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Can an amino acid-based oral rehydration solution be effective in managing immune therapy-induced diarrhea?

ABSTRACT: Immune checkpoint inhibitor (ICPi) therapy has transformed the way we treat cancer. However, its immune related adverse events (irAEs) can be debilitating and life threatening. Immune therapy-induced diarrhea (ITID) is one of the most commonly encountered irAEs and can lead to expensive and prolonged hospitalizations. The current standard of care for grade 3 or 4 ITID involves ICPi discontinuation, the initiation of steroids, and infliximab for refractory disease. This treatment regimen reverses the desired anti-tumor effect of ICPis, can lead to side effects, and is cost-ineffective. We report the first case of the successful treatment of grade 3 ITID with steroids and an amino acid-based oral rehydration solution (AA-ORS), enterade. Research suggests that AA-ORS may be used to reduce diarrhea and adequately hydrate patients, in contrast to glucose-based oral rehydration solutions, which have been implicated as a contributing factor to diarrhea in cancer patients. We hypothesize that an AA-ORS may mitigate ITID via safer and more economically viable means than the current standard of care, but more controlled trials are needed to test this hypothesis.

SUBMITTER: Hendrie JD

PROVIDER: S-EPMC9281899 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Can an amino acid-based oral rehydration solution be effective in managing immune therapy-induced diarrhea?

Hendrie J D JD Chauhan A A Nelson N R NR Anthony L B LB

Medical hypotheses 20190327

Immune checkpoint inhibitor (ICPi) therapy has transformed the way we treat cancer. However, its immune related adverse events (irAEs) can be debilitating and life threatening. Immune therapy-induced diarrhea (ITID) is one of the most commonly encountered irAEs and can lead to expensive and prolonged hospitalizations. The current standard of care for grade 3 or 4 ITID involves ICPi discontinuation, the initiation of steroids, and infliximab for refractory disease. This treatment regimen reverses ...[more]

PMID: 31088651

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Project description:AimThis paper aims to identify factors that systematically predict why some countries that have tried to scale up oral rehydration solution (ORS) have succeeded, and others have not.MethodsWe examined ORS coverage over time, across countries, and through case studies. We conducted expert interviews and literature and data searches to better understand the history of ORS scale-up efforts and why they failed or succeeded in nine countries. We used qualitative, pairwise (or three-country) comparisons of geographically or otherwise similar countries that had different outcomes in terms of ORS scale-up. An algorithm was developed which scored country performance across key supply, demand and financing activities to quantitatively assess the scale-up efforts in each country.ResultsThe vast majority of countries have neither particularly low nor encouragingly high ORS use rates. We observed three clearly identifiable contrasts between countries that achieved and sustained high ORS coverage and those that did not. Key partners across sectors have critical roles to play to effectively address supply- and demand-side barriers. Efforts must synchronize demand generation, private provider outreach and public sector work. Many donor funds are either suspended or redirected in the event of political instability, exacerbating the health challenges faced by countries in these contexts. We found little information on the cost of scale-up efforts.ConclusionsWe identified a number of characteristics of successful ORS scale-up programs, including involvement of a broad range of key players, addressing supply and demand generation together, and working with both public and private sectors. Dedicated efforts are needed to launch and sustain success, including monitoring and evaluation plans to track program costs and impacts. These case studies were designed to inform programmatic decision-making; thus, rigorous academic methods to qualitatively and quantitatively evaluate country ORS scale-up programs might yield additional, critical insights and confirm our conclusions.

Project description:BackgroundReduction of gross diarrhea rate in excess of that seen over time with intravenous therapy and appropriate antibiotics is not usually achieved by oral glucose-electrolyte rehydration therapy for cholera and cholera-like diarrheas.Methodology and principal findingsThis prospective randomized clinical trial at a tertiary referral hospital in southern India was undertaken to determine whether amylase resistant starch, substituting for glucose in hypo-osmolar oral rehydration solution, would reduce diarrhea duration and weight in adults with acute severe dehydrating diarrhea. 50 adult males with severe watery diarrhea of less than three days' duration and moderate to severe dehydration were randomized to receive hypo-osmolar ORS (HO-ORS) or HO-ORS in which amylase resistant high amylose maize starch 50g/L substituted for glucose (HAMS-ORS). All remaining therapy followed standard protocol. Duration of diarrhea (ORS commencement to first formed stool) in hours was significantly shorter with HAMS-ORS (median 19, IQR 10-28) compared to HO-ORS (median 42, IQR 24-50) (Bonferroni adjusted P, P(adj)<0.001). Survival analysis (Kaplan-Meier) showed faster recovery from diarrhea in the HAMS-ORS group (P<0.001, log rank test). Total diarrhea fecal weight in grams (median, IQR) was not significantly lower in the HAMS-ORS group (2190, 1160-5635) compared to HO-ORS (5210, 2095-12190) (P(adj) = 0.08). However, stool weight at 13-24 hours (280, 0-965 vs. 1360, 405-2985) and 25-48 hours (0, 0-360 vs. 1080, 55-3485) were significantly lower in HAMS-ORS compared to HO-ORS group (P(adj) = 0.048 and P = 0.012, respectively). ORS intake after first 24 hours was lower in the HAMS-ORS group. Subgroup analysis of patients with culture isolates of Vibrio cholerae indicated similar significant differences between the treatment groups.ConclusionsCompared to HO-ORS, HAMS-ORS reduced diarrhea duration by 55% and significantly reduced fecal weight after the first 12 hours of ORS therapy in adults with cholera-like diarrhea.Trial registrationCurrent Controlled Trials ISRCTN72841333.

Project description:BackgroundMore than 3 million children under 5 years in developing countries die from dehydration due to diarrhea, a preventable and treatable disease. We conducted a comparative analysis of two Demographic Health Survey (DHS) cycles to examine changes in ORS coverage in Zimbabwe, Zambia and Malawi. These surveys are cross-sectional conducted on a representative sample of the non-institutionalized individuals.MethodsThe sample is drawn using a stratified two-stage cluster sampling design with census enumeration areas, typically, selected first as primary sampling units (PSUs) and then a fixed number of households from each PSU. We examined national and sub-regional prevalence of ORS use during a recent episode of diarrhea (within 2 weeks of survey) using DHSs for 2007-2010 (1st Period), and 2013-2016 (2nd Period). Weighted proportions of ORS were obtained and multivariable- design-adjusted logistic regression analysis was used to obtain Odds Ratios (aORs) and 95% confidence intervals (CIs) and weighted proportions of ORS coverage.ResultsCrude ORS coverage increased from 21.0% (95% CI: 17.4-24.9) in 1st Period to 40.5% (36.5-44.6) in 2nd Period in Zimbabwe; increased from 60.8% (56.1-65.3) to 64.7% (61.8-67.5) in Zambia; and decreased from 72.3% (68.4-75.9) to 64.6% (60.9-68.1) in Malawi. The rates of change in coverage among provinces in Zimbabwe ranged from 10.3% over the three cycles (approximately 10 years) in Midlands to 44.2% in Matabeleland South; in Zambia from - 9.5% in Eastern Province to 24.4% in Luapula; and in Malawi from - 16.5% in the Northern Province to - 3.2% in Southern Province. The aORs for ORS use was 3.95(2.66-5.86) for Zimbabwe, 2.83 (2.35-3.40) for Zambia, and, 0.71(0.59-0.87) for Malawi.ConclusionORS coverage increased in Zimbabwe, stagnated in Zambia, but declined in Malawi. Monitoring national and province-level trends of ORS use illuminates geographic inequalities and helps identify priority areas for targeting resource allocation.. Provision of safe drinking-water, adequate sanitation and hygiene will help reduce the causes and the incidence of diarrhea. Health policies to strengthen access to appropriate treatments such as vaccines for rotavirus and cholera and promoting use of ORS to reduce the burden of diarrhea should be developed and implemented.

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Can an amino acid-based oral rehydration solution be effective in managing immune therapy-induced diarrhea?

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Can an amino acid-based oral rehydration solution be effective in managing immune therapy-induced diarrhea?

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