Evaluation of bowel preparation regimens for colonoscopy including a novel low volume regimen (Plenvu): CLEANSE study.

BACKGROUND: Poor bowel preparation is the leading cause of failed colonoscopies and increases costs significantly. Several, split preparation, 2 day regimens are available and recently, Plenvu, a low-volume preparation which can be given on 1 day has been introduced. AIMS: Assess efficacy and tolerability of commonly used purgative regimens including Plenvu. METHOD: In this service evaluation, patients undergoing screening colonoscopy at St Mark's Hospital, London (February 2020-December 2021) were provided Plenvu (1 or 2 days), Moviprep (2 days) or Senna & Citramag (2 days).Boston Bowel Preparation Scale (BBPS) score, fluid volumes and procedure times were recorded. A patient experience questionnaire evaluated taste, volume acceptability, completion and side effects. RESULTS: 563 patients were invited to participate and 553 included: 218 Moviprep 2 days, 108 Senna & Citramag 2 days, 152 Plenvu 2 days and 75 Plenvu 1 day.BBPS scores were higher with Plenvu 1 and 2 days vs Senna & Citramag (p=0.003 and 0.002, respectively) and vs Moviprep (p=0.003 and 0.001, respectively). No other significant pairwise BBPS differences and no difference in preparation adequacy was seen between the groups.Patients rated taste as most pleasant with Senna & Citramag and this achieved significance versus Plenvu 1 day and 2 days (p=0.002 and p<0.001, respectively) and versus Moviprep (p=0.04). CONCLUSION: BBPS score was higher for 1 day and 2 days Plenvu versus both Senna & Citramag and Moviprep. Taste was not highly rated for Plenvu but it appears to offer effective cleansing even when given as a same day preparation.

Sennoside A protects mitochondrial structure and function to improve high-fat diet-induced hepatic steatosis by targeting VDAC1.

Mitochondrial dysfunction is mainly associated with high-fat-diet (HFD)-induced hepatic steatosis. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve energy metabolism and insulin resistance. However, the effect and mechanism of SA on HFD-induced hepatic steatosis remain largely unknown. The aim of this study was to determine the effect and mechanism of SA on HFD-induced hepatic steatosis in mice. We examined the liver and body weight of mice to evaluate the physical changes in the liver. Hematoxylin and eosin (H&E) and oil red O staining were used to detect the lipid accumulation. The mitochondrial structure and function were tested by transmission electron microscopy and the Seahorse XF24 Analyzer. Furthermore, mitochondrial complexes I, II, and IV and voltage-dependent anion channel 1 (VDAC1) protein activity were detected to understand the mechanism of the protective effect on mitochondria. As a result, damage to the structure and function in the hepatic mitochondria of HFD-induced hepatic steatosis was observed in mice. The structural damage was in the form of loss of cristae, mitochondrial swelling, vacuolization and even rupturing of the outer mitochondrial membrane (OMM). Functional alterations were found by activation of complex I and deficiency in complexes II and IV. The VDAC1 activity and the total ATP in the liver tissue was increased under hepatic steatosis conditions. The above effects were reversed by SA. These data suggest that inhibition of VDAC1 may be an underlying mechanism of SA for protecting mitochondria in HFD-induced hepatic steatosis in mice. Thus, VDAC1 may be a promising target for treating fatty liver disease.

Are Senna based laxatives safe when used as long term treatment for constipation in children?

BACKGROUND AND AIM: Senna is a stimulant laxative commonly used by pediatricians, pediatric gastroenterologists, and pediatric surgeons. Many clinicians avoid Senna for reasons such as tolerance or side effects but this has little scientific justification. We recently found several patients we were caring for developed perineal blistering during the course of Senna treatment. Because of this we chose to review the literature to identify side effects in children taking this medication as well as to analyze our Center's experience with Senna's secondary effects. METHODS: We performed a literature review (MEDLINE, PUBMED) using the keywords of Senna, sen, sennosides and children, and pediatric and functional (idiopathic) constipation. We looked for articles with information regarding perineal blisters related to Senna as well as other secondary effects of Senna laxatives in children when used on a long-term basis. We also reviewed the charts of our patients who had previously taken Senna or are currently taking Senna, looking for adverse reactions. RESULTS: Eight articles in the literature reported perineal blisters after administration of Senna laxatives in 28 patients. Of those occurrences, 18 patients (64%) had accidental administration of Senna and 10 (36%) had Senna prescribed as a long term treatment. All of the blistering episodes were related to high dose, night-time accidents, or intense diarrhea with a long period of stool to skin contact. At our institution, from 2014 to 2017, we prescribed Senna and have recorded data to 640 patients. During the study period, 17 patients (2.2%) developed blisters during their treatment. Patients who developed blisters had higher doses 60mg/day; 60 [12-100] vs. 17.5 [1.7-150] (p<0.001). All of the blistering episodes were related to night-time accidents, with a long period of stool to skin contact. 83 (13%) patients presented minor side effects such as abdominal cramping, vomiting or diarrhea which resolved once the type of laxatives were changed or enemas were started. The doses of Senna was not significantly different in these patients 15mg/day [4.4-150] vs. 17.5mg/day [1.5-150]. There were no other long-term side effects from Senna found in the pediatric literature for long-term treatment besides abdominal cramping or diarrhea during the first weeks of administration. We found no evidence of tolerance to Senna in our review. CONCLUSION: There is a paucity of information in the literature regarding side effects of sennosides as a long-term therapy, and to our knowledge, this is the first review of Senna side effects in children. Senna induced dermatitis is rare, but may occur when patients need a higher dose. All of the cases described had a long period of exposure of the skin to stool. Besides the perineal rash with blisters, we could find no other described major side effect with Senna administration in the pediatric population or evidence of the frequently mentioned concern of the development of tolerance to Senna. Pediatric caregivers should advise families of the rare side effect of skin blistering and educate them to change the diaper frequently in children who are not toilet- trained to reduce stool to skin exposure. We can conclude from this review that Senna is a safe treatment option for constipation in children. LEVEL OF EVIDENCE: IV.

Idiopathic constipation: A challenging but manageable problem.

PURPOSE: A protocol to treat idiopathic constipation is presented. METHODS: A contrast enema is performed in every patient and, when indicated, patients are initially submitted to a "clean out" protocol. All patients are started on a Senna-based laxative. The initial dosage is empirically determined and adjusted daily, during a one week period, based on history and abdominal radiographs, until the amount of Senna that empties the colon is reached. The management is considered successful when patients empty their colon daily and stop soiling. If the laxatives dose provokes abdominal cramping, distension, and vomiting, without producing bowel movements, patients are considered nonmanageable. RESULTS: From 2005 to 2012, 215 patients were treated. 121 (56%) were males. The average age was 8.2years (range: 1-20). 160 patients (74%) presented encopresis. 67 patients (32%) needed a clean out. After one week, 181 patients (84%) achieved successful management, with an average Senna dose of 67mg (range: 5-175mg). In 34 patients (16%) the treatment was unsuccessful: 19 were nonmanageable, 3 noncompliant, and 12 continued soiling. At a later follow-up (median: 329days) the success rate for 174 patients was 81%. CONCLUSION: We designed a successful protocol to manage idiopathic constipation. The key points are clean out before starting laxatives, individual adjustments of laxative, and radiological monitoring of colonic emptying. TREATMENT STUDY: Level IV.

Assessment and treatment options for patients with constipation.

Constipation is a common complaint for people of all ages, with prevalence increasing with age and during pregnancy. Women are more likely to be affected than men. Severity of constipation varies from person to person; most people experience short periods of constipation during their lives, including possibly after surgery, while others have constipation as a chronic long-term condition that can significantly affect their quality of life. There are a number of factors that can contribute to developing constipation including diets low in fibre, changes in lifestyle, side effects of certain medications and low fluid intake. People can successfully treat constipation by making changes to their diet and lifestyle. However, medication may be required to manage constipation for some.

Effectiveness of senna vs polyethylene glycol as laxative therapy in children with constipation related to anorectal malformation.

PURPOSE: Constipation is present in 80% of children with corrected anorectal malformations, usually associated to rectal dilation and hypomotility. Osmotic laxatives are routinely used for idiopathic constipation. Senna is a stimulant laxative that produces contractions improving colonic motility without affecting the stool consistency. We designed this trial to study the effectiveness of Senna versus polyethylene glycol for the treatment of constipation in children with anorectal malformation. METHODS: A randomized controlled crossover design clinical trial, including a washout period, was conducted, including children with corrected anorectal malformations with fecal continence and constipation. The sample size was calculated for proportions (n=28) according to available data for Senna. Effectiveness of laxative therapy was measured with a three variable construct: 1) daily bowel movement, 2) fecal soiling, 3) a "clean" abdominal x-ray. Data analysis included descriptive statistics and a Fisher's exact test for the outcome variable (effectiveness). RESULTS: The study was terminated early because the interim analysis showed a clear benefit toward Senna (p = 0.026). The sample showed a normal statistical distribution for the variables age and presence of megarectum. The maximum daily dose of Senna (sennosides A and B) was 38.7mg and 17g for polyethylene glycol. No adverse effects were identified. CONCLUSION: Therapy with Senna should be the laxative treatment of choice as part of a bowel management program in children with repaired anorectal malformations and constipation, since the stimulation of colonic propulsion waves could lead to stool evacuation without modification of its consistency which can affect fecal continence. LEVEL OF EVIDENCE: I - randomized controlled trial with adequate statistical power.

Osmotic and stimulant laxatives for the management of childhood constipation.

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.

Opioid consumption and bowel dysfunction in adolescents after spinal surgery.

The study, outlined in this article, aimed to ascertain the effect of length of surgery and opioid consumption on length of stay and bowel dysfunction, and to review current post-operative bowel practices. A retrospective case note review was carried out of all patients with a diagnosis of adolescent idiopathic scoliosis (n=44) who had undergone a posterior spinal fusion between January 2012 and May 2014. Mean length of surgery was 3:24 hours (±0:40 hours), while average length of stay was 6 days (mean 6.27 days ±2.39). Average opioid consumption post-operatively was 152.15mg (±60.95mg). There were no statistically significant associations. Some form of laxative was received by 93% of (n=41) patients. Of those, 20 required an enema before discharge. This was most commonly administered on post-operative days four and five (65%). This service evaluation demonstrated that length of surgery and amount of opioid have no significant effect on length of stay for young people following a posterior spinal fusion. It is suggested that lactulose and senna are given in combination at doses as per the British National Formulary for Children starting on post-operative day two, which should avoid the need to administer an enema.

[Preliminary study of history of senna be used in China--On phenomenon about "reign medicine localized"].

Senna is one of the commonly used traditional Chinese medicine at present. After the preliminary research that the drug medication history in China is not long, in our country ancient times, only "Hui prescription" in the records, other all kinds of traditional Chinese medicine literature rarely mentioned. Since modern times, the Chinese medicine in the medicine in the literature of the time and the modern western medicine books in the Chinese version of the time generally close, may be related to the introduction of Western medicine. At the end of Qing Dynasty and the early Republic of China, Chinese literature about the drug property theory of herbal medicine is seldom discussed, and had been seen as "western medicine" (foreign medicine), with the medication experience continue to accumulate, widespread popularity and other factors, the drug gradually Chinese scholars have constructed a relatively complete theory of the resistance, so as to realize the "localization".

Contrast enema as a guide for senna-based laxatives in managing overflow retentive stool incontinence in pediatrics.

OBJECTIVES: Overflow retentive stool incontinence (ORSI) is secondary to constipation and fecal loading. In our study, the dose and duration of senna-based laxatives (SBL) treatment to achieve full defecatory control will be examined for possible correlation with new parameters measured from the initial contrast enema. METHODS: Initially, an observational study was conducted prospectively on a group of patient with ORSI to define the optimum dose of SBL to achieve full defecatory control with measurement of six parameters in the initial contrast enema (level of colonic dilatation, recto-anal angle, ratio of maximal diameter of dilated colon to last lumbar spine, ratio of maximum diameter of dilated colon to normal descending colon, immediate and after 24-h post-evacuation residual contrast). The result was analyzed statistically to reach a correlation between the radiological data and prescribed dose. RESULTS: Over 2 and half years, 72 patients were included in the study; their mean age was 6.3 ± 3.33 years. The mean effective starting dose of SBL was 57 ± 18.13 mg/day and the mean effective ending dose was 75 ± 31.68 mg/day. Time lapsed till full defecatory control ranged from 1 to 16 weeks. Statistical correlation revealed that mean effective ending dose of SBL treatment significantly increased with higher levels of colonic dilatation. A weak positive correlation was found for both the mean effective starting and ending doses with the ratio of maximum colonic diameter to last lumbar spine and descending colonic diameters ratio. CONCLUSION: Senna-based laxatives are effective treatment for overflow retentive stool incontinence and their doses can be adjusted initially depending on the analysis of the radiological data.

What is the main target: a clearer colon with a sennoside-based regime, or adequate bowel cleansing before colonoscopy with a PEG-EL-based regime?

BACKGROUND/AIM: Even though polyethylene glycol-electrolyte lavage (PEG-EL)-based regimes have become the gold standard in recent years, to finish drinking 4 L of PEG-EL solution can be difficult. The quality of sennoside-based bowel-cleansing regimes used in Turkey has been known for some time. Therefore, we aimed to investigate the efficacy of both bowel-cleansing regimes. MATERIALS AND METHODS: Patients over 18 years old undergoing elective colonoscopic procedures between January and March 2011 were included in the study. The patients were divided into 2 groups; in Group 1, 91 patients were given sennoside a + b calcium 500 mg/250 mL (X-M solution, Yenisehir Laboratuari, Ankara, Turkey), and in Group 2, 94 patients were given 4 L of PEG-EL (Golytely, Boston, MA, USA). RESULTS: The mean age of the patients and the male distribution were similar in the 2 groups. Both inadequate bowel cleansing and the best cleansed bowels were seen in Group 1. The number of inadequate colonoscopies declined when using a whole bowel-cleansing regime from 24.5% to 19.3% in Group 2, but it did not decline in Group 1. CONCLUSION: The best bowel cleansing can be achieved with sennoside-based regimes, whereas a greater proportion of adequate results via colonoscopy were reached with the PEG-EL-based regimes.

Laxatives for the management of constipation in people receiving palliative care.

BACKGROUND: This article describes the second update of a Cochrane review on the effectiveness of laxatives for the management of constipation in people receiving palliative care. Previous versions were published in 2006 and 2010 where we also evaluated trials of methylnaltrexone; these trials have been removed as they are included in another review in press. In these earlier versions, we drew no conclusions on individual effectiveness of different laxatives because of the limited number of evaluations. This is despite constipation being common in palliative care, generating considerable suffering due to the unpleasant physical symptoms and the availability of a wide range of laxatives with known differences in effect in other populations. OBJECTIVES: To determine the effectiveness and differential efficacy of laxatives used to manage constipation in people receiving palliative care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), MEDLINE, EMBASE, CINAHL and Web of Science (SCI & CPCI-S) for trials to September 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating laxatives for constipation in people receiving palliative care. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data. The appropriateness of combining data from the studies depended upon clinical and outcome measure homogeneity. MAIN RESULTS: We identified five studies involving the laxatives lactulose, senna, co-danthramer, misrakasneham, docusate and magnesium hydroxide with liquid paraffin. Overall, the study findings were at an unclear risk of bias. As all five studies compared different laxatives or combinations of laxatives, it was not possible to perform a meta-analysis. There was no evidence on whether individual laxatives were more effective than others or caused fewer adverse effects. AUTHORS' CONCLUSIONS: This second update found that laxatives were of similar effectiveness but the evidence remains limited due to insufficient data from a few small RCTs. None of the studies evaluated polyethylene glycol or any intervention given rectally. There is a need for more trials to evaluate the effectiveness of laxatives in palliative care populations. Extrapolating findings on the effectiveness of laxatives evaluated in other populations should proceed with caution. This is because of the differences inherent in people receiving palliative care that may impact, in a likely negative way, on the effect of a laxative.

Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid-induced constipation: a double-blind, active-comparator trial.

AIM: To investigate the efficacy of lubiprostone compared to Senna on bowel symptoms and constipation in post-operative orthopedic patients treated with opioids. METHODS: In this double blind, randomized, active comparator trial, adults who required opioids for analgesia following orthopedic procedures and who were admitted in inpatient rehabilitation were randomized following baseline assessments to lubiprostone (Amitza(®)), orally twice a day or Senna (generic) two capsules administered daily for six days. Subjects were assessed using the patient assessment of constipation (PAC)-symptoms (PAC-SYM) and the PAC-quality of life (PAC-QOL) scales measured at baseline and Day 7; Subjects were assessed daily for secondary measures included the Bristol stool scale bowel consistency, specific bowel symptom score (Nausea, cramping, straining, completeness, abdominal pain, time per lavatory attempt, assistance needed), adverse events and rescue medications required. Function was measured using the functional independence measure (FIM) at admission and discharge; length of stay (LOS) and missed treatments due to gastrointestinal symptoms were also assessed. RESULTS: 64 adults were enrolled; 56 participants (28 in each group) had baseline and follow up measures and were included in the intention to treat (ITT) analyses. 43 participants completed the study, 21 in the active lubiprostone and 22 in the active Senna group. The mean age of the participants was 71.5 years (SD = 11.4 years, range: 28-96 years). In the ITT analyses, participants showed significant improvement in bowel symptoms as measured by the PAC-SYM (mean ± SD, -0.28 ± 0.60, range: -1-2.33) and PAC-QOL (mean ± SD, 0.33 ± 0.81, range: -1.5-2.0) over time, but there were no significant differences between the lubiprostone and Senna groups in mean change in the PAC-SYM (-0.20 ± 0.60 vs -0.36 ± 0.61, P = 0.61 respectively) or the PAC-QOL (0.29 ± 0.76 vs 0.37 ± 0.87, P = 0.61 respectively). The mean change in each bowel symptom also did not significantly differ between treatment groups on ITT analyses, except for completeness of bowel movement, with the Senna group showing greater negative mean change in bowel movement completeness (-0.56 ± 1.01 vs -2.00 ± 1.41, P = 0.03) and for reduction of abdominal pain, favoring Senna (-0.14 ± 0.73 vs -0.73 ± 1.08, P = 0.04). Fifteen (75%) participants in the lubiprostone and in the Senna group requested rescue treatments. Participants made significant functional improvement from admission to discharge over a median LOS of 12 d, with a mean FIM change of 29.13 ± 13.58 and no significant between group differences (27.0 ± 9.2 vs 31.5 ± 16.6, P = 0.27). CONCLUSION: Both lubiprostone and Senna improved constipation-related symptoms and QOL in opioid-induced constipation, with no significant between-group differences.

Comparative effectiveness of senna to prevent problematic constipation in pediatric oncology patients receiving opioids: a multicenter study of clinically detailed administrative data.

CONTEXT: Pediatric oncology patients often receive prolonged courses of opioids, which can result in constipation. OBJECTIVES: Comparing patients who received senna matched with similar patients who received other oral bowel medications, determine the subsequent risk of "problematic constipation," assessed as the occurrence of the surrogate markers of receiving an enema, escalation of oral bowel medications, and abdominal radiographic imaging. METHODS: This was a retrospective cohort study of hospitalized pediatric oncology patients less than 21 years of age in 78 children's and adult hospitals between 2006 and 2011 who were started on seven consecutive days or more of opioid therapy and were started on an oral bowel medication within the first two days of opioid therapy. Clinically detailed administrative data were used from the Pediatric Health Information System and the Premier Perspective Database. After performing propensity score matching of similar patients who started senna and who started a different oral bowel medication, Cox regression modeling was used to compare the subsequent hazard of the surrogate markers. RESULTS: The final matched sample of 586 patients averaged 11.5 years of age (range 0-20 years); 41.8% (n = 245) had blood cancer, 50.3% (n = 295) had solid tumor cancer, and 7.9% (n = 46) had brain cancer. Initiating senna therapy within two days of starting the prolonged opioid course, compared with initiating another oral bowel medication, was significantly associated with a lower hazard during the ensuing five days for receipt of an enema (hazard ratio [HR], 0.31; 95% CI, 0.11-0.91) or undergoing abdominal radiographic imaging (HR, 0.74; 95% CI, 0.55-0.98), was marginally associated with a lower hazard of oral bowel medicine escalation (HR, 0.78; 95% CI, 0.59-1.03), and overall was significantly associated with a lower hazard of the composite end point of problematic constipation (HR, 0.70; 95% CI, 0.56-0.88). CONCLUSION: Initiating senna therapy, compared with other oral bowel medications, diminishes the subsequent risk of surrogate markers of problematic constipation in this population.

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

BACKGROUND: Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. METHODS/DESIGN: This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. DISCUSSION: This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. TRIAL REGISTRATION: NCT01695850.

Cochrane Review: Osmotic and stimulant laxatives for the management of childhood constipation (Review).

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. PLAIN LANGUAGE SUMMARY: Laxatives for the management of childhood constipation Constipation within childhood is an extremely common problem. Despite the widespread use of laxatives by health professionals to manage constipation in children, there has been a long standing lack of evidence to support this practice. This review included eighteen studies with a total of 1643 patients that compared nine different agents to either placebo (inactive medications) or each other. The results of this review suggest that polyethylene glycol preparations may increase the frequency of bowel motions in constipated children. Polyethylene glycol was generally safe, with lower rates of minor side effects compared to other agents. Common side effects included flatulence, abdominal pain, nausea, diarrhoea and headache. There was also some evidence that liquid paraffin (mineral oil) increased the frequency of bowel motions in constipated children and was also safe. Common side effects with liquid paraffin included abdominal pain, distention and watery stools. There was no evidence to suggest that lactulose is superior to the other agents studied, although there were no trials comparing it to placebo. The results of the review should be interpreted with caution due to methodological quality and statistical issues in the included studies. In addition, these studies were relatively short in duration and so it is difficult to assess the long-term effectiveness of these agents for the treatment of childhood constipation. Long-term effectiveness is important, given the often chronic nature of this problem in children.

Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

CONTEXT: The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. OBJECTIVES: To assess the efficacy of docusate in hospice patients. METHODS: This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. RESULTS: A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). CONCLUSION: There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

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.