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Aims: Cinnamaldehyde (CA), the main active constituent of cinnamon oil, is reported to have neuroprotective effects. However, the potential benefits of CA for brain protection in hepatic encephalopathy (HE) are still not understood. Thus, the present study investigates the possible ameliorative effect of CA (70 mg/kg/day, I.P.) either alone or in combination with lactulose (Lac) (5.3 g/kg/day, oral) against thioacetamide (TAA)-induced hepatic encephalopathy in rats., Materials and Methods: For induction of HE, TAA (200 mg/kg) was intraperitoneally administered for 1 week at alternative days. CA, Lac and Lac+CA were administered for 14 days prior to and for further 7 days together with TAA injection., Key Findings: CA, Lac and Lac+CA combination effectively attenuated TAA-induced HE; as indicated by the improvement in behavioral tests, mitigation of pathological abnormalities in both liver and brain, the significant reduction in serum hyperammonemia and amelioration in liver function biomarkers; ALT and AST. This was accompanied with a substantial restoration of redox state in liver and brain; MDA and GSH levels. Moreover, CA, Lac and Lac+CA combination reduced neuroinflammation as demonstrated by the notable attenuation of P2X7R, NLRP3, caspase-1, IL-1β, GFAP and Iba1 brain levels, as well as the amelioration of brain edema as manifested by reduction in AQP4 levels in brain., Significance: Our study has demonstrated that CA in combination with Lac possesses a superior neuroprotective effect over Lac alone against TAA-induced HE by attenuation of P2X7R/NLRP3 mediated neuroinflammation and relieving brain edema., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Colonoscopy is currently considered as one of the principal techniques to diagnose the colorectal diseases. Admittedly, qualified bowel preparation before colonoscopy is a premise for high-quality examination. Lower quality bowel preparation might seriously impede visualization of the intestinal mucosa, resulting in missed and misdiagnosed intestinal lesions. Therefore, it is necessary to choose the appropriate oral laxative based on the guarantee of safety and efficacy., Methods: This prospective randomized controlled study was conducted to compare lactulose oral solution and polyethylene glycol (PEG) electrolyte powder for bowel preparation using the following indicators: Boston Bowel Preparation Scale, Bowel Bubble Score, detection rate of adenoma and lesion, patients' satisfaction, and adverse effects. Our study investigated the suitability of 2 bowel preparation reagents for patients with different body mass indices mainly based on body mass index (BMI)., Results: In the lactulose group, there was a significant improvement in the quality of bowel preparation compared with those in the PEG group ( P < 0.05), especially in people with normal BMI and higher BMI. Compared with the PEG group, individuals in the lactulose group had a significantly higher adenoma detection rate (50% vs 33.5%, P < 0.05) and taste scores (8.82 vs 6.69, P < 0.05), as well as significantly fewer adverse reactions (6.5% vs 32.5%, P < 0.05)., Discussion: Lactulose oral solution is superior to PEG in bowel preparation quality and taste, especially in normal BMI and higher BMI groups. It can be used clinically as a potential and promising bowel preparation agent in the future. Clinical Trial registration number: ChiCTR2100054318., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective Rifaximin is used to treat hepatic encephalopathy. However, whether or not rifaximin and lactulose combination therapy can enhance the treatment outcomes and reduce the hospitalization rate of patients with hepatic encephalopathy that are resistant to lactulose has yet to be determined. The present study investigated the hospitalization rate before and after rifaximin add-on therapy in patients resistant to lactulose. Methods A total of 36 patients who were resistant to lactulose with add-on rifaximin therapy were enrolled. Patients who were hospitalized and/or did not achieve normalization of ammonia levels under lactulose administration were defined as treatment-resistant. The primary outcome was the change in hospitalization rate due to hepatic encephalopathy at 24 weeks before and after rifaximin administration. Results Before rifaximin administration, 15 (41.6%) patients were hospitalized due to hepatic encephalopathy. After rifaximin administration, 8 (22.2%) patients were hospitalized due to hepatic encephalopathy. The hospitalization rates were significantly reduced after rifaximin administration (p=0.02). The median (interquartile range) ammonia levels upon rifaximin administration (baseline) and 8, 12, and 24 weeks after rifaximin administration were 124 (24-310) μg/dL, 78 (15-192) μg/dL, 67 (21-233) μg/dL, and 77 (28-200) μg/dL, respectively. Furthermore, the ammonia levels were significantly reduced by rifaximin add-on therapy (p=0.005, p=0.01, and p=0.01). Conclusion The addition of rifaximin to lactulose treatment in treatment-resistant patients decreases the hospitalization rate among patients with hepatic encephalopathy and may be used as an add-on treatment.

Introduction: Hepatic encephalopathy (HE) is a peculiar kind of brain dysfunction typical of liver cirrhosis characterized by nonspecific neurological and psychiatric manifestations. HE ranges from minimal hepatic encephalopathy (MHE) to the most severe form characterized by alteration of consciousness or coma (overt HE, OHE). Once the diagnosis of OHE is made, every effort to identify and correct the precipitating cause is essential for the resolution of symptoms. Clinical studies that assessed the prevalence and incidence of any type of HE (MHE and OHE) in patients affected by cirrhosis were included in this review. No language, publication date, or publication status restrictions were imposed. The studies were identified by searching electronic databases (PubMed and SCOPUS)., Areas Covered: The most widely empirical pharmacological approach consists of non-absorbable antibiotics (rifaximin) and non-absorbable disaccharides (lactulose, lactitol per os and per enemas). Other agents (including branched-chain amino acids, probiotics, other antibiotics, or intravenous L-ornithine L-aspartate) are available, but the evidence supporting their efficacy remains under debate., Expert Opinion: Gray areas and future needs remain the therapeutic approach to MHE and issues in the design of therapeutic studies for HE which have been extensively discussed in this review.

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome associated with liver failure and/or portal systemic shunting. Polyethylene glycol (PEG) electrolyte solution is a commonly used for catharsis of gut, which has been demonstrated to relieve HE in a number of randomized controlled trials. The aim of this paper was to evaluate the comparative efficacy and safety of PEG with lactulose for current HE treatment., Methods: PEG electrolyte solution versus lactulose of HE was deeply studied by conducting a systematic search in electronic databases and other sources until December 31, 2020. The PRISMA statement recommended the use of meta-analysis with 95% confidence interval (CI), relative risk (RR), and weighted mean deviation (WMD) as the estimated effect size. A sensitivity analysis was performed comprehensively to present the risk of bias and the source of heterogeneity., Results: A total of 434 patients were involved in 7 randomized studies. It is found that there was a significant advantage of PEG therapy in the increase of clinical efficacy (RR=1.46; 95% CI: 1.26-1.68; P=0.000; I2=0.0%) and the decrease of hospital stay (WMD=-1.78; 95% CI: -2.72 to 0.85; P=0.000; I2=90.1%). There was no significant difference in the incidence of adverse events (RR=0.75; 95% CI: 0.48-1.19; P=0.222>0.05; I2=7.2%) and the level of serum ammonia (WMD=9.02; 95% CI: -14.39 to 32.43; P=0.45>0.05; I2=84.9%) after 24 hours between the 2 groups., Conclusions: The results prove that PEG has a beneficial effect on the treatment of HE. Compared with lactulose, PEG can lead to more rapid HE resolution during the first 24 hours and shorten the length of stay without increasing the rate of adverse effects., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To assess the effectiveness of partially hydrolyzed guar gum (PHGG) in improving constipation and reducing the use of laxatives among long term care facility (LTCF) residents., Design: A single-center, prospective, randomized, placebo-controlled, single-blinded parallel-group trial from September 2021 to November 2021., Setting: Four LTCF in Hong Kong., Participants: Fifty-two LTCF residents with chronic constipation (mean age: 83.9±7.6 years, male 38%)., Intervention: 5g PHGG mixed with 200ml water per day for 4 weeks was given to intervention group participants. Control group received 200ml water for 4 weeks. Participants continued their usual as-needed laxative (lactulose, senna or dulcolax) on their own initiative., Measurements: Baseline measurements included age, gender, Charlson comorbidity index, Roackwood's Clinical Frailty Scale, body mass index and daily dietary fiber intake. Outcome measures were fecal characteristics assessed by Bristol Stool Form Scale, bowel opening frequency and laxative use frequency at baseline, first, second, third and fourth week of trial. Adverse events were measured. The study was registered on ClinicalTrial.gov; identifier: NCT05037565., Results: There was no significant difference in bowel frequency and stool characteristics between the treatment group and control group. However, there was a significantly lower frequency of lactulose, senna, and total laxative use in the treatment group compared with controls in the third and fourth week. There was no significant difference in adverse effects between the two groups., Conclusion: This study showed that daily dietary fibre supplementation by using PHGG for 4 weeks in LTCF residents results in significantly less laxative use than placebo. It may be an effective way to reduce laxative dependence among older people living in LTCFs., Competing Interests: The authors declare no conflict of interest

Background & Aims: Hepatic encephalopathy (HE) is associated with increased morbidity, mortality, and health care resource use. In this phase 2b study, we evaluated the efficacy and safety of ornithine phenylacetate (OP), an ammonia scavenger, in hospitalized patients with cirrhosis, increased levels of ammonia at screening, and acute or overt HE., Methods: We conducted a double-blind study of 231 patients with cirrhosis and HE at multiple sites in North America, Europe, Israel, and Australia from January 7, 2014, through December 29, 2016. Patients were assigned randomly to groups that received placebo or OP (10, 15, or 20 g/d, based on the severity of liver disease), plus each institution's standard of care (eg, lactulose to achieve 2-3 bowel movements with or without rifaximin, in accordance with guidelines). The primary end point was time to confirmed clinical response, defined as reduction to HE staging tool (HEST) stage 2 from baseline HEST stages 3/4 or improvement to HEST stages 0/1 from baseline stage 2, in the intent-to-treat population (all patients with increased levels of ammonia at screening, determined by a local laboratory)., Results: Median times to clinical improvement, based on ammonia measurements at local laboratories, did not differ significantly between the groups given OP vs the placebo group (P = .129). Analyses of central laboratory-confirmed increases in levels of ammonia at baseline (n = 201) showed clinical improvement in HE at a median of 21 hours sooner in groups given OP vs placebo. The percentages of patients with any specific adverse event did not differ significantly between groups. Serious adverse events occurred in 25% of patients in the OP group and in 29% in the placebo group (P = .552)., Conclusions: In a randomized controlled trial of patients with cirrhosis and HE, we found no significant difference in time to clinical improvement between patients given OP vs placebo. However, OP appears to be safe and should undergo further testing for treatment of hyperammonemia in hospitalized patients receiving treatment for the underlying precipitant of acute or overt HE. ClinicalTrials.gov no: NCT01966419., (Copyright © 2021 by the AGA Institute. Published by Elsevier, Inc. Published by Elsevier Inc. All rights reserved.)

Pneumatosis intestinalis (PI) occurs when gas is discovered in the intestinal wall and is categorized into two types: primary PI which is idiopathic and mainly occurs in the colon, and secondary PI which occurs more often in the small bowel but has variable presentation and etiology. We report a case of a patient status post-orthotopic deceased liver transplantation complicated by a portal vein thrombus on chronic lactulose for portosystemic encephalopathy who presented due to pyelonephritis and persistent diarrhea. The patient underwent colonoscopy with random biopsies and subsequently developed acute sepsis with Escherichia coli bacteremia. The findings of PI were noted on computed tomography imaging obtained 5 days post-colonoscopy, due to persistent post-procedure abdominal pain. The patient was treated with discontinuation of lactulose, supportive care, and antibiotics for her bacteremia with resolution of her PI 3 days later. This suggests that a combination of factors may lead to the development of PI, and while some cases require emergent intervention including surgery, others may be treated conservatively. Awareness of risk factors that may precipitate PI and specific clinical predictors may help to both mitigate and manage PI appropriately., (© 2021. Japanese Society of Gastroenterology.)

Background: Few head-to-head comparisons of the different classes of laxatives have been conducted., Objective: The objective of this work is to compare the efficacy of lactulose plus paraffin vs polyethylene glycol in the treatment of functional constipation (non-inferiority study)., Methods: This randomised, parallel-group, multicentre phase 4 study recruited patients with functional constipation diagnosed according to Rome III criteria. Patients received lactulose plus paraffin or polyethylene glycol for 28 days. The primary end point was the change from baseline in the Patient Assessment of Constipation-Symptoms (PAC-SYM) score., Results: A total of 363 patients were randomised to lactulose plus paraffin ( n  = 179) or polyethylene glycol ( n  = 184). On day 28, the mean PAC-SYM score decreased significantly vs baseline with both treatments ( p  < 0.001). The lower boundary of the 95% CI exceeded the pre-specified limit of -0.25, therefore establishing non-inferiority of lactulose plus paraffin vs polyethylene glycol. At least one adverse event occurred in 20 patients (11.2%) in the lactulose plus paraffin group and in 26 patients (14.2%) in the polyethylene glycol group, most of which were of mild or moderate severity and unrelated to study drugs., Conclusion: Lactulose plus paraffin may be used interchangeably with polyethylene glycol for the pharmacological treatment of functional constipation. Trial registration: EudraCT number 2015-003021-34.

A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.

Introduction: Clostridioides difficile infection (CDI) is common in patients with cirrhosis and is associated with poor outcomes. CDI risk factors in this population have been well characterized; however, risk factors of recurrent CDI (R-CDI) after treatment have not been explored. We sought to estimate the incidence of R-CDI and its associated risk factors in patients with cirrhosis., Methods: We performed a cohort study of patients with cirrhosis hospitalized with CDI between 2012 and 2016. We collected patient characteristics, including detailed information on the CDI, features of the underlying liver disease, and outcomes including R-CDI, hospital readmission, and mortality. R-CDI was defined as CDI occurring 2-8 weeks after the initial episode. Cox proportional hazards model was used to identify variables independently associated with the outcomes., Results: A total of 257 hospitalized patients with cirrhosis and CDI were included. CDI was community associated in 22.6%. The incidence of R-CDI was 11.9%. R-CDI was not significantly associated with medications at hospital admission or discharge. Independent risk factors of R-CDI included increased Charlson Comorbidity Index (hazard ratio [HR] 1.30; 95% confidence interval [CI]: 1.09-1.55) and use of lactulose (HR 2.58; 95% CI: 1.09-6.09). The 30-day readmission rate was 37%, and readmission was associated with increased Charlson Comorbidity Index (HR 1.12; 95% CI: 1.03-1.23) and Model for End-Stage Liver Disease score (HR 1.04; 95% CI: 1.01-1.07). The 90-day mortality was 22.8%., Discussion: In patients with cirrhosis, R-CDI is associated with comorbidity burden and lactulose use. Attention to these factors might aid clinicians in efforts to prevent R-CDI and improve outcomes in this population.

Background and Aim: Few case reports exist that link lactulose use with pneumatosis intestinalis in cirrhotics. This study investigates the relationship between lactulose use and idiopathic pneumatosis intestinalis in a cohort of cirrhotic patients., Methods: This case series considers several notable cases of patients with idiopathic pneumatosis intestinalis and concurrent lactulose use. Idiopathic pneumatosis intestinalis was defined as pneumatosis intestinalis with no identifiable etiology. A cohort of 119 patients with cirrhosis and pneumatosis intestinalis were identified in a tertiary care setting, via chart review by a multidisciplinary team. Eleven of these patients were found to have idiopathic pneumatosis intestinalis. Nine of these patients were being treated with lactulose., Results: Six out of 9 patients with idiopathic pneumatosis intestinalis that were being treated with lactulose saw resolution of pneumatosis intestinalis following discontinuation of treatment., Conclusions: The etiology of idiopathic pneumatosis intestinalis is likely multifactorial, but lactulose might play a preventable role in its formation., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Clinical evidence of lactulose for chronic constipation in Japan was lacking. We performed a randomized, double-blind, placebo-controlled, dose-finding study in Japanese patients with chronic constipation to estimate the optimal clinical dose of lactulose., Methods: Overall, 250 patients were randomized to receive SK-1202 (13, 26, or 39 g/day, as crystalline lactulose dosage) or placebo twice daily (morning and evening) orally for 2 weeks. The primary endpoint was the change from baseline frequency of spontaneous bowel movements (SBMs) at Week 1. The secondary endpoints included the change from baseline of SBMs at Week 2, percentage of patients experiencing SBM within 24 and/or 48 h of the initial dose, stool consistency, and constipation severity, and adverse events were also evaluated., Results: The 26 and 39 g/day of SK-1202 induced significantly and dose-dependently more increase in SBM at Week 1 than placebo (p = 0.003, p < 0.001). These groups also showed significant improvements in the secondary endpoints. There were no significant differences in the incidence of adverse drug reactions (ADRs) between the placebo and SK-1202 groups. Gastrointestinal disorder was the most common ADR, and diarrhea developed in 6 patients (9.7%) treated with 39 g/day; however, the symptoms were mild in severity and resolved after follow-up, dose reduction, or dose suspension. SK-1202 was generally well tolerated up to 39 g/day., Conclusion: Our results suggest that SK-1202 is useful in Japanese patients with chronic constipation, and optimal dose of SK-1202 is 26 g/day.

A consolidated overview of evidence for the effectiveness and safety/tolerability of hepatic encephalopathy (HE) treatment over the long term is currently lacking. We identified and assessed published evidence for the long-term (≥6 months) pharmacological management of HE with lactulose and/or rifaximin. A literature search was conducted in PubMed (cutoff date 05 March 2018) using the search terms 'hepatic encephalopathy+rifaximin' and 'hepatic encephalopathy+lactulose'. All articles containing primary clinical data were manually assessed to identify studies in which long-term (≥6 months) effectiveness and/or safety/tolerability end points were reported for lactulose and/or rifaximin. Long-term effectiveness outcomes were reported in eight articles for treatment with lactulose alone and 19 articles for treatment with rifaximin, alone or in combination with lactulose. Long-term safety/tolerability outcomes were reported in six articles for treatment with lactulose alone and nine articles for treatment with rifaximin, alone or in combination with lactulose. These studies showed that lactulose is effective for the prevention of overt HE recurrence over the long term and that the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone, without compromising tolerability. Current evidence therefore supports recommendations for the use of lactulose therapy for the prevention of overt HE recurrence over the long term, and for the additional benefit of adding rifaximin to lactulose therapy. Addition of rifaximin to standard lactulose therapy may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization.

Objectives: The aim of this study was to compare the clinical efficacy and tolerance of polyethylene glycol 3350 (PEG) and lactulose for the treatment of functional constipation in infants and children., Methods: This randomized, multicenter study covered 12 weeks of treatment and 4 weeks of follow-up of patients with functional constipation. Patients were randomized (central randomization) to receive either PEG or lactulose. The primary end points were the number of defecations per week after 12 weeks of treatment and improvement in stool consistency of at least 2 points in the Bristol scale. The secondary end point was the presence of adverse events. Bowel movements ≥3 per week and stool consistency ≥2 (Bristol scale) were considered as successful treatment., Results: We enrolled 102 patients (M 57, F 45) aged 3.62 ± 1.42 years and 88 completed the study. At week 12, good clinical outcome was achieved in 98% (PEG) and 90% (lactulose). The PEG group had more defecations per week compared with the lactulose group (7.9 ± 0.6 vs 5.7 ± 0.5, P = 0.008) and both groups had similar frequency of defecation with pain (5% vs 5%, P = 0.9), stool retention (7% vs 10%, P = 057), large volume of stools (30% vs 31%, P = 0.9) and hard stools (7% vs 13%, P = 0.58). There were more patients with side effects in the lactulose group (15 vs 23, P = 0.02), mostly bloating and abdominal pain., Conclusions: PEG 3350 is more effective and causes fewer side effects than lactulose in the treatment of constipation in infants and children.

Background: Rifaximin and lactulose are common effective agents for hepatic encephalopathy (HE). Whether a combination of rifaximin and lactulose improves the efficacy and mortality in patients with HE compared with lactulose alone needs to be analyzed., Methods: A systematic search was performed in electronic databases and other sources for possible studies focusing on combination therapy of rifaximin and lactulose for HE between January 2000 and February 2018. A meta-analysis was performed by the method recommended by the Cochrane Collaboration, and estimated effect size was presented as risk difference (RD), 95% CI, and the number needed to treat (NNT). Subgroup analysis, sensitivity analysis, and Trial Sequence Analysis were comprehensively performed to indicate the source of heterogeneity and risk of bias., Results: Five randomized and five observational studies involving 2,276 patients were included. Combination therapy had a significant advantage in both clinical efficacy increase (RD 0.26, 95% CI 0.19-0.32, NNT 5) and mortality decrease (RD -0.16, 95% CI -0.20-0.11, NNT 9) in overall analysis. In the pooled analysis of randomized studies, combination therapy showed similar results in clinical efficacy (RD 0.25, 95% CI 0.16-0.35, NNT 4) and mortality (RD -0.22, 95% CI -0.33-0.12, NNT 5). Compared with lactulose, hospital stay was also reduced in combination therapy, and there was no significant difference in treatment-related adverse events between the two groups., Conclusion: Combination of rifaximin and lactulose has beneficial effects on HE. Compared with lactulose alone, additional rifaximin increases clinical efficacy and decreases mortality. However, its effects on different types of HE are still uncertain., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Overt hepatic encephalopathy (HE) is a frequent complication of cirrhosis and one of the most debilitating manifestations that necessitates hospitalization. Although many treatment modalities are being investigated, none of them are satisfactory. So, newer treatment modalities have to be tried., Objective: To evaluate the safety and efficacy of polyethylene glycol (PEG) versus lactulose in the management of HE., Patients and Methods: This clinical trial included 100 patients with post-hepatitis C cirrhosis who were admitted with HE. Patients were randomized into two equal groups: group I patients received lactulose and group II patients received PEG. The clinico-epidemiological characteristics of patients, Child-Pugh score, and HE scoring algorithm were registered before and 24 h after administration of the drug. Moreover, any suspected adverse effects were recorded., Results: All 100 patients received treatment. Three patients died within 24 h of admission and did not complete the follow-up period. According to intention-to-treat approach, they were considered as treatment failure. On analysis, 36/50 (72%) patients improved one grade or more in HE scoring algorithm score after 24 h of lactulose therapy versus 47/50 (94%) of those on PEG therapy (P<0.05). The time needed for resolution of HE and length of hospital stay were significantly lower in PEG group versus lactulose group (P<0.001). Both therapies were tolerated, and no significant adverse events were reported., Conclusion: Both lactulose and PEG were safe and effective in the treatment of HE. PEG significantly decreased the time needed for resolution of HE and significantly shortened the hospital stay.

Objectives: Estimate incidence, determine risk factors and propose a prediction model for the development of incontinence- associated dermatitis critically ill adult patients., Method: Concurrent cohort study with 157 critically ill patients. Data collection was daily performed between February and July 2015, at a public teaching hospital of Belo Horizonte, Minas Gerais. Data was entered in a database and subjected to descriptive, survival and multivariate analysis., Results: An overall incidence of 20.4% was obtained. Nineteen (19) risk factors significantly associated with the disorder were found. The variables identified in the risk prediction model were male, trauma, use of hypnotics/sedatives, lactulose, nutritional support, loose stools and complaints of burning., Conclusion: The results showed that dermatitis is a common clinical finding in critically ill adult patients and requires special attention from the nursing staff.

Introduction: Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE., Material and Methods: In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months., Results: Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn't. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse., Conclusion: Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Objectives: To assess the tolerance and potential nutritional consequences of long-term repeated doses of PEG 4000 (10 to 30 g/day) in elderly patients with chronic constipation as compared to lactulose (10-30 g/day)., Design: Single blind, randomised, multicentre, parallel group comparative study., Setting: Community-dwelling patients and nursing homes residents aged 70 years and older with a history of chronic constipation. Treatment intervention: PEG 4000 (10-30 g/day) or lactulose (10-30 g/day) for six months., Assessments: Clinical nutritional status (Mini Nutritional Assessment), blood and stool samples were taken at baseline and after three and six months for assay of nutritional and absorption parameters. A patient diary documented digestive symptoms and adverse events were recorded. Information on efficacy (stool frequency and consistency) was collected as a secondary outcome measure., Results: Of the 316 patients screened, 245 eligible patients constituted the ITT population (PEG 4000: N = 118; lactulose group: N = 127). The proportion of patients receiving PEG 4000 with abnormal levels of electrolytes, nutritional markers or vitamins did not significantly change in the six months after initiating laxative treatment and do not differ between the two groups. After a D-xylose challenge test, the proportion of patients with abnormally low xylosaemia (suggesting malabsorption) varied from 24.6% at baseline to 35.8% after six months in the PEG 4000 group and from 29.1% to 42.4% in the lactulose group, with no significant between-group or within-group differences. The proportion of patients with poor nutritional status (MNA score <17) varied from 8.5% at baseline to 9.8% after 6 months in the PEG 4000 group and from 3.9% to 5.0% in the lactulose group. No changes in stool fat or total or soluble stool nitrogen were observed in the minority of patients for whom stool analysis was performed. A significantly higher stool frequency (p <0.05) and improved stool consistency (p <0.05) was observed in the PEG 4000 group compared to the lactulose group at each monthly evaluation period., Conclusions: After six months of treatment with PEG 4000, no clinically relevant changes in biochemical and nutritional parameters and no unanticipated treatment-related adverse events were detected, demonstrating the good clinical tolerance of PEG 4000 in this population of elderly constipated patients. This tolerance was associated with a better clinical efficacy of PEG 4000 compared to lactulose., Competing Interests: This study was initiated and funded by IPSEN (Boulogne-Billancourt, France), the manufacturer of PEG 4000 (Forlax®). PC was the principal investigator of the study and advised on the study design, the interpretation of data, the writing of the report, and in the decision to submit the paper for publication. PG and HMF are employees of Ipsen; PC received consultancy fees in recognition of his contribution to the study.

Background: Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice., Objectives: We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation., Search Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialized Trials Register from inception to 10 March 2016. There were no language restrictions. We also searched the references of all included studies, personal contacts and drug companies to identify studies., Selection Criteria: Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives to placebo or another intervention, with participants aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events., Data Collection and Analysis: Relevant papers were identified and two authors independently assessed the eligibility of trials, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. For continuous outcomes we calculated the mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated the risk ratio (RR) and 95% CI using a fixed-effect model. The Chi(2) and I(2) statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity. We assessed the overall quality of the evidence supporting the primary and secondary outcomes using the GRADE criteria., Main Results: Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed guar gum and lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95)., Authors' Conclusions: The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil). There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin. The optimal dose of PEG also warrants further investigation.

The aim of the study was to investigate the efficacy of combined application of lactulose oral solution and polyethylene glycol electrolyte powder compared with conventional method in preparing for colonoscopy bowel cleanliness in patients with constipation. Ninety patients, who had constipation and needed to have colonoscopy, were divided into study group and control group with 45 cases in each group, respectively. One day before the colonoscopy, patients in the experimental group were given lactulose oral solution and polyethylene glycol electrolyte powder, whereas the patients in the control group were given oral polyethylene glycol electrolyte powder only. The following parameters were then obtained: time of the first defecation (duration of the time from taking the drugs to the first bowel movement), defecation frequency, completion of bowel cleaning (duration from the first bowel movement to the stool becoming clear), and adverse reaction. Cleansing effect in the study group bowel preparation was significantly better than that in the control group (P < 0.05). Specifically, time of the first defecation and completion of bowel cleaning were statistically shorter in the study group than those in the control group (P < 0.05), and defecation frequency was significantly higher in the study group than that in the control group (P < 0.05). Incidence of adverse reaction, however, was not significantly different between the 2 groups (P > 0.05). Combined application of lactulose oral solution and polyethylene glycol electrolyte powder is superior to the conventional method of polyethylene glycol electrolyte powder alone for colonoscopy bowel preparation in patients with constipation. Therefore, combined clinical application of the 2 compounds is strongly recommended for colonoscopy bowel preparation in patients with constipation.

Background & Aims: Lactulose and rifaximin have already been shown to improve both cognitive functions and health related quality of life (HRQOL) in MHE patients. We aimed to compare the efficacy of rifaximin with lactulose in reversal of MHE and improvement in HRQOL in cirrhotic patients with MHE., Method: This prospective, randomized, open label, non-inferiority trial, was conducted at the Gastroenterology department of a tertiary care institute in Northern India. MHE was diagnosed if any two of the five neuro-psychometric (NP) tests were positive. HRQOL was assessed using the sickness impact profile (SIP) questionnaire (John Hopkins University, USA)., Results: Of 527 cirrhotics screened, 351 were found eligible and tested for MHE. A total of 112 (31.9%) patients were found to have MHE and then randomized into two groups group A (lactulose; 30-120 ml/day) and B (Tablet. rifaximin; 400 mg thrice a day). Based on the intention-to-treat population, the proportion of patients with MHE reversal at 3 months was 73.7% (42/57) in the rifaximin arm and 69.1% (38/55) in the lactulose arm [4.6% difference (90% CI -9.3% to 18.4%)]. However, non-inferiority of rifaximin over lactulose could not be established as the pre-specified non-inferiority margin (-5%) lies within the two-sided 90% confidence interval of the difference. HRQOL was significantly improved in both groups (P = 0.20). However, the proportion of patients with flatulence (P = 0.004) and diarrhoea (P = 0.0002) was significantly higher in patients who took lactulose., Conclusion: Non-inferiority of rifaximin over lactulose for MHE reversal was not established., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To manage chronic constipation, numerous lifestyle modification schemes and recommendations as well as applications of natural medicaments have been mentioned in manuscripts of traditional Persian medicine (TPM). This study was aimed to compare the impacts of some of those recommendations with lactulose, on functional chronic constipation., Methods: Via a blocked randomization, 100 patients were enrolled. Schemes and recommendations from TPM as intervention group were evaluated versus lactulose as control by weekly follow-ups with standard questionnaire for 3 months. Stool frequency, hard stool, painful defecation, incomplete evacuation sensation, anorectal obstruction sensation and manual maneuvers were considered as outcome measures., Results: Eighty-six patients (42 in schemes and 44 in lactulose groups) completed the study. Median weekly stool frequency in 0, 4, 8 and 12 weeks of treatment was 1.76±1.79, 2.88±0.89, 2.95±1.05 and 2.93±1.11 in the schemes and 2.41±1.67, 2.57±0.90, 2.84±0.91 and 2.77±1.00 in lactulose groups, respectively (p=0.10, 0.11, 0.60, 0.51). Thirty-two (76.2%) patients in schemes and 24 (54.5%) patients in lactulose groups were treated at the end of the protocol as they did not meet the Rome III criteria for constipation (p=0.04). In schemes group, patients reported no undesirable effects, whereas seven (15.9%) in lactulose group reported flatulence (p=0.02)., Conclusions: Studied schemes were as effective as lactulose, a gold standard to manage constipation. Results demonstrated that TPM schemes and recommendations, as lifestyle modification, for at least 3 months can be introduced as cheap, available and accessible approaches for the management of constipation.

Background: Postprandial discomfort following intake of poorly absorbable, but fermentable carbohydrates is a common complaint in patients with irritable bowel syndrome (IBS). We used lactulose as a model substance for this group of symptom triggering carbohydrates, aiming to visualize the intestinal response in IBS patients compared to healthy controls., Methods: Patients with IBS according to Rome III criteria (n = 52) and healthy controls (n = 16) underwent a lactulose challenge test. By using magnetic resonance imaging, we measured small bowel water content (SBWC), and distension (diameter) of the distal ileum and the colon, both in fasting state and 1 h after ingestion of 10 g lactulose. We recorded symptoms after lactulose ingestion., Key Results: Lactulose provoked significantly more symptoms in IBS patients than in healthy controls (p < 0.0001). SBWC increased more in the patient group compared to the control group (p = 0.0005). The postprandial diameter of the terminal ileum was larger in patients with IBS and the postprandial diameter of the ascending colon was smaller in patients with diarrhea-predominant phenotype (IBS-D). Symptoms were not correlated with change in SBWC (r = 0.05; p = 0.11), nor to the diameters of the terminal ileum or the colon., Conclusions & Inferences: Compared to healthy controls, IBS patients developed more symptoms and had an abnormal accumulation of fluid in the small bowel in response to ingestion of the unabsorbable carbohydrate lactulose. This may be due to impaired motor activity of the small intestine or impaired function of the ileocecal segment., (© 2014 John Wiley & Sons Ltd.)

Background: Colonoscopy is the most frequent exam used to evaluate colonic mucosa, allowing the diagnosis and treatment of many diseases. The appropriate bowel preparation is indispensable for the realization of colonoscopy. Therefore, it is necessary the use of laxative medications, preferentially by oral administration., Aim: To compare two medications used in bowel preparation in adult patients going to ambulatory colonoscopy and to analyze the patients' profile., Methods: A double-blind prospective study with 200 patients, randomized in two groups: one that received polyethilene glycol and another that received lactulose. The patients answered to questionnaires to data compilation, as tolerance, symptoms and complications related to preparation. Besides, it was also evaluated the prepare efficacy related to the presence of fecal residue., Results: Intestinal habit alterations and abdominal pain were the main reasons to realize the exams and hypertension was the most prevalent comorbidity. Ten percent of the ones who received lactulose didn't get to finish the preparation and 50% considered the taste "bad, but tolerable". The most common subjective symptom after the medication was nausea, especially after lactulose. During the exam, most of the patients who used lactulose had a "light discomfort" and the ones who used polyethilene glycol considered the discomfort as "tolerable". The quality of the preparation was good in 75%, undependable of the medication that was used., Conclusion: Polyethilene glycol was more tolerable when compared to lactulose, without difference on the quality of the preparation.

Unlabelled: Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality., Objectives: To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults., Methods: A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria., Conclusions: Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Chronic functional constipation is a common disorder in childhood. The treatment most often consists of the modalities education, disimpaction and maintenance. In a recent Cochrane review of maintenance treatment polyethylene glycol (PEG) seems to be superior to placebo and to other laxatives including lactulose. This conclusion is in line with practice at most paediatric departments in Denmark. Still, larger randomized controlled studies with the curing of constipation as the primary end point are needed.

Background: It has been reported that adequate calcium intake decreases body fat and appropriate intakes of magnesium suppress the development of the metabolic syndrome. Furthermore, lactulose increases the absorption of calcium and magnesium. An optimal combination of calcium, magnesium and lactulose may therefore reduce body fat mass., Methods: An open-label randomized controlled trial was conducted to investigate the body fat-reducing effects of a test food containing 300 mg calcium, 150 mg magnesium, and 4.0 g lactulose. Body composition parameters and blood hormone and urine mineral concentrations were measured at baseline and at 6 and 12 months thereafter. Whole-body fat mass was measured with dual-energy x-ray absorptiometry., Results: Seventy-six middle-aged Japanese women (47.5±4.7 years) were randomized to the intake group (n=48) or the non-intake control group (n=28). At 12 months the difference in body fat mass change between the two groups (intake group - control group) was -0.8 kg (95% CI: -1.5 - 0.0 kg, p=0.046), although there were no differences in anthropometric data between the two groups. Body fat percentage at 12 months tended to be lower in the intake group, but the difference was not significant (p=0.09)., Conclusions: These findings may suggest that calcium in combination with magnesium and lactulose can reduce body fat mass in middle-aged Japanese women. However, the contribution of magnesium and lactulose are unclear in this study. Further studies are needed to clarify these contributions.

Background and Aim: Development of overt hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of overt HE using lactulose in patients who never had HE earlier., Methods: Consecutive cirrhotic patients who never had an episode of overt HE were randomized to receive lactulose (Gp-L) or no lactulose (Gp-NL). All patients were assessed by psychometry (number connection test [NCT-A and B], figure connection test if illiterate [FCT-A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed every month for 12 months for development of overt HE., Results: Of 250 patients screened, 120 (48%) meeting the inclusion criteria were randomized to Gp-L (n = 60) and Gp-NL (n = 60). Twenty (19%) of 105 patients followed for 12 months developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp-L) group and 14 (28%) of 50 in the Gp-NL (P = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp-NL and five (9%) of 55 patients in the Gp-L group died, P = 0.16. Number of patients with minimal hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp-L vs Gp-NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp-L. Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were 52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate analysis, Child's score and presence of MHE at baseline were significantly associated with development of overt HE., Conclusions: Lactulose is effective for primary prevention of overt hepatic encephalopathy in patients with cirrhosis., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice., Objectives: We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation., Search Methods: The search (inception to May 7, 2012) was standardised and not limited by language and included electronic searching (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register), reference searching of all included studies, personal contacts and drug companies., Selection Criteria: Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives with either placebo or another intervention, with patients aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events., Data Collection and Analysis: Relevant papers were identified and the authors independently assessed the eligibility of trials. Methodological quality was assessed using the Cochrane risk of bias tool.The Cochrane RevMan software was used for analyses. Patients with final missing outcomes were assumed to have relapsed. For continuous outcomes we calculated a mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated an odds ratio (OR) and 95% confidence intervals (95% CI) using a fixed-effect model. The chi square and I(2) statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity, Main Results: Eighteen RCTs (1643 patients) were included in the review. Nine studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Meta-analysis of 4 studies with 338 participants comparing PEG with lactulose showed significantly greater stools per week with PEG (MD 0.95 stools per week, 95% CI 0.46 to 1.44), although follow up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent of PEG patients required additional therapies compared to 30% of lactulose patients (OR 0.49, 95% CI 0.27 to 0.89). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools/wk was significantly greater with PEG (MD 0.69 stools per week, 95% CI 0.48 to 0.89). However, the magnitude of this difference is quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring paraffin (MD 4.94 stools per week, 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), and PEG and liquid paraffin (1 study, 158 patients, MD 0.70, 95% CI -0.38 to 1.78)., Authors' Conclusions: The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow up. However, PEG appears safe and well tolerated. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil), which was also well tolerated.There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin.

Objective: To evaluate the clinical efficacy of lactulose in patients with minimal hepatic encephalopathy (MHE)., Methods: Randomized controlled trials (RCTs) comparing lactulose with placebo or with no intervention in the management of MHE that were conducted from January 1990 to July 2011 were searched from MEDLINE, EMBASE, SCI, Cochrane Controlled Trials Register, and China Biological Medicine Database. Studies with a Jadad score higher than 3 were included in the meta-analysis and evaluated using RevMan5.0 software for relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (95% CI). Sensitivity analysis was performed on the ethnical differences and quality of the trials. Publication bias was observed using an inverted funnel plot., Results: Nine studies with 434 patients were included in the meta-analysis. Compared with placebo or no intervention, lactulose significantly reduced the risk of no improvement in neuropsychological tests (RR: 0.52, 95% CI: 0.44-0.62, P<0.00001), the time required for the completion of the number connection test-A (WMD: -26.95, 95% CI: -37.81 to -16.10, P<0.00001), and the mean number of abnormal neuropsychological tests (WMD: -1.76, 95% CI: -1.96 to -1.56, P<0.00001). Furthermore, the meta-analysis also showed that lactulose prevented the progression to overt hepatic encephalopathy (RR: 0.17, 95% CI: 0.06-0.52, P=0.002), reduced blood ammonia levels (WMD: -9.89 µmol/l, 95% CI: -11.01 to -8.77 µmol/l, P<0.00001), and improve health-related quality of life (WMD: -6.05, 95% CI: -6.30 to -5.20, P<0.00001). However, no significant difference was observed in the mortality of patients with MHE (RR: 0.75, 95% CI: 0.21-2.72, P=0.66), and lactulose significantly increased the incidence of diarrhea (RR: 4.38, 95% CI: 1.35-14.25, P=0.01)., Conclusion: Lactulose has significant beneficial effects for patients with MHE compared with placebo or no intervention.

Background and Aims: Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB., Methods: Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group-L) or no lactulose (Group-P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization., Results: Seventy patients were randomized into group-L (Gp-L, n = 35) and group-P (Gp-P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp-L vs Gp-P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp-L and 14 patients (40%) in Gp-P, P = 0.03. The median grade of HE was 2 (range 2-4) and median time interval of development of HE after randomization was 2 days (range 1-4). Nine patients (13%) died; three (8.5%) patients in Gp-L and six (17%) patients in Gp-P, P = 0.23. Patients who developed HE had significantly higher baseline Child-Turcotte-Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10,505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE., Conclusions: Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Previous studies suggest that rifaximin is efficacious in the treatment of hepatic encephalopathy., Objective: To evaluate the efficacy and safety of rifaximin in addition to lactulose in improving hospitalization outcomes in patients with hepatic encephalopathy., Methods: Hospital records of patients evaluated for liver transplantation at a single center between January 2006 and May 2008 were reviewed. Hospitalizations for hepatic encephalopathy and other conditions and the incidence of spontaneous bacterial peritonitis and adverse events were analyzed., Results: Charts of 65 patients who were treated with rifaximin and lactulose were analyzed. Patients received lactulose (20-120 g/d; lactulose phase) before treatment with rifaximin (400- 1200 mg/d; rifaximin phase). During the rifaximin phase, the risk, number, and duration of hospitalizations for hepatic encephalopathy were reduced compared with the lactulose phase. Treatment, age, and Model for End-Stage Liver Disease score were independent predictors of hospitalizations for hepatic encephalopathy (P < .05). The rifaximin phase had fewer hospitalizations than the lactulose phase (36 vs 47, respectively) and a smaller percentage of patients with repeated hospitalizations than the lactulose phase (5% vs 14%, respectively; P = .006) for conditions other than hepatic encephalopathy. A smaller percentage of patients had evidence of spontaneous bacterial peritonitis during the rifaximin phase than the lactulose phase (2% vs 12%, respectively; P = .02). Rifaximin was better tolerated than lactulose., Conclusions: Addition of rifaximin to lactulose therapy significantly reduced the risk and duration of hospitalizations for hepatic encephalopathy., (Copyright © 2010. Published by Elsevier Inc.)

Background/aims: In the present study, we aimed to investigate if partially hydrolyzed guar gum (PHGG) can be used safely as a fiber source for treatment of constipation in children and to compare its success with the most commonly used osmotic laxative, lactulose., Methods: A randomized prospective controlled study on 61 patients (partially hydrolyzed guar gum group, n: 31; lactulose group, n: 30) was performed. Patients were given lactulose or partially hydrolyzed guar gum for four weeks. Using a standardized bowel diary, defecation frequency, stool consistency, and presence of flatulence and abdominal pain were recorded. Family questionnaires about the success, safety and side effect profile of both treatment arms were also obtained., Results: No significant differences were found in the baseline daily fiber (fruits and vegetables) intake between the two groups. Bowel movement frequency per week and stool consistency improved significantly in both treatment groups (p<0.05). The percent of children with abdominal pain and stool withholding also decreased eminently in both groups (p<0.05). Weekly defecation frequency increased from 4±0.7 to 6±1.06 and from 4±0.7 to 5±1.7 in the lactulose and partially hydrolyzed guar gum treated groups, respectively (p<0.05). According to the family questionnaire, the parents complained of bad taste, flatulence and necessity to ingest a high amount of drug in the lactulose treatment group. In the partially hydrolyzed guar gum treatment group, parents were satisfied with the defecation frequency of their children., Conclusions: Treatment with partially hydrolyzed guar gum is as effective as lactulose treatment in relieving stool withholding and constipation-associated abdominal pain, and its use improves stool consistency. Lactulose seemed to have more side effects, including flatulence and sensation of bad taste.

Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use. Management of HE primarily involves avoidance of precipitating factors, limitation of dietary protein intake, and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and select antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. However, multiple adverse events have been associated with their use. In addition, recent literature has questioned the true efficacy of the disaccharides for this indication. Neomycin, metronidazole and vancomycin may be used as alternative treatments for patients intolerant or unresponsive to non-absorbable disaccharides. Antimicrobials reduce bacterial production of ammonia and other bacteria-derived toxins through suppression of intestinal flora. Neomycin has been reported to be as effective as lactulose, and similar efficacy has been reported with vancomycin and metronidazole for the management of HE. However, the adverse effects frequently associated with these antimicrobials limit their use as first-line pharmacological agents. Neomycin is the most commonly used antimicrobial for HE and, although poorly absorbed, systemic exposure to the drug in sufficient amounts causes hearing loss and renal toxicity. Long-term neomycin therapy requires annual auditory testing and continuous monitoring of renal function. Long-term use of metronidazole has been associated with neurotoxicity in patients with cirrhosis, including dose-dependent peripheral neuropathy. Vancomycin may be a safer option for HE in patients with chronic liver disease; however, limited experience, possible bacterial overgrowth and risk for enteric bacteria resistance preclude the routine use of vancomycin for HE. Rifaximin is a novel antimicrobial agent with a wide spectrum of activity that has shown promise as an alternative antimicrobial treatment option for HE. Several clinical trials have compared rifaximin to the disaccharides, lactulose and lactitol, and the antimicrobial neomycin. Rifaximin appears to be at least as effective as conventional drug therapy and has been associated with fewer adverse effects due to its limited systemic absorption. The available clinical data appear to support a favourable benefit-risk ratio for rifaximin, which has shown efficacy with an improved tolerability profile. Future studies are needed in order to truly characterize its cost effectiveness in today's healthcare environment. Other less frequently utilized alternative treatment options include administration of benzodiazepine receptor antagonists, branched-chain amino acids, ornithine aspartate, zinc supplementation, sodium benzoate, dopamine receptor agonists, acarbose and probiotics. Presently, there is relatively limited clinical data supporting their routine use in HE.

Background: Lactulose is considered first-line therapy for hepatic encephalopathy. However, the effect of adherence with lactulose on recurrence of hepatic encephalopathy outside clinical trials remains unclear., Aim: To determine the association of lactulose use with recurrence of hepatic encephalopathy episodes., Methods: Patients with cirrhosis who were initiated on lactulose after an index hepatic encephalopathy episode in a liver-transplant centre were retrospectively reviewed. Recurrence of hepatic encephalopathy, precipitating factors and adherence on lactulose were investigated using chart review and electronic pharmacy records. Patients with/without hepatic encephalopathy recurrence were compared, and predictors of recurrence were analysed., Results: A total of 137 patients with cirrhosis (age 55 +/- 6years, MELD 17 +/- 7) who were initiated on lactulose after the index hepatic encephalopathy episode were included. Of these, 103 patients developed recurrent hepatic encephalopathy 9 +/- 1 months after their index episode; 39 (38%) of these were not adherent on lactulose, 56 (54%) were adherent and 8 (8%) had lactulose-associated dehydration leading to recurrence. Recurrent hepatic encephalopathy precipitants in lactulose-adherent patients were sepsis (19%), GI bleeding (15%), hyponatremia (4%) and TIPS (7%). Overall, all patients who did not suffer recurrence were adherent on lactulose. In contrast, the adherence rate for those who recurred was only 64% (P = 0.00001). On multivariate regression, lactulose non-adherence (OR 3.26) and MELD score (OR 1.14) were the factors that predicted recurrence., Conclusion: Lactulose non-adherence and lactulose-associated dehydration were associated with nearly half of recurrent hepatic encephalopathy episodes.

Noncompliance with treatment protocols produces an increased burden on the health care system. Reports show that 23% of annual admissions to nursing homes in the United States (380,000 patients) are due to noncompliance, resulting in overall costs of over $31 billion. More than 10% of all patients (3.5 million) are hospitalized each year due to complications related to noncompliance, with over $15 billion spent. In addition, nearly half of the 2 billion prescriptions filled each year are not taken correctly. Patients with cirrhosis and hepatic encephalopathy who are prescribed lactulose experience a greater frequency of adverse effects, require more hospitalizations, and suffer more disease recurrence than those prescribed rifaximin.