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Asthma and influenza are two pathologic conditions of the respiratory tract that affect millions worldwide. Influenza virus of the 2009 pandemic was highly transmissible and caused severe respiratory disease in young and middle-aged individuals. Asthma was discovered to be an underlying co-morbidity that led to hospitalizations during this influenza pandemic albeit with less severe outcomes. However, animal studies that investigated the relationship between allergic inflammation and pandemic (p)H1N1 infection, showed that while characteristics of allergic airways disease were exacerbated by this virus, governing immune responses that cause exacerbations may actually protect the host from severe outcomes associated with influenza. To better understand the relationship between asthma and severe influenza during the last pandemic, we conducted a systematic literature review of reports on hospitalized patients with asthma as a co-morbid condition during the pH1N1 season. Herein, we report that numerous other underlying conditions, such as cardiovascular, neurologic, and metabolic diseases may have been underplayed as major drivers of severe influenza during the 2009 pandemic. This review synopses, (1) asthma and influenza independently, (2) epidemiologic data surrounding asthma during the 2009 influenza pandemic, and (3) recent advances in our understanding of allergic host-pathogen interactions in the context of allergic airways disease and influenza in mouse models. Our goal is to showcase possible immunological benefits of allergic airways inflammation as countermeasures for influenza virus infections as a learning tool to discover novel pathways that can enhance our ability to hinder influenza virus replication and host pathology induced thereof.

Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities.

Despite gains in controlling mortality relating to diarrhoeal disease, the burden of disease remains unacceptably high. To refocus health research to target disease-burden reduction as the goal of research in child health, the Child Health and Nutrition Research Initiative developed a systematic strategy to rank health research options. This priority-setting exercise included listing of 46 competitive research options in diarrhoeal disease and their critical and quantitative appraisal by 10 experts based on five criteria for research that reflect the ability of the research to be translated into interventions and achieved disease-burden reduction. These criteria included the answerability of the research questions; the efficacy and effectiveness of the intervention resulting from the research; the maximal potential for disease-burden reduction of the interventions derived from the research; the affordability, deliverability, and sustainability of the intervention supported by the research; and the overall effect of the research-derived intervention on equity. Experts scored each research option independently to delineate the best investments for diarrhoeal disease control in the developing world to reduce the burden of disease by 2015. Priority scores obtained for health policy and systems research obtained eight of the top 10 rankings in overall scores, indicating that current investments in health research are significantly different from those estimated to be the most effective in reducing the global burden of diarrhoeal disease by 2015.

ResearchDetermine the age of acquisition of H. pylori infection in diverse populations and the mode of transmission.InterventionValidate noninvasive methods for determining H. pylori colonisation in childhood.EducationTrain physicians to identify early indicators of long-term morbidity (i.e., gastri

The transjugular intrahepatic portosystemic shunt procedure is an accepted treatment for adults with complications of portal hypertension. We performed a retrospective review of all pediatric TIPS placements performed at the University of California, San Francisco between 1990 and 1996. Twelve procedures were attempted in nine children, with a mean age (+/- SD) of 9.4 +/- 3.9 years (range, 5 to 15 years) and a mean weight of 31 +/- 18 kg (range, 16 to 70 kg). The indications for TIPS placement were portal hypertension complicated by chronic variceal hemorrhage not controlled with sclerotherapy (n = 7) and hypersplenism with thrombocytopenia (n = 2). TIPS placement was successfully completed initially in seven of nine (78%) patients. Unfavorable vascular anatomy was the cause of failure in two cases. The seven patients who underwent successful TIPS placement were followed up for an average of 136 days (range, 1 to 800 days); two still have patent shunts, three underwent liver transplantation, one had a splenorenal shunt after stenosis, and one died of underlying liver disease. Variceal bleeding was controlled in four of five patients who successfully underwent TIPS placement. Shunt occlusion occurred in four patients; patency was restored by transjugular shunt revision in three, and a splenorenal shunt was performed in one.

We prospectively studied clinical outcome and nutrition absorption in male children (6-36 months of age) with persistent diarrhea (PD) and severe protein-energy malnutrition (mean z score for age, -4.2 +/- 0.8). Fifty-one children were randomly allocated to receive a combination of khitchri, a rice-lentil mixture, yogurt, and half-strength buffalo milk (group A; n = 26) or full-strength soy formula (group B; n = 25) for 14 days. The initial caloric intake (p < 0.02) and mean weight gain (p < 0.02) were greater in the group B patients. The mean stool volume and frequency were comparable between the two groups. Seven children in group A were considered clinical failures by criteria of weight loss and PD, compared to three in group B. The coefficients of absorption (COA) for protein were similar between the two groups, but group B patients had higher values of COA for energy and fat (p < 0.05) in the second week of nutritional rehabilitation. The majority (63%) of the children improved on the khichri-yogurt-milk diet but the nutritional outcome was not as good as with the soy formula. These data indicate that a traditional diet can be successfully used in the dietary management of PD and severe malnutrition but that a more optimal composition, yielding a higher success rate, should be sought.

Serum retinol and hemoglobin levels were determined in 532 children aged 6-60 months living in urban slums of Karachi, Pakistan. Overall 67% (358 of 532) of children had hemoglobin levels of less than 11 g/dl, the World Health Organization definition of anemia for this age group. Estimations for red blood cell indices (hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red blood cell count) were done on a sample of 391 children to classify anemia morphologically. A similar percentage (69.8% [273 of 391 children]) of anemia was found in this group. The anemia was predominantly microcytic and hypochromic. Normocytic normochromic anemia was present in only 16.5%. Serum retinol levels were significantly correlated with hemoglobin (P < 0.002), hematocrit (P < 0.01), and red blood cell (P < 0.001) levels. However, anemia was found to be a poor predictor (positive predictive value [PPV] = 2.5%) for the presence of vitamin A deficiency (retinol < 10 micrograms/dl). The PPV increased to 54% if 20 micrograms/dl, which is an indicator of marginal vitamin A status, was used as the cutoff point. The sensitivity of the hemoglobin test was found to be 75% in correctly identifying vitamin A deficiency when retinol levels of 10 micrograms/dl and 20 micrograms/dl were both used as the cutoff points for deficiency. The specificity for the hemoglobin test varied from 33% to 40% when levels of 10 micrograms/dl and 20 micrograms/dl were used as the cutoff points for vitamin A deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Rice based oral rehydration therapy (ORT) solutions have been shown to be superior to glucose oral rehydration salts (World Health Organisation (WHO) ORS) in reducing stool volume and duration of diarrhoea in children and adults. Rice based ORT has been used only sparingly in young infants, however, because of theoretical concerns about digestibility. A randomised controlled trial of rice based ORT (50 g rice and electrolytes identical to WHO ORS) and WHO ORS was carried out in 52 male infants less than 6 months old with moderately severe acute diarrhoea to evaluate efficacy and digestibility. Nineteen (70%) of 27 children who received rice based ORT and 18 (72%) of 25 children who received WHO ORS were treated successfully. The mean (SD) diarrhoeal stool output for the first 24 hours of treatment was significantly lower in the infants receiving the rice based ORT than in those receiving WHO ORS (101.0 (60.5) v 137.1 (74.6) g/kg). The stool output was also significantly less in the rice based ORT group in the second 24 hours. Infants in the rice based ORT group drank significantly less rehydration solution than infants in the WHO ORS group (mean (SD) 165.4 (77.4) v 217.9 (86.1) during the first 24 hours of treatment. There was no difference in the duration of diarrhoea between the groups. The volume of breast and formula feeding was similar in the two groups. No difference was seen in the frequency of finding reducing substances or acid pH in the stools of either group of children. The results suggest that rice based ORT is as effective as WHO ORS in infants with moderately severe diarrhoea and that rice based ORT is as well tolerated as WHO ORS in infants.

We assessed the vitamin A status of 532 children with an age range of 6-60 months who were living in slum areas of Karachi, Pakistan, using three methodologies: clinical eye examination, dietary vitamin A intake, and serum retinol level. No definite clinical signs of xerophthalmia were observed in any of these children. The mean +/- SD vitamin A intake estimated from a food frequency questionnaire for the group with inadequate (low and deficient) serum retinol levels (20 micrograms/dl) was 362 +/- 332 retinol equivalents (RE) compared with 431 +/- 332) RE in the group with adequate serum levels (P0.005). Deficient serum retinol levels (10 micrograms/dl) were present in 12 children (2%); two of these had a healed corneal scar. Low serum retinol levels (10-19 micrograms/dl) were present in 46%, while 51% children had adequate levels (or = 20 micrograms/dl). The mean +/- SD serum retinol level for the inadequate (20 micrograms/dl) and adequate groups were 15.3 +/- 2.8 and 26.6 +/- 6.7 micrograms/dl, respectively. These results suggest that a significant number of children in these communities have low vitamin A levels and thus may constitute an at risk group. These results also suggest that the dietary intake method may be a simple and inexpensive screening tool for assessment of vitamin A status in communities.

An educational program on oral rehydration therapy (ORT) for diarrhea was instituted in our residents' continuity clinics to evaluate the impact that residents teaching parents would have on the knowledge and practices of both groups. Sixty-one residents and 287 parents answered the initial written questionnaire before the teaching program began, and 48 residents and 147 parents completed a second questionnaire at the end of the program. Nineteen residents in two clinics were told to participate frequently in teaching the parents, while 29 residents in three other clinics were given no such instructions. The parents were divided into three groups: 58 received teaching and an instructional handout on the management of diarrhea; 73 received only the instructional handout; and 16 received neither intervention. The 19 "teaching" residents had a significantly improved overall score compared with the "nonteaching" residents (p

Although the causes of persistent diarrhea are largely unknown, dietary protein sensitivity has been identified as one possible mechanism. Since nutritional therapy appears to be an essential component of treatment for persistent diarrhea, a clearer understanding of the importance of dietary protein allergy is needed to provide optimal dietary recommendations. This paper reviews the current concepts of the pathophysiology, clinical features and criteria for diagnosis of dietary protein sensitivity. Evaluation of the results of several clinical studies indicates that dietary protein sensitivity does occur especially in young infants fed cows' milk but that it is an uncommon event, especially in older infants and children.

In a prospective study we randomized 102 male children (age 6-36 months) with persistent diarrhea to receive a traditional rice-lentil (Khitchri) diet and yogurt (K-Y) or a soy formula (alone for seven days and then in combination with K-Y for seven days). Of 73 children satisfying the study criteria, 66 were successfully treated and there were 7 treatment failures. There was poor concordance between parental accounts of severity of diarrhea or vomiting and that observed after admission. Significant risk factors associated with treatment failure included younger age (p0.005) and vomiting at presentation (p0.02). The greatest number of risk factors associated with delayed recovery (10 days) were identified during an initial evaluation period (the first 8 h after admission). These included greater severity of watery diarrhoea (p0.01) and increased ORS intake (p0.02). Our data suggest that an initial evaluation period, including objective observations, may identify children with persistent diarrhea who are at greatest need of hospitalization.

The Department of Child and Adolescent Health and Development (CAH) of the World Health Organization (WHO) and the Child Health and Nutrition Research Initiative (CHNRI) applied the CHNRI priority- setting methodology to address research priority issues on childhood diarrhoea to improve the rate of progress in reducing global diarrhoea mortality by 2015, as set out in the UN’ s Millennium Development Goal #4. CAH/WHO invited 24 technical experts to systematically list and then score 154 research questions on diarrhoeal diseases according to likelihood of their (i) answerability, (ii) potential contribution to effectiveness, (iii) deliverability, affordability and sustainability, (iv) maximum potential for death burden reduction and (v) predicted effect on equity. The top 10% of research investment priorities were dominated by health systems and policy research questions and epidemiological questions. They were mainly targeted at better understanding the barriers towards implementation, the effectiveness and optimization of use of available interventions and programmes such as oral rehydration solution, zinc supplementation, exclusive breastfeeding and integrated management of childhood illness.

Feeding practices may have an important impact on diarrheal diseases in developing countries. This study evaluated feeding practices in three groups of male children aged 6-36 mo: 100 with persistent diarrhea (PD), 79 with acute diarrhea (AD), and 86 in a comparison group (CG). The children came from comparably poor socioeconomic settings in Karachi, Pakistan, except that the literacy rates were higher in mothers of the CG (P = 0.0001). Although greater than 95% of all infants were breast-fed, delayed initiation of breast-feeding was more common in the diarrhea groups. Children with diarrhea were also more likely to receive supplemental milk (PD = 92%, AD = 87%) than were children in the CG (69%, P less than 0.05). Feedings were not withheld during diarrhea but changes were made in the nature of foods given. These results indicate that several feeding practices may be important risk factors for diarrhea in Pakistan.

Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication.

IN an editorial in the Journal in 1982,1 Charles Carpenter wrote: We physicians all presumably accept the "primum non nocere" principle. On the basis of... studies... this principle would dictate that oral rehydration be accepted not only as an equal, but perhaps as the superior, means of treating acute diarrheal illnesses in the sophisticated and sanitized medical centers of the Western world as well as in rural Bangladesh. Despite such editorials based on the large volume of research data available and despite the endorsements of such organizations as the American Academy of Pediatrics, the World Health Organization (WHO), and the . . .

Serum electrolytes were measured for persons treated for diarrhoea at home with prepackaged or locally available sugar and salt oral rehydration therapy (ORT) solutions and for persons with diarrhoea who received no ORT but were treated according to local customs. No detrimental effect was found for persons treated with ORT at home; no significant difference was found in the frequency at which members of the groups had hypernatraemia. The rates of hyponatraemia and hypokalaemia were significantly lower for persons who took estimated appropriate volumes of ORT than for those who took less than appropriate volumes or for persons treated according to local customs without ORT. These laboratory results indicate that ORT administered in rural homes in Bangladesh was safe and effective under the conditions of our study.As part of an oral rehydration therapy (ORT) field trial, the serum electrolytes of 3 groups with diarrhea were analyzed: 1) persons receiving premixed packet fluids, 2) those receiving locally available salt (labon) and sugar (gur) fluids, and 3) those receiving no ORT intervention and treated according to local custom. Village workers provided instruction and supervision in the preparation of ORT during bimonthly home visits. Questionnaires and serum electrolyte measurements were available from 81 persons in the packet villages and 75 persons from the labon-gur villages. 5 persons treated with packet ORT (6%) and 3 persons treated with labon-gur ORT (4%) had electrolyte abnormalities, but all of them were taking less than appropriate volumes of ORT. In addition, serum electrolytes were evaluated in 489 persons admitted to a medical center after home treatment for diarrhea. No cases who took an appropriate volume of either type of ORT had hyponatremia or hypokalemia. There was no indication that electrolyte abnormalities varied by season or pathogen. Although the close supervision given to study participants and small size limit extrapolation of these results, the study suggests that ORT can be made and safely administered by villagers and that ORT administered at home may be a beneficial effect in preventing hyponatremia and hypokalemia.

To obtain information on the attitudes and practices concerning oral rehydration therapy in the United States and Canada, a questionnaire was sent to the chairmen of departments of pediatrics of 142 medical colleges. Some form of oral fluid therapy for treatment of diarrheal dehydration is used by the institutions of all 128 survey respondents. The most commonly used fluids, commercial sugar-electrolyte solutions (89%), clear liquids (78%), and fruit juices (58%) have very different compositions and concentrations of ingredients. Oral therapy is based on a specific written protocol at 30% of the institutions and is used most frequently to treat outpatients with mild dehydration. To determine a uniform and optimal approach to oral fluid treatment for diarrhea, comparative clinical trials are needed to assess which fluid compositions and concentrations are most effective in preventing dehydration and in treating dehydration once it has occurred.

Serum levels of equine-botulism antitoxin to toxin types A, B, and E were measured in four type-A botulism patients who had received equine-botulism antitoxin. High circulating levels capable of neutralizing in excess of 1 X 10(8), 9 X 10(7), and 6 X 10(6) 50% mouse lethal doses of toxin of types A, B, and E, respectively, were detected. There was little depletion of type-A antitoxin even though two of the patients had circulating type-A toxin before treatment. The half-life for antitoxin persistence for one patient was calculated as being 6.5, 7.6, and 5.3 days for antitoxin types A, B, and E, respectively. Antitoxin levels were not proportionate to the amount (range, 2-4 vials) injected and did not appear to be affected by whether the route of administration was iv or im. Peak serum levels of antitoxin were 10-1,000 times higher than amounts needed to neutralize the toxin measured in the serum of these and other patients with botulism.

In the period November 13-18, 1978, seven cases of type A botulism occurred in persons who had eaten in a restaurant in Colorado. The outbreak was recognized when two persons who had independently eaten at the restaurant were hospitalized with an illness compatible with botulism. Surveillance efforts identified five additional cases. Potato salad made at the restaurant and available for service during an 11-day period was epidemiologically incriminated as the vehicle of botulinal toxin transmission (p less than 0.00001). Laboratory studies showed that Clostridium botulinum spores on the surface of potatoes could survive baking in the manner used by the restaurant and that botulinal toxin could be produced in potatoes contaminated with C. botulinum spores.

Eosinophilic gastroenteritis is known to cause gastric outlet obstruction in adults, but has been reported only rarely in infants presenting with pyloric stenosis, a common form of gastric outlet obstruction in children. We describe two infants who presented with classic clinical and radiographic evidence of pyloric stenosis and who were found to have histologic evidence of eosinophilic gastroenteritis on gastric antral biopsies. Their presentation is compared with the clinical and laboratory findings of 47 other infants with pyloric stenosis.

To determine the modes of transmission of cholera in the regency of Pidie, Indonesia, and to consider strategies for its control, we set up a laboratory to identify Vibrio cholerae 01 from patients with severe diarrhea in all government clinics in the regency and questioned culture-positive cases and neighborhood controls about possible exposures to V. cholerae 01. Between 12 July and 15 August 1982, 63 of 138 suspected cholera cases were confirmed by the laboratory; 53 of these patients were seen and followed up. We were unable to identify a single, indisputable mode of transmission for cholera which was amenable to immediate control. Nonetheless, a number of factors, including exposure to water from the Tiro-Sigli River and consumption of ice, were associated with disease. Other findings bring into question the value of current practices of chlorinating dugwells and disinfecting homes with Lysol® during a cholera outbreak. The case-control approach to investigating the mode of transmision of cholera has distinct limitations when applied in endemic setting where there may not be a single predominant vehicle of transmission, or where the vehicle such as river water is used by all and is only periodically contaminated.

An invasive strain of Escherichia coli (ONT:NM) was isolated from stool specimens from 7 of 10 ill passengers who developed diarrhea during a 5-day ocean cruise. The ill passengers had shared no common exposures off the ship before or during the cruise. Three of the persons whose stools were cultured were part of a tour group of 219 persons, and a food consumption and health history questionnaire was completed by 190 members (87%) of this tour group. Forty-seven (25%) had had diarrhea during the cruise; other symptoms among those with diarrhea included nausea (72%), abdominal cramps (68%), headache (68%), chills (60%), dizziness (53%), myalgias (43%), subjective fever (36%), and vomiting (26%). The median duration of symptoms was 3 days. Eating at cold buffets on ship and eating potato salad, a buffet food item, were significantly associated with illness. No evidence of secondary spread of illness in household contacts of the ill person was found.

Only ten cases of cholera in US travelers have been reported since the current cholera pandemic began in 1961. No important risk factors were apparent from assessing the age, place of acquisition, duration or mode of travel before infection, or history of cholera vaccination of the travelers who acquired cholera. All of the patients received medical treatment and all recovered; there were no secondary cases. Nine of the ten were infected by Vibrio cholerae 01 El Tor, the strain responsible for the current pandemic. Using the number of US citizens returning to the United States by commercial air carrier from Asia, Africa, and Oceania to estimate the population at risk, we found that the chance of acquiring a reported case of cholera is less than one case per 500,000 returning travelers. ( JAMA 1982;247:2268-2269)

In September and October 1978, after a case of cholera had been discovered in southwestern Louisiana, 10 more Vibrio cholerae O-Group 1 infections were detected in four additional clusters. All 11 infected persons had recently eaten cooked crabs from five widely separated sites in the coastal marsh, and a matched-triplet case-control study showed a significant relation between cholera and eating such crabs (P = 0.007). V. cholerae O1 was isolated from estuarine water, from fresh shrimp, from a leftover cooked crab from a patient's refrigerator, and from sewage in six towns, including three without identified cases. All isolates in Louisiana and an isolate from a single unexplained case in Texas in 1973 were biotype El Tor and serotype inaba; they were hemolytic and of a phage type unique to the United States--suggesting that the organism persisted undetected along the Gulf Coast for at least five years.

To estimate the prevalence of residual paralysis from poliomyelitis in children in one area of rural Bangladesh, a survey of the amount and original cause of lameness was undertaken. The International Center for Diarrhoeal Disease Research, Bangladesh Matlab field area, which has been under demographic surveillance for 13 years, provided the study population of 25,000 children aged 5–14 years. The cause of the lameness identified for a child in the survey was based on criteria obtained from a health history questionnaire and a physical examination performed by a physician. The prevalence rate for residual paralysis of poliomyelitis estimated from the lameness survey was 0.84/1,000 children aged 5–14 years. Since lower extremity paralysis occurs in only about 80% of children with paralytic poliomyelitis, the prevalence rate for all cases of residual paralysis of poliomyelitis was calculated to be 1.05/1,000 children in this age group.