Daijokito Administration in Critically Ill Patients Increasing the Stool Volume: A Retrospective Observational Study

Introduction:Daijokito, a traditional Japanese herbal medicine (Kampo), has been used to treat abdominal distention of the middle yang stage pattern. The use of Daijokito has not been thoroughly investigated in critical care. To investigate a new Kampo approach to defecation control in critically ill patients, our study aimed to assess the effects of Daijokito on fecal management.Methods: We analyzed 30 consecutive patients treated with Daijokito in the intensive care unit (ICU) between March 2017 and February 2021. The eligibility criteria were patients who were newly prescribed Daijokito in the ICU during the study period. Exclusion criteria were patients who were started on other laxatives within one day of beginning Daijokito. The study's primary outcome was defecation volume three days before and three days after starting Daijokito. We recorded the most dominant stool quality within three days after the start of Daijokito.Results: Twenty-one patients were included in the analysis. The median age was 69.0 years, and the median sequential organ failure assessment score on admission to the ICU was 6.0. Major diseases included trauma, pancreatitis, and burns. Administration of Daijokito resulted in defecation in 17 of twenty-one patients (81.0%). Comparison of defecation volume between 3 days before Daijokito administration and three days, including the day of Daijokito administration, showed that defecation volume increased significantly after Daijokito administration, with a median of 0 to 360 g (p < 0.001). At the three-day follow-up, six of 17 (35.3%) patients defecated on the day of Daijokito administration, and nine (52.9%) defecated on the day after administration. One patient was judged to have excessive defecation, and Daijokito administration was discontinued. Stool quality was normal in one (5.9%) of the 17 patients, soft-formed in two (11.8%), loose-unformed in 11 (64.7%), and liquid in three (17.6%).Discussion:Daijokito administration in critically ill patients caused defecation in 81% of the patients and significantly increased stool volume. The novelty of this study is that it sheds light on the Kampo treatment of defecation control in critically ill patients. In addition to the present report, further studies are warranted to quantify the therapeutic efficacy and safety of Daijokito.

Are oral rehydration solutions optimized for treating diarrhea?

Background: A historical turning point occurred in the treatment of diarrhea when it was discovered that glucose could enhance intestinal sodium and water absorption. Adding glucose to salt water (oral rehydration solution, ORS) more efficiently replaced intestinal water and salt losses. Aim: Provide a novel hypothesis to explain why mainstream use of ORS has been strongly recommended, but weakly adopted. Methods: Traditional (absorptive) and novel (secretory) physiological functions of glucose in an ORS were reviewed. Results: Small amounts of glucose can stimulate both intestinal absorption and secretion. Glucose can exacerbate a net secretory state and may aggravate pathogen-induced diarrhea, particularly for pathogens that affect glucose transport. Conclusion: A hypothesis is made to explain why glucose-based ORS does not appreciably reduce diarrheal stool volume and why modern food science initiatives should focus on ORS formulations that replace water and electrolytes while also reducing stool volume and duration of diarrhea.

Evaluating efficacy of oral zinc as adjuvant therapy in acute diarrhea in children.

Objectives: To evaluate the efficacy of oral zinc as adjuvant therapy in acute diarrhea comparing frequency and volume of stool and duration of diarrhea in children. Study Design: Case Control study. Setting: Department of Paediatrics, Shaheed Muhtrama Benazir Bhutto Medical College Layari General Hospital, Karachi. Period: September 2017 to August 2018. Material & Methods: A sample of 200 children, age 5- 15 years, suffering from acute diarrhea was divided into control and cases (study group). Oral zinc therapy (20 mg once daily) was given 14 days and its efficacy was observed in terms of stool frequency, stool volume and duration of diarrhea. Variables were noted at 24 hours and 48 hours and on 7th day of hospitalization. Data was analyzed on SPSS statistical software (version 22.0) at 95% confidence interval (P≤ 0.05). Results: Mean ± SD age in control and study group was noted as 9.1± 5.43 years and 9.5±6.02 years respectively (P=0.053). 89% of children of study group were discharged on 3rd day of hospitalization compared to only 45% from control group. Zinc treated study group shows significant decrease in frequency of loose stools, stool volume and lesser duration of hospital stay. Conclusion: Oral zinc therapy was effective in decreasing the frequency of loose stools and volume and lesser duration of hospital stay in children.

Cholera and Pancreatic Cholera: Is VIP the Common Pathophysiologic Factor?

Background: Cholera remains a major global health problem, causing high output diarrhea leading to severe dehydration and shock in developing countries. We aimed to determine whether vasoactive intestinal polypeptide (VIP), the mediator of pancreatic cholera syndrome, has a role in the pathophysiology of human cholera. Methods: We conducted a prospective observational study of cholera cases hospitalized with severe dehydration. Plasma and stool water levels of VIP were measured just after admission, after complete rehydration (3–4 h), at 24 h post-rehydration and at discharge after diarrhea ceased. Results: In total, 23 cholera patients were examined between January and August 2018. The geometric mean of stool VIP (sVIP) and plasma VIP (pVIP) on admission were 207.67 and 8.34 pmol/L, respectively. pVIP values were all within the normal range (</= 30 pcmol/L); however, sVIP levels were very high at all timepoints, though less so just after rehydration. In multivariable GEE models, after adjustment for covariates, sVIP levels were significantly associated with duration of hospitalization (p = 0.026), total stool volume (p = 0.023) as well as stool output in the first 24 h (p = 0.013). Conclusions: The data suggest that VIP, which is released by intestinal nerves, may play an important role in human choleragenesis, and inhibitors of intestinal VIP merit testing for potential therapeutic benefits.

Bowel movement improvement by Mulukhiyah (Corchorus olitorius)-containing food (AOTSUBU®) consumption: A randomized, double-blind, placebo-controlled, parallel- group comparison trial

Background: Mulukhiya (Corchorus olitorius) richly contains dietary fiber and is suggested to improve bowel movement.Objective: This study aimed to investigate the effects of mulukhiya-derived dietary fiber (MDF) on the intestinal environment in healthy Japanese adult subjects.Methods: This randomized, double-blinded, placebo-controlled study enrolled 22 healthy Japanese adult subjects who typically defecate three to five times per week and do not consume enough dietary fiber. All subjects were randomly allocated into the MDF group (4 men and 7 women; 45.1 ± 11.4 years) or the placebo group (3 men and 8 women; 41.6 ± 9.5 years) by using a computerized random number generator. Each subject was administered with assigned 30 tablets (active [77-mg dietary fiber] or placebo) daily for two weeks. We asked the subjects to record their defecation condition in a bowel movement diary from 1 week before the start of test food consumption to the day before two weeks after the start of the test-food consumption (three weeks in total). Then, we evaluated the items in the bowel movement diary such as the occupancy rate of enteric, organic acids in feces, and subjective symptoms related to constipation.Results: At one and two weeks after the start of the test-food consumption, the MDF group exhibited a significant increase in stool days, stool frequency, and stool volume compared with the placebo group (P < 0.05). Regarding the occupancy rate of enteric bacteria, Prevotella (P = 0.025) and Clostridium cluster IV (P = 0.045) were significantly increased in the MDF group compared with those in the placebo group at 2 weeks after the start of the test-food consumption. As for organic acids in feces, n-butyric acid was significantly higher in the MDF group than in the placebo group at 2 weeks after the start of the test-food consumption (P = 0.037). Furthermore, no safety concerns were noted.Conclusions: The consumption of MDF-containing food for 2 weeks resulted in the increase of stool frequency, stool volume, useful enteric bacteria, and organic acids in feces in healthy Japanese adult subjects.Clinical trial registration number: UMIN-CTR: UMIN000035613.Keywords: Mulukhiya, enterobacterial flora, dietary fiber, stool frequency, organic acid levels

Systematic Review with Meta-Analysis: Lactobacillus reuteri DSM 17938 for Treating Acute Gastroenteritis in Children. An Update

The effectiveness of Lactobacillus reuteri DSM 17938 (L. reuteri) for the management of acute gastroenteritis (AGE) has been recently questioned. We performed a systematic review to update evidence on L. reuteri for treating AGE in children. We searched MEDLINE, EMBASE, the Cochrane Library databases, and additional data sources from January 2016 (end of search for our 2016 systematic review) to August 2019. The primary outcomes were stool volume and duration of diarrhea. Four RCTs were included. None of them evaluated stool volume. Compared with placebo or no treatment, L. reuteri reduced diarrhea duration (four RCTs, n = 347, mean difference, MD −0.87 days, 95% CI [−1.43, −0.31]). L. reuteri use was also associated with a reduced duration of hospitalization (three RCTs, n = 284, MD −0.54 days, 95% CI [−1.09, 0.0]). The small effect sizes of limited clinical relevance and methodological limitations of the included trials should be noted when interpreting these findings.

More accuracy estimation of the worm burden in the ascariasis of children in Kinshasa

ABSTRACTThe present study aims to give a better estimate of the worm burden (ascariasis) to address accurately the impact of intestinal parasitosis on the children growth in Africa.The study was conducted on 20 subjects aged 10 months to 10 years (Mean ± SD: 5.6 ± 2.3 years). They were treated with 10 mg/kg of Pyrantel pamoate. The next day, the stools were collected, washed and filtered to harvest all adult ascaris. In total, 141 ascaris (71 males and 70 females) were extracted for 879.9 g of stool. The geometric mean of eggs counted was 29 by 2 mg of stool. The daily eggs laying per female was estimated to 202,500 eggs/days (CI95%: 128,800 – 276,200).Statistical analysis shows that the parasitic worm burden was proportional both to the number eggs counted per unit of stool volume, and to age of infested subject. A regression model based on these two parameters, with a coefficient of determination equal to 59 %, was retained. Thus, for an old subject respectively of 1, 5 and 10 years, at which 1 egg of ascaris in approximately 2 mg of a preparation would lodge a respective parasitic mass of 1, 3 and 9 g. The results are in the form of confidence interval. For example, for a 5 years old subject with an average of 10 eggs (CI95% = 5.6 - 14.4) after reading of 2 separated preparations coming from the same specimen, the estimated parasitic load is laying between 7 and 11 g.

Effects of 4-week continuous ingestion of champignon extract on bowel movements and intestinal putrefaction products: a randomized, placebo-controlled, double-blinded, parallel-group comparative trial

Background: The aim of this study was to analyze the putrefaction products in the feces of subjects from a previous study (age range 50–79 years) which assessed the improvement of breath, body, and fecal odor after ingesting champignon extract.Methods: The study was designed as a randomized, placebo-controlled, double-blinded, and parallel-group comparative trial. Subjects were divided into four groups, including the placebo (n=20), champignon extract at 50 mg/day (n=20), champignon extract at 500 mg/day (n=20), and champignon extract at 1000 mg/day (n=20) for 4 weeks.Results: The results revealed significant reduction in ammonia and p-cresol levels (both of which are intestinal putrefaction products) among subjects who ingested 50, 500, and 1000 mg of champignon extract per day compared with subjects in the placebo group. Additionally, a significant difference was observed in indole levels in the group that consumed 500 mg/day of the extract compared to the placebo group.Conclusions: The re-analysis of bowel movement in each test group revealed that the extract improved the number of days with bowel movement, number of bowel movements, and stool volume, which suggests the intestinal environment was improved.Clinical trial registration: UMIN000014256Keywords: ammonia, champignon, fecal odor, p-cresol, putrefaction

Guidelines for the Standardization of Acute Graft-Versus-Host Disease Clinical Data Collection: An International Consensus Report

Clinical GVHD staging varies between centers and is not agreed upon by independent reviewers (Weisdorf, BBMT 2003). These inconsistencies help explain why promising GVHD treatments from single center studies have not reproduced in multicenter trials. To address this issue, our international GVHD research consortium has developed guidance that has been refined through consensus following case discussions, resulting in uniform and reproducible GVHD clinical symptom reporting. We record all raw target organ symptom data and apply staging based upon this data (Table 1). Only areas of erythema, bullae and desquamation are quantified because other skin changes are not typical of active GVHD rash. Upper GI symptoms must meet thresholds to diagnose GVHD: anorexia with associated weight loss, nausea and/or 2+ vomiting episodes/day lasting 3+ days. For lower GI GVHD we collect stool volumes excluding formed/mostly-formed stools. Unquantified episodes are counted at 200 ml per episode (3 ml/kg for children <50kg) based upon a chart review of 300 patients with post-BMT diarrhea from any cause. Non-GVHD rectal bleeding that results in flecks or streaks of blood in the stool are ignored for staging. We use the highest daily stool output in the 3 days prior to the diagnosis of lower GI GVHD to determine onset stage and, when available, a 3-day average stool volume for subsequent staging to smooth daily variability. We classify biopsy report interpretation into four standardized categories: Positive (unequivocal presence of GVHD), Equivocal (findings suggestive of GVHD, but the pathologist cannot confirm the diagnosis), Non-diagnostic (no abnormalities or subtle findings insufficient to determine etiology), and Non-GVHD etiology (definitive evidence of another diagnosis without concomitant features suggestive of GVHD). We then combine the biopsy interpretation with clinical decision making to assign an overall confidence level to the diagnosis of GVHD in each target organ (Table 2): Confirmed (positive biopsy, regardless of clinician treatment decision), Probable (GVHD diagnosis is sufficiently favored that treatment is given without a positive biopsy), Possible (symptoms present without a positive biopsy; not treated as GVHD), Negative (no symptoms or symptoms are present but a GVHD diagnosis is not entertained and a non-GVHD etiology is identified). Uniform clinical data collection is essential for future GVHD trials and requires application of clear guidance. While still subject to refinement, these guidelines, in use for 2 years by an international research consortium, are designed to be clear, easy to apply, and for clinical trial use. Table 1. GVHD Target Organ Staging Stage Skin (active erythema only) Liver (bilirubin) Upper GI Lower GI (stool output/day) 0 No active (erythematous) GVHD rash < 2 mg/dl No or intermittent nausea, vomiting or anorexia Adult: < 500 ml/day or <3 episodes/day Child: < 10 ml/kg/day or <4 episodes/day 1 Rash < 25% BSA 2-3 mg/dl Persistent nausea, vomiting or anorexia Adult: 500-999 ml/day or 3-4 episodes/day Child: 10 -19.9 ml/kg/day or 4-6 episodes/day 2 Rash 25 - 50% BSA 3.1-6 mg/dl - Adult: 1000-1500 ml/day or 5-7 episodes/day Child: 20 - 30 ml/kg/day or 7-10 episodes/day 3 Rash > 50% BSA 6.1-15 mg/dl - Adult: >1500 ml/day or >7 episodes/day Child: > 30 ml/kg/day or >10 episodes/day 4 Generalized rash (>50% BSA) and bullous formation or desquamation > 5% BSA >15 mg/dl - Severe abdominal pain with or without ileus, or grossly bloody stool (volume independent) Table 2. Confidence Levels Pathologic evidence Clinician assessment Treatment for acute GVHD Comments Confirmed Unequivocal evidence of GVHD GVHD is the etiology for symptoms Not required GVHD is clearly present even if other etiologies co-exist simultaneously Probable Not required (includes equivocal and non-diagnostic biopsies) GVHD most likely etiology for symptoms Yes GVHD is most likely present but other etiologies may also explain the symptoms and there insufficient evidence to make a confirmed diagnosis Possible GVHD in differential diagnosis (but no treatment is being provided) No GVHD may be present, but other etiologies are favored Negative Unequivocal evidence of a diagnosis other than GVHD (e.g., drug rash) GVHD is not considered as an explanation for the symptoms No and the symptoms resolve without GVHD treatment A "negative" biopsy (e.g., normal skin) is not unequivocal evidence of a diagnosis other than GVHD Disclosures Devine: Genzyme: Research Funding. Chen:Bayer: Consultancy, Research Funding. Porter:Novartis: Patents & Royalties, Research Funding. Levine:Novartis: Consultancy.

Effect of vitamin A on severity of acute diarrhea in children

Background Vitamin A deficiency may increase the risk or bea cause of diarrhea. Many studies have been conducted on theefficacy of vitamin A in the management of acute diarrhea, butthe outcomes remain inconclusive.Objective To determine the effectiveness of vitamin A in reducingthe severity of acute diarrhea in children.Methods We performed a single􀁈blind􀁈randomized controlledtrial in the Secanggang District, Langkat Regency, North ofSumatera, from August 2009 to January 2010 in children aged6 months to 5 years, who had diarrheas. Subjects were dividedinto two groups. Group 1 received a single dose of vitamin A(100,000 IU for subjects aged 6 to 11 month old or with bodyweights :s 10 kg, or 200,000 IU for subjects aged 2: 12 month oldor with body weights> 10 kg). Group 2 received a single doseof placebo. The establishment of severity was based on changesin diarrheal frequency, stool consistency, volume and durationof diarrhea after treatment. We performed independent T􀁈testand Chi square tests for statistical analyses. The study was anintention􀁈to􀁈treat analysis.Results We enrolled 120 children who were randomized intotwo groups of 60 subjects each. Group 1, received vitamin Aand group 2 received a placebo. The results showed significantdifferences between the two groups in stool volume starting onthe first day (95%CI 192.30 to 3237.51; P􀁉O.OOI), as well asdiarrheal frequency (P=O.OOl) and stool consistency (P=O.OOl)on the second day observation and duration of diarrhea followingtreatment (95%CI - 40.60 to - 25.79; P􀁉O.OOI;).Conclusions Vitamin A supplementation is effective in reducingthe severity of acute diarrhea in children under five years of age.[Paediatr lndones. 2013;53:125-31.]