Oral rehydration formula containing alanine and glucose for treatment of diarrhoea: a controlled trial.

OBJECTIVE--To determine whether adding L-alanine to the glucose based oral rehydration solution recommended by the World Health Organisation would improve its efficacy in treating acute diarrhoea. DESIGN--Randomised double blind controlled trial of oral rehydration solution containing L-alanine and glucose. SETTING--Inpatient service of a hospital treating diarrhoea. PATIENTS--97 Male patients aged 6-59 years admitted to the hospital with acute and severe dehydration due to diarrhoea associated with Vibrio cholerae or enterotoxigenic Escherichia coli. Forty nine received the standard glucose based oral rehydration solution (control group) and 48 this solution with alanine added (study group). INTERVENTIONS--All of the patients received rapid intravenous acetate solution for the initial four hours after admission, which fully corrected the signs of dehydration. They were then admitted to the study and randomised. Immediately after the intravenous treatment oral rehydration treatment was started. All of the patients received oral tetracycline for 48 hours, starting 24 hours after start of the study. If signs of dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until they were fully corrected and then continued to take the assigned oral rehydration solution. END POINT--Passage of the last watery stool. MEASUREMENTS and MAIN RESULTS--The median stool output/kg body weight during the initial 24 hours of oral rehydration treatment and until diarrhoea stopped was reduced in the study group compared with the control group from 309 ml to 196 ml and from 393 ml to 236 ml respectively. Intake of oral rehydration solution and intravenous acetate solution was reduced from 455 ml to 308 ml and from 616 ml to 425 ml respectively. Two patients in the study group compared with 18 patients in the control group required unscheduled rapid intravenous acetate solution to correct signs of dehydration during oral rehydration treatment. CONCLUSION--Oral rehydration solution containing L-alanine was considerably better than standard oral rehydration solution at reducing the severity of symptoms and the need for fluid of male patients with diarrhoea associated with V cholerae and enterotoxigenic E coli.     

Oral hydratation with a low osmolality solution in dehydrated children with diarrheic diseases: controlled clinical trial

A clinical trial was conducted to compare the efficacy of a low-osmolarity solution (245 mOsm/L), and a standard oral rehydration solution (ORS) recommended by WHO for children dehydrated by diarrhea. Group 1 (69 children) received WHO/ORS (311 mOsml/L) and group 2 (71 children) received a low-osmolarity solution (245 mOsm/L). Rehydration was successful in 88.4% in group 1 and 92.9% in group 2 (p = 0.35). Rehydration was completed in 5.2 h (SD +/- 1.8) in group 1 and 5.5 (SD +/- 1.7) in group 2 (p = 0.31). Stool output was 6.3 g/kg/h (SD +/- 5.0) in group 1 and 5.6 g/kg/h (SD +/- 5.1) in group 2 (p = 0.94). Sodium at rehydration-completion was 139.3 mEq/L (SD +/- 7.1) in group 1 and 136.7 mEq/L (SD +/- 4.3) in group 2 (p = 0.014). Group 1 was under observation for 21 hours (SD +/- 5.7) and group 2, for 22 hours (SD +/- 5.6). Stool output in group 1 was 5.2 g/kg/h (SD 4.1) and 4.2 gr./kg/h (SD +/- 4.1) in group 2 (p = 0.16). In group 1, 23.1% required intravenous solutions and 9.8% in group 2 (p = 0.03). In treating dehydrated children, the low-osmolarity solution diminished the need for intravenous solutions, corrected most plasmatic sodium disorders, and produced no-risk of developing hyponatremia.     

Randomised double blind trial of single dose doxycycline for treating cholera in adults.

OBJECTIVE--To compare the efficacy of a single dose of doxycycline (200 or 300 mg) with the standard multiple doses of tetracycline in patients with cholera. DESIGN--Randomised double blind controlled trial. Patients were given a single 200 mg dose of doxycycline, a single 300 mg dose of doxycycline, or multiple doses of tetracycline (500 mg, six hourly intervals). SETTING--Hospital in Bangladesh treating diarrhoea. PATIENTS--261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae. All vibrios isolated from the stools and rectal swabs of patients, including those patients with prolonged excretion of vibrios, were sensitive to tetracycline. The stools of all patients at admission were negative for shigella and salmonella. INTERVENTIONS--All patients received rapid intravenous acetate solution for the first four hours after admission to hospital. They were then entered in the study and randomised. Oral rehydration was started immediately after the intravenous treatment. If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected. MAIN OUTCOME MEASURES--Stool output in first 24 hours and till diarrhoea stopped, total intake of oral rehydration fluid, duration of diarrhoea, and excretion of vibrio after receiving antibiotic treatment. RESULTS--The median stool outputs during the first 24 hours (275 ml/kg body weight) and till diarrhoea stopped (296 ml/kg body weight) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either standard tetracycline (242 ml/kg body weight and 254 ml/kg body weight) or 300 mg doxycycline (226 ml/kg body weight and 255 ml/kg body weight). Similarly, median consumption of oral rehydration solution (18.45 l) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline (16.10 l) or standard tetracycline (14.80 l). Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment. Patients treated with doxycycline (low or high dose), however, had more prolonged excretion of bacteria. CONCLUSIONS--A single 300 mg dose of doxycycline is as effective as the standard multiple dose tetracycline treatment for cholera in terms of stool output, duration of diarrhoea, vomiting, and requirement for oral rehydration solution.     

Control of diarrhoeal disease in Tonga 1978-83.

Tonga, like many developing countries, suffers from a shortage of medical staff and a high morbidity and mortality from paediatric diarrhoeal disease. In 1980 a programme was started to train medical assistants and village administrators in the correct use of oral rehydration salt solution for rehydration. The effect on morbidity, mortality, and admission to hospital over the six years 1978-83 was assessed. After the introduction of the scheme the number of deaths due to diarrhoea fell considerably and the state of hydration in children admitted to hospital with diarrhoea greatly improved. It is recommended that similar programmes be adopted where clinical problems of diarrhoea with dehydration persist. Instruction in the use of oral rehydration fluid was most effectively given by non-medical staff to groups of mothers, rather than by paediatricians in their inevitably brief, although important, explanation given in hospital.     

Adhesion of Vibrio cholerae to granular starches

Cholera is a severe diarrheal disease caused by specific serogroups of Vibrio cholerae that are pathogenic to humans. Cholera can become epidemic and deadly without adequate medical care. Appropriate rehydration therapy can reduce the mortality rate from as much as 50% of the affected individuals to <1%. Thus, oral rehydration therapy (ORT) is an important measure in the treatment of this disease. To further reduce the symptoms associated with cholera, improvements in oral rehydration solution (ORS) by starch incorporation were suggested. Here, we report that V. cholerae adheres to starch granules incorporated in ORS. Adhesion of 98% of the cells was observed within 2 min when cornstarch granules were used. Other starches showed varied adhesion rates, indicating that starch source and composition play an important role in the interaction of V. cholerae and starch granules. Sugars metabolized by V. cholerae showed a repressive effect on the adhesion process. The possible mechanisms involved are discussed. Comparing V. cholerae adhesion with the adhesion of other pathogens suggests the involvement of starch degradation capabilities. This adhesion to granular starch can be used to improve ORT.     

Randomised controlled trial comparing oral and intravenous rehydration therapy in children with diarrhoea.

OBJECTIVE--To determine the effectiveness of oral rehydration in children with moderate dehydration caused by gastroenteritis, and to compare the complications of oral and intravenous treatment. DESIGN--Randomised controlled trial. SETTING--Emergency department and infectious diseases ward in a large urban teaching hospital. PATIENTS--111 children aged 3-36 months who had been previously healthy, had had diarrhoea for seven days or less, had clinical signs of dehydration, and were not in shock. Six children were withdrawn because the diagnosis was incorrect (four in oral group, two in intravenous group) and one (oral group) was withdrawn at her parents'' request. INTERVENTIONS--Oral rehydration fluid was given by mouth or nasogastric tube, or both to 52 children. The remaining 52 received intravenous rehydration fluids but were allowed to drink. MAIN OUTCOME MEASURES--Success or failure of rehydration. Number of times child vomited or passed stool after starting treatment. Time taken to rehydrate. RESULTS--Oral treatment failed in two children (failure rate 3.8%, upper 95% confidence limit 11.6%) and intravenous treatment in none. Vomiting was more common in the oral group (p less than 0.01): 26 of 50 children (52%) in the oral group and 11 of 50 (22%) in the intravenous group vomited during rehydration. There was no significant difference between the two treatment groups in the number of stools passed during rehydration (p = 0.09). None of the children had serious complications of treatment. CONCLUSION--Rehydration by mouth or nasogastric tube is a safe and effective treatment for moderately dehydrated children with gastroenteritis.     

Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.

OBJECTIVE--To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN--Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS--The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION--Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES--Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS--The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS--The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.     

Adhesion of Vibrio cholerae to Granular Starches

Cholera is a severe diarrheal disease caused by specific serogroups of Vibrio cholerae that are pathogenic to humans. Cholera can become epidemic and deadly without adequate medical care. Appropriate rehydration therapy can reduce the mortality rate from as much as 50% of the affected individuals to <1%. Thus, oral rehydration therapy (ORT) is an important measure in the treatment of this disease. To further reduce the symptoms associated with cholera, improvements in oral rehydration solution (ORS) by starch incorporation were suggested. Here, we report that V. cholerae adheres to starch granules incorporated in ORS. Adhesion of 98% of the cells was observed within 2 min when cornstarch granules were used. Other starches showed varied adhesion rates, indicating that starch source and composition play an important role in the interaction of V. cholerae and starch granules. Sugars metabolized by V. cholerae showed a repressive effect on the adhesion process. The possible mechanisms involved are discussed. Comparing V. cholerae adhesion with the adhesion of other pathogens suggests the involvement of starch degradation capabilities. This adhesion to granular starch can be used to improve ORT.     

Loperamide in acute diarrhoea in childhood: results of a double blind,placebo controlled multicentre clinical trial. Diarrhoeal Diseases Study Group (UK).

A total of 315 young children with acute diarrhoea were included in a double blind, hospital based multicentre trial of loperamide at two dose levels (0.8 mg and 0.4 mg/kg/24 h), given with standard oral rehydration therapy versus placebo plus oral rehydration therapy. The overall recovery rate was slowest in the placebo group and fastest in the group given loperamide 0.8 mg. Comparisons between weights on admission and weights by day 3 showed that a larger proportion of children in the loperamide groups gained weight than in the placebo group. No serious side effects of loperamide were observed, but the drug was withdrawn in one infant because of mild abdominal distention. The results indicate that loperamide, in the doses employed, is safe and may in selected cases be a useful adjunct to oral rehydration in the management of acute diarrhoea in well nourished children.     

Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis

Context

Gastroenteritis remains a leading cause of childhood morbidity.

Objective

Because prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected.

Data Sources

MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings.

Study Selection

Randomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate.

Data Extraction

The study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models.

Results

31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92).

Conclusions

There is a paucity of patient-centered outcome evidence to support many interventions. Since ORT is a low-cost, non-invasive intervention, it should continue to be used. Routine probiotic use cannot be endorsed at this time in outpatient children with gastroenteritis. Despite some evidence that ondansetron administration increases diarrhea frequency, emergency department use leads to reductions in intravenous rehydration and hospitalization. No benefits were associated with ondansetron use following emergency department discharge.     

Estimation of serum zinc and copper in children with acute diarrhea

Diarrhea is, in reality, as much a nutritional disease as one of fluid and electrolyte loss. Children who die from diarrhea, despite good management of dehydration, are usually malnourished and often severely so. In this study, we determined the serum levels of zinc and copper before and after standard oral rehydration solution (ORS) therapy in children with acute diarrhea and correlated it with diarrheal duration and severity. One hundred ten children suffering from acute diarrhea were included. Serum zinc and copper levels of these children were estimated at the time of enrollment and after treatment with standard ORS therapy. This study shows that children suffering from acute diarrhea show a statistically significant decrease of 13.1% and 12.8% in serum zinc and copper concentrations, respectively, compared to normal. These levels further decrease by 22.6% and 22.4%, respectively, after treatment with standard ORS therapy. Our study shows that children with the lower plasma zinc and copper levels suffered with more severe and longer duration of diarrhea. Zinc and copper supplementation could be added to standard ORS therapy for the reduction in morbidity and mortality associated with acute diarrhea in children.     

口服补液减轻40%血容量失血大鼠肠组织缺血性损伤

目的：研究口服葡萄糖-电解质液（GES）对大鼠40%血容量失血时肠组织缺血性损伤的影响。方法：雄性SD大鼠,用氯胺酮-速眠新Ⅱ肌注复合麻醉后,行右颈动脉插管。随机分为3组（n=24）：GES对照组（GES）,失血性休克组（HS）和失血性休克＋口服GES液组（HS＋GES）。GES组：不放血,手术后口服GES;HS和HS＋GES组按全身血容量的40%分两次间隔15min放血制作失血性休克模型。HS＋GES组于失血后0.5h、1h和6h分3次给予3倍失血量的GES灌胃。用激光多谱勒血流仪测定失血后2h、4h和24h肠组织血流量（IBF）后,处死动物后取肠组织检测二胺氧化酶（DAO）和Na^＋-K^＋-ATP酶活性,测定肠组织含水率（WG）,并做病理学检查。结果：HS＋GES组IBF和Na-K-ATP酶活性均显著高于HS组（P〈0.05）,但显著低于GES组（P〈0.05）;失血各组肠WG显著高于GES组（P〈0.05）,24h时HS＋GES组WG显著低于HS组（P〈0.05）;HS＋GES组24hDAO活性均显著高于HS组（P〈0.05）,但显著低于GES组（P〈0.05）;失血后24h病理检查HS＋GES组肠组织水肿和充血改变比HS组明显减轻。结论：口服GES液能显著增加大鼠失血性休克早期IBF,提高Na^＋-K^＋-ATP酶和DAO活性,减轻肠组织水肿和缺血性损伤。     

Honey in the treatment of infantile gastroenteritis.

A clinical study was undertaken using honey in oral rehydration solution in infants and children with gastroenteritis. The aim was to evaluate the influence of honey on the duration of acute diarrhoea and its value as a glucose substitute in oral rehydration. The results showed that honey shortens the duration of bacterial diarrhoea, does not prolong the duration of non-bacterial diarrhoea, and may safely be used as a substitute for glucose in an oral rehydration solution containing electrolytes. The correct dilution of honey, as well as the presence of electrolytes in the oral rehydration solution, however, must be maintained.     

Appearance of D2O in sweat after oral and oral-intravenous rehydration in men

Intravenous (IV) rehydration is common in athletics, but its thermoregulatory benefits and ergogenicity have not been elucidated. Availability of orally ingested fluid is dependent on gastric emptying and intestinal absorption rate. Deuterium oxide (D2O) has been used to demonstrate that fluid ingested during exercise appears in sweat within 10 minutes. The purpose of this study was to determine the effect of concurrent IV rehydration on D2O appearance in sweat samples after per ora rehydration with D2O labeled fluid. We hypothesized that the combination method would not be superior to the oral method. Ten fit men (age 23 ± 4, VO2max 59.49 ± 4.09 L·min(-1)) underwent 20 hours of fluid restriction resulting in 1.95 ± 0.25% body weight loss before beginning treadmill exercise and cycling. Exercise was performed in an environmental chamber (35.6 ± 0.2° C, 35.0 ± 1.8% relative humidity) for 2 hours at 55% VO2max, and the participants exhibited a mean body weight deficit of 4.50 ± 0.04%. Thermoregulatory measures were recorded while subjects were rehydrated with oral (OR) or oral combined with intravenous (IVO) fluid traced with D2O. After 30 minutes of rehydration and 30 minutes of seated recovery, the subjects began treadmill exercise at 55-60% VO2max. Forehead sweat samples were collected 0, 5, 10, 20, and 75 minutes from the start of rehydration. The samples were analyzed for D2O via isotope ratio mass spectrometry. D2O did not appear in the sweat within 20 minutes of rehydration; however, it did appear during the subsequent exercise bout. There was no significant difference between rehydration modes. Plasma volume increases and decreased volume of orally ingested fluid did not significantly alter transit time from ingestion to appearance in excreted sweat. The IVO method does not appear to be superior to the traditional OR method of rehydration.     

The role of i.v. ibandronate administration in osteoporosis therapy

Osteoporosis is a chronic disease of the osseous system characterised by decreased strength of bone tissue, which in turn leads to increased fracture risk. It has been demonstrated that osteoporosis affects more than 30% of women after the menopause (WHO, 1994). However, the disease is also observed in men. The primary goals of osteoporosis therapy include prevention of low-energy fractures and general improvement of quality of life. Any patient with diagnosed osteoporosis requires, besides prevention, the application of proper treatment. Of the available therapeutic options, the best are bisphosphonates, medical agents with well identified properties, therapeutic efficacy, and safety which has been confirmed in many clinical studies. Therefore, they are recommended as first line drugs for osteoporosis. The efficacy of oral preparations may be limited, due to low bioavailability, complications and adverse effects from the gastrointestinal tract. So the parenteral administration of bisphosphonates is a valuable alternative. A fine example of such therapy is the intravenous administration of ibandronate. Short injection time periods and the relatively long, three-month intervals between administrations are unquestionable advantages of this therapy mode. In addition, the therapy does not constrain a patient's everyday activity, and simultaneously provides regular contact with doctors and the therapeutic centre. Additionally, a good tolerance of the drug and its high therapeutic efficacy, proven by appreciably reduced fracture risks, significantly improves the quality of life of patients suffering from osteoporosis. This paper is a thorough review of current knowledge on the efficacy and safety of i.v. ibandronate in osteoporosis therapy, as presented in the latest literature reports.     

Oral care training in the basic education of care professionals

doi:10.1111/j.1741‐2358.2009.00304.x
Oral care training in the basic education of care professionals Objective: To investigate the quantity and quality of oral care training in the basic education of future long‐term care (LTC) professionals in Norway. Background: The level of oral hygiene has often proved inadequate in LTC facilities. It has been maintained that this could be due to insufficient knowledge of oral care among care professionals. Materials and methods: A self‐administered questionnaire was sent to all 270 schools in Norway which offered basic education of LTC personnel in 2004/05. Information on theoretical and practical oral care training, scope of oral care in teaching material and curriculum, educational background of the teaching staff and schools opinion regarding adequacy of their training programme was collected. Results: Of the 203 respondents (75% response rate), 188 (participants) included oral care in their educational programme. Approximately two‐thirds of the participating schools provided 3 h or more of oral care training and many of the important themes were presented in the textbooks that were recommended. Moreover, the practical exercises performed in practice placement supplemented the knowledge. Conclusion: The results could not confirm that LTC professional’s basic education concerning oral care was inadequate. There may therefore be other explanations for the poor oral hygiene in many LTC facilities.     

Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis

Background

The use of antiemetics for children with vomiting is one of the most controversial decisions in the treatment of gastroenteritis in developed countries. Ondansetron, a selective serotonin receptor antagonist, has been found to be effective in improving the success of oral rehydration therapy. However, North American and European clinical practice guidelines continue to recommend against its use, stating that evidence of cost savings would be required to support ondansetron administration. Thus, an economic analysis of the emergency department administration of ondansetron was conducted. The primary objective was to conduct a cost analysis of the routine administration of ondansetron in both the United States and Canada.

Methods and Findings

A cost analysis evaluated oral ondansetron administration to children presenting to emergency departments with vomiting and dehydration secondary to gastroenteritis from a societal and health care payer''s perspective in both the US and Canada. A decision tree was developed that incorporated the frequency of vomiting, intravenous insertion, hospitalization, and emergency department revisits. Estimates of the monetary costs associated with ondansetron use, intravenous rehydration, and hospitalization were derived from administrative databases or emergency department use. The economic burden in children administered ondansetron plus oral rehydration therapy was compared to those not administered ondansetron employing deterministic and probabilistic simulations. We estimated the costs or savings to society and health care payers associated with the routine administration of ondansetron. Sensitivity analyses considered variations in costs, treatment effects, and exchange rates. In the US the administration of ondansetron to eligible children would prevent approximately 29,246 intravenous insertions and 7,220 hospitalizations annually. At the current average wholesale price, its routine administration to eligible children would annually save society US$65.6 million (US$49.1–US$81.1) and health care payers US$61.1 million (US$46.2–US$76.3). In Canada the administration of ondansetron to eligible children would prevent 4,065 intravenous insertions and 1,003 hospitalizations annually. Its routine administration would annually save society CDN$1.72 million (CDN$1.15–CDN$1.89) and the health care system CDN$1.18 million (CDN$0.88–CDN$1.41).

Conclusions

In countries where intravenous rehydration is often employed, the emergency department administration of oral ondansetron to children with dehydration and vomiting secondary to gastroenteritis results in significant monetary savings compared to a no-ondansetron policy. Please see later in the article for the Editors'' Summary     

The Recognition of and Care Seeking Behaviour for Childhood Illness in Developing Countries: A Systematic Review

Background

Pneumonia, diarrhoea, and malaria are among the leading causes of death in children. These deaths are largely preventable if appropriate care is sought early. This review aimed to determine the percentage of caregivers in low- and middle-income countries (LMICs) with a child less than 5 years who were able to recognise illness in their child and subsequently sought care from different types of healthcare providers.

Methods and Findings

We conducted a systematic literature review of studies that reported recognition of, and/or care seeking for episodes of diarrhoea, pneumonia or malaria in LMICs. The review is registered with PROSPERO (registration number: CRD42011001654). Ninety-one studies met the inclusion criteria. Eighteen studies reported data on caregiver recognition of disease and seventy-seven studies on care seeking. The median sensitivity of recognition of diarrhoea, malaria and pneumonia was low (36.0%, 37.4%, and 45.8%, respectively). A median of 73.0% of caregivers sought care outside the home. Care seeking from community health workers (median: 5.4% for diarrhoea, 4.2% for pneumonia, and 1.3% for malaria) and the use of oral rehydration therapy (median: 34%) was low.

Conclusions

Given the importance of this topic to child survival programmes there are few published studies. Recognition of diarrhoea, malaria and pneumonia by caregivers is generally poor and represents a key factor to address in attempts to improve health care utilisation. In addition, considering that oral rehydration therapy has been widely recommended for over forty years, its use remains disappointingly low. Similarly, the reported levels of care seeking from community health workers in the included studies are low even though global action plans to address these illnesses promote community case management. Giving greater priority to research on care seeking could provide crucial evidence to inform child mortality programmes.     

From a pump handle to oral rehydration therapy: a model of translational research

Few afflictions have attracted as much attention and impacted on as many societal and biomedical areas as cholera. Dr. John Snow's studies launched the field of epidemiology, were early applications of medical cartography, and promoted the use of statistical methods in medicine. The finding that cholera was due to the ingestion of contaminated water lent to the demise of the prevalent "miasmatic theory of contagion," set the platform for the "germ theory of disease," and promoted the growth of public health concerns for water purification and sanitation. More recent attention to this disease led to the notion of "secretory diarrhea" and the translation of basic principles to the development of oral rehydration therapy and its "spin-offs" (Gatorade and Pedilyte).     

Cryopreservation of wheat (Triticum aestivum L.) egg cells by vitrification

A procedure has been developed for the cryopreservation of wheat female gametes. The procedure involves loading the cells with 25% concentrated vitrification solution consisting of 30% glycerol, 10% sucrose, 120 mM ascorbic acid (AA) and 5% propylene glycol (PG), dehydration in 80% concentrated vitrification solution, droplet vitrification and storage in liquid nitrogen, unloading and rehydration of the cells by gradual addition of isolation solution. Supplementation with AA significantly increased the proportion of viable egg cells after de- and rehydration. During the early phase of rehydration AA reduced the probability of membrane damage caused by rapid water uptake. Maintaining the temperature of the cells at 0°C during the de- and rehydration processes increased cell survival. Microscopic examination of the semi-thin sections of untreated and viable cryopreserved cells revealed that the vitrification process might cause changes in cell structure.