Chemical profiling, toxicity assessment, anti-diarrhoeal, anti-inflammatory and antinociceptive activities of Canarium schweinfurthii Engl. (Burseraceae) bark in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Canarium schweinfurthii is used in ethnomedicine for the treatment of diabetes, pain, malaria, fever and diarrhoea. AIM OF THE STUDY: The chemical phytoconstituents, antidiarrheal, anti-inflammatory and antinociceptive effects and safety profile of the aqueous extract of Canarium schweinfurthii bark (AECSB) were investigated. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to analyse the phytochemical composition. In the acute toxicity test, AECSB were administered up to 2 g/kg by oral gavage. For the subacute toxicity test (28 days), rats in group 1 (control) received no AECSB, while rats in groups 2-4 were administered different doses of AECSB. Charcoal meal transit and castor oil-induced diarrhoea models were used to study the antidiarrheal effect, while egg albumin/carrageenan and acetic acid/tail immersion models were used for the anti-inflammatory and antinociceptive studies, respectively. With the exception of the acute toxicity experiment, AECSB was administered orally at doses of 200, 400 and 800 mg/kg. RESULTS: Bioactive phytoconstituents identified include p-cymene, δ-terpinene, linalool and phytol. No adverse effects or mortality were observed in acute and subacute studies. Treatment with AECSB (28 days) had no significant effect on organ weight, biochemical, hematologic and histopathologic parameters compared to the control groups (p > 0.05). Comparable antidiarrheal and antinociceptive effects were observed in both AECSB- and standard drug-treated groups, while the 400 and 800 mg/kg AECSB-treated groups showed remarkable anti-inflammatory effects compared to the standard drug-treated and control groups (p < 0.05). CONCLUSION: AECSB has antidiarrheal, antinociceptive and anti-inflammatory effects and can be safely used for therapeutic purposes.

A situational assessment of treatments received for childhood diarrhea in the Federal Republic of Nigeria.

We assess progress towards improved case management of childhood diarrhea in Nigeria over a period of targeted health systems reform from 2013 to 2018. Individual and community data from three Demographic and Health Survey rounds are leveraged in a geospatial model designed for stratified estimation by venue of treatment seeking and State. Our analysis reveals a highly regionalised health system undergoing rapid change. Nationally, there have been substantial increases in the proportion of children under 5 years old with diarrhea receiving the recommended oral rehydration therapy after seeking treatment at either a health clinic (0.57 [0.44-0.69; 95% CI] in 2008; 0.70 [0.54-0.83] in 2018) or chemist/pharmacy (0.28 [0.17-0.42] in 2008; 0.48 [0.31-0.64] in 2018). Yet State-level variations in venue attendance and performance by venue have conspired to hold the overall proportion receiving this potentially life-saving therapy (0.45 [0.35-0.55] in 2018) to well-below ideal coverage levels. High performing states that have demonstrated significant improvements include Kano, Jigawa and Borno, while under-performing states that have suffered declines in coverage include Kaduna and Taraba. The use of antibiotics is not recommended for mild cases of childhood diarrhea yet remains concerningly high nationally (0.27 [0.19-0.36] in 2018) with negligible variation between venues. Antibiotic use rates are particularly high in Enugu, Kaduna, Taraba, Kano, Niger and Kebbi, yet welcome reductions were identified in Jigawa, Adamawa and Osun. These results support the conclusions of previous studies and build the strength of evidence that urgent action is needed throughout the multi-tiered health system to improve the quality and equity of care for common childhood illnesses in Nigeria.

Treatment-Free Interval: A Novel Approach to Assessing Real-World Treatment Effectiveness and Economic Impact Among Patients with Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA. METHODS: Adult patients (18-64 years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics® Plus database (10/01/2015-12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30 consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences. RESULTS: There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1 years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30 days (76.2% vs. 66.7%), ≥ 60 days (67.0% vs. 47.0%), ≥ 90 days (61.0% vs. 38.7%), ≥ 180 days (51.7% vs. 31.0%), and ≥ 240 days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30 days, mean TFI durations were 8.3 and 6.0 months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437; p = 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250; p < 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1 million per year or $0.18 per-member-per-month. CONCLUSIONS: This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.

Qualitative Assessment of a Smartphone-Based Mobile Health Tool to Guide Diarrhea Management in Bangladesh.

Diarrheal diseases are a major cause of morbidity and mortality in children worldwide and a significant contributor to antimicrobial resistance. In the absence of laboratory diagnostics to establish diarrhea etiology, electronic clinical decision support tools can help physicians make informed treatment decisions for children with diarrhea. In Bangladesh, we assessed the feasibility and acceptability of an electronic Diarrhea Etiology Prediction algorithm (DEP tool) embedded into a rehydration calculator, which was designed to help physicians manage children with diarrhea, including decisions on antibiotic use. A team of Bangladeshi anthropologists conducted in-depth interviews with physicians (N = 13) in three public hospitals in Bangladesh about their experience using the tool in the context of a pilot trial. Physicians expressed positive opinions of the DEP tool. Participants perceived the tool to be simple and easy to use, with structured guidance on collecting and entering clinical data from patients. Significant strengths of the tool were as follows: standardization of protocol, efficiency of clinical decision-making, and improved clinical practice. Participants also noted barriers that might restrict the widespread impact of the tool, including physicians' reluctance to use an electronic tool for clinical decision-making, increasing work in overburdened healthcare settings, unavailability of a smartphone, and patients' preferences for antibiotics. We conclude that an electronic clinical decision support tool is a promising method for improving diarrheal management and antibiotic stewardship. Future directions include developing and implementing such a tool for informal healthcare physicians in low-resource settings, where families may first seek care for pediatric diarrhea.

Prevalence of Enteric Infections in Patients on Immune Checkpoint Inhibitors and Impact on Management and Outcomes.

BACKGROUND: Stool pathogen testing is recommended as part of the initial evaluation for patients with new-onset diarrhea on immune checkpoint inhibitors (ICIs), yet its significance has not been well-studied. We aimed to determine the impact of multiplex gastrointestinal (GI) pathogen PCR testing on the clinical course and use of immunosuppressive therapy in patients who develop diarrhea on ICIs. METHODS: This retrospective cohort included individuals who underwent GI pathogen panel PCR for diarrhea on ICIs at Memorial Sloan Kettering between 7/2015 and 7/2021. The primary outcome was use of immunosuppressive therapy for suspected immunotherapy-related enterocolitis (irEC). Secondary outcomes included diarrhea severity and endoscopic and histologic disease patterns. RESULTS: Among 521 ICI-treated patients tested for GI pathogens, 61 (11.7%) had a positive PCR. Compared to patients without detectable infections, patients with infections had more frequent grades 3-4 diarrhea (37.7% vs. 19.6%, P < .01) and colitis (39.3% vs. 14.7%, P < .01). However, patients with infections did not have higher rates of persistent or recurrent diarrhea and were less likely to receive steroids (P < .01) and second-line immunosuppressive agents (P = .03). In 105 patients with lower endoscopy, similar trends were observed and no differences in endoscopic severity or histologic patterns were noted between groups. CONCLUSIONS: GI infections in ICI-treated patients presenting with diarrhea are linked to more severe but self-limited clinical presentations and may be optimally treated with observation and supportive care alone. Routine and timely stool pathogen testing may help avert unnecessary empiric immunosuppression for suspected irEC, which has been linked to blunted antitumor responses and numerous adverse effects.

Assessment of The Effect of Antidiarrheal Drugs and Plant Extracts on Drosophila melanogaster.

To study human gastrointestinal physiology, biomedical scientists have relied on the use of model organisms. Although many researchers have used mice as a model to study intestinal function, only a few reports have focused on Drosophila melanogaster (D. melanogaster). Compared to mice, fruit flies present many advantages, such as a short life cycle, cost-effective and simple maintenance, and no ethical issues. Furthermore, the mammalian gastrointestinal physiology, anatomy, and signaling pathways are highly conserved in D. melanogaster. Plant extracts have been used traditionally to treat diarrhea and constipation. For example, Psidium guajava (P. guajava) is one of the most known antidiarrheal agents in the tropics. However, no studies have evaluated the effect of antidiarrheal and laxative drugs and plant extracts in D. melanogaster, and it remains unknown if similar effects (e.g., smaller, more concentrated, and less abundant fecal deposits in the case of antidiarrheal drugs) can occur in the fruit flies compared to mammals. In this study, an antidiarrheal effect induced by P. guajava is demonstrated in a D. melanogaster strain that presents a diarrheic phenotype. Fecal sampling produced by flies is monitored using a dye-supplemented food. This protocol outlines the method used for preparing food with drugs, evaluating the fecal deposits of flies fed on these food preparations, and interpreting the data obtained.

Selling antibiotics without prescriptions among community pharmacies and drug outlets: a simulated client study from Ghana.

BACKGROUND: Selling antibiotics without prescriptions is mostly illegal worldwide, including in Ghana, and promotes antimicrobial resistance. We evaluated the prevalence and practice of selling antibiotics without prescriptions among community pharmacies (CPs) and drug outlets, for the first time, in Ghana to quantify and characterize this issue to inform future interventions. RESEARCH DESIGN AND METHODS: Two scenarios utilizing the Simulated Client Methodology were enacted: an upper respiratory tract infection of viral origin (scenario one); and pediatric diarrhea (scenario two). CPs/Outlets were selected by stratified proportional random sampling from four metropolitan cities (~14% of the total Ghanaian population). Selling of antibiotics was assessed at three demand levels and its overall prevalence was estimated, then stratified by the study variables. RESULTS: Out of the 265 sampled CPs/outlets, the prevalence of selling antibiotic without prescription was 88.3% (n = 234/265), with variations not only across the four regions [92.5% (n = 123/133) in Kumasi, 87.5% (n = 14/16) in Cape Coast, 84.1% (n = 69/82) in Accra, and 82.4% (n = 28/34) in Tamale] but also across CPs [90% (n = 121/134)] and drug outlets [86% (n = 113/131)]. CONCLUSIONS: A very high prevalence/sub-optimal practice of selling antibiotics without prescriptions was found. This highlights the need to increase compliance with antibiotic dispensing legislation through evidence-based interventions including education of key stakeholders.

Antibiotic Prescription Patterns in Children Under 5 Years of Age With Acute Diarrhea in Quito-Ecuador.

BACKGROUND: Diarrheal disease remains a significant cause of child mortality, particularly in regions with limited access to healthcare and sanitation. Inappropriate practices, including unjustified medication prescriptions, pose challenges in the management of acute diarrhea (AD), especially in low- and middle-income countries. OBJECTIVE: This study analyzed antibiotic prescription patterns and assessed compliance with Integrated Management of Childhood Illness (IMCI) guidelines in children under 5 with AD in the Ministry of Public Health (MOPH) Ambulatory Care Centers of Quito city, Ecuador. METHODS: A cross-sectional design was used, collecting electronic health records (EHR) of patients diagnosed with AD from 21 health facilities in District 17D03. A probabilistic and stratified sampling approach was applied. Patient characteristics, prescriber characteristics, treatments, and compliance of IMCI guideline recommendations were evaluated. A stepwise logistic regression analysis examined the association between antibiotic prescription and patient and physician characteristics. RESULTS: A total of 359 children under 5 years of age were included, with 58.77% being girls. 85.24% of the cases of AD were attributed to gastroenteritis and colitis of infectious and unspecified origin. Amebiasis and other protozoal intestinal diseases accounted for 13.37% and 1.11% of the cases, respectively. The completion rates of recording various IMCI parameters varied; parameters such as duration of diarrhea, presence of blood in stool, and evidence of sunken eyes had high completion rates (100%, 100%, and 87.47%, respectively), while parameters like state of consciousness, presence of thirst, and type of diarrhea had low completion rates (0.28%, 0.28%, and 0.84%, respectively). None of the cases had all parameters fully recorded. Antimicrobials were prescribed in 38.72% of the cases. Children aged 3 to 5 years had higher odds of receiving antimicrobial prescription for AD (aOR: 4.42, 95% CI 2.13-9.18, P < .0001) compared to those under 1 year, after adjusting for the number of loose stools per day, gender, and age of the health professional. CONCLUSION: Variations in IMCI guideline compliance were observed, with no cases fully adhering to the guidelines. Antimicrobial prescription rates were notably high, especially among older children. Further research and specialized interventions are necessary to gain comprehensive insight into the factors underlying non-compliance with the IMCI guidelines.

Assessment of integrated community case management of childhood illness (ICCM) practices by trained patent and proprietary medicine vendors (PPMVs) in Ebonyi and Kaduna states, Nigeria.

INTRODUCTION: An Integrated Community treatment of Childhood disease (ICCM)- focused intervention involving a large number of Patent and proprietary medicine vendors (PPMVs) was conducted by Society for Family Health Nigeria to improve management of childhood, malaria, pneumonia and diarrhea with an intervention approach focused on knowledge and skill improvement. The intervention was conducted in Kaduna and Ebonyi state; recruited and trained 15 interpersonal communication agents (IPCAs) who were saddled with the responsibility to sensitize and mobilize caregivers with children within the age bracket of 2 months to 5 years to our mapped PPMVs within the communities, on the account of Malaria, Diarrhea, and Pneumonia; while the IPCAs in return monitor the quality-of-service delivery. Following the intervention, the Society for Family health conducted a study to demonstrate the effectiveness of interventions such as ICCM training, supervision and linkage to quality ICCM commodities, among PPMVs to achieve high levels of knowledge and performance in diagnosing and treating common childhood illnesses. METHODS: Longitudinal research (before and after study) was adopted for the study. From the 387 PPMVs recruited and trained by SFH, 165 PPMVs were systematically selected to participate in the study, before and after the implementation of the intervention. Using SPSS version 22, data from the observation and completed questionnaires were analyzed and a chi-square test was used to examine the associations between the categorical information collected prior and after the intervention. The analysis was conducted at 5% level of significance. RESULTS: More than 50 % of the study participants were females (56.4%) and majority were either Junior community extension workers (35%) or Senior community extension worker (27%). About 21.8% trained PPMVs could not appropriately treat malaria in the first quarter of the intervention, however, there was a significant decrease to 1.8% in second quarter in the number of those that cannot appropriately diagnose and treat malaria. There was also a decrease in the number of those who could not treat cough and fast breathing from 47(28.5%) to 14(8.5%) in the second quarter and for diarrhea from 33.3% in the first quarter to 2.4% in the second quarter. CONCLUSION: The study revealed a significant improvement in the quality of treatment provided by the trained PPMVs across the three disease areas. PPMVs in hard-to-reach areas should be trained and supported to continuously provide quality services to change the indices of under-5 mortality in Nigeria.

Medical cost of acute diarrhea in children in ambulatory care.

OBJECTIVE: The aim of this study was to estimate the direct medical cost per episode and the annual cost for acute diarrhea (AD) in children under five years of age in Ambulatory Care Centers of the Ministry of Public Health (MOPH) of Ecuador. METHODS: A cost of illness study with a provider perspective was carried out through a micro-costing of health resources and valuated in international dollars. Medical consultations and laboratory tests were valued using the tariff framework of services for the National Health System and for the prescribed medications, a reported cost registry of pharmacy purchases made in the year of study was used. RESULTS: A total of 332 electronic health records of children under five years of age were included in the analysis. Laboratory tests were performed on 37.95% (126/332), medications were prescribed to 93.67% (311/332) of the children, and antimicrobials were prescribed to 37.35% (124/332) of the children, representing an antibiotic prescription rate of 26.51% (88/332) and an antiparasitic prescription rate of 10.84% (36/332). The mean cost of the MOPH per child per episode of AD was US$45.24 (2019 dollars) (95% CI:43.71 to 46.76). CONCLUSION: The total estimated cost of AD in children under five years of age for the MOPH in 2019 was about US$6,645,167.88 million (2019 dollars) (95% CI: 6,420,430.77 to 6,868,436.12). A high proportion of the direct medical cost of AD in children under five years of age in outpatient settings is due to unnecessary laboratory tests.

Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea.

OBJECTIVES: Antibiotics are associated with increased risk of Clostridioides difficile infection, which has limited treatment options. We assessed in vitro activity of omadacycline (an aminomethylcycline antibiotic) against the C. difficile infection strain and efficacy in a hamster model of C. difficile-associated diarrhoea. METHODS: Omadacycline, clindamycin, tigecycline, vancomycin, and metronidazole minimum inhibitory concentrations (MICs) for the infection-model strain (C. difficile ATCC 43596) were determined. Hamsters were pretreated with subcutaneous clindamycin (10 mg/kg) and infected 24 h later with C. difficile ATCC 43596; 24 h post infection, they received oral omadacycline (50 mg/kg/day), vancomycin (50 mg/kg/day), or vehicle for 5 days. Efficacy was reported as survival. RESULTS: Omadacycline was as active as tigecycline, vancomycin, and metronidazole (MIC 0.06 mg/L); clindamycin showed no activity. Median survival in hamsters was: 12 days, omadacycline; 2 days, vancomycin; 4 days, clindamycin pretreatment only. CONCLUSION: Omadacycline exhibited potent in vitro activity against C. difficile and showed efficacy in a model of C. difficile-associated diarrhoea.

Porcine Epidemic Diarrhea: Causative Agent, Epidemiology, Clinical Characteristics, and Treatment Strategy Targeting Main Protease.

AIMS: This aimed to study the causative agent, epidemiology, clinical characteristics, and treatment strategy targeting the main protease in porcine epidemic diarrhea. BACKGROUND: Porcine epidemic diarrhea (PED) is a contagious intestinal viral infection causing severe diarrhea, vomiting, and dehydration in pigs. High rates of mortalities and severe morbidities, approaching 100%, are reported in piglets infected with PEDV. In recent years, PED has been observed to influence the swine-farming nations in Europe, Asia, the USA, South Korea, and Canada. The PED virus (PEDV) transmission takes place through a faecal-oral route. OBJECTIVE: The objective is to review the characteristics of PEDV and its role in the disease. In addition, we aim to outline some possible methods to combat PED infection, including targeting the main protease of coronavirus and their future perspectives. METHODS: This study is a review of literature on the PED virus. RESULTS: Apart from symptomatic treatment and supportive care, there is no available specific treatment for PEDV. Appropriate disinfectants and cleaning are pivotal for the control of PEDV. To date, apart from anti-PEDV inhibitors, there are no specific drugs available commercially to treat the disease. Therefore, 3C-like protease (3CLpro) in PEDV that has highly conserved structure and catalytic mechanism serves as an alluring drug as it plays a vital role during viral polyprotein processing at the time of infection. CONCLUSION: A well synchronized and collective effort of scientists, swine veterinarians, pork industry experts, and associated authorities is essential for the accomplishment of proper execution of these required measures.

Evaluating the cost utility of racecadotril in addition to oral rehydration solution versus oral rehydration solution alone for children with acute watery diarrhea in four low middle-income countries: Egypt, Morocco, Philippines and Vietnam.

AIM: To evaluate the cost utility of adjunct racecadotril and oral rehydration solution (R + ORS) versus oral rehydration solution (ORS) alone for the treatment of diarrhoea in children under five years with acute watery diarrhoea in four low-middle income countries. METHOD: A cost utility model, previously developed and independently validated, has been adapted to Egypt, Morocco, Philippines and Vietnam. The model is a decision tree, cohort model programmed in Microsoft Excel. The model structure represents the country-specific clinical pathways. The target population is children under the age of five years presenting with symptoms of acute watery diarrhea to an outpatient clinic or general physician practice. A healthcare payer perspective has been analysed with the model parameterised with local data, where available. Most recent cost data has been used to inform the drug, outpatient and inpatient costs. Uncertainty has been explored with univariate deterministic sensitivity. RESULTS: According to the base case models, R + ORS is dominant (cost-saving, more effective) versus ORS alone in Egypt, Morocco, Philippines and Vietnam. The incremental cost-effectiveness ratios in each country fall in the southeast (cost-saving, more effective) quadrant and represent a cost savings of -304,152 EGP per QALY gain in Egypt; -6,561 MAD per QALY gain in Morocco; -428,612 PHP per QALY gain in Philippines and -113,985,734 VND per QALY gain in Vietnam. Univariate deterministic sensitivity analysis shows that the three most influential parameters across all country adaptations are the utility of children without diarrhea; the utility of inpatient children with diarrhea and the cost of one night of inpatient care. CONCLUSION: In keeping with similar findings in upper-middle and high-income countries, the cost utility of R + ORS versus ORS is favourable in low-middle income countries for the treatment of children under five with acute watery diarrhoea.

PLAIN LANGUAGE SUMMARYDecision-makers rely on cost utility models to inform decisions about whether to publicly fund treatments as part of Universal Health Care. In low-middle income countries, the capacity to prepare cost utility models may be limited and using existing validated models is a practical solution to assist decision making. This study uses a cost utility model developed and independently validated for the United Kingdom, and adapts it to Philippines, Egypt, Morocco and Vietnam. The model evaluates the clinical benefit and economic impact of using racecadotril in addition to rehydration solution to treat diarrhoea in children. The results show that racecadotril is cost-saving and improves the quality of life for children in Philippines, Egypt, Morocco and Vietnam.

Comparing Costs and Outcomes of Treatments for Irritable Bowel Syndrome With Diarrhea: Cost-Benefit Analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most expensive gastroenterological conditions and is an ideal target for developing a value-based care model. We assessed the comparative cost-benefit of treatments for IBS with diarrhea (IBS-D), the most common IBS subtype from insurer and patient perspectives. METHODS: We constructed a decision analytic model assessing trade-offs among guideline-recommended and recently FDA-approved drugs, supplements, low FODMAP diet, cognitive behavioral therapy (CBT). Outcomes and costs were derived from systematic reviews of clinical trials and national databases. Health-gains were represented using quality-adjusted life years (QALY). RESULTS: From an insurer perspective, on-label prescription drugs (rifaximin, eluxadoline, alosetron) were significantly more expensive than off-label treatments, low FODMAP, or CBT. Insurer treatment preferences were driven by average wholesale prescription drug prices and were not affected by health gains in sensitivity analysis within standard willingness-to-pay ranges up to $150,000/QALY-gained. From a patient perspective, prescription drug therapies and neuromodulators appeared preferable due to a reduction in lost wages due to IBS with effective therapy, and also considering out-of-pocket costs of low FODMAP food and out-of-pocket costs to attend CBT appointments. Comparative health outcomes exerted influence on treatment preferences from a patient perspective in cost-benefit analysis depending on a patients' willingness-to-pay threshold for additional health-gains, but health outcomes were less important than out-of-pocket costs at lower willingness-to-pay thresholds. CONCLUSIONS: Costs are critical determinants of IBS treatment value to patients and insurers, but different costs drive patient and insurer treatment preferences. Divergent cost drivers appear to explain misalignment between patient and insurer IBS treatment preferences in practice.

Intervention to Improve Diarrhea-Related Knowledge and Practices Among Informal Healthcare Providers in Slums of Kolkata.

BACKGROUND: In the densely populated slums of Kolkata, informal healthcare providers' (IHP) diarrhea-related knowledge and rationality of practices should be improved to reduce risk of adverse outcome, expenditure, and antimicrobial resistance. METHODS: A multicomponent intervention was conducted among 140 representative IHPs in the slums of 8 wards in Kolkata to assess its impact on their diarrhea-related knowledge and practice. Six intervention modules in local languages were provided (1 per month) with baseline (N = 140) and postintervention (N = 124) evaluation. RESULTS: Mean overall (61.1 to 69.3; P < .0001) and domain-specific knowledge scores for etiology/spread (5.4 to 8.1; P < .0001), management (6.4 to 7.2; P < .0001), and oral rehydration solution ([ORS] 5.7 to 6.5; P < .0001) increased significantly (at α = 0.05) after intervention and were well retained. Impact on knowledge regarding etiology/spread (adjusted odds ratio [aOR] = 5.6; P < .0001), cholera (aOR = 2.0; P = .0041), management (aOR = 3.1; P < .0001), ORS (aOR = 2.3; P = .0008), and overall (aOR = 4.3; P < .0001) were significant. Intervention worked better for IHPs who practiced for ≥10 years (aOR = 3.2; P < .0001), untrained IHPs (aOR = 4.8; P < .0001), and pharmacists (aOR = 8.3; P < .0001). Irrational practices like empirical antibiotic use for every cholera case (aOR = 0.3; P < .0001) and investigation for every diarrhea case (aOR = 0.4; P = .0003) were reduced. Rationality of testing (aOR = 4.2; P < .0001) and antibiotic use (aOR = 1.8; P = .0487) improved. CONCLUSIONS: Multicomponent educational intervention resulted in sustainable improvement in diarrhea-related knowledge and practices among IHPs in slums of Kolkata. Policy implications should be advocated along with implementation and scale-up.

Cost-Effectiveness Analysis of Community Case Management of Childhood Diarrhea in Burundi.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of community case management (CCM) program of childhood diarrhea by providing oral rehydration salts and zinc through community health workers in Burundi. METHODS: A cost-effectiveness analysis study using a Markov modeling approach was undertaken to assess the CCM program of diarrhea from both provider and societal perspectives. The CCM program was compared with the routine management of childhood diarrhea at health facilities. Primary data on the cost of childhood diarrhea management were collected. Both economic and health outcomes were assessed for a period of 5 years, and a discount rate of 3% was applied. One-way and probabilistic sensitivity analyses were performed. RESULTS: The CCM program was found to be both less costly and more effective resulting to a negative value of incremental cost-effectiveness ratios, indicating that the program was dominant producing cost savings. Compared with the routine treatment of diarrhea at health facilities, the CCM program would avert 2749 additional disability-adjusted life years over a period of 5 years. The economic burden was reduced of US$1 056 699 and US$2 328 531 from the provider and societal perspectives, respectively. The cost-effectiveness estimates were mostly sensitive to the discount rate and the cost of outpatient visits at health facilities. The intervention remained dominant with a 100% probability of cost savings within 10 000 simulations of the sensitivity analysis. CONCLUSIONS: Providing inexpensive diarrheal treatment (oral rehydration salts and zinc) in communities is an attractive cost-effective intervention. Evidence from this study should be used to scale up the coverage of this life- and cost-saving intervention.

Determinants of trends in reported antibiotic use among sick children under five years of age across low-income and middle-income countries in 2005-17: A systematic analysis of user characteristics based on 132 national surveys from 73 countries.

OBJECTIVES: This study aimed to analyze any reported antibiotic use for children aged <5 years with fever, diarrhea or cough with fast or difficult breathing (outcome) from low-income and middle-income countries (LMICs) during 2005-2017 by user characteristics: rural/urban residence, maternal education, household wealth, and healthcare source visited. METHODS: Based on 132 demographic and health surveys and multiple indicator cluster surveys from 73 LMICs, the outcome by user characteristics for all country-years was estimated using a hierarchical Bayesian linear regression model. RESULTS: Across LMICs during 2005-2017, the greatest relative increases in the outcome occurred in rural areas, poorest quintiles and least educated populations, particularly in low-income countries and South-East Asia. In low-income countries, rural areas had a 72% relative increase from 17.8% (Uncertainty Interval (UI): 5.2%-44.9%) in 2005 to 30.6% (11.7%-62.1%) in 2017, compared to a 29% relative increase in urban areas from 27.1% (8.7%-58.2%) in 2005 to 34.9% (13.3%-67.3%) in 2017. Despite these increases, the outcome was consistently highest in urban areas, wealthiest quintiles, and populations with the highest maternal education. CONCLUSION: These estimates suggest that the increasing reported antibiotic use for sick children aged <5 years in LMICs during 2005-2017 was driven by gains among groups often underserved by formal health services.

Assessment of pharmacological activities of Lygodium microphyllum Cav. leaves in the management of pain, inflammation, pyrexia, diarrhea, and helminths: In vivo, in vitro and in silico approaches.

Lygodium microphyllum Cav. (Family: Lygodiaceae) is a perennial, snake fern and an invasive weed in Florida and also known as old world climbing fern. This study is intended to evaluate the antipyretic, analgesic, anti-inflammatory, antidiarrheal and anthelmintic activity of methanol extract of Lygodium microphyllum Cav. leaves (MELM) by in vivo, in vitro and in silico approaches. In addition, Biovia, PyRx autoDock Vina, UCSF Chimera have been applied to investigate the docking study in order to evaluate the binding interaction and an online tool was used to explore the ADME/T properties of selected bioactive compounds. In acetic acid induced writhing study, MELM inhibited 44.28% and 56.61% of writhes at 200 and 400 (mg/kg) respectively compared to standard drug Diclofenac-Na (10 mg/kg) (74.42% inhibition). In anti-inflammatory experiment by formalin triggered licking method, MELM caused significant (p < 0.05) inhibition of licking in both early phase (42.97%, 63.30%) and late phase (43.35%, 63.03%) at the doses of 200 and 400 mg/kg respectively, whereas reference drug Ibuprofen inhibited paw licking 77.18% in early phase and 76.86% in late phase. MELM also showed promising antipyretic potential where the maximum reduction of fever was produced by MELM 400 mg/kg whose fever lowering capacity is close to the prescribe drug Indomethacin 4 mg/kg, i.p. In Castor oil triggered diarrhea method, MELM delayed the onset time of diarrhea, continuous persistence of wet feces, and decreased the weight of wet feces remarkably. Defection inhibition was achieved 27.56% and 51.72%, for MELM 200 and at 400 (mg/kg) respectively while loperamide 2 (mg/kg) yields 55.17% inhibition of the diarrheal defecation. In anthelmintic bioassay, MELM took 5.83 ± 0.83 and 41.67 ± 1.78 min respectively for paralyzing and death compared to standard drug albendazole; (paralysis time 4.00 ± 0.73 min and death time 31,00 ± 1.71 min). Isoeleutherol, isoquercetin and quercetin were found prominent in molecular docking study and ADME/T analysis verified their drug likeliness. The research validates the moderate analgesic, anti-inflammatory, and remarkable antipyretic, antidiarrheal, anthelmintic activities of the plant extract which can be used an alternative source of novel therapeutics.

Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea.

BACKGROUND: A large number of studies have evaluated the pharmacology, safety, and/or efficacy of bismuth subsalicylate for the relief of common gastrointestinal symptoms, diarrhea and vomiting due to acute gastroenteritis. In addition, short-term (48 h) medication with bismuth subsalicylate is known to be effective against infectious gastroenteritis such as travelers' diarrhea. AIMS: Previous studies have documented the bacteriostatic/bactericidal effects of bismuth subsalicylate against a variety of pathogenic gastrointestinal bacteria. However, meta-analyses of the clinical efficacy of bismuth subsalicylate for both prevention and treatment of travelers' diarrhea have not yet been published. METHODS: A total of 14 clinical studies (from 1970s to 2007) comprised the core data used in this assessment of efficacy of bismuth subsalicylate against infectious (including travelers') diarrhea. These studies allowed for statistical meta-analyses regarding prevention (three travelers' diarrhea studies) and treatment of infectious diarrhea (11 studies [five travelers' diarrhea]). RESULTS: The results show that subjects treated with bismuth subsalicylate for up to 21 days have 3.5 times greater odds of preventing travelers' diarrhea compared with placebo (95% CI 2.1, 5.9; p < 0.001). In addition, subjects with infectious diarrhea treated with bismuth subsalicylate had 3.7 times greater odds of diarrhea relief (recorded on diaries as subjective symptomatic improvement) compared to those receiving placebo (95% CI 2.1, 6.3; p < 0.001). CONCLUSIONS: This systematic review and meta-analysis suggests that bismuth subsalicylate can be beneficial for those at risk or affected by food and waterborne diarrheal disease such as traveler's (infectious) diarrhea, and may decrease the risk of inappropriate antibiotic utilization.