Antidiarrheal Research Articles

EFEK ANTIDIARE EKSTRAK ETANOL UMBI RUMPUT TEKI (Cyperus rotundus L.) TERHADAP MENCIT PUTIH

ABSTRACT
 Diarrhea is a disease characterized by stimulation of bowel movements continuously and feces that
 are not formed or liquid that has a frequency of more than 3 times in 24 hours. The incidence of
 diarrhea can occur throughout the world and causes 4% of all deaths and 5% of health losses to
 cause disability. Cyperus rotundus L. can be used as an antidiarrheal drug because it contains a
 compound such as tannins and flavonoids. This research is an experimental study with a Post-test
 only Control Group Design. The subjects using white male mice (Mus muscullus) 25 mice and
 divided into 5 groups: positive control, negative control, ethanol extracts of rubers Cyperus
 rotundus L. with a dose of 250 mg/kgBB, 500 mg/kgBB and 1000 mg/kgBB. Before the treatment,
 mice fasted and induced diarrhea (oleum ricini). Obsevations was made by observing the
 parameters of diarrhea: duration of diarrhea, frequency of diarrhea and feces consistency every 30
 minutes for 4 hours. The numerical data was then processed using SPSS with one way ANOVA test.
 The results obtained showed that the administration of extract with a dose of 250 mg/kgBB, 500
 mg/kgBB and 1000 mg/kgBB had an antidarrheal with effective dose is 500 mg/kgBB.
 Keywords: antidiarrheal, ethanol extract of tubers Cyperus rotundus L., oleum ricini, Cyperus
 rotundus

"Stoma or no stoma": First report of intestinal transplantation without stoma.

Recent data suggest that frequent endoscopy and biopsy without evidence of graft dysfunction does not appear to confer survival advantage after intestinal transplantation. After abandoning protocol surveillance, endoscopic examination was decreased significantly at our center. These observations led us to question the need for stoma creation in intestinal transplantation. Herein, we report clinical outcomes of intestinal transplantation without stoma, compared to conventional transplant with stoma. Data analysis was limited to adult intestinal transplantation without liver allograft between 2015 and 2018. We compared patient and graft survival, frequency of endoscopic evaluation, episodes of acute rejection, nutritional therapy, and renal function between "Control group (with stoma)," n=18 grafts in 16 patients and "Study group (without stoma)," n=16 grafts in 15 patients. Overall outcome was similar between the 2 groups with respect to graft and patient survival, episodes of acute rejection, and its response to treatment. Nutritional outcomes were similar in both groups. Fewer antidiarrheal medications were required in the study group, but this did not translate into demonstrable gains in preservation of renal function, despite an apparent trend to improvement. Intestinal transplantation without stoma appears to be an acceptable practice model without obvious adverse impact on outcome.

The interplay of the inhibitory effect of nifuroxazide on NF-κB/STAT3 signaling attenuates acetic acid-induced ulcerative colitis in rats

Ulcerative colitis (UC) is a disease of increased worldwide prevalence. UC progression is associated with serious complications that leave the patient with considerable health burdens. Nifuroxazide is an oral nitrofuran antibiotic used as antidiarrheal medication. The current study places an emphasis on investigating the potential therapeutic effectiveness of nifuroxazide (10 mg/kg) and (20 mg/kg) against acetic acid (AA)-induced UC. Intra-rectal AA induced a significant colonic injury and impairment of colonic biochemical and functional incidences. Nifuroxazide in a dose-dependent manner significantly corrected UC associated injury. Macroscopic scoring of UC, serum lactate dehydrogenase (LDH) activity, C-reactive protein (CRP) titer, colon malondialdehyde (MDA) and total nitric oxide (NOx) contents significantly declined. Meanwhile, serum total antioxidant capacity (TAC) and colon catalase, superoxide dismutase (SOD) and glutathione transferase (GST) activities and reduced glutathione (GSH) concentration significantly increased in a dose-dependent way. Ultimately, histopathological, immunohistochemical and ultramicroscopic analysis of colon specimen revealed significant improvement. To pinpoint the mechanistic pathway underlying the curative effect of nifuroxazide, colon expression of NF-κB, caspase-3 was evaluated along with STAT-3 activation. Nifuroxazide induced a dose-dependent significant suppression of NF-κB and caspase-3 signaling together with STAT3 signaling. In conclusion; nifuroxazide can be proposed as a therapeutic candidate to attenuate UC and its associated symptoms. The potential underlying mechanism involves suppression of NF-κB/STAT-3/caspase- signaling.

A novel role of nifuroxazide in attenuation of sepsis-associated acute lung and myocardial injuries; role of TLR4/NLPR3/IL-1β signaling interruption

Acute lung injury (ALI) and the subsequent multi-system organ failure is a serious health problem with devastating impacts on the health care systems. Indeed, the world has been facing an un-preceded situation in the past couple of months following COVID-19 infestation and the associated high-mortality rates mainly attributed to sepsis and the associated multiple organ failures of particular concern; acute respiratory distress syndrome post lung injury. The current study provides evidence on the ameliorative impact of nifuroxazide, and FDA approved antidiarrheal drug in attenuation of lipopolysaccharide (LPS)-induced ALI and myocarditis when administrated either in prophylactic or curative regimens. Nifuroxazide administration was associated with a significant improvement in lung and heart histopathological characteristics and architecture with retraction of LPS-induced inflammatory-infiltration. This was associated with retraction in serum biomarkers of cellular injury of which; LDH, CK-MB, and ALP. Nifuroxazide administration was associated with a significant improvement in both lung and heart oxidative status. Such positive outcomes were underlined by a significant inhibitory effect of nifuroxazide on lung and heart contents of toll-like receptor (4) (TLR4)/the inflammasome NALPR3/interleukin- 1β (IL-1β). In conclusion: Nifuroxazide attenuates LPS-induced ALI and myocardial injury via interruption of TLR4/NALPR3/IL-1β signaling. Thus it can offer a potential approach for attenuation of sepsis in critically ill patients.

Is chronic refractory colitis from immune checkpoint inhibitor associated with good cancer outcome?

e15102 Background: Immune checkpoint inhibitors (ICIs) are efficacious in treating many advanced malignancies. However, drug induced colitis limits their use significantly. We present cases with chronic refractory ICI colitis requiring long term immunosuppressive therapy and favorable cancer outcomes. Methods: We identified 3 cases who developed ICI colitis and persisted for longer than 6 months requiring long term immunosuppressant therapy. The patients’ clinical data was collected. Results: All patients were male, with median age of 55. Two had melanoma, one urothelial cancer. All patients received PD-1(L)-1 agents with colitis onset about 3-6 months after ICI treatment. All patients were taken off ICI permanently due to colitis over a duration of 19-30 months (peak grade of 3). Endoscopy of all three were grossly unremarkable, with lymphocytic colitis on pathology in all three. Patient A’s colitis achieved clinical and histological remission after 5 doses of vedolizumab, however recurred after 9 months with biopsy proven recurrence. Current management is anti-diarrheal medication given mild symptom. Patient B had more aggressive disease, with first recurrence after 2 doses of infliximab and steroid, achieved initial histological remission after 3 doses of vedolizumab and 2 additional infliximab, then had 2nd recurrence after 3 months. Fecal microbiota transplantation as compassionate treatment was not effective. Thereafter, patient was resumed on vedolizumab ever since with clinical remission. Last histology evaluation showed persistent lymphocytic colitis 30 months after initial diagnosis. The third case had initial histological remission after 3 doses of vedolizumab, followed by recurrence after 4 months, which triggered another 3 doses of vedolizumab, with persistent grade 3 diarrhea despite resolution of histological inflammation after total 6 doses of vedolizumab. Patient was subsequently treated with steroid and ustekinumab with clinical remission. At the end of follow up, all three patients have sustained cancer remission over 19-31 months. Conclusions: IMC is a common adverse event from ICI, and could progress to a chronic inflammatory condition that require long term treatment. Histological remission does not preclude future recurrence of colitis. Persistent toxicity could be a surrogate marker for enduring ICI effect which may be associated with favorable cancer outcome. Long term immunosuppression can be essential for refractory ICI colitis cases for clinical remission.

Amino acid mixture (enterade) as a new approach to reducing cancer therapy-induced gastrointestinal toxicity: A retrospective study.

e24107 Background: Gastrointestinal toxicity is a common side effect of cancer therapy. Pre-clinical studies using a proprietary mixture of amino acids, demonstrated a reduction in mucositis and gastrointestinal toxicity following irradiation via tightening of the mucosal barrier, increasing proliferation of crypt cells, increasing villous height and increasing absorption of fluid, electrolytes and nutrients. A novel 5-amino acid mixture “enterade” was previously evaluated in a Phase II clinical trial for anti-diarrheal effects in post bone marrow transplant patients at Dana Farber Cancer Institute (NCT02919670). Signs of anti-diarrheal efficacy were found in treatment-compliant patients.Enterade is currently being tested in two prospective Phase II studies (NCT03722511 and NCT04073017) in neuroendocrine tumor patients with quality of life limiting diarrhea. We conducted a pilot study to evaluate early antidiarrheal signals in oncologic treatment-induced diarrhea. Methods: An IRB-approved retrospective chart review was conducted at Markey Cancer Center between Sept 2019 and Dec 2019. Medical records were retrospectively reviewed for all solid tumor patients who received enterade for chemotherapy or immunotherapy-induced diarrhea. Patients were instructed to consume one 8-oz bottle of enterade twice a day for at least one week in addition to standard of care antidiarrheal medications. Results: A total of 46 patients were offered enterade. Antidiarrheal efficacy data was available on 17 patients. 11 were female and the mean age of the cohort was 64 years. Six out of 17 patients had a previous history of bowel resection. Four patients had immune checkpoint induced colitis. Three patients developed diarrhea from TKI use and rest were on cytotoxic chemotherapy at the time of the diarrheal episode. Eighty-eight percent (15/17) of patients reported a reduction in diarrhea frequency after consuming enterade. On average, patients noticed an improvement in diarrhea frequency after 3.6 days of enterade consumption, with 86% (13/15) of responders reporting at least 50% reduction in diarrhea frequency. Conclusions: Patient-reported diarrheal improvement after enterade consumption is consistent with pre-clinical data. Results suggest the amino acid mixture may alleviate symptoms of cancer therapy-induced gastrointestinal toxicity (i.e. diarrhea). A prospective clinical trial is warranted to substantiate the observed improvement in chemotherapy and immunotherapy induced diarrhea.

Efficacy and safety of ceritinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer: A systematic review and meta-analysis.

What is known and objectiveCeritinib is a new, oral, potent and selective second‐generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration of the United States in April 2014. It is active in crizotinib‐resistant patients, especially in patients with non‐small cell lung cancer (NSCLC) and brain metastasis. The aim of this study was to analyse the effects and side effects of ceritinib in ALK‐rearranged NSCLC.MethodsWe searched articles published from January 1980 to March 2019 in PubMed, EMBASE, Cochrane Library and Web of Science. The pooled estimate and 95% CI were calculated with DerSimonian‐Laird method and the random effect model.Results and discussionFrom 15 articles, 2,598 patients were included in the meta‐analysis. Eleven studies reported the ORR, and the DCR was presented in 10 studies. The ORR and DCR of ceritinib were 0.48 (95% CI, 0.39‐0.57) and 0.76 (95% CI, 0.69‐0.82), respectively. The PFS and OS were presented in nine and three eligible studies, respectively. The PFS and OS of ceritinib were 7.26 months (95% CI, 5.10‐9.43) and 18.73 months (95% CI; 14.59‐22.87). These results suggested that ceritinib can effectively treat patients with ALK‐rearranged NSCLC. Diarrhoea, nausea and vomiting were the three most common AEs and occurred in 69% (95% CI 51.7‐87.1%), 66% (95% CI 47.0‐85.8%) and 51% (95% CI 35.9‐66.8%) of patients, respectively. Considering serious gastrointestinal AEs, antiemetic and antidiarrhoeal drugs should be considered to improve a patient's tolerance to ceritinib.What is new and conclusionCeritinib is effective in the treatment of patients with ALK‐rearranged NSCLC with crizotinib resistance. The DCR was up to 76%, and PFS was extended to 7.6 months. The AEs were acceptable.

Efficacy and safety of Shengjiang Xiexin decoction in prophylaxis of chemotherapy-related diarrhea in small cell lung cancer patients: study protocol for a multicenter randomized controlled trial

BackgroundDiarrhea is a common adverse reaction in patients with cancer receiving chemotherapy, for which there is currently no effective method of treatment. Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medicine (TCM) formula, has shown efficacy in alleviating irinotecan-induced diarrhea in preliminary clinical studies. The current study is designed to assess the efficacy and safety of SXD for prophylaxis against irinotecan-induced diarrhea. Additionally, we employ a new approach to analyze and evaluate the data based on the patients’ uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype, which predicts the risk of diarrhea.Methods and designA prospective, double-blind, randomized, placebo-controlled trial will be conducted in patients with small cell lung cancer (SCLC) from five hospitals in China. For this study, 100 irinotecan-naïve patients will be randomly allocated to either the SXD or placebo arms in a 1:1 ratio. Stratified randomization will be used to divide subjects by UGT1A1 genotype into groups with differing risk of diarrhea. The trial will consist of two cycles of chemotherapy with 14 days of oral administration of SXD or placebo administered beginning between 3 days before and up to 11 days after initiation of each chemotherapy cycle. The primary study outcome is the incidence of diarrhea. Secondary outcomes include the degree of diarrhea, the degree of neutropenia, the rate of alterations in chemotherapy regimens, the amount of antidiarrheal drug taken, the rate of hospitalization, and evaluation of chemotherapy efficacy.DiscussionThis study is the first to use the UGT1A1 genotype to stratify patients into groups based on their risk of diarrhea, and to provide a complete assessment of chemotherapy-related diarrhea (CRD), including records of diarrhea duration, grading the severity of diarrhea, and evaluating concomitant symptoms. Study results will provide high-level clinical evidence on the use of SXD as prophylaxis for CRD.Trial registrationChinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. Retrospectively registered. http://www.chictr.org.cn/edit.aspx?pid=25250&htm=4c

Antibacterial Activity Test of Trema orientalis L. Blumae (Anggrung) Granule Extract Against Bacteria Salmonella sp with The Wet Granulation Method

Diarrhea is a cause of increasing mortality in infants and toddlers around the world. Diarrhea is a dangerous disease because it causes death and makes a case of outbreak. In Indonesia, the Trema orientalis L. plant is known as Anggrung. Trema orientalis L. leaves contain tannins especially polyphenols which have the ability to retain potassium which can cure ongoing diuresis. This study aims to determine the antibacterial activity of Anggrung leaves as an antidiarrheal drug caused by bacteria that cause diarrhea, namely Salmonella sp and the preparation of granules from leaves of Trema orientalis L. (Anggrung) which can inhibit the growth of Salmonella sp. and become an antidiarrheal drug. The results of the research carried out namely the leaf extract of Trema orientalis L. (Anggrung) has a strong inhibitory power due to the high concentration of the extract used. And for leaf granules Trema orientalis L. (Anggrung) preparations have a strong inhibitory power because the composition of the extract used is greater so it forms a large inhibitory zone. From the research conducted it can be concluded that the antibacterial testing of extracts and leaf granules preparations of Trema orientalis L. (Anggrung) has antibacterial activity.

Formulation and Evaluation of Dispersible Tablet of an Anti-Diarrhoeal Drug

Formulation and Evaluation of Dispersible Tablet of an Anti-Diarrhoeal Drug

Tolerability of nintedanib-related diarrhea in patients with idiopathic pulmonary fibrosis

BackgroundNintedanib is an important drug for the treatment of idiopathic pulmonary fibrosis (IPF). However, the drug is discontinued in some patients who present with diarrhea. In this study, we aimed to assess the drug continuation rate in patients who developed diarrhea during nintedanib therapy and to evaluate if antidiarrheal drugs or nintedanib dose reductions improved clinical tolerability and efficacy. MethodsEighty-six patients with IPF were treated in our institution between December 2015 and March 2018. Among them, 50 patients who experienced nintedanib-related diarrhea were analyzed regarding tolerability and persistence rate. ResultsIn 50 patients who experienced nintedanib-related diarrhea, 26 (n = 11, without reduction and n = 15, with reduction) continuously received nintedanib. Meanwhile, the drug was discontinued in 24 patients (n = 13, without reduction and n = 11, with reduction). In 9 of 24 patients, the drug was discontinued due to diarrhea. The annual rate of decline in forced vital capacity and the duration of nintedanib administration were not significantly different between groups with and without dosage reduction. Moreover, 23, 13, 8, and 2 patients received 1, 2, 3, and 4 agents, respectively. Clostridium butyricum is a probiotic bacterium most commonly used as an antidiarrheal agent. In this study, it was used in 28 of 46 patients. The total durations of nintedanib administration differed significantly according to the number of antidiarrheal drugs taken: 853 ± 221 days, more than three agents; 424 ± 365 days, without an agent (p = 0.043); and 460 ± 142, one agent (p = 0.0003). ConclusionsWhen diarrhea occurs within a year after using nintedanib, the dose reduction may be acceptable without affecting pulmonary function. Moreover, treatment with multiple antidiarrheals may be a practical option to maintain the use of nintedanib therapy compared with monotherapy and no therapy.

Protective effect of SKB_Gutbiotic against castor oil and E.coli induced diarrhea in laboratory animals

The aim of this study is to evaluate antidiarrheal activity of SKB_Gutbiotic against Castor oil and E.coli induced diarrhea in Swiss albino mice and Sprague Dawley rats. In present study three doses of SKB_Gutbiotic were tested against castor oil induced diarrhea in mice. Its effect on co-administration with l-arginine was studied. SKB_Gutbiotic delayed onset of diarrhea, reduced fecal output and fecal weight. In Gastrointestinal transit time and Castor oil induced enteropooling, SKB_Gutbiotic significantly reduced peristaltic index and volume of intestinal content respectively. In E.coli induced diarrhea model, E.coli suspension was administered for 3 days for inducing diarrhea. SKB_Gutbiotic significantly and dose dependently reduced fecal output, improved fecal consistency, reduced fecal water content and improved WBC count. Histopathological images showed improvement in damage caused to the mucosal epithelium due to E.coli and also improved complete crypt cell architecture and integrity of goblet cells. These results indicated that SKB_Gutbiotic can be used as an antidiarrheal agent against castor oil and E.coli induced diarrhea. It inhibits colonization of E.coli bacteria on colonic epithelium which results into decreased intestinal hypersecretion and motility which is very useful in the management of infectious diarrhea. Thus SKB_Gutbiotic could be an effective alternative to standard antidiarrheal drugs.

Mouse model of metformin-induced diarrhea

ObjectiveMetformin, an oral medication used for type 2 diabetes mellitus, is the most commonly prescribed drug with less economic burden of patients. Although metformin’s efficacy and safety have long been...

Rapid transit in the left-sided colon is related to poor defecatory function at early period after stoma closure

Sphincter-saving surgery (SSS) is the gold standard for rectal cancer surgery but results in a wide spectrum of bowel dysfunction. This study investigated the impact of colonic dysmotility on the incontinent form of bowel dysfunction. Bowel function of patients who received SSS with loop ileostomy for treating rectal cancer was reviewed retrospectively from June 2013 two August 2015 at a single hospital. Immediately after closure of a diverting stoma, patients were tested for the colonic transit time (CTT) using radiopaque markers. Bowel dysfunction at 6 and 12 months after SSS was measured as the severity of fecal incontinence according to the Cleveland Clinic Incontinence Score (CCIS) and the use of an anti-diarrheal drug. A short CTT for the left colonic segment was significantly associated with the high CCIS and use of an antidiarrheal agent at 6 months after sphincter preservation. However, the CTT didn’t correlate with the CCIS at 12 months after SSS. Rather, age and surgical method demonstrated a significant association. Colonic dysmotility after SSS appears to intensify fecal incontinence for a relatively short period. Its impact abates within a year.

Abstract P5-14-05: The impact of food on tolerability of abemaciclib in patients with previously treated hormone receptor-positive, HER2-negative, metastatic breast cancer: An open-label, randomized phase 2 study

Abstract Background: Abemaciclib is an orally administered inhibitor of cyclin-dependent kinase (CDK) 4/6, dosed twice daily (BID) on a continuous schedule. Diarrhea is a frequently associated adverse event. It is predictable and manageable with antidiarrheal medication, typically occurs within the first month of therapy, and decreases over the duration of treatment. In the MONARCH 1, 2, and 3 studies, Grade 3 diarrhea was experienced by 9% to 20% of patients (pts) receiving abemaciclib. Study design/Objectives: Study I3Y-MC-JPCP (ClinicalTrials.gov, NCT03703466) was a multicenter, randomized, open-label phase 2 study designed to evaluate the impact of food on the incidence of Grade 3 or prolonged Grade 2 diarrhea in HR+, HER2− metastatic breast cancer (mBC) pts receiving abemaciclib monotherapy 200 mg orally BID during the first 3 cycles of study treatment. Methods: Pts with HR+, HER2− mBC and ECOG performance status ≤1 who had progressed after prior anti-estrogen therapy for mBC and received prior treatment with ≥1 chemotherapy regimen for mBC, but were CDK4/6i naive, were randomly assigned 1:1:1 to receive abemaciclib with a meal, in a modified fasted condition (defined as ≥1 h before or ≥2 h after a meal), or without regard to food. Primary study endpoints were the incidence of ≥Grade 3 diarrhea; incidence of Grade 2 diarrhea lasting >7 days; dose reductions, dose interruptions, and treatment discontinuations due to diarrhea; and use of antidiarrheal agents. Secondary endpoints included overall safety and pharmacokinetic analysis. A pt-held electronic diary was used to record daily information on number of stools, diarrhea, loperamide use, and timing of abemaciclib intake relative to meals. Compliance with diary completion was centrally monitored. Multicenter training and implementation of e-diaries used a variety of paper and electronic resources tailored to end user (research staff, site staff, patient). Physicians had real-time access to data enabling accurate assessment of diarrhea. Results: This study randomized 72 pts in five countries from December 2018 to April 2019; 71 pts (median age 56.0 y) were treated with abemaciclib in one of three study arms: with a meal (Arm 1, n=24), modified fasted condition (Arm 2, n=23) and without regard to food (Arm 3, n=24). Mean compliance for e-diary completion was 95.7% for the overall population. Mean compliance with meal conditions was 99.5% in Arm 1 and 95.2% in Arm 2 (not applicable for Arm 3). In Arms 1, 2 and 3, 83.3%, 78.3% and 91.7% of pts received ≥3 cycles, respectively. Primary endpoints during the first three treatment cycles are summarized (Table). Table 1Arm 1 (n=24)Arm 2 (n=23)Arm 3 (n=24)Overall (n=71)≥1 Grade 2 diarrhea lasting >7 days, %8.317.420.815.5≥1 Grade 3 diarrhea, %4.2*001.4≥1 Grade 4 diarrhea, %0000≥1 Dose reduction due to diarrhea, %16.78.712.512.7≥1 Dose interruption due to diarrhea, %16.74.38.39.9Treatment discontinued due to diarrhea, %0000Loperamide use, %95.891.395.894.4* Duration of Grade 3 diarrhea was 1 day. This study was descriptive and not powered to analyze differences between study arms. Overall, the most frequently reported Grade 3/4 treatment-emergent adverse events related to treatment were neutropenia (28.2%), leukopenia (11.3%), thrombocytopenia (7.0%), fatigue (5.6%), nausea (5.6%) and lymphopenia (5.6%). Details on patient-reported diarrhea incidence and management, and PK analyses will be presented at conference. Conclusions: Global compliance with e-diary completion and meal condition was >95%. Diarrhea at high grade occurred at much lower incidence than previously reported (1.4% overall) and was of short duration (1 day). Diarrhea was predominantly low grade and managed with loperamide and dose modifications in all meal cohorts. Citation Format: Elgene Lim, Frances Boyle, Meena Okera, Sherene Loi, Sema Sezgin Goksu, Gertjan van Hal, Daisy G Hartman, Jonathon Colby Gable, Gregory L Price, Anwar Hossain, M C Gainford, Meritxell Bellet Ezquerra. The impact of food on tolerability of abemaciclib in patients with previously treated hormone receptor-positive, HER2-negative, metastatic breast cancer: An open-label, randomized phase 2 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-05.

Drugs in Focus

Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant anti-diarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant anti-diarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.

Pelvic floor rehabilitation to improve functional outcome and quality of life after surgery for rectal cancer: study protocol for a randomized controlled trial (FORCE trial)

BackgroundAfter low anterior resection (LAR), up to 90% of patients develop anorectal dysfunction. Especially fecal incontinence has a major impact on the physical, psychological, social, and emotional functioning of the patient but also on the Dutch National Healthcare budget with more than €2000 spent per patient per year. No standardized treatment is available to help these patients. Common treatment nowadays is focused on symptom relief, consisting of lifestyle advices and pharmacotherapy with bulking agents or antidiarrheal medication. Another possibility is pelvic floor rehabilitation (PFR), which is one of the most important treatments for fecal incontinence in general, with success rates of 50–80%. No strong evidence is available for the use of PFR after LAR. This study aims to prove a beneficial effect of PFR on fecal incontinence, quality of life, and costs in rectal cancer patients after sphincter-saving surgery compared to standard treatment.MethodsThe FORCE trial is a multicenter, two-armed, randomized clinical trial. All patients that underwent LAR are recruited from the participating hospitals and randomized for either standard treatment or a standardized PFR program. A total of 128 patients should be randomized. Optimal blinding is not possible. Stratification will be done in variable blocks (gender and additional radiotherapy). The primary endpoint is the Wexner incontinence score; secondary endpoints are health-related and fecal-incontinence-related QoL and cost-effectiveness. Baseline measurements take place before randomization. The primary endpoint is measured 3 months after the start of the intervention, with a 1-year follow-up for sustainability research purposes.DiscussionThe results of this study may substantially improve postoperative care for patients with fecal incontinence or anorectal dysfunction after LAR. This section provides insight in the decisions that were made in the organization of this trial.Trial registrationNetherlands Trial Registration, NTR5469, registered on 03-09-2015.Protocol FORCE trial V18, 19-09-2019.Sponsor Radboud University Medical Center, Nijmegen.

Evaluation of rationality of antimicrobial and antidiarrheal fixed dose combination available in Indian market

Background: Literature reports growing concern on ever-burgeoning list of irrational fixed dose combinations (FDCs) flooding the Indian market. Current study addresses availability and rationality of two most common group of FDC used clinically, that is, antimicrobial (AM) and antidiarrheal (AD). Aim and Objective: Analysis of rationality of AM and AD, FDCs, and available in Indian market. Materials and Methods: AM and AD, FDCs listed in Indian Drug Review 2017 and 2018, were analyzed using a validated eight- point criteria tool. Results: Out of 138 FDCs, 102 (73.91%) belonged to AM group and 36 (26.08%) belonged to AD group. Out of 102 AM FDC’s, 46 (45.09%) were rational and 56 (54.90%) were irrational. Out of 36 AD, FDCs, 10 (27.77%) were rational and 26 (72.22%) were irrational. Mean rationality score of AM and AD, FDC’s, was (7.72 ± 0.33) and (7.5 ± 0.78), respectively. Conclusion: Analysis reveals that a number of FDCs available in Indian market is irrational.

Surgical and functional outcomes after colectomy and ileorectal anastomosis in patients with familial adenomatous polyposis

Introduction Familial adenomatous polyposis (FAP) is a distressing genetic disease for both symptomatic and asymptomatic carriers. Thus, early management is paramount to reduce risk of malignancy. Surgical management options for FAP become more variable; but each option comes with a cost. While restorative proctocolectomy with ileal pouch anal anastomosis is considered the gold standard, further surgeries surpass its advantages after critical selection of candidates. Total colectomy with ileorectal anastomosis (IRA) can be the future gold standard when candidates are wisely selected. This study evaluates the surgical, functional, and oncological outcomes of IRA. Patients and methods This study is a prospective cohort study conducted between June 2013 and June 2018 with a minimum follow-up of 12 months and included 33 patients with FAP. All patients underwent total colectomy followed by IRA. Then they were followed up for a mean period of 28.4 months to evaluate the postoperative surgical and functional outcomes as a primary endpoint with evaluation of long-term risk of rectal carcinoma as a secondary endpoint. Results Thirty-three patients had total colectomy followed by IRA. Ten patients developed early postoperative complications and seven had late complications. Bowel function was well preserved in 94% of patients and only 30% of the patients continued to use antidiarrheal medications beyond 6 months after the operation. One month postoperatively, the mean of bowel motions was 4.8 a day, which decreased to 2.6 times after 1 year of follow-up. Recurrence of polyposis was detected in 30% of patients, and only one patient had developed rectal malignancy. Conclusions With appropriate patient selection, IRA provides better surgical, functional, and oncological outcomes. Patient characteristics and disease features should be considered in surgical decision making.

OTC medication use in pregnancy

The use of medications during pregnancy has increased In the last three decades. Pregnant women use medications including both over-the-counter drugs and prescription medications. The pregnant women reported using at least one prescription or over-the-counter medication during pregnancy, including during the first trimester, a critical period of organogenesis. Common over-the-counter drugs categories of readily accessible medications include antipyretics, analgesics, nonsteroidal anti-inflammatory drugs, H-antihistamines, decongestants, expectorants, antacids, antidiarrheal, and topical dermatological medications. For most medications commonly used in pregnancy, there are insufficient data available to characterize the exact fetal risk, limiting the opportunity for informed clinical decisions about the best management of acute and chronic disorders during pregnancy.