Successful de-implementation of an ineffective practice: The fall of docusate.

BACKGROUND: Reducing wasteful practices optimizes value in medicine. Docusate lacks treatment efficacy yet is widely prescribed. This quality improvement project aimed to de-implement docusate in place of a new evidence-based order set. METHODS: This is an ambidirectional study of inpatient laxative orders from 2018 to 2022 â€‹at one institution. We stratified docusate data by service/unit to target prospective deimplementation initiatives. A new evidence-based constipation order set was embedded in Cerner. RESULTS: There were 701,732 docusate orders across 75 services on 68 units. Top docusate ordering services were Trauma, Obstetrics and Hospitalist. Docusate administration rates were higher than for other laxatives. Our efforts reduced docusate orders by 44% over 4 months. PEG and senna orders increased by 58% and 35%. CONCLUSION: Docusate has no efficacy yet is widely prescribed. A structured de-implementation strategy can drive systematic change by leveraging technology and applying multidisciplinary improvement efforts. Our work removed docusate from the inpatient formulary.

Radiologically supervised bowel management program outcome in patients with chronic idiopathic constipation.

PURPOSE: This study aimed to analyze our radiologically supervised bowel management program (RS-BMP) outcomes in patients with chronic idiopathic constipation (CIC). METHODS: A retrospective study was conducted. We included all patients with CIC who participated in our RS-BMP at Children´s Hospital Colorado from July 2016 to October 2022. RESULTS: Eighty patients were included. The average time with constipation was 5.6 years. Before our RS-BMP, 95% had received non-radiologically supervised treatments, and 71% had attempted two or more treatments. Overall, 90% had tried Polyethylene Glycol and 43% Senna. Nine patients had a history of Botox injections. Five underwent anterograde continence procedure, and one a sigmoidectomy. Behavioral disorders (BD) were found in 23%. At the end of the RS-BMP, 96% of patients had successful outcomes, 73% were on Senna, and 27% were on enemas. Megarectum was detected in 93% of patients with successful outcomes and 100% with unsuccessful outcomes (p = 0.210). Of the patients with BD, 89% had successful outcomes, and 11% had unsuccessful. CONCLUSION: Our RS-BMP has been proven to be effective in treating CIC. The radiologically supervised use of Senna and enemas was the appropriate treatment in 96% of the patients. BD and megarectum were associated with unsuccessful outcomes.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Inhibitory effect of Bofutsushosan (Fangfengtongshengsan) extract on the absorption of fructose in rats and mice.

Bofutsushosan (BTS; fangfengtongshengsan in Chinese) is a formula in traditional Japanese Kampo and Chinese medicine comprising 18 crude drugs and used to treat obesity and metabolic syndrome. In our previous study, BTS boiling water extract inhibited the uptake of fructose absorbed via glucose transporter 5 into cultured cells. In this study, the inhibitory effect of BTS extract on the absorption of fructose from the intestine was investigated in vivo. The extract of BTS was orally administered to rats at doses equivalent to 25-fold of the daily dose for humans. One minute after sample administration, fructose was orally administered and blood samples were collected from the jugular vein 0.5, 1, 1.5, 2, and 4 h after the administration of fructose. The absorption of fructose from the intestine was significantly reduced by treatment with BTS extract, and this in vivo study reproduced previous in vitro results. Subsequently, the blood samples were collected from the portal vein 30 min after the oral administration of fructose in mice. BTS extract significantly reduced fructose absorption in mice, and compared the effect of modified BTS samples by removing one to several crude drugs from BTS. We found that the dried rhizome of Rheum palmatum (RR) significantly contributed to the inhibitory effect of BTS on fructose absorption. We found sennoside A to be the active ingredient of RR for the inhibition of fructose absorption, and that its effect almost saturated at a dose of 3 mg/kg. These results support the action mechanisms of BTS when used for the treatment of obesity in clinics and drug stores.

Sennoside A alleviates inflammatory responses by inhibiting the hypermethylation of SOCS1 in CCl4-induced liver fibrosis.

Liver fibrosis is the consequence of chronic liver injury and is a major challenge to global health. However, successful therapy for liver fibrosis is still lacking. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve hepatic disease, but the underlying mechanisms remain largely elusive. Here, we show for the first time that SA enhanced suppressor of cytokine signaling 1 (SOCS1) expression in a DNA methyltransferase 1 (DNMT1)-dependent manner and thereby attenuated liver fibrosis. Consistently, SA inhibited the expression of the liver fibrogenesis markers α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) and suppressed inflammatory responses in vivo and in vitro. Coculture experiments with macrophages/hepatic stellate cells (HSCs) revealed that SA suppressed HSC proliferation by downregulating proinflammatory cytokines in macrophages. Mechanically, SA promoted the aberrant expression of SOCS1 in liver fibrosis. However, blocking SOCS1 expression weakened the inhibitory effect of SA on HSC proliferation, indicating that SOCS1 may play an important role in mediating the antifibrotic effect of SA. Furthermore, SA inhibited DNMT1-mediated SOCS1 and reduced HSC proliferation by inhibiting inflammatory responses in carbon tetrachloride (CCl4) -induced liver fibrosis.

The Effectiveness of a Senokot Cocktail for Postoperative Constipation.

A senior staff registered nurse on an orthopaedic inpatient rehabilitation unit in an urban orthopaedic hospital utilized a "cocktail" of warm prune juice, lemon juice, and Senokot liquid for patients who presented to the rehabilitation unit after orthopaedic surgery without having had an initial postoperative bowel movement (BM). A pilot study (n = 30) using a quasi-experimental design was conducted to evaluate the effect of the cocktail versus liquid Senokot alone on the first postoperative BM. Several measurement tools were used, including the Bristol Stool Scale, visual analog scales to determine pain and strain, and a BM quality scale. A small sample size became even smaller when only 80% of participants had a BM within the study time frame. Therefore, significant findings were difficult to establish. Additional research is needed to adequately assess the effect of the Senokot "cocktail" on postoperative constipation in the rehabilitation population.

Senna Versus Magnesium Oxide for the Treatment of Chronic Constipation: A Randomized, Placebo-Controlled Trial.

INTRODUCTION: This is the first prospective, double-blinded, randomized, placebo-controlled trial to evaluate the safety and efficacy of a stimulant laxative compared with an osmotic agent for the treatment of chronic idiopathic constipation. METHODS: Patients were randomly administered stimulant laxative (senna, 1.0 g), osmotic agent (magnesium oxide [MgO], 1.5 g), or placebo for 28 consecutive days. The primary endpoint was overall symptom improvement. Secondary endpoints were spontaneous bowel movement (SBM), complete SBM, and patient assessment of constipation quality of life (QOL). RESULTS: Ninety patients (mean age, 42 years; 93% women; mean duration of symptoms, 9.9 years) were enrolled; all completed the study. The response rate for overall improvement was 11.7% in the placebo group, 69.2% in the senna group, and 68.3% in the MgO group (P < 0.0001). Change in SBM was significantly greater in the senna and MgO groups than that in the placebo group (P < 0.001). Similarly, change in complete SBM was significantly greater in the senna and MgO groups than that in the placebo group (P < 0.01). On the patient assessment of constipation QOL, significant improvements were seen in the senna and MgO groups compared with those in the placebo group (senna, P < 0.05; MgO, P < 0.001). The frequency of severe treatment-related adverse events was 0%. DISCUSSION: Senna and MgO significantly improved the frequency of bowel movements and QOL score and seem to be effective in the treatment of constipation.

Effect of Court-Type Thai Traditional Massage Versus Senokot Treatment on Chronic Constipation: A Randomized Controlled Trial.

Chronic constipation is the disturbances of intestinal motility which is a challenge in primary healthcare around the world. In this study, Court-type Thai traditional massage and Senokot, treatments were assessed and compared in terms of their efficacy in relieving constipation. Forty subjects diagnosed with constipation were recruited and randomized into the massage group and drug group. For 7 days, Thai traditional abdominal massage was provided regularly for the patients in the massage group, while the drug group was subjected to Senokot treatment only. The Bristol stool chart scale and demographics questionnaire were used as instruments. As a result, both court type Thai traditional massage and Senokot are effective in relieving constipation. However, although both treatment options can increase the frequency of defecations and the sensation of complete evacuation, the court type Thai traditional massage seems to be better since it leads to normal defecations rather than watery or entirely liquid defecations with no solid pieces (p < 0.05). This randomized controlled trial suggested that Thai traditional abdominal massage can be used as an optional public health treatment for constipation.

Sennoside A prevents liver fibrosis by binding DNMT1 and suppressing DNMT1-mediated PTEN hypermethylation in HSC activation and proliferation.

Hepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Phosphatase and tension homolog deleted on chromosome 10 (PTEN) is a negative regulator of this process. DNA methyltransferase 1 (DNMT1), which catalyzes DNA methylation and subsequently leads to the transcriptional repression of PTEN, is selectively induced in myofibroblasts from diseased livers. Sennoside A (SA), a major purgative constituent of senna and the Chinese herb rhubarb, is widely used in China and other Asian countries as an irritant laxative. SA is reported to improve hepatic steatosis. However, the effect and mechanism of SA on liver fibrosis remain largely unknown. We recently identified a novel strategy for protecting liver fibrosis via epigenetic modification by targeting DNMT1. A Surface Plasmon Resonance (SPR) assay first reported that SA could directly bind DNMT1 and inhibit its activity. Administration of SA significantly prevented liver fibrosis, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) protein levels in a CCl4 -induced mouse hepatic fibrosis model and in TGF-ß1-activated HSC-T6 cells, in vivo and in vitro. SA decreased the expression of Cyclin D1, CDK, and C-myc, indicating that SA may inhibit the activation and proliferation of TGF-ß1-induced HSC-T6. Moreover, SA significantly promoted the expression of PTEN and remarkably inhibited the expression of p-AKT and p-ERK in vitro. Blocking PTEN or overexpressing DNMT1 could reduce the effect of SA on liver fibrosis. These data suggest that SA directly binds and inhibits the activity and that attenuated DNMT1-mediated PTEN hypermethylation caused the loss of PTEN expression, followed by the inhibition of the AKT and ERK pathways and prevented the development of liver fibrosis. Hence, SA might be employed as a promising natural supplement for liver fibrosis drug therapy.

Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits.

Accumulating evidences implicate that gut microbiota play an important role in the onset and prolongation of fat inflammation and diabetes. Sennoside A, the main active ingredient of Rhizoma Rhei (rhubarb), is widely used for constipation as a kind of anthranoid laxative (e.g., senna). Here, we put forward the hypothesis that the structural alteration of gut microbiota in obesity mice may be involved in the pathogenesis of type 2 diabetes (T2D) which may be ameliorated by Sennoside A. We investigated the appearance of obesity, insulin resistance, host inflammation, and leaky gut phenotype with or without Sennoside A in db/db mice. Horizontal fecal microbiota transplantation (FMT) was used to confirm the critical roles of gut microbiota in the amelioration of the indices in T2D mice after Sennoside A treatment. As a result, we found that Sennoside A administration markedly improved the indices in T2D mice and obesity-related traits including blood glucose level, body weight, lipid metabolism disorder, and insulin resistance. The gut microbiota changed quickly during the onset of T2D in db/db mice, which confirmed the hypothesis that gut microbiota was involved in the pathogenesis of T2D. Sennoside A altered gut microbial composition which might mediate the antiobesogenic effects in T2D remission. Sennoside A also reduced inflammation and increased tight junction proteins in the ileum in gene-deficient mice via gut microbiota alteration. FMT lowered the blood glucose level and improved insulin resistance, corroborating that Sennoside A perhaps exerted its antiobesogenic effects through gut microbiota alteration. Chemical Compounds Studied in This Article. Compounds studied in this article include Sennoside A (PubChem CID: 73111) and metformin hydrochloride (PubChem CID: 14219).

Chronic Constipation in the United States: Results From a Population-Based Survey Assessing Healthcare Seeking and Use of Pharmacotherapy.

OBJECTIVES: Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%-20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS: We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS: Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P < 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation: over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION: We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.

PEG vs. sennosides for opioid-induced constipation in cancer care.

PURPOSE: This randomized double-blind, double-dummy, 2-treatment, 2-period crossover study aimed to compare the efficacy and tolerability of polyethylene glycol (PEG) and sennosides in ambulatory cancer patients with opioid-induced constipation. METHODS: Outpatients ≥ 18 years old with cancer, at risk of or already experiencing opioid-induced constipation, were randomly assigned to begin a standard bowel protocol of escalating doses of sennosides or PEG, plus a dummy preparation. After 3 weeks, the patients switched to the alternate active product and dummy preparation. Constipation was assessed using the revised Victoria Bowel Performance Scale (rBPS) at the end of each of the 2 consecutive 21-day study periods for the number of days with a satisfactory bowel movement, the time in days to goal rBPS (G), and the treatment preference of each patient. RESULTS: Seventy patients were recruited, with 42 completing their first treatment period and 28 completing both treatment periods. For the typical patient, the expected number of days with a satisfactory bowel movement per days of treatment was found to be 1.21 times higher on PEG than on sennosides in a particular period (95% credible interval 0.96 to 1.55). Patients taking PEG were 1.47 times more likely to reach a rBPS of G before patients taking sennosides in the first period (95% confidence interval 0.74 to 2.94). There was no evidence of a difference in patient preference between laxatives. CONCLUSION: Our study found weak evidence that PEG is superior to sennosides with respect to overall effectiveness in cancer patients with opioid-induced constipation.