Low-osmolarity oral rehydration solution (ORS)

New formulation of Oral Rehydration Salts (ORS) with reduced osmolarity

Background: Two decades ago diarrhoea was responsible for around 5 million deaths annually. Through major public health efforts primarily aimed at preventing and treating dehydration this figure has decreased to around 2 million deaths. Prevention of dehydration is primarily achieved by ensuring that children with diarrhoea are provided with more fluids than usual, and/or increased frequency of breastfeeding, during the acute episode. The combination of increased home fluids and the use of Oral Rehydration Salts (ORS) for the treatment of dehydration have proven to be a very powerful intervention for the prevention of childhood deaths from diarrhoea.

Purpose:

For more than 25 years UNICEF and WHO have recommended a single formulation of glucose-based ORS to prevent or treat dehydration from diarrhoea irrespective of the cause or age group affected. This product, which provides a solution containing 90 mEq/l of sodium with a total osmolarity of 311 mOsm/l, has proven effective and without apparent adverse effects in worldwide use. It has been well established, however, that ORS solution does not reduce stool output or duration of diarrhoea. For this reason the current ORS might have had less than optimal acceptance by mothers and health workers, preferring a treatment that causes diarrhoea to stop. During the past 20 years numerous studies have been undertaken to develop an 'improved' ORS. The goal was a product that would be at least as safe and effective as standard ORS for preventing or treating dehydration from all types of diarrhoea but which, in addition, would reduce stool output or have other important clinical benefits. One successful approach is based on reducing the osmolarity of ORS solution to avoid possible adverse effects of hypertonicity on net fluid absorption. This was done by reducing the solution's glucose and salt (NaCl) concentrations.


Studies to evaluate this approach were reviewed at a meeting in July 2001*, and technical recommendations were made to WHO and UNICEF on the efficacy and safety of reduced osmolarity ORS in children with acute non-cholera diarrhoea, and in adults and children with cholera.


Launch of new formulation:

At UNICEF Supply Division, a bid for Reduced Osmolarity ORS was launched in September 2003 and two manufacturers were approved for the supply of new ORS formulation. The new ORS is in stock at UNICEF Supply Division. Phase out of the old ORS and phase in of the new ORS is taking place and the old ORS will for a short period of time remain part of the New Emergency Health Kit, as a certain stock of these kits was packed before the introduction of the new ORS. For the moment, the price of new ORS is approximately 15 per cent lower than the old ORS formulation.


Formulation:

Reduced osmolarity ORS	grams/litre	Reduced osmolarity ORS	mmol/litre
Sodium chloride	2.6	Sodium	75
Glucose, anhydrous	13.5	Chloride	65
Potassium chloride	1.5	Glucose, anhydrous	75
Trisodium citrate, dihydrate	2.9	Potassium	20
		Citrate	10
		Total Osmolarity	245

Composition of standard and reduced osmolarity ORS solutions

	Standard ORS solution	Reduced Osmolarity ORS solutions
	(mEq or mmol/l)	(mEq or mmol/l) (21)	(mEq or mmol/l) (6, 14, 22-27)	(mEq or mmol/l) (13, 15-18, 28-29)
Glucose	111	111	75-90	75
Sodium	90	50	60-70	75
Chloride	80	40	60-70	65
Potassium	20	20	20	20
Citrate	10	30	10	10
Osmolarity	311	251	210-260	245

Questions and Answers:

1. Why has a “New” Oral Rehydration Salts (ORS) formula been developed?
2. Why “reduced osmolarity”?
3. Is diarrhoea really that much of a problem for children?
4. When will the new ORS be available?
5. What do I do with the old ORS solution? Should I discard it and only use the new low osmolarity ORS solution?
6. What about local production of the new ORS?
7. How should the new ORS solution be given?
8. Is there any risk associated with the use of this new ORS?
9. What is the cost of the new ORS?

Frequently Asked Technical Questions:

1. What should we advise mothers to give at home to a child with diarrhoea, but who has no signs of dehydration?
2. Should I continue to breastfeed my child with diarrhoea?
3. Should we advise mothers to continue to feed a child who has diarrhoea?
4. When should I take my child with diarrhoea to a health centre?
5. What should I do in case of vomiting?
6. What should I do in case of electrolyte disturbances in a child with diarrhoea?
7. What should I do if intravenous therapy is not available for a severely dehydrated child?
8. When should I suspect cholera in a child with diarrhoea?
9. How can I assess for dehydration in a severely malnourished child?
10. What should I do in case of fever in a child with diarrhoea?
11. What should I do in case of convulsions in a child with diarrhoea?
12. Should we give vitamin A to a child with diarrhoea?
13. Should we give zinc supplementation to a child with diarrhoea?
14. Can I give anti-diarrhoeal drugs to a child with diarrhoea?
15. What antimicrobials can be used with ORS in the clinical management of diarrhoea?
16. How can we protect our water?
17. How important is handwashing?

New item numbers:

The item numbers will change as follows, as the new formulation replaces the existing ORS:

Old formulation	New formulation
1561110 - ORS, 1L sachet/Box-100	1561120 - ORS, 1L sachet/Box-100
1561111 - ORS, 1 L sachet/CAR-1000	1561121 - ORS, 1 L sachet/CAR-1000

1561120 Oral reh.salts,new formula,1L s/BOX-100
1561121 Oral reh.salts,new formula,1L s/CAR-1000
1561111 Oral rehydration salts 1L sach./CAR-1000


02 PHARMACEUTICALS
26 Water & electrolytes
00

General Description: NEW REDUCED OSMOLARITY ORS

Oral Rehydration Salts (ORS), a new reduced osmolarity formulation, sachet for 1 litre, box of 100 sachets.

Mixture of glucose and electrolytes, dry, powdered homogenous, packed in hermetically sealed, laminated sachets each to contain:
Anhydrous glucose: 13.5 grams / litre.
Sodium chloride: 2.6 grams / litre.
Trisodium citrate dihydrate: 2.9 grams / litre.
Potassium chloride: 1.5 grams / litre.
Suitable flow agent may be used as an excipient.

Minimum requirements for raw materials:
Glucose: food grade
Other ingredients: BP, USP, Int. Ph. or Eur.ph.

Moisture of the finished product at the time of delivery less than 2%.
The contents of one sachet to be readily soluble in one litre of cold water to give a clear colourless solution containing:
Glucose: 75 mEq ± 10%
NA+: 75 mEq or mmol / litre ± 10%
CL-: 65 mEq or mmol / litre ± 10%
Citrate: 10 mmol / litre ± 10%
K+: 20 mEq or mmol / litre ± 10%
Osmolarity: 245 mmol / litre

Specification for packing foil:
Polyethylene 50 microns,
Aluminium minimum 9 microns
Polyester 12 microns.
Size of sachet: Approximately 60 x 90 mm.
Sachet should have a cut or v-shaped nick for easy opening without spillage.

The oral powder must comply with the requirements stated under Oral Powder BP and Oral Rehydration Salts BP.

Packaging and labelling:
Box of 100 sachets.

Required label text:
Blue on white background in English/French/Spanish languages on each sachet.
The UNICEF name/logo must be included.

Uses:
Dehydration from acute diarrhoea.

Precautions:
Renal impairment.
In case of cholera a higher concentration of sodium may be required.

Dosage:
Fluid and electrolyte loss in acute diarrhoea, by mouth,
ADULT: 200 to 400 ml solution after every loose motion.
INFANT and CHILD: according to plans A, B or C.
(Please refer to WHO Formulary 2004 for details).

Adverse Effects:
Vomiting. May indicate too rapid administration; hypernatraemia and
hyperkalaemia may result from overdose in renal impairment or
administration of too concentrated a solution.

Component of a kit:
9906604 - New emergency health kit - basic unit.




* Reduced osmolarity oral rehydration salts (ORS) formulation
Report from a meeting of experts jointly organized by UNICEF and WHO. WHO/CAH/01.22; (back to text)

Programme Division and Supply Division have prepared detailed questions and answers (Q&A) on the new ORS and common technical issues, provided below.

For more details, please contact the Pharmaceutical & Micronutrients Team, UNICEF Supply Division, at [email protected].
Copyright © the United Nations Children’s Fund (UNICEF), Supply Division, April 2004.

---

11 December 2002

Application to change the composition of
Oral Rehydration Salts (ORS) in the next revision of the
WHO Model List of Essential Medicine

1. Summary Statement

For more than 25 years WHO and UNICEF have recommended a single formulation of glucose-based Oral Rehydration Salts (ORS) to prevent or treat dehydration from diarrhoea irrespective of the cause or age group affected. This product, which provides a solution containing 90 mEq/l of sodium with a total osmolarity of 311 mOsm/l, has proven effective and without apparent adverse effects in worldwide use. It has contributed substantially to the dramatic global reduction in mortality from diarrhoeal disease during the period.

For the past 20 years, numerous studies have been undertaken to develop an “improved” ORS. The goal was a product that would be at least as safe and effective as standard ORS for preventing or treating dehydration from all types of diarrhoea but which, in addition, would reduce stool output or have other important clinical benefits. One approach has consisted in reducing the osmolarity of ORS solution to avoid possible adverse effects of hypertonicity on net fluid absorption. This was done by reducing the solution’s glucose and salt (NaCl) concentrations .

Studies to evaluate this approach were reviewed at a consultative technical meeting held in New York (USA) in July 2001 1, and technical recommendations were made to WHO and UNICEF on the efficacy and safety of reduced osmolarity ORS in children with acute non-cholera diarrhoea, and in adults and children with cholera.

These studies showed that the efficacy of ORS solution for treatment of children with acute non-cholera diarrhoea is improved by reducing its sodium concentration to 75 mEq/l, its glucose concentration to 75 mmol/l, and its total osmolarity to 245 mOsm/l. The need for unscheduled supplemental IV therapy in children given this solution was reduced by 33%. In a combined analysis of this study and studies with other reduced osmolarity ORS solutions (osmolarity 210-268 mOsm/l, sodium 50-75 mEq/l) stool output was also reduced by about 20% and the incidence of vomiting by about 30% . The 245 mOsm/l solution also appeared to be as safe and at least as effective as standard ORS for use in children with cholera.

The reduced osmolarity ORS containing 75 mEq/l sodium, 75 mmol/l glucose (total osmolarity of 245 mOsm/l) is as effective as standard ORS in adults with cholera. However, it is associated with an increased incidence of transient, asymptomatic hyponatraemia. This reduced osmolarity ORS may be used in place of standard ORS for treating adults with cholera, but careful monitoring is advised to better assess the risk, if any, of symptomatic hyponatraemia.

Because of the improved effectiveness of reduced osmolarity ORS solution, especially for children with acute, non-cholera diarrhoea, WHO and UNICEF now recommend that countries use and manufacture the following formulation in place of the previously recommended ORS solution with a total osmolarity of 311 mOsm/l.

Formulation:

Reduced osmolarity ORS	grams/litre	Reduced osmolarity ORS	mmol/litre
Sodium chloride	2.6	Sodium	75
Glucose, anhydrous	13.5	Chloride	65
Potassium chloride	1.5	Glucose, anhydrous	75
Trisodium citrate, dihydrate	2.9	Potassium	20
		Citrate	10
		Total Osmolarity	245

2. Name of the Focal Point

This application is presented by the Department of Child and Adolescent Health and Development (CAH) of the WHO. The focal point in this Department is:

Dr O. Fontaine Medical Officer, CAH

3. Organizations consulted or supporting the application

The new ORS formulation was officially released by WHO and partners during the United Nations General Assembly Special Session on Children in New York, 8 May. Dr Brundtland, Director General of WHO, Ms Bellamy, Executive Director of UNICEF, Dr Peterson, Assistant Administrator of USAID, and the Minister of Human Resources from India launched the new formula in a press and photo event.

UNICEF, USAID and MSF are supporting this application.

4. International Non-proprietary name of the medicine

Oral Rehydration Salts

5. Individual medicine

Although ORS is an individualised medicine, with a very precise composition, the EDL could also include the fact that WHO/UNICEF have published criteria for acceptable ORS formulations. These criteria are listed below; they specify the desired characteristics of the solution after it has been prepared according to the instructions on the packet:

The total substance concentration:	(including that contributed by glucose) should be within the range of 200-310 mmol/l
The individual substance concentration:
Glucose	should at least equal that of sodium but should not exceed 111 mmol/l
Sodium	should be within the range of 60-90 mEq/l
Potassium	should be within the range of 15-25 mEq/l
Citrate	should be within the range of 8-12 mmol/l
Chloride	should be within the range of 50-80 mEq/l

6. Public Health Relevance

We estimate that the dramatic improvement in home management of diarrhoea that has taken place between 1990 and 1995 has saved about 1 million children annually. In 1990, oral rehydration salts (ORS) were used in approximately a third of diarrhoea cases, and by mid-decade the average was 85% among 33 countries that accounts for almost half of the world’s under-five population.

7. Treatment details

These have not changed at all and the information contained on page 397 of the WHO Model Formulary is still perfectly adequate.

8. Effectiveness/Efficacy

For children with acute non-cholera diarrhoea, reduced osmolarity ORS solutions (215-245 mOsm/l) with 75 mEq/l or less of sodium and 75-90 mmol/l of glucose are safe. When compared with standard ORS solution, these solutions were associated with reduced stool output, reduced vomiting and, especially, reduced need for unscheduled IV therapy. With regard to reduced stool output and reduced vomiting, this benefit may be somewhat greater for solutions with <75 mEq/l sodium (210-260 mOsm/l) than for a solution with 75 mEq/l sodium (245 mOsm/l). However, in terms of reduced need for unscheduled IV therapy, the benefit was similar for solutions with 75 mEq/l sodium (245 mOsm/l) and for those with <75 mEq/l sodium (210-260 mOsm/l).

For children with cholera, reduced osmolarity ORS solutions (245-268mOsm/l) containing 70-75 mEq/l of sodium and 75-90 mmol/l glucose were at least as effective as standard ORS and, although further data should be obtained during routine use, appeared to be safe.

For adults with cholera, a reduced osmolarity ORS solution with 75 mEq/l of sodium and 75 mmol/l of glucose is as effective as standard WHO/UNICEF ORS solution.

All this information is available in tow recently published document:

(a) Reduced osmolarity oral rehydration salts (ORS) formulation – A report from a meeting of experts jointly organised by UNICEF and WHO – Unicef House, New York, USA, 18 July 2001 (WHO/FCH/CAH/01.22)

(b) S.K. Hahn, Y.J. Kim, P. Garner. Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review. Brit Med J 2001, 323:81-5.

9. Safety

In adults with cholera, some concern remained about the possible risk of symptomatic hyponatraemia with this solution. This concern was not considered sufficient to prevent the use of this solution to treat adults with cholera. It was agreed, however, that, to gain additional clinical data on the safety of reduced osmolarity ORS, the incidence of biochemical and symptomatic hyponatraemia should be monitored when this solution is first introduced for routine use. Because seizures are rare in adults with cholera, an increase in the incidence of this symptom should be easily recognised.

10. Summary of data on comparative cost and cost effectiveness

A decision analysis model to evaluate possible economic benefits of using reduced osmolarity ORS in place of standard ORS was considered. Assumptions used in the analysis were based on consensus and results of randomized clinical trials (where available) concerning (i) the incidence of unscheduled intravenous fluid therapy in patients given standard or reduced osmolarity ORS (15% for standard ORS, 9% for reduced osmolarity ORS; range tested, 0%-100%), (ii) the probability of seizures in patients who develop hyponatraemia (1%; range tested, 0%-20%) and, (iii) the probability of death when intravenous fluid therapy is not available for patients in whom dehydration is not corrected by oral therapy, or recurs during therapy (50%; range tested, 1%-100%). A revised model was developed that also included costs to the health care system for standard and reduced osmolarity ORS, intravenous fluid therapy, evaluation and treatment of seizures, and death.

The model was constructed as a decision tree with standard ORS and reduced osmolarity ORS as the two options, with a time horizon of two days. The constructed model, where possible, was biased against reduced osmolarity ORS. The probability of needing IV under standard ORS therapy was taken as 0.15, based on the recently published meta-analysis (19). The reduction of 30 % in the need of IV if given reduced osmolarity ORS was based on the same source. The probability of IV access was taken as 0.50, based on opinion of the assembled experts. The probability of death, given the need for IV therapy, but none available, was taken as 0.50, also based on the opinion of the assembled experts. The probability of seizures, when given reduced osmolarity ORS therapy, was taken as 0.01, the upper limit of rates observed in all clinical trials of reduced osmolarity ORS indexed in Medline. Standard ORS therapy was deemed not to lead to any electrolyte-based morbidities. The following costs were included, all based on expert opinion:

cost of reduced osmolarity ORS per patient cost of standard ORS per patient cost of IV therapy per patient cost of seizure diagnostic and treatment cost of death, to health system

US$0.50 US$0.50 US$10.00 US$5.00 US$1,000.

All results were checked by one-way and two-way sensitivity analyses on all variables.

Comparing the reduction in need for intravenous fluids, the incidence of seizures, as well as costs (excluding the start-up cost of implementing the program), the decision analysis model favoured the reduced osmolarity ORS in all comparisons. Specifically, a total of 14,000 deaths per million episodes of diarrhoea with some dehydration (moderate dehydration) would be avoided with the reduced osmolarity ORS, by reducing the number of treatment failures. This would be associated with a possible addition of 10,000 seizures per million episodes of diarrhoea with some dehydration, almost all in young children. In other words, the estimated number of seizures per death averted would be 0.7. This could result in a cost savings of $500 per death averted, or $7.1 million per million episodes. Using sensitivity analysis, reduced osmolarity ORS was always preferred, regardless of changes in the rate of deaths with this model.

11. Summary of regulatory status of the medicine

Unchanged.

12. Pharmacopoieal standards

The old formulation is included in the British Pharnacopoeia and the International Pharmacopoeia.

We are going to contact the British Pharmacopoeia to explore the possibility to have the new formulation of ORS included in their next revision in 2004.

13. Proposed revised text for the WHO Model Formulary

The only change would concern the table on page 398, in section 26.1.1 entitled “Oral rehydration”, which should be changed with the following one:

Oral rehydration salts Glucose salt solution
Sodium chloride	2.6 g/litre of clean water
Glucose (anhydrous)	13.5 g/litre of clean water
Potassium chloride	1.5 g/l of clean water
Trisodium citrate	2.9 g/l of clean water

When glucose and trisodium citrate are not available, they may be replaced by

Sucrose (common sugar) 27 g/litre of clean water
Sodium bicarbonate 2.5 g/litre of clean water

Eventually, an additional paragraph could be included to indicate what is considered by WHO/UNICEF as an acceptable ORS formulation.

[1] Reduced osmolarity oral rehydration salts (ORS) formulation – Report from a meeting of experts jointly organised by UNICEF and WHO. WHO/CAH/01.22

http://www.who.int/child-adolescent-health/New_Publications/CHILD_HEALTH/Expert_consultation.htm

Low-osmolarity ORS On-line Resources A complete and up-to-date list of the following and related resources can be found at Enhanced Diarrheal Disease Control Resource Center Clinical management of acute diarrhoea (2004) This official joint statement updates previous WHO/UNICEF recommendations on the management of acute diarrhea, taking into consideration new research findings that indicate the success of interventions incorporating reduced-osmolarity ORS and zinc supplementation. World Health Organization (WHO), UNICEF pdf English 241 kb | pdf Español 409 kb | pdf Français 418 kb Diarrhoea treatment guidelines including new recommendations for the use of ORS and zinc supplementation for clinic-based healthcare workers (2005) These guidelines were developed to advise clinic-based health workers on implementing the latest WHO/UNICEF recommendations for ORS and zinc supplementation in the clinical management of diarrhoea. US Agency for International Development (USAID) Micronutrient Program pdf English 401 kb Guidelines for new diarrhea treatment protocols for community-based healthcare workers (2005) These guidelines were developed to advise community health care workers who assist parents with home treatment of children with diarrhea with regard to the latest WHO/UNICEF recommendations. USAID Micronutrient Program pdf English 128 kb The treatment of diarrhoea: A manual for physicians and other senior health workers (2005) Developed for physicians treating infectious diarrhea in young children, this manual has been updated to include guidelines for the use of reduced-osmolarity ORS and zinc supplements. WHO pdf English 1 mb General information The evolution of diarrhoeal and acute respiratory disease control at WHO: Achievements 1980–95 in research, development and implementation (1999) This document summarizes the evolution of WHO’s strategy toward researching and implementing interventions for diarrheal disease and acute respiratory disease control in the developing world, including a focus on current integrated strategies for child health. WHO (WHO/CHS/CAH/99.12) pdf English 504 kb Expert consultation on oral rehydration salts (ORS) formulation (2001) This meeting report provides background information essential to an expert committee’s consensus toward reducing the osmolarity of previous ORS standards. WHO, UNICEF (WHO/FCH/CAH/01.22) Improved formula for oral rehydration salts to save children’s lives (2006) This press release announces WHO and UNICEF adoption of the new, reduced-osmolarity formulation of ORS and provides links to informative resources from both organizations. WHO, UNICEF Monograph for oral rehydration salts (2005) This updated monograph on the new, low-osmolarity formula of ORS was revised to provide the quality specifications as adopted by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in October 2005. The monograph was prepared for inclusion in the fourth edition of The International Pharmacopoeia, currently in press. WHO, The International Pharmacopoeia Oral rehydration salts: Production of the new ORS (2006) Updated in 2006, this manual provides comprehensive information on manufacturing the new formula of low-osmolarity ORS. WHO, UNICEF (WHO/FCH/CAH/06.1) pdf English 2.3 mb Treatment guidelines Implementing the new recommendations on the clinical management of diarrhoea: Guidelines for policy makers and programme managers (2006) This manual provides information to guide to introduction and/or scale up of the new ORS formulation and zinc for clinical management of diarrhoeal diseases. WHO pdf English 385 kb Managing acute gastroenteritis among children: Oral rehydration, maintenance, and nutritional therapy (2003) This publication provides guidelines for the use of ORS for clinical management of diarrhea, discusses various formulations of ORS, addresses challenges related to the administration of ORS, and encourages the use of ORS in the home to potentially avoid clinic visits and hospitalizations. US Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. 52(RR-16):1-16. pdf English 450 kb Reducing deaths from diarrhea through oral rehydration therapy (2000) This report evaluates global use of ORS and its impact on reducing diarrheal disease mortality. The authors call for continued and improved data collection regarding the use of ORS and note the benefits such data offer toward informing public health policies and programs. Victora CG, Bryce J, Fontaine O, Monasch R. Bulletin of the World Health Organization. 78(10):1246-1255. pdf English 336 kb Treatment of diarrhoeal diseases: Information for pharmacists and other drug sellers (2001) This guide aims to improve the practices of pharmacists and drug sellers by providing details on avoiding inappropriate interventions for diarrhea, including underuse of ORS and overuse of antibiotics. WHO Department of Child and Adolescent Health and Development Research Clinical trials of improved oral rehydration salt formulations: A review (1994) The authors of this review assess the efficacy and use of different formulations of ORS, as determined in previously published studies. Bhan M, Mahalanabis D, Fontaine O, Pierce N. Bulletin of the World Health Organization. 72(6):945–955. pdf English 882 kb Falling diarrhoea mortality in Northeastern Brazil: Did ORT play a role? (1996) This study provides data that supports the impact of ORS on dramatic reductions in diarrhea deaths recorded after its introduction in Brazil in the 1980s. Victora C, Olinto M, Barros F, Nobre L. Health Policy and Planning. 11(2):132–141. pdf English 707 kb Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrhoeal diseases in Mexico (1996) This study evaluates the impact of education, ORS introduction, and sanitation improvements on the incidence of diarrheal disease mortality in Mexico between 1978 and 1993. Gutierrez G, et al. Bulletin of the World Health Organization.74(2):189–197. pdf English/Español 430 kb Multicentre evaluation of reduced-osmolarity oral rehydration salts solution (abstract only; 1995) The investigators in this study compared the efficacy of reduced-osmolarity and standard ORS in children with acute diarrhea in four developing countries and determined that reduced-osmolarity ORS is the more appropriate intervention for children with non-cholera diarrhea. International Study Group on Reduced-osmolarity ORS Solutions. Lancet. 345(8945):282-285. Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: Systematic review (2001) Hahn S, Kim Y, Garner P. British Medical Journal; 323:81–85. Another evaluation of standard versus reduced-osmolarity ORS, this analysis involved data from 15 trials and determined that treatment with reduced-osmolarity solution resulted in decreased stool output and vomiting and reduced the need for intravenous infusions. pdf English 122 kb

updated: 23 April, 2014