Assessment and management of constipation in post-operative patients in the spinal surgery ward: a best practice implementation project.

INTRODUCTION AND OBJECTIVE: Constipation is a common complication following spinal surgery that can result in distension, abdominal pain, infection, and even intestinal perforation. This study reports on an evidence-based implementation project to reduce the incidence of constipation in spinal surgery wards. METHODS: The project was conducted in the spinal surgery ward of a general tertiary hospital in Changsha City, China, from March to August 2022. We used the JBI Implementation Framework and the JBI Model of Evidence-Based Healthcare for audits and feedback. Data were collected and analyzed using JBI's Practical Application of Clinical Evidence System (PACES) software. Seven audit criteria were developed based on the best practice recommendations summarized by JBI. A baseline audit was conducted with 20 nurses and 50 patients in the spinal surgery ward, and a follow-up audit was conducted using the same sample size and setting. RESULTS: The baseline audit revealed compliance below 46% for five of the seven criteria. Strategies developed to address poor compliance included educating nurses and patients, developing a post-operative constipation risk assessment sheet, organizing stakeholder focus group meetings, establishing a constipation management routine, and effective empowerment of nurses. The follow-up audit showed positive compliance results, with the highest rate for Criterion 7 (100%) and the greatest increase for Criterion 2 (from 0% to 78%). Furthermore, the incidence of post-operative constipation decreased from 48% to 16%. CONCLUSION: The project improved compliance with audit criteria, reduced the incidence of constipation, and enhanced the efficiency of quality management in the spinal surgery ward. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A186.

Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.

Efficacy of Bowel Regimen in Decreasing Postoperative Constipation in Bariatric Surgery Patients.

PURPOSE: Postoperative constipation after bariatric surgery is a common complaint, decreasing patient quality of life. No literature exists examining the efficacy of a preoperative bowel regimen in reducing postoperative constipation in this cohort. This study aims explore the efficacy of a well-established bowel regimen, polyethylene glycol (PEG), in reducing constipation frequency and severity after bariatric surgery. METHODS: This was a retrospective study of adult patients undergoing primary and revisional bariatric procedures. The use of PEG bowel prep for bariatric patients was introduced as an institutional quality improvement measure. Patients during the first 3 months after PEG implementation were surveyed for postoperative constipation. For the year after implementation, patients were followed for 30-day emergency room visits or hospitalization secondary to constipation. This cohort was compared to historical controls from the previous year. Student t-tests were used for statistical analysis. RESULTS: During the 3-month exploratory phase, 28/49 (57.14%) patients fully completed the bowel regimen. In total, 0/56 (0%) patients reported preoperative constipation, and 5/28 (17.9%) patients reported constipation at the 3-week follow-up. In the 1 year post-implementation cohort, 2/234 (0.85%) patients had constipation-related occurrences at 30-day follow-up, compared to 8/219 patients (3.65%) in the historical cohort (p = 0.04). CONCLUSIONS: The implementation of a PEG-based bowel regimen did not eliminate self-reported constipation. However, there were significant differences in rates of constipation-related ED visits and hospital readmissions, suggesting that the bowel regimen decreases rates of severe constipation. Finally, patient compliance was limited. Future work should aim towards increasing compliance.

A Retrospective Observational Study of Factors Affecting the Efficacy of Concurrent Prescription of Naldemedine for Opioid-Induced Constipation Caused by Oxycodone Tablets.

Naldemedine is indicated for the treatment of opioid-induced constipation (OIC), but reports on its efficacy in preventing OIC are few. Therefore, we retrospectively investigated factors affecting the efficacy of concurrent prescription of naldemedine on OIC. Outpatients with cancer who were started on oxycodone 10 mg/d were included in the study. The eligible patients were classified by their physicians into the following three groups: Group A used regular laxatives before the introduction of oxycodone and initiated naldemedine treatment simultaneously with oxycodone administration, Group B did not take laxatives before the introduction of oxycodone and started naldemedine simultaneously with oxycodone administration, and Group C had been administering regular laxatives before the introduction of oxycodone and were not prescribed naldemedine simultaneously with oxycodone treatment. The Support Team Assessment Schedule Japanese edition score for constipation, frequency of defecation, Bristol Stool Form Scale, sense of incomplete rectal evacuation, and development or worsening of straining to pass bowel movements were compared among the three groups before and after oxycodone administration. In Group B, there was significant worsening of the four parameters except for the sense of incomplete rectal evacuation, whereas Groups A and C did not present any changes. In logistic regression analysis, body weight ≥51.8 kg was a factor significantly decreasing the preventive effect of naldemedine on OIC, and regular use of laxatives was a factor significantly increasing the preventive effect of naldemedine on OIC. Thus, the initiation of naldemedine should be considered depending on the body weight and regular laxative use.

Effects of Abdominal Massage for Preventing Acute Postoperative Constipation in Hip Fractures: A Prospective Interventional Study.

Background: This prospective randomized controlled study aimed to determine the effects of abdominal massage on constipation management in elderly patients with hip fractures. Methods: From August 2017 to December 2018, patients aged above 65 years with hip fractures (n = 88) were randomly assigned to a massage group that received a bowel massage (n = 48) or a control group that did not receive a bowel massage (n = 40). Patients in the bowel massage group received a bowel massage from a trained caregiver after breakfast at approximately 9:00 AM for an hour. On admission, 5 days after surgery, and on the day of discharge, the patient's normal and actual defecation pattern, stool consistency, and any problems with defecation were assessed through a structured interview. The questionnaire comprising the Bristol Stool Scale, patient assessment of constipation, time to defecation, medication for defecations, failure to defecate, cause of admission, admission period, and date of surgery were recorded. Statistical analyses were performed 5 days after surgery and on the day of discharge. Results: The mean age of the study cohort was 81.4 years (range, 65-99 years). The number of constipation remedies was significantly lower in the massage group than in the control group on postoperative day (POD) 5 and at discharge (9 vs. 15, p = 0.049 and 6 vs. 11, p = 0.039, respectively). The number of defecation failures was significantly lower in the massage group than in the control group (10 vs. 17, p = 0.028) on POD 5. However, the number of defecation failures at discharge was not significantly different between the two groups (p = 0.131). The development of postoperative ileus (p = 0.271) and length of hospital stay (p = 0.576) were not different between the groups. Conclusions: The number of constipation remedies was significantly lower in the massage group than in the control group on POD 5 and discharge, and the number of defecation failures was significantly lower in the massage group than in the control group on POD 5. Therefore, abdominal massage may be considered as an independent nursing initiative for constipation management.

Association between dietary carotenoids intake and chronic constipation in American men and women adults: a cross-sectional study.

BACKGROUND: Dietary carotenoids have been proven to improve intestinal disorders like inflammatory bowel disease and colon cancer, yet little is known about the link between dietary carotenoids and constipation. This study aims to examine the relationship between dietary carotenoids intake and constipation, using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. METHODS: A total of 11,722 participants were enrolled. Chronic constipation was defined as type 1 (separate hard lumps, like nuts) and type 2 (sausage-like, but lumpy) in the Bristol stool form scale (BSFS). Carotenoids intake was obtained from the average of two 24-hour dietary recall questionnaires (if only one 24-hour was available, we used it) and divided into quartiles (Q). The prevalence of constipation was calculated across men and women individuals. The relationship between dietary carotenoids intake and constipation in men and women was assessed with weighted logistic regression and smoothed curve fitting after adjusting confounders, with results displayed as weighted odds ratio (OR) with 95% confidence intervals (95% CI). The model was further stratified by age, race, and HEI 2015 scores (with median as cutoff) among men and women. RESULTS: The total weighted prevalence of chronic constipation in this study was 8.08%, 11.11% in women and 5.18% in men. After multivariable adjustment, compared with the lowest intake, participants with the highest dietary lycopene intake (ORQ4 vs. Q1= 0.55, 95% CI: 0.36-0.84, p for trend = 0.01) and total lycopene intake (ORQ4 vs. Q1 = 0.52, 95% CI: 0.34-0.80, p for trend = 0.01) were negatively associated with the risk of chronic constipation in men, whereas increased dietary α-carotene intake reduced the risk of chronic constipation in women (ORQ4 vs. Q1 = 0.69, 95% CI: 0.48-0.98, p for trend = 0.04). Smoothing curve fitting further supported these results and provided evidence of dose-response effects. No association was found between other types of carotenoids and chronic constipation in men and women. CONCLUSIONS: Increasing lycopene intake may improve bowel function in men while increased α-carotene intake may reduce the risk of chronic constipation in women. Further studies are essential to explore the role that the intake of carotenoids plays in chronic constipation.

Magnesium hydroxide versus macrogol/electrolytes in the prevention of opioid-induced constipation in incurable cancer patients: study protocol for an open-label, randomized controlled trial (the OMAMA study).

BACKGROUND: Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. METHODS: Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of < 30 on the Bowel Function Index (BFI), measured on day 14. The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed. DISCUSSION: In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022-000408-36.

[Survey of Prophylactic Administration of Naldemedine for Opioid-induced Constipation].

Opioid-induced constipation (OIC), an adverse event that occurs due to opioid analgesics, reportedly causes poor quality of life and adherence to opioid analgesics in patients. Therefore, this issue must be addressed appropriately. Naldemedine (NAL), a peripherally-acting µ-opioid receptor antagonist, is currently recommended for treating OIC when other laxatives are ineffective, but there have been no clinical reports of NAL being used prophylactically for OIC. Therefore, we conducted a retrospective survey of hospitalized patients who received NAL as prophylaxis for OIC with strong opioid analgesics to clarify the reality of this situation and to consider points to be taken into account in its clinical implementation. In this study, 61.7% of the subjects had an Eastern Cooperative Oncology Group performance status score of 3 or higher. The rate of addition of new laxatives and increased laxatives during seven days of NAL prophylaxis was 46.8%, and the rate of diarrhea was 6.1%. This study suggests that patients initiated with strong opioid analgesics during hospitalization often presented with poor performance status, and it is important to pay attention to constipation even under NAL prophylaxis. However, the incidence of diarrhea was low, and the safety of NAL prophylaxis was considered to be good.

Prevention of Loperamide-Induced Constipation in Mice and Alteration of 5-Hydroxytryotamine Signaling by Ligilactobacillus salivarius Li01.

Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae_RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.

Constipation Severity and Quality of Life among Patients with Cancer Who Received Prophylactic Laxatives: Quasi-Experimental Study.

BACKGROUND: Prophylactic laxatives were associated with decreasing the incidence of Opioid-induced constipation among patients with cancer. This study aims to evaluate the effectiveness of early prophylactic laxatives therapy on the severity of constipation and quality of life among patients with cancer receiving opioids. METHODS: Using a quasi-experimental design with 64 patients assigned to control group and 66 patients assigned to intervention group. The final sample was composed from 112 patients (57 in control group and 55 in intervention group), who were selected from an oncology clinic. Patients in the intervention group have received prophylactical laxatives The intervention included an oral colonic stimulant laxative (i.e., Bisacodyl, Dose= 3 tab/ day and/or Senna 6.8 mg twice daily) and an oral colonic osmotic laxative (i.e., Lactulose, Dose = 15 ml three times per day). Patients in the control group continue to receive their routine care without laxatives. RESULTS: Patients in the intervention group have reported a significant reduction in the severity of constipation symptoms at eight weeks post the intervention (p < 0.001). Furthermore, the patients in the intervention group have revealed a significant improvement in their quality of life (QoL) (p< 0.001). CONCLUSIONS: Patients with cancer need to use the first line of laxatives as prophylactic alongside with opioids to minimize the severity of Opioid-induced constipation symptoms and to enhance the QoL.

Does prophylactic use of postcesarean section laxatives favor bowel movements?

Introduction: Chronic constipation (CC) is a highly prevalent disease in Western society. Chronic constipation can have a different etiology in patients who underwent a cesarean section and result from postoperative stress and metabolic response to trauma, analgesic agents, immobilization, and dietary restrictions. Chronic constipation may also occur due to puerperium-related psychological changes and to the stretching and weakening of the perineal and abdominal muscles after childbirth. Objectives: The present study analyzes intestinal transit restoration after a cesarean section and the influence of osmotic laxative agents. Methods: The present prospective, nonrandomized sample study used the ROME III questionnaire and the Bristol stool scale in adult women who underwent a cesarean section. We divided the subjects into 2 groups, each with 30 patients, to compare the effect of the prophylactic administration of an osmotic laxative. Results: We evaluated 60 randomly-chosen pregnant women from the Obstetrics ward of Hospital Santa Marcelina, São Paulo, SP, Brazil, from October 2019 to March 2020. Their mean age was 26.8 years old, and the mean gestation time was 37.95 weeks. Ten patients (16.7%) presented with constipation before the cesarean section, and 38 (63.3%) had a bowel movement after the procedure. However, in 84.2% of these patients, the usual stool consistency worsened. After the cesarean section, 46.7% of the women who did not receive laxative agents had a bowel movement, compared with 80% of those who did (p = 0.0074). Conclusion: Some factors, including those related to the procedure, may hamper intestinal transit restoration after a cesarean section. Osmotic laxative agents can facilitate transit restoration with no negative effects in this group of patients. (AU)

An Evaluation of Docusate Monotherapy and the Prevention of Opioid-Induced Constipation after Surgery.

Our purpose was to determine if docusate monotherapy is effective in preventing opioid-induced constipation in patients receiving opioids following orthopedic surgery. Our single-center, retrospective, cohort study evaluated 212 orthopedic patients who received opioids between May 1, 2018, and December 31, 2018. All patients were aged 18 years and older, hospitalized for more than 48 hours, and received docusate for primary prevention of constipation post-operatively. The primary outcome was the proportion of patients taking opioid medications who experienced docusate failure, defined as patients who did not have a bowel movement within 5 days of starting docusate after surgery or those patients who required the use of additional laxative agents to produce a bowel movement. After excluding patients which did not meet the inclusion criteria, 79.9% (n = 159/199) experienced docusate treatment failure. Of these patients, 42.8% (68/159) failed to have a bowel movement or had a bowel movement greater than 5 days post-surgery. The remaining 57.2% (91/159) of patients required an additional laxative to produce a bowel movement. Docusate monotherapy was not effective in preventing constipation in patients receiving opioids following elective orthopedic surgery. Based on these findings, we propose utilization of stimulant bowel products with proven efficacy as primary therapy after surgery to prevent constipation. Future multi-centered, randomized controlled trials are necessary to evaluate the differences in efficacy and safety between common bowel regimens in treating opioid-induced constipation in patients who undergo elective orthopedic surgery.

Reducing Opioid-Induced Constipation Post-Cardiac Surgery: An Improvement Project in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: Pain management with opioids and underutilization of prophylaxis for constipation can prolong a patient's hospital length of stay and impede pain management efforts. PROBLEM: In pediatric postoperative cardiac patients, opioid therapy is a common approach to pain management but often places them at greater risk for constipation due to anatomy and age. METHODS: A retrospective review of 50 patients' medical records for baseline data was conducted, and a survey evaluated providers' current knowledge and practice. INTERVENTIONS: The intervention was an electronic order set that provided decision support. Additionally, prophylactic measures were supported by a validated assessment tool that created a common language to report constipation risk. RESULTS: Although not statistically significant, postintervention data demonstrated a 21.5% decrease in postoperative constipation and a 57% increase in ordered bowel regimens. CONCLUSION: More focus is needed toward prophylactic bowel regimens to reduce the risk in this already high-risk population.

Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF. They share similar symptoms e.g. bloating, abdominal pain, but are distinct conditions. Constipation occurs when there is gradual faecal impaction of the colon, but DIOS occurs when there is an accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine. The mass may partially block the intestine (incomplete DIOS) or completely block the intestine (complete DIOS). Symptoms of DIOS can affect quality of life and other aspects of CF health, such as airway clearance, exercise, sleep and nutritional status. Treatment of constipation and prevention of complete bowel obstruction are required for gastrointestinal management in CF. However, many different strategies are used in clinical practice and there is a lack of consensus. The importance of this topic was highlighted in a recent research priority setting exercise by the James Lind Alliance. OBJECTIVES: To evaluate the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of search: 09 September 2021. We also searched online trial registries. Date of last search: 12 October 2021. SELECTION CRITERIA: Randomised and quasi-randomised controlled parallel trials comparing laxative therapy for preventing DIOS (including osmotic agents, stimulants, mucolytics and substances with more than one action) at any dose to placebo, no treatment or an alternative laxative therapy, in people of any age with pancreatic sufficient or insufficient CF and any stage of lung disease. Randomised cross-over trials were judged on an individual basis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion, extracted outcome data and performed a risk of bias assessment for the included data. We judged the certainty of the evidence using GRADE criteria. MAIN RESULTS: We included one cross-over trial (17 participants) with a duration of 12 months, in which participants were randomly allocated to either cisapride (a gastro-prokinetic agent) or placebo for six months each. The trial had an unclear risk of bias for most domains but had a high risk of reporting bias. Radiograph scores revealed no difference in occurrence of DIOS between cisapride and placebo (narrative report, no data provided). There were no adverse effects. Symptom scores were the only secondary outcome within the review that were reported. Total gastrointestinal symptom scores favoured cisapride with a statistically significant mean difference (MD) of -7.60 (95% confidence interval (CI) -14.73 to -0.47). There was no significant difference at six months between cisapride and placebo for abdominal distension, MD -0.90 (95% CI -2.39 to 0.59) or abdominal pain, MD -0.4 (95% CI -2.05 to 1.25). The global symptom scores (whether individuals felt better or worse) were reported in the paper to favour cisapride and be statistically significant (P < 0.05). We assessed the available data to be very low certainty. There was a great deal of missing data from the included trial and the investigators failed to report numerical data for many outcomes. The overall risk of bias of the trial was unclear and it had a high risk for reporting bias. There was also indirectness; the trial drug (cisapride) has since been removed from the market in several countries due to adverse effects, thus it has no current applicability for preventing DIOS. The included trial also had very few participants, which downgraded the certainty a further level for precision. AUTHORS' CONCLUSIONS: There is an absence of evidence for interventions for the prevention of DIOS. As there was only one included trial, we could not perform a meta-analysis of the data. Furthermore, the included trial compared a prokinetic agent (cisapride) that is no longer licensed for use in a number of countries due to the risk of serious cardiac events, a finding that came to light after the trial was conducted. Therefore, the limited findings from the trial are not applicable in current clinical practice. Overall, a great deal more research needs to be undertaken on gastrointestinal complications in CF, as this is a very poorly studied area compared to respiratory complications in CF.

In vivo acute toxicity, laxative and antiulcer effect of the extract of Dryopteris Ramose.

Dryopteris ramosa (D. ramosa) is one of the most traded medicinally important plants of Himalayan region. Apart from other uses, D. ramosa is traditionally also used to treat gastric ulcers and as a laxative. The present study was designed to investigate the role of methanolic crude extract of Dryopteris Ramosa (MEDR) in acute toxicity, against loperamide induced constipated mice model, antiulcer effect of methanolic extract of D. Ramosa and cholinomimetic like effect of methanolic extract of D. Ramosa. The crude extract was investigated for the presence of active compounds (secondary metabolites) such as alkaloids, flavonoids, carbohydrates, glycosides, terpenoids, phenolic compounds, saponins, and tannins following the standard methods. The antiulcer effect was investigated in mice using the ethanol induced ulcer model at various doses i.e. 50 mg/kg, 100 mg/kg and 200 mg/kg doses. Constipation was induced in the mice via loperamide (3mg/kg body weight). The control group received normal saline. Different doses of plant extracts (50, 100, 150 and 200 mg/kg body weight/day) were administered for 7 days. Various parameters like feeding characteristics, gastrointestinal transit ratio, body weight, fecal properties and the possible mechanism of action of D. Ramosa on intestinal motility were monitored. Various Phytochemicals like saponins, glycosides, flavonoids, tannins, phenols, carbohydrate, alkaloids and triterpenes were found in D. Ramosa. The acute toxicity study showed that MEDR was associated with no mortality except mild and moderate sedation at the highest tested doses (1500 and 2000 mg/kg). MEDR also showed significant antiulcer activity against ethanol-induced ulcerogenesis. The extract enhanced the intestinal motility, normalized the body weight of constipated mice and increased the fecal volume which are indications of laxative property of the herb. The 200 mg/kg body weight dose of the extract was found effective. The presence of various Phytochemicals such as flavonoids, glycosides and tannins might be responsible for the antiulcer activity of D. Ramosa. This study provides the scientific background for the folkloric use of D. Ramosa as antiulcer agent. The laxative action of the extract compares positively with Duphalac, (standard laxative drug). These findings have therefore evidence scientific background to the folkloric use of the herb as a laxative agent.

Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function.

The purpose of this study is to investigate the mitigatory effect of a novel synbiotic (SBT) on constipation from the perspective of gut microbiome and metabolome. Here, intake of SBT effectively attenuated diphenoxylate-induced constipation, recuperated colonic epithelial integrity and increased serum levels of gastrointestinal excitatory neurotransmitters (P substance, vasoactive intestinal peptide, motilin, gastrin and serotonin). 16S rRNA sequencing showed that SBT intake rehabilitated the composition and functionality of gut microbiota. Relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Lactobacillus, Faecalibaculum and Bifidobacterium were elevated by administration of SBT. The gas chromatography-mass spectrometry analysis confirmed that fecal concentrations of propionate and butyrate were significantly increased in the rats intervened with SBT. In addition, SBT ingestion reduced the relative levels of opportunistic pathogens, such as Oscillibacter, Parasutterella and Parabacteroides. Microbial functional prediction showed that the relative abundances of lipopolysaccharide (LPS) biosynthesis and arachidonic acid metabolism were downregulated with SBT administration, which were in accordance with the serum metabolomics results. Furthermore, serum levels of LPS, tumour necrosis factor alpha and interleukin 6 were significantly decreased, indicating that SBT supplementation suppressed inflammatory responses. Therefore, this study demonstrated that consumption of SBT ameliorated constipation possibly by regulating gut microbiota, promoting the SCFAs production and inhibiting inflammatory responses in rats. Our study also indicated that SBT may provide a novel alternative strategy for the treatment of constipation clinically in future.

Colonic Motility Is Improved by the Activation of 5-HT2B Receptors on Interstitial Cells of Cajal in Diabetic Mice.

BACKGROUND & AIMS: Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown. METHODS: We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT2B receptor (HTR2B) antagonist or agonist. RESULTS: Colonic transit was delayed in males with diabetes, although colonic Tph1+ cell density and 5-HT levels were increased. Colonic transit was not further reduced in diabetic mice by EC cell depletion. The HTR2B protein, predominantly expressed by colonic ICCs, was markedly decreased in the colonic muscles of males and ovariectomized females with diabetes. Ca2+ activity in colonic ICCs was decreased in diabetic males. Treatment with an HTR2B antagonist impaired CMMCs and colonic motility in healthy males, whereas treatment with an HTR2B agonist improved CMMCs and colonic motility in males with diabetes. Colonic transit in ovariectomized females with diabetes was also improved significantly by the HTR2B agonist treatment. CONCLUSIONS: Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.

Anal Fissure in Children.

Anal fissure is a common clinical problem in children and is defined as a longitudinal tear in the anal canal. The typical presentation is painful defecation and rectal bleeding. The etiology of anal fissure is unknown, but passage of hard stools and increased internal anal sphincter pressure are considered important factors. The treatment is oriented to relieve the spasm of the internal anal sphincter, which prevents healing of the fissure. Conservative management with stool softeners, topical analgesics, and sitz baths is recommended as first-choice therapy. Surgical treatment has been replaced by nonoperative management as definitive therapy, which is associated with a marginally higher success rate than placebo. Most recent studies have focused on nonoperative treatment with glyceryl trinitrate, calcium channel blockers, or botulinum toxin injection treatment. There are a few controlled studies to compare the different nonoperative treatment options in children. Success rates vary between the studies, and there is no clear evidence about which is the optimal nonoperative treatment. A significant recurrence rate has been reported after nonoperative management of anal fissure. It is important to treat constipation to avoid recurrent tears in the anal canal.

Surgical Management of Rectal Prolapse in Infants and Children.

The surgical management of children with rectal prolapse is wide ranging and without consensus within the pediatric surgical community. While the majority of rectal prolapse in infants and children resolves spontaneously or with the medical management of constipation, a small but significant subset of patients may require intervention for persistent symptoms. In this review, we discuss the etiology and pathophysiology of rectal prolapse in both infants and children, options for medical management, described interventions and surgical options and their outcomes, and future avenues for research and investigation.