4380.00 annually. In comparison, diapers/incontinence briefs ranged from $131.40 to $4343.50 annually. The median annual income of patients across 41 states ranged from $32,192 to $225,119. CONCLUSIONS: Our findings emphasize the importance of proper counseling families regarding medication costs in the market, intending to promote long-term treatment adherence. They also serve as a data source to advocate for improved insurance coverage of the medications required to manage these chronic conditions successfully. LEVEL OF EVIDENCE: IV.

Pelvic Floor Ultrasound Findings and Symptoms of Pelvic Floor Dysfunction During Pregnancy.

INTRODUCTION AND HYPOTHESIS: Pregnancy and childbirth predispose to pelvic floor dysfunction (PFD), coinciding with functional and anatomical changes in the pelvic floor. To some extent, these can be assessed by transperineal ultrasound (TPUS), yet the correlation between ultrasound findings and symptoms has not been well elucidated. We hypothesised that pregnant women with PFD would show different findings at TPUS. METHODS: This is a planned secondary analysis of a prospective cohort study. Pregnant women were asked to fill out standardised questionnaires on PFD and undergo TPUS at 12-14 weeks and 28-32 weeks of gestation. We compared bladder neck descent, urethral rotation, retrovesical angle, pelvic organ descent, genital hiatus dimensions and the presence of anal sphincter defects between women with and those without PFD using t test and Fisher's exact test. Linear mixed-effects models were used to assess the correlation between TPUS findings and PFD severity. As this is a secondary subgroup analysis of participants who underwent TPUS, no sample size was determined upfront. RESULTS: At Valsalva, women with urinary incontinence had more pronounced bladder neck descent (p = 0.02) and urethral rotation (p < 0.01), as well as wider retrovesical angles (p = 0.04) and larger genital hiatus areas (p < 0.01). After controlling for age, BMI and parity, the retrovesical angle was the only persistent predictor of urinary incontinence. No correlation was observed between any TPUS marker and symptoms of either prolapse or anorectal dysfunction. CONCLUSIONS: In pregnant women, symptoms of urinary incontinence, but not of prolapse and anorectal dysfunction, are associated with differences in pelvic floor anatomy at TPUS.

Inadequate management of opioid-induced constipation in European cancer pain patients: results of a real-world, multicentre, observational study ("E-StOIC").

PURPOSE: The objectives of the study were to determine the prevalence of (uncontrolled) OIC, relevant medications / interventions employed by healthcare professionals, and the additional strategies utilised by patients, amongst European patients with cancer pain. METHODS: This study was a prospective observational study conducted at 24 research sites in ten European countries. Cancer patients receiving opioid analgesics for at least a week were recruited, and asked to complete a questionnaire including background information, single question (Are you constipated?), Rome IV diagnostic criteria for OIC, Bowel Function Index (BFI), and Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL). Participants were characterised as having / not having OIC on the basis of the Rome IV diagnostic criteria. RESULTS: 1200 participants completed the study. 59.5% met the Rome IV diagnostic criteria for OIC: only 61.5% that met these criteria self-reported constipation. 72% participants were prescribed a regular conventional laxative / peripherally acting mu-opioid receptor antagonist (PAMORA). However, only 66% took their prescribed laxatives every day. Many participants had utilised other strategies / interventions to manage their OIC. Furthermore, 27% had needed to use suppositories, 26.5% had needed to use an enema, and 8% had had a manual evacuation. The use of PAMORAs, and other novel effective medications, was relatively uncommon. CONCLUSION: The results of this study suggest that management in Europe is often inadequate, and this undoubtedly relates to a combination of inadequate assessment, inappropriate treatment, and inadequate reassessment.

Synbiotic supplementation may globally improve non-motor symptoms in patients with stable Parkinson's disease: results from an open label single-arm study.

Gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in people with Parkinson's Disease (PD). Probiotics and prebiotics are emerging as a potential therapeutic approach for PD patients. The aim of this paper was to assess the neurological and gastroenterological effects in PD patients with constipation after the administration of a synbiotic product, with a focus on behavioral and cognitive symptoms. We enrolled patients with stable PD who met diagnostic criteria for functional constipation and/or irritable bowel syndrome with constipation according to Rome IV Criteria. Patients received a synbiotic treatment (Enterolactis Duo, containing the probiotic strain Lacticaseibacillus paracasei DG and the prebiotic fiber inulin) for 12 weeks. A neurological and a gastroenterological evaluation were collected before and after the treatment. In addition, 16S rRNA gene profiling and short chain fatty acid quantification were performed to characterize the microbial ecosystem of fecal samples collected before (n = 22) and after (n = 9) the synbiotic administration. 30 patients were consecutively enrolled. After treatment, patients performed better in MDS-UPDRS part 1 (p = 0.000), SCOPA-AUT (p = 0.001), TAS-20 (p = 0.014), HAM-D (p = 0.026), DIFt (p = 0.003), PAS-A (p = 0.048). Gastroenterological evaluations showed improvements in PAC-SYM score (p < 0.001), number of complete bowel movement (p < 0.001) and BSFS (p < 0.001). After the synbiotic administration, we observed a significant increase in the abundance of the order Oscillospirales, as well as the Oscillospiraceae family and the species Faecalibacterium prausnitzii within this order in fecal samples. Synbiotic treatment demonstrates potential efficacy in ameliorating non-motor features in PD patients.

Integration of UPLC-MS/MS-based metabolomics and desorption electrospray ionization-mass spectrometry imaging reveals that Shouhui Tongbian Capsule alleviates slow transit constipation by regulating bile acid metabolism.

Slow transit constipation (STC) is a common intestinal disorder. Some studies reported that Shouhui Tongbian Capsule (SHTB) can effectively mitigate STC symptoms. A detailed understanding of the changes in the endogenous metabolite profile of rats is crucial for a more accurate comprehension of the molecular pathological characteristics of SHTB in treating STC. In the present study, a method integrating metabolomics based on Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI) was proposed to investigate serum, feces and colon tissue metabolic alterations of STC rats induced by diphenoxylate and the effect of SHTB treatment on metabolism. Then, Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis for verifying the potential mechanism of SHTB in treating STC. As a result, we first indicated that SHTB significantly improved intestinal peristalsis and low fecal water content in STC rats. Furthermore, after treatment with SHTB, the thickness of muscle layers was increased, demonstrated SHTB's effectiveness in reducing intestinal injury in STC rats. Besides, bile acid (BA) metabolomics based on UPLC-MS/MS revealed significant increase in serum levels of Cholic acid (CA), Deoxycholic acid (DCA), Chenodeoxycholic acid (CDCA), Ursodeoxycholic acid (UDCA), and Glycolithocholic acid (GLCA), whereas the contents of CA and DCA in feces were significantly decreased in STC rats. Nonetheless, they returned to the control levels after the SHTB administration. ELISA results showed that SHTB significantly hindered the excessive reabsorption of BAs by inhibiting apical sodium-dependent bile acid transporter (ASBT), organic solute transporter alpha (OSTα) and organic solute transporter beta (OSTß) in the ileum tissue of STC rats. Furthermore, the DESI-MSI analysis revealed that SHTB remarkably enhanced DCA in the colon tissue of STC rats. The WB results indicated that SHTB reinstated Takeda G-protein-coupled receptor 5 (TGR5) expression, a receptor for BAs and a key regulator of colonic motility. Consequently, DCA exerted its effects on TGR5, leading to the promotion of colonic motility. This study provided more comprehensive and detailed information about the BA metabolomics in the serum, feces and colon of STC rats. These findings highlighted the promising potential of metabolomics based on UPLC-MS/MS and DESI-MSI method for application in the study of STC diseases.

Laxative and purgative actions of phytoactive compounds from beetroot juice against loperamide-induced constipation, oxidative stress, and inflammation in rats.

BACKGROUND: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the phytochemical composition of beetroot juice (BJ) and its laxative potential in an experimental model of constipation and colonic dysmotility induced by loperamide (LOP) in Wistar rats. METHODS: Animals were concurrently pretreated with LOP (3 mg/kg, b.w., i.p.) and BJ (5 and 10 mL/kg, b.w., p.o.), or yohimbine (2 mg/kg, b.w., i.p.), during 1 week. The laxative activity was determined based on the weight, frequency, and water content of the feces matter. The gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods. KEY RESULTS: The in vivo study revealed that LOP induced a significant inhibition of gastrointestinal motility, negative consequences on defecation parameters, oxidative stress, and colonic mucosa lesions. Conversely, administration of BJ reestablished these parameters and restored colonic oxidative balance. Importantly, BJ treatment protected against LOP-induced inflammatory markers (pro-inflammatory cytokines and WBC) and the increase in intracellular mediators such as hydrogen peroxide, free iron, and calcium levels. CONCLUSIONS & INFERENCES: This study demonstrated that the bioactive compounds in BJ provided an anti-constipation effect by modulating intestinal motility and regulating oxidative stress and inflammation induced by LOP intoxication.

Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO). METHODS: This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 µg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test. KEY RESULTS: The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal. CONCLUSION & INFERENCES: The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

Antegrade Continence Enemas for Pediatric Functional Constipation: A Systematic Review.

BACKGROUND: Despite optimal conservative and medical treatment, some children with functional constipation (FC) continue to experience symptoms. Antegrade continence enema (ACE) surgery has been suggested as the primary surgical option after less invasive pharmacological and non-pharmacological interventions have not been effective. The purpose of this systematic review was to assess the outcomes of ACE for children with FC. METHODS: Electronic databases were searched (inception-March 2024) for studies evaluating ACE surgery performed in children with FC. The primary outcome was treatment success (as defined in the original manuscript), including at least defecation frequency and/or fecal incontinence frequency. Secondary outcomes were cessation of ACE, complications, health-related quality of life (HRQoL) and patient/parent satisfaction. Quality of evidence was evaluated based on tools from the New-Ottawa Scale and Joanna Bridge Institute. RESULTS: Thirteen studies were included, representing 477 children with FC treated with either an appendicostomy or a cecostomy. Reported treatment success rates varied widely, ranging from 32% to 100%. ACE treatment was stopped in 15% due to treatment success and in 8% due to treatment failure, leading to more invasive surgery. Complication rates ranged from 6% to 100%, requiring surgical intervention in 0% to 34%. An improvement in HRQoL following ACE treatment was reported in all three studies that assessed HRQoL. The two studies assessing patient/parent satisfaction, reported high satisfaction rates. CONCLUSION: Reported treatment success and complication rates following ACE surgery for children with FC vary widely. This systematic review highlights the necessity for uniform definitions and treatment guidelines for ACE surgery in children with FC. LEVEL OF EVIDENCE: III.

Navigating Solitary Rectal Ulcer Syndrome: A Surgeon's Conundrum With Rectal Carcinoma in a Young Adult.

Solitary rectal ulcer syndrome is a rare, chronic, and benign disorder. It can be observed as ulcers in the rectal mucosa, solitary or multiple lesions. It can often be misdiagnosed with other intestinal morbidities, due to its clinical similarities. It can be diagnosed by clinical symptoms, radiological tools, and histopathological examination. Management is carried out by conservative methods such as lifestyle and dietary modifications with medical and surgical therapy. This is a case of a 37-year-old female with a major complaint of per-rectal bleeding. Proctoscopy revealed an irregular-ulcerated mass in the rectum, which was managed conservatively. The patient showed improved symptoms after a colonoscopy, at a six-month follow-up.

Recurrence of Sigmoid Volvulus Associated With Constipation: A Retrospective Cohort Study.

Introduction Sigmoid volvulus is a gastrointestinal condition characterized by twisting the sigmoid colon, leading to obstruction and potentially severe complications. It is associated with factors such as advanced age, constipation, and the use of certain medications. Despite treatment, recurrence is common and significantly impacts patients' quality of life. This study aimed to identify factors influencing the recurrence of sigmoid volvulus to develop effective preventive strategies. Methods A retrospective cohort study was conducted at Fuchu Hospital, Osaka, including 44 patients diagnosed with sigmoid volvulus between May 2013 and May 2023. Data on variables such as age, gender, constipation, cardiac and neuropsychiatric diseases, hypertension, diabetes mellitus, sigmoid colon overgrowth, and BMI were collected from electronic medical records. Recurrence was defined as two or more diagnoses of sigmoid volvulus during the study period. Logistic regression analysis was used to identify significant predictors of recurrence. Results Of the 44 patients, 20 experienced recurrences. Single regression analysis identified constipation, neuropsychiatric disorders, and sigmoid colon overgrowth as significant factors. Logistic regression analysis confirmed constipation as an important predictor of recurrence (OR: 8.84, 95% CI: 2.05-38.1, p=0.0034). The area under the receiver operating characteristic (ROC) curve for the model was 0.804 (95% CI: 0.67-0.938), indicating good predictive accuracy. Conclusion Constipation is a significant risk factor for the recurrence of sigmoid volvulus, likely due to chronic fecal overload leading to elongation and dilation of the sigmoid colon. Effective management of constipation is crucial in preventing recurrence. Future prospective studies with larger sample sizes are needed to validate these findings and explore additional preventive measures.

Can depression lead to chronic constipation, or does chronic constipation worsen depression? NHANES 2005-2010 and bidirectional mendelian randomization analyses.

BACKGROUND: Depression and chronic constipation often co-occur, but the reciprocal influence between the two remains unclear. The purpose of this study is to explore the potential association between depression and chronic constipation. METHODS: This study initially utilized data from National Health and Nutrition Examination Survey (NHANES) 2005-2010 to explore the correlation between depression scores and chronic constipation, assessing the non-linear relationship between the two. Subsequently, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between depression and major depression with chronic constipation. The Inverse Variance Weighting (IVW) method served as the primary reference, supplemented by sensitivity tests. Finally, a reverse MR analysis was performed to assess the presence of any reverse causation. The STROBE-MR checklist for the reporting of MR studies was used in this study. RESULTS: In the NHANES analysis, survey-weighted logistic regression revealed a significantly positive correlation between depression scores and chronic constipation (OR = 1.04, 95% CI = 1.02-1.07, p = 0.002), even after adjusting for the included covariates. The nonlinear analysis using Restricted Cubic Splines (RCS) enhanced the robustness of the association (P-non-liner = 0.01). The MR analysis also confirmed the causal relationship between depression (OR = 11.43, 95% CI = 1.85-70.67, p = 0.008) and major depression (OR = 1.12, 95% CI = 1.03-1.22, p = 0.007) with chronic constipation, passing rigorous sensitivity tests. No evidence of reverse causation was observed in the reverse MR analysis (P > 0.05). CONCLUSIONS: Depression is positively correlated with the risk of chronic constipation. Therefore, enhancing attention to chronic constipation in patients with depression may be effective in clinical practice.

Integrated serum pharmacochemistry, 16S rDNA sequencing, and metabolomics to reveal the material basis and mechanism of Shouhui Tongbian capsule against diphenoxylate-induced slow transit constipation in rats.

BACKGROUND: Slow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear. METHODS: After quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods. RESULTS: SHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc. CONCLUSIONS: Combined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC.

Composite Functional and Quality of Life Outcomes in Adults Operated for Cloacal Malformation.

INTRODUCTION: Composite long-term outcomes of cloacal malformations remain unclear. We aimed to evaluate bowel and bladder control, sexual function, reproductive health, and quality of life in adulthood. METHODS: A Nordic multi-center cross-sectional observational study evaluating the outcome of adult patients with cloacal malformations was performed. Patient characteristics were retrieved from case records. Established questionnaires were sent to the patients to evaluate bowel- bladder- and sexual function and quality of life. RESULTS: Thirty-four of 48 (70%) eligible patients with median age 28 years (18-45) responded. Eight (24%) patients had a common channel >3 cm. Imaging-confirmed spinal and sacral abnormalities were present in 4 and 17 patients respectively. 85% (n = 29/34, four patients with permanent urinary diversions after bladder neck closure excluded) reported no urinary leakage without physical activity or urge to urinate. Three patients had a permanent enterostomy. 42 % (n = 11/26) reported acceptable bowel function according to Bowel Function Score (with eventual ongoing bowel management). The median Profile of Female Sexual Function Score was below normative values. Quality of life was comparable to the reference population, but thirty percent scored within the distress domains. Eight patients (24%) had been pregnant (15 pregnancies), resulting in seven live births, but the need of assisted reproduction techniques (40%, n = 6/15) and miscarriage (40%, n = 6/15) was common. CONCLUSIONS: Adequate spontaneous bowel control was rare, while most patients were dry for urine without additional procedures. Cloacal malformation also have a negative impact on sexual function health related quality of life and reproductive health. Long-term follow-up is crucial, not only regarding bowel and bladder function, but also for sexual and reproductive function, which may be important negative factors for health-related quality of life. LEVEL OF EVIDENCE: Level IV.

Functional anticholinergic activity of drugs classified as strong and moderate on the anticholinergic burden scale on bladder and ileum.

Several medications are commonly administered to older Japanese patients. Since some of them have not been included in previously developed scales to estimate the anticholinergic burden, we have developed a new muscarinic receptor binding-based anticholinergic burden scale. This study aimed to investigate the functional inhibitory effects of 60 medications, classified as anticholinergic burden scales 3 and 2 by the anticholinergic burden scale, on muscarinic receptor-mediated contractions in the bladder and ileum. The relaxation response induced by these drugs on isolated rat bladders and ileum smooth muscles constricted by carbachol was assessed using the organ bath method. All drugs inhibited smooth muscle contractile responses induced by the muscarinic receptor activation in a concentration-dependent manner in the rat bladder and ileum. Notably, variations were observed in the relaxation responses of the drugs, and the function EC50 values were positively correlated with the binding IC50 values in the bladder and ileum. The results of this study provide functional pharmacological evidence for the muscarinic receptor binding-based anticholinergic burden scale. Implementation of this scale may help reduce the risk of constipation and urinary retention, which are common side effects associated with anticholinergic drugs.

The effect of fiber supplementation with agave fructans or psyllium plantago in symptoms of constipation and its relation with whole and regional transit time and pH.

BACKGROUND: Supplementation with the Agave tequilana Weber blue variety fructans is a feasible treatment option for functional constipation (FC). However, its effects on colonic function have not yet been studied. This study assessed whole gut transit time (WGTT) and regional transit time using a wireless motility capsule (WMC) before and after supplementation with different fiber treatments in patients with FC. METHODS: A secondary analysis was performed on data collected from a randomized, double-blind clinical trial comparing agave fructans with psyllium plantago. WGTT, regional transit time, contractility, and pH were measured using WMC before and after fiber supplementation. Comparisons were performed using nonparametric tests. KEY RESULTS: Twenty patients with FC were evaluated, with a median age of 39 (25-54 years), and 18 (90%) were women. Five patients were included in each intervention group. There were no changes in WGTT or regional transit times between the groups (p > 0.05). Similarly, there were no differences in the changes experienced by regional or general contractility among the groups (p > 0.05). The cecal pH profile did not differ between the groups before and after fiber supplementation (p > 0.05). The percentages of clinical responses and consistency of bowel movements between the groups were similar. CONCLUSIONS & INFERENCES: FC presents a clinical response to a fiber challenge, regardless of the administered intervention. However, this response was not associated with improvement in contractility or regional transit time. We speculate that there are other mechanisms by which fiber consumption may improve FC.

Burden of illness and treatment attitudes among participants meeting Rome IV criteria for irritable bowel syndrome: A nationwide survey in the United States.

BACKGROUND: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by abdominal pain and altered bowel habits, with patient-perceived dissatisfaction of treatment symptom control. We assessed disease burden, satisfaction with medication use, and impact on activities, in participants with IBS with constipation (IBS-C) and diarrhea (IBS-D). METHODS: This study assessed data from a large, United States survey of adults querying demographics, comorbid conditions, quality of life, medication use, satisfaction with symptom control, and work productivity. Participants were grouped into the IBS-C or IBS-D cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self-reported. KEY RESULTS: Nine hundred and ten participants with IBS-C and 669 with IBS-D were matched to controls. The most reported symptoms were abdominal discomfort for IBS-C and abdominal pain and abdominal discomfort for IBS-D. Among the IBS-C and IBS-D cohorts, 74.2% and 65.9%, respectively, took prescription and/or over-the-counter medication for their symptoms. Respondents were more dissatisfied than satisfied with control of their symptoms. Respondents taking prescription medication(s) with or without over-the-counter medication(s) reported better symptom control than respondents only taking over-the-counter medications (p < 0.001). There was significantly higher mean presenteeism, work productivity loss, and daily activity impairment (p < 0.001 for all) in respondents with IBS compared with controls. CONCLUSIONS AND INFERENCES: This study provides insight into respondents' experiences of IBS symptoms, including the impact on daily activity, as well as satisfaction with control of symptoms and prescription and over-the-counter medications.

Potty Stools, a Pilot Study to Step Up the Management of Functional Constipation in Children.

Functional constipation (FC) comprises 30% of pediatric gastroenterology clinic visits. FC results from withholding behaviors that can be worsened by poor toileting posture. The use of a defecation posture modification device (DPMD)-a potty stool-has demonstrated benefit in adults. The aim of this study was to assess the risks and benefits of incorporating a DPMD as an adjunct to the FC treatment plan for children. Toilet-trained children aged ≥4 years meeting the Rome IV criteria for FC were enrolled and offered a DPMD at no cost and were followed for 4 months. There were no injuries or treatment-related adverse events reported by the 43 subjects who completed the study. Notably, 98% (n = 42) of respondents would recommend the DPMD to assist other children with FC. DPMD users showed a 33% reduction in fecal incontinence compared with 60% non-users. The DPMD represents a safe adjunct to incorporate into the FC management plan of children.