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.

An international comparison of the cost of fluid resuscitation therapies.

OBJECTIVE: Fluid resuscitation is a ubiquitous intervention in the management of patients treated in the intensive care unit, which has implications for intensive care unit resourcing and budgets. Our objective was to calculate the relative cost of resuscitation fluids in several countries to inform future economic evaluations. METHODS: We collected site-level data regarding the availability and cost of fluids as part of an international survey. We normalised costs to net present values using purchasing power parities and published inflation figures. Costs were also adjusted for equi-effective dosing based on intravascular volume expansion effectiveness and expressed as US dollars (USD) per 100 mL crystalloid equivalent. RESULTS: A total of 187 sites had access to cost data. Between countries, there was an approximate six fold variation in the cost of crystalloids and colloids overall. The average cost for crystalloids overall was less than 1 USD per 100 mL. In contrast, colloid fluids had higher average costs (59 USD per 100 mL). After adjusting for equi-effective dosing, saline was ∼27 times less costly than albumin (saline: 0.6 USD per 100 mL crystalloid equivalent; albumin 4-5%: 16.4 USD; albumin 20-25%: 15.8 USD) and ∼4 times less costly than hydroxyethyl starch solution (saline: 0.6 USD; hydroxyethyl starch solution: 2.5 USD). Buffered salt solutions, such as compound sodium acetate solutions (e.g., Plasmalyte®), had the highest average cost of crystalloid fluids, costing between 3 and 4 USD per 100 mL. CONCLUSION: The cost of fluid varies substantially between fluid types and between countries, although normal (0.9%) saline is consistently less costly than colloid preparations and some buffered salt solutions. These data can be used to inform future economic evaluations of fluid preparations.

Availability and affordability of priority life-saving medicines for under-five children in health facilities of Tigray region, northern Ethiopia.

BACKGROUND: In developing countries, child health outcomes are influenced by the non-availability of priority life-saving medicines at public sector health facilities and non-affordability of medicines at private medicine outlets. This study aimed to assess availability, price components and affordability of priority life-saving medicines for under-five children in Tigray region, Northern Ethiopia. METHODS: A cross-sectional study was conducted in Tigray region from December 2015 to July 2016 using a standard method developed by the World Health Organization and Health Action International (WHO/HAI). Data on the availability and price of 27 priority life-saving medicines were collected from 31 public and 10 private sectors. Availability and prices were expressed in percent and median price ratios (MPRs), respectively. Affordability was reported in terms of the daily wage of the lowest-paid unskilled government worker. RESULTS: The overall availability of priority life-saving drugs in this study was low (34.1%). The average availabilities of all surveyed medicines in public and private sectors were 41.9 and 31.5%, respectively. The overall availability of medicines for malaria was found to be poor with average values of 29.3% for artemisinin combination therapy tablet, 19.5% for artesunate injection and 0% for rectal artesunate. Whereas, the availability of oral rehydration salt (ORS) and zinc sulphate dispersible tablets for the treatment of diarrhea was moderately high (90% for ORS and 82% for zinc sulphate). Medicines for pneumonia showed an overall percent availability in the range of 0% (ampicillin 250 mg and 1 g powder for injection and oxygen medicinal gas) to 100% (amoxicillin 500 mg capsule). The MPRs of 12 lowest price generic medicines were 1.5 and 2.7 times higher than the international reference prices (IRPs) for the private and public sectors, respectively. About 30% of priority life-saving medicines in the public sector and 50% of them in the private sector demanded above a single daily wages to purchase the standard treatment of the prevalent diseases of children. CONCLUSIONS: The lower availability, high price and low affordability of lowest price generic priority life-saving medicines in public and private sectors reflect a failure to implement the health policy on priority life-saving medicines in the region.

A retrospective evaluation of the perioperative drug use and comparison of its cost in robotic vs open surgery for endometrial cancer.

To compare the usage and cost of analgesics (opioid and non-opioids), antiemetics, and IV fluids and its associated costs in robotic vs open staging surgery for endometrial cancer (EC). This retrospective study was performed at a single academic institution from January 2014 to June 2017 in the department of Gynecology Oncology at Amrita Institute of Medical Science, Kerala, India. The study included women with biopsy confirmed clinically early stage endometrial cancer or atypical hyperplasia, who underwent robotic-assisted or open staging surgery. Data on surgical time, blood loss, post-anaesthesia care unit (PACU) stay, and length of hospital (LOH) stay; analgesic, antiemetic, and IV fluid use were collected for three distinct periods: intra-operative, PACU, and ward. Direct medicine and material costs associated with the administration of intravenous (IV) fluids, analgesics, and antiemetics were collected. All parameters were compared between two surgical groups. The study included 133 (54 open and 79 robotic-assisted) patients. As compared to open surgery, robotic-assisted surgery was associated with significantly reduced: surgical time (p = 0.007), estimated blood loss (p < 0.001), PACU stay (p < 0.001), LOH stay (p < 0.001); IV fluids (crystalloid and colloid; p < 0.001); opioids (p < 0.001), non-opioids (intravenous acetaminophen, oral acetaminophen, diclofenac; all p < 0.001); incidence of post-operative nausea and vomiting and the requirement of rescue antiemetics (p < 0.001). EC staging using robotic-assisted surgery was associated with significantly lower medicine and material costs attributed to IV fluids, analgesia, and antiemetics (p < 0.001). As compared to open surgery, robotic surgery was associated with the total saving of $107.7 ($19.5 in IV fluids, $49.2 in analgesics, $1.33 in antiemetics, and $37.8 in material). Robotic-assisted surgical staging for endometrial cancer is associated with decreased requirement and expenditure attributable to post-operative pain, post-operative nausea and vomiting, and maintenance and replacement fluid therapy.

Tracking Cholera through Surveillance of Oral Rehydration Solution Sales at Pharmacies: Insights from Urban Bangladesh.

BACKGROUND: In Bangladesh, pharmacy-purchased oral rehydration solution (ORS) is often used to treat diarrhea, including cholera. Over-the-counter sales have been used for epidemiologic surveillance in the past, but rarely, if ever, in low-income countries. With few early indicators for cholera outbreaks in endemic areas, diarrhea-related product sales may serve as a useful surveillance tool. METHODOLOGY/PRINCIPAL FINDINGS: We tracked daily ORS sales at 50 pharmacies and drug-sellers in an urban Bangladesh community of 129,000 for 6-months while simultaneously conducting surveillance for diarrhea hospitalizations among residents. We developed a mobile phone based system to track the sales of ORS and deployed it in parallel with a paper-based system. Our objectives were to determine if the mobile phone system was practical and acceptable to pharmacists and drug sellers, whether data were reported accurately compared to a paper-based system, and whether ORS sales were associated with future incidence of cholera hospitalizations within the community. We recorded 47,215 customers purchasing ORS, and 315 hospitalized diarrhea cases, 22% of which had culture-confirmed cholera. ORS sales and diarrhea incidence were independently associated with the mean daily temperature; therefore both unadjusted and adjusted models were explored. Through unadjusted cross-correlation statistics and generalized linear models, we found increases in ORS sales were significantly associated with increases in hospitalized diarrhea cases up to 9-days later and hospitalized cholera cases up to one day later. After adjusting for mean daily temperature, ORS was significantly associated with hospitalized diarrhea two days later and hospitalized cholera one day later. CONCLUSIONS/SIGNIFICANCE: Pharmacy sales data may serve as a feasible and useful surveillance tool. Given the relatively short lagged correlation between ORS sales and diarrhea, rapid and accurate sales data are key. More work is needed in creating actionable algorithms that make use of this data and in understanding the generalizability of our findings to other settings.

Global burden of childhood diarrhea and interventions.

PURPOSE OF REVIEW: Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. RECENT FINDINGS: There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the 'Lives Saved' tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. SUMMARY: The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction.

Survey of total mercury in infant formulae and oral electrolytes sold in Canada.

Total mercury (Hg) was measured in 150 infant formula products (as sold) and oral electrolyte solutions purchased in Canada in 2003. Results less than the limit of detection (LOD) were reported as the numeric value of the LOD. Electrolytes contained the lowest concentrations, averaging 0.026 ng/g. Average levels in milk-based ready-to-use, concentrated liquid and powdered concentrate were 0.028, 0.069 and 0.212 ng/g, respectively. In soy-based formulae, the respective mean concentrations were 0.049, 0.101 and 0.237 ng/g. These concentrations cannot be considered on an absolute basis because 76% of sample concentrations fell below the limit of detection. Despite the inability to measure many of the actual background concentrations, the method was sufficiently sensitive to identify clear cases of low-level Hg contamination (up to 1.5 ng/g) of individual lots of powdered formula. Also, all the different lots of one brand of concentrated liquid infant formulae had significantly higher concentrations of Hg than those of all other concentrated liquid products. After dilution with preparation water, the Hg concentrations in all products would be lower than the Canadian Drinking Water Guideline for Hg of 1 ng/mL and too low to impact on health.

Prospective evaluation of indirect costs due to acute rotavirus gastroenteritis in Spain: the ROTACOST study.

BACKGROUND: The effect of rotavirus in developed countries is mainly economic. This study aimed to assess the indirect costs induced by rotavirus acute gastroenteritis (RVAGE) in Spain. METHODS: A prospective observational study was conducted from October 2008 to June 2009. It included 682 children up to 5 years of age with acute gastroenteritis (AGE) who attended primary care (n = 18) and emergency room/hospital settings (n = 10), covering the regions of Galicia and Asturias (North-west Spain). All non-medical expenses incurred throughout the episode were recorded in detail using personal interviews and telephone contact. RESULTS: Among the 682 enrolled children, 207 (30.4%) were rotavirus positive and 170 (25%) had received at least one dose of rotavirus vaccine. The mean (standard deviation) indirect cost caused by an episode of AGE was estimated at 135.17 (182.70) Euros. Costs were 1.74-fold higher when AGE was caused by rotavirus compared with other etiologies: 192.7 (219.8) Euros vs. 111.6 (163.5) Euros (p < .001). The costs for absenteeism were the most substantial with a mean of 91.41 (134.76) Euros per family, resulting in a loss of 2.45 (3.17) days of work. In RVAGE patients, the absenteeism cost was 120.4 (154) Euros compared with 75.8 (123) for the other etiologies (p = .002), because of loss of 3.5 (3.6) vs 1.9 (2.9) days of work (p < .001). Meals costs were 2-fold-higher (48.5 (55) vs 24.3 (46) Euros, p < .001) and travel costs were 2.6-fold-higher (32 (92) vs 12.5 (21.1) Euros, p = .005) in RVAGE patients compared with those with other etiologies. There were no differences between RVAGE and other etiologies groups regarding costs of hiring of caregivers or purchase of material. Patients with RVAGE were admitted to hospital more frequently than those with other etiologies (47.8% vs 14%, p < .001). CONCLUSIONS: Rotavirus generates a significant indirect economic burden. Our data should be considered in the decision-making process of the eventual inclusion of rotavirus vaccine in the national immunization schedule of well developed countries.

Hospital health care cost of diarrheal disease in Northern Ghana.

Diarrhea caused by rotaviruses is one of the most frequent causes of hospitalization among pediatric patients in rural communities of developing countries in sub-Saharan Africa and Southeast Asia, and it is a major cause of death in these communities. The complexity of diarrhea and the increasing cost of treatment puts additional burden on the health sector. To demonstrate the economic burden of diarrhea to policy makers, this study was conducted to estimate the treatment cost of diarrhea in children <5 years old in Ghana using the World Health Organization protocol for cost data collection and estimation. The study was undertaken in Navrongo War Memorial Hospital in northern Ghana. Cost estimates were made for 3 treatment scenarios observed: (1) treatment by rehydration, (2) treatment by rehydration and antibiotics, and (3) treatment of diarrhea and other diseases. The average outpatient treatment costs for the 3 treatment scenarios were US$3.86, $4.10, and $4.35 respectively, and the average treatment costs for hospitalization (inpatient care) were $65.14, $97.40, and $133.86 respectively. The annual national treatment costs, based on the 3 treatment scenarios, ranged from $907,116 to $1,851,280 for outpatients clinic visits and from $701,833 to $4,581,213 for hospitalizations. The average length of stay for the inpatients ranged from 2.3 to 4.9 days. The study did not cover patient costs (ie, household costs).

[Consumption of medications during the cholera epidemic in Douala, Cameroon (2004)]. / Consommation de médicaments lors de l'épidémie de choléra de Douala (2004).

To prepare for cholera outbreaks, stockpiles of supplies, rehydration salts/ solutions and appropriate antibiotics must be placed in strategic locations to ensure a prompt and effective response. However specific needs have not been evaluated up to now. The purpose of this report is to give an accurate account of medical supplies that were consumed during the cholera epidemic in Douala in 2004. Consumption of medication for the entire epidemic was measured by crosschecking data from the provincial pharmaceutical supply centre with the order forms, stock sheets and records of hospitals. Cost was calculated based on pricing data from the National Supply Center. For the 5 020 confirmed cases of cholera that were treated in the 14 hospitals in Douala from January to September 2004, consumption consisted of 499,746 doxycycline tablets, 235,881 amoxicilline tablets, 122,781 rehydration salt packets, and 60,217 units of Ringer Lactate (500 ml). The total cost of medications and consumables was 52,229,311 CFAF (approximately 80,000 Euro). Although updated recommendations are not available, comparison with the existing ones shows that the consumption levels observed were 5 times higher for both rehydration and antibiotherapy. The mean cost of treatment in Douala was 13 Euro per reported patient. This cost rose to 15 Euro if antibiotic prophylaxis was prescribed for all contacts. These findings can be useful in planning for future epidemics by allowing recommendations to be updated. We propose the follow supply levels for 50,000 inhabitants with an attack rate of 0.2%: 10,000 doxycycline tablets, 5000 amoxicilline tablets (500 mg), 2500 SRO packs (for 2500 liters) and 600 liters of Ringer Lactate.

Cost-effectiveness of zinc as adjunct therapy for acute childhood diarrhoea in developing countries.

OBJECTIVE: To analyse the incremental costs, effects and cost-effectiveness of zinc used as adjunct therapy to standard treatment of acute childhood diarrhoea, including dysentery, and to reassess the cost-effectiveness of standard case management with oral rehydration salt (ORS). METHODS: A decision tree was used to model expected clinical outcomes and expected costs under four alternative treatment strategies. The best available epidemiological, clinical and economic evidence was used in the calculations, and the United Republic of Tanzania was the reference setting. Probabilistic cost-effectiveness analysis was performed using a Monte-Carlo simulation technique and the potential impacts of uncertainty in single parameters were explored in one-way sensitivity analyses. FINDINGS: ORS was found to be less cost-effective than previously thought. The use of zinc as adjunct therapy significantly improved the cost-effectiveness of standard management of diarrhoea for dysenteric as well as non-dysenteric illness. The results were particularly sensitive to mortality rates in non-dysenteric diarrhoea, but the alternative interventions can be defined as highly cost-effective even in pessimistic scenarios. CONCLUSION: There is sufficient evidence to recommend the inclusion of zinc into standard case management of both dysenteric and non-dysenteric acute diarrhoea.A direct transfer of our findings from the United Republic of Tanzania to other settings is not justified, but there are no indications of large geographical differences in the efficacy of zinc. It is therefore plausible that our findings are also applicable to other developing countries.

Life and death of children: the price of life.

Nearly 2 million children die of simple diarrhea each year in developing countries. Those children would not have died if they were given Oral Rehydration Solution, which costs 100 yen for treating one child. In developed countries like Japan, treating one patient with intracranial aneurysm will cost over 2 million yen. The cost for treating one such patient could save 10,000 children with diarrhea even after adjusting with purchasing power parity in developing countries. Such inequity and inequality cannot be acceptable. We who are concerned about such a status quo have to work together for the betterment of children living in developing countries. In this review the author explores the root causes behind such unjust global structures.

Fluid management: the pharmacoeconomic dimension.

Cost is a key concern in fluid management. Relatively few data are available that address the comparative total costs of care between different fluid management regimens in particular clinical indications. Relevant costs of fluid-associated morbidity and mortality, including those incurred after intensive care unit or hospital discharge, also need to be considered in evaluating the cost-benefit ratios of administered fluids. Rigorously designed pharmacoeconomic studies are needed to delineate the costs and benefits of various approaches to fluid management.

Safety and effectiveness of homemade and reconstituted packet cereal-based oral rehydration solutions: a randomized clinical trial.

OBJECTIVES: Parents may be deterred from obtaining commercial oral rehydration solutions (ORS) for their young children with acute diarrheal disease because of its availability and/or cost, especially if they are poor. We conducted a randomized clinical trial to determine 1) whether low-income parents could safely mix and administer cereal-based ORS (CBORS) both from ingredients commonly found in the home and from a premixed packet; 2) whether these CBORS were as effective in maintaining hydration as commercial glucose-based ORS; and 3) whether CBORS were more effective in reducing severity and duration of illness. METHODS: Children 4 to 36 months of age discharged from emergency departments and health centers with acute diarrheal disease were randomized to receive either homemade CBORS, reconstituted packet CBORS, or Pedialyte. A study nurse saw the child at home each day until the illness resolved, and obtained capillary blood for serum sodium at enrollment and at 24 to 48 hours; a sample of CBORS for sodium concentration; stool for pathogen analysis; and daily fluid intake, stool frequency, and weight. RESULTS: A total of 232 children were enrolled, of whom 203 (88%) completed the study. Two parents (3%) in the homemade CBORS group and one parent (1%) in the packet CBORS group made mixing errors resulting in a high sodium concentration (>100 mEq/L); their children refused the solution and had normal serum sodium values. Mean CBORS sodium concentration for the remainder of the homemade CBORS group was 60 +/- 10 mEq/L, and for the packet CBORS group, 54 +/- 13. Eighteen children (11%) had abnormal serum sodium values at presentation, which returned to normal in all groups in most cases. Three children (4.5%) in the homemade CBORS group, 4 (6%) in the packet CBORS group, and 1 child (1.4%) in the Pedialyte group failed therapy. Children refused to take homemade CBORS and packet CBORS (43% and 32%, respectively) more often than Pedialyte (9%), and those in the CBORS groups tended to take less ORS and total fluids. There were no significant differences among the three groups in incidence of daily vomiting or stooling, duration of diarrhea, or weight gain. CONCLUSIONS: CBORS do not offer a clinically significant advantage over glucose-based ORS. Homemade CBORS represent a treatment option in carefully selected cases, but it is not the safest alternative for regular clinical use.

Use of rice-based oral rehydration solution in a large diarrhoea treatment centre in Bangladesh: in-house production, use and relative cost.

Glucose-based oral rehydration salt (ORS) is an appropriate and cost-effective tool to treat diarrhoeal dehydration. In patients with a high purging rate, particularly due to cholera, rice-based ORS has been shown to substantially reduce stool output compared to glucose ORS. However, it is not used in the hospitals or diarrhoea treatment centres largely because of the non-availability of a ready-to-use inexpensive packaged product and because of the problem of cooking. In a large diarrhoea treatment centre in Bangladesh (with an annual ORS consumption of approximately 140,000 litres), we have maintained in-house production of rice ORS and used it routinely for more than 600,000 patients over the last nine years. Semi-literate health workers cook rice ORS and supervise mothers in its use. Rice ORS is less costly (US $0.15 per patient treated compared with US $0.37 for glucose ORS) and is well accepted. It is an attractive alternative to glucose ORS in many fixed facility treatment centres in countries where rice is a staple and cholera is endemic. The process of its in-house preparation and use is described in this report which may assist hospitals wishing to use rice ORS in treating diarrhoea patients. Availability of a low cost ready-to-use rice ORS packet (which needs no cooking) with adequate shelf-life will increase its use at fixed facilities.

Rehydration and nutritional management.

Diarrhoea remains a leading worldwide cause of morbidity and mortality. In developing countries alone, 1.5 billion episodes of diarrhoea occur per year in children under 5 years of age and approximately 4,000,000 of these result in death. Early, appropriate therapy decreases the risk of complications and death due to diarrhoea. Regardless of the causative agent, oral rehydration and nutritional management are the mainstays of good management of infants, children and adults with diarrhoea. Diarrhoeal disease control programmes throughout the developing world have adopted the WHO case management plan as a standard. In this chapter, we review the history, successes and shortcomings of various oral rehydration therapies and recommend a case management approach that is similar to the WHO plan. Although ORT is safe, effective, convenient and economical, this therapy has not been universally implemented in health care settings. The challenge for clinical and public health practitioners in developing and developed countries is to identify and overcome the barriers that exist so that all patients with diarrhoea will have the opportunity to receive optimal care.