In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

A clinical tool to predict failed response to therapy in children with severe pneumonia.

Severe pneumonia in children under 5 years of age continues to be an important clinical entity with treatment failure rates as high as 20%. Where severe pneumonias are common, predictive tools for treatment failure like chest radiography and pulse oximetry are not available or affordable. Thus, there is a need for development of simple, accurate and inexpensive clinical tools for prediction of treatment failure. Using clinical, chest radiographic and pulse oximetry data from 1702 children recruited in the Amoxicillin Penicillin Pneumonia International Study (APPIS) trial we developed and validated a simple clinical tool. For development, a randomly derived development sample (n = 889) was used. The tool which was based on the results of multivariate logistic regression models was validated on a separate sample of 813 children. The derived clinical tool in its final form contained three clinical predictors: age of child, excess age-specific respiratory rate at baseline and at 24 hr of hospitalization. This tool had a 70% and 66% predictive accuracy in the development and validation samples, respectively. The tool is presented as an easy-to-use nomogram. It is possible to predict the likelihood of treatment failure in children with severe pneumonia based on clinical features that are simple and inexpensive to measure.

Comparison of diagnostic accuracy of non-invasive tests for Helicobacter pylori infection in children.

OBJECTIVE: To compare urea breath and stool antigen in children, with histological diagnosis for Helicobacter pylori (H.pylori) infection. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: From June 2005 to December 2005 carried out at KRL Hospital, Islamabad and Children Hospital, PIMS, Islamabad. PATIENTS AND METHODS: Children between 3 and 15 years of age reporting in pediatric outpatient department with upper gastrointestinal symptoms were included. All the participating children underwent an upper gastrointestinal endoscopy and 3 tests namely: histopathological identification of H. pylori (the traditional gold standard), urea breath test and stool antigen test were carried out on each child. The sensitivity, specificity, and positive predictive values were calculated for each noninvasive test used in the study. RESULTS: A total of 54 patients completed the study with a mean age of 8.2 years. On histological examination, 72% (39) were positive for H. pylori infection. On gross endoscopic examination, only 9 patients had signs of gastritis as compared to 39 histological positives. The sensitivity, specificity and positive predictive value of stool antigen test were: 77%, 73% and 89% respectively whereas the same for urea breath test were: 79%, 80% and 91% respectively. CONCLUSION: Both the noninvasive tests were found to be sensitive and specific as compared with histological identification, for the diagnosis of H. pylori in our pediatric population. The accuracy of urea breath test was better than the stool antigen test but later was easier to perform and could fulfill the criteria for a rapid bedside diagnostic test.

Brief hospitalization and pulse oximetry for predicting amoxicillin treatment failure in children with severe pneumonia.

OBJECTIVE: In settings with limited assessment tools, we sought to determine whether early clinical signs and symptoms and blood oxygen saturation would predict amoxicillin treatment failure in children with severe pneumonia (as defined by the World Health Organization). METHODS: Data were from a previously reported, multinational trial of orally administered amoxicillin versus injectable penicillin for the treatment of World Health Organization-defined severe pneumonia in children 3 to 59 months of age. We assessed all 857 participants assigned randomly to the experimental amoxicillin arm. Six multivariate logistic regression models were created and evaluated for their ability to predict failure after 48 hours of therapy. Regression models included vital signs, symptoms, and laboratory data collected at baseline and after 12 or 24 hours of observation. Oxygen saturation data were included in 3 models. RESULTS: Clinical treatment failure occurred for 18% of children. Younger age, increased initial respiratory rate, and baseline hypoxia predicted treatment failure in all models. Data available after 24 hours improved the ability to predict failure compared with data available at baseline or 12 hours. The inclusion of oximetry data improved the predictive ability at baseline, 12 hours, and 24 hours. The ability to predict failure after 12 hours of observation with oximetry data was similar to the predictive ability after 24 hours without pulse oximetry data. CONCLUSIONS: Assessment of clinical parameters at presentation and after 24 hours improved the ability to predict clinical failure of oral amoxicillin therapy, compared with assessment at presentation alone or at presentation and after only 12 hours, for children with World Health Organization-defined severe pneumonia.

Clinical outcome in children hospitalized with complicated measles.

OBJECTIVE: To determine the association of clinical outcome of measles in children with demographic profile and complications. DESIGN: A cross-sectional analytical study. PLACE AND DURATION OF STUDY: Isolation ward, The Children's Hospital, Pakistan Institute of Medical Sciences (PIMS), from January 2003 to August 2004. PATIENTS AND METHODS: Detailed history and physical examination of all the hospitalized patients with complications of measles was filled in case report form. Immunization cards were assessed for measles vaccination status. Data was analyzed by using SPSS version 10 software. The clinical outcome of measles was compared with demographic profile and complications by using Chi-square test and p-values were obtained. RESULTS: Two hundred and five hospitalized patients with complications of measles were studied. There were 61.5% males. Mean age was 46.1 months and 57% patients were vaccinated against measles. Malnourished patients were 71.2% and had a longer hospital stay (p=0.010). Pneumonia (40.0%) and diarrhoea (38.5%) were the commonest complications. Seven children died. Mortality was significantly associated with younger age (p=0.04), unvaccinated status (p=0.04) and presence of encephalitis (p=0.00001). CONCLUSION: The most common complications of measles are pneumonia and diarrhoea with dehydration requiring hospitalization. Malnourished children experience more complications and have longer hospital stay. Mortality is significantly associated with infancy, unvaccinated status and encephalitis. A second dose of measles should be introduced at 15 months of age.

Serum zinc levels and effects of oral supplementation in pregnant women.

OBJECTIVE: To evaluate the effects of oral zinc supplementation on the serum zinc levels of pregnant women. DESIGN: Experimental (double blinded randomized controlled trial). PLACE AND DURATION OF STUDY: PIMS and KRL Hospital, Islamabad, and community in tehsil Kahuta from April 2003 to April 2004. PATIENTS AND METHODS: Pregnant women of 10 to 16 weeks gestation were invited to enter the study on their booking visit. A sample size of 125 in each group was calculated. After taking an informed consent, they were assigned to control or test group by simple random sampling technique. A detailed questionnaire was filled-up by trained staff and initial evaluation along with serum zinc samples was collected. The subjects were given either zinc sulphate powder, equivalent to 20 mg elemental zinc, or were given placebo treatment along with routine supplements. These patients were followed up throughout the pregnancy by health care providers and their compliance was monitored. At delivery, serum samples were again collected for zinc estimation. The data was entered on computer, cleaned and analyzed. Paired t-test was used for comparison of means. RESULTS: The data of 242 subjects was analyzed at the end of the study. The mean age of the study participants was 25.7 +/- 4.8 years (range 16 to 40). Both the groups were similar in other demographic variables as socioeconomic status, education, BMI, height and weight. One-third of the patients had serum zinc levels below 64 microg/dl at the start of the study. A 128 pairs of pre and post-serum zinc levels were analyzed in the two groups (64 pairs in each group) to compare the means. The zinc supplemented women showed a mean increase of 14.7 microg/dl (95% CI 5-23) (P = 0.002). On the other hand the non-supplemented group showed an actual decrease in the serum zinc level which, however, did not reach statistical significance (P = 0.47). CONCLUSION: Oral zinc supplementation of pregnant women with 20 mg elemental zinc was effective in raising the serum levels of zinc. It is suggested that supplementation trials with larger dose of zinc should be carried out.

Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study.

BACKGROUND: Injectable penicillin is the recommended treatment for WHO-defined severe pneumonia (lower chest indrawing). If oral amoxicillin proves equally effective, it could reduce referral, admission, and treatment costs. We aimed to determine whether oral amoxicillin and parenteral penicillin were equivalent in the treatment of severe pneumonia in children aged 3-59 months. METHODS: This multicentre, randomised, open-label equivalency study was undertaken at tertiary-care centres in eight developing countries in Africa, Asia, and South America. Children aged 3-59 months with severe pneumonia were admitted for 48 h and, if symptoms improved, were discharged with a 5-day course of oral amoxicillin. 1702 children were randomly allocated to receive either oral amoxicillin (n=857) or parenteral penicillin (n=845) for 48 h. Follow-up assessments were done at 5 and 14 days after enrollment. Primary outcome was treatment failure (persistence of lower chest indrawing or new danger signs) at 48 h. Analyses were by intention-to-treat and per protocol. FINDINGS: Treatment failure was 19% in each group (161 patients, pencillin; 167 amoxillin; risk difference -0.4%; 95% CI -4.2 to 3.3) at 48 h. Infancy (age 3-11 months; odds ratio 2.72, 95% CI 1.95 to 3.79), very fast breathing (1.94, 1.42 to 2.65), and hypoxia (1.95, 1.34 to 2.82) at baseline predicted treatment failure by multivariate analysis. INTERPRETATION: Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia treatment in controlled settings. Potential benefits of oral treatment include decreases in (1) risk of needle-borne infections; (2) need for referral or admission; (3) administration costs; and (4) costs to the family.