A randomized controlled trial of hospital versus home based therapy with oral amoxicillin for severe pneumonia in children aged 3 - 59 months: The IndiaCLEN Severe Pneumonia Oral Therapy (ISPOT) Study.

BACKGROUND: Pneumonia is the leading cause of child mortality under five years of age worldwide. For pneumonia with chest indrawing in children aged 3-59 months, injectable penicillin and hospitalization was the recommended treatment. This increased the health care cost and exposure to nosocomial infections. We compared the clinical and cost outcomes of a seven day treatment with oral amoxicillin with the first 48 h of treatment given in the hospital (hospital group) or at home (home group). METHODS: We conducted an open-label, multi-center, two-arm randomized clinical trial at six tertiary hospitals in India. Children aged 3 to 59 months with chest indrawing pneumonia were randomized to home or hospital group. Clinical outcomes, treatment adherence, and patient safety were monitored through home visits on day 3, 5, 8, and 14 with an additional visit for the home group at 24 h. Clinical outcomes included treatment failure rates up to 7 days (primary outcome) and between 8-14 days (secondary outcome) using the intention to treat and per protocol analyses. Cost outcomes included direct medical, direct non-medical and indirect costs for a random 17% subsample using the micro-costing technique. RESULTS: 1118 children were enrolled and randomized to home (n = 554) or hospital group (n = 564). Both groups had similar baseline characteristics. Overall treatment failure rate was 11.5% (per protocol analysis). The hospital group was significantly more likely to fail treatment than the home group in the intention to treat analysis. Predictors with increased risk of treatment failure at any time were age 3-11 months, receiving antibiotics within 48 h prior to enrolment and use of high polluting fuel. Death rates at 7 or 14 days did not differ significantly. (Difference -0.0%; 95% CI -0.5 to 0.5). The median total treatment cost was Rs. 399 for the home group versus Rs. 602 for the hospital group (p < 0.001), for the same effect of 5% failure rate at the end of 7 days of treatment in the random subsample. CONCLUSIONS: Home based oral amoxicillin treatment was equivalent to hospital treatment for first 48 h in selected children of chest indrawing pneumonia and was cheaper. Consistent with the recent WHO simplified guidelines, management with home based oral amoxicillin for select children with only fast breathing and chest-indrawing can be a cost effective intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01386840, registered 25th June 2011 and the Indian Council of Medical Research REFCTRI/2010/000629.

Coordination polymer: synthesis, spectral characterization and thermal behaviour of starch-urea based biodegradable polymer and its polymer metal complexes.

A starch-urea-based biodegradable coordination polymer modified by transition metal Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) was prepared by polycondensation of starch and urea. All the synthesized polymeric compounds were characterized by Fourier transform-infrared spectroscopy (FT-IR), (1)H-NMR spectroscopy, (13)C-NMR spectroscopy, UV-visible spectra, magnetic moment measurements, differential scanning calorimeter (DSC), and thermogravimetric analysis (TGA). The results of electronic spectra and magnetic moment measurements indicate that Mn(II), Co(II), and Ni(II) complexes show octahedral geometry, while Cu(II) and Zn(II) complexes show square planar and tetrahedral geometry, respectively. The thermogravimetric analysis revealed that all the polymeric metal complexes are more thermally stable than the parental ligand. In addition, biodegradable studies of all the polymeric compounds were also carried out through ASTM standards of biodegradable polymers by CO(2) evolution method.

An investigation into the avoidability of adverse drug reactions using the LAAT and modified Hallas tools.

An adverse drug reactions avoidability tool called the Liverpool ADR avoidability assessment tool (LAAT) was recently developed (for research purposes), and subsequently validated with mixed interrater reliability (IRR). We investigated the comparative IRR of this tool in an inpatient cohort to ascertain its practical application in this setting.The patient population was comprised of 44 ADR drug pairs drawn from an observational prospective cohort of patents with ADR attending a Weill Cornell Medicine-affiliated tertiary medical Centre in Doha Qatar (Hamad General Hospital). Using the LAAT, and modified Hallas tools, 4 independent raters (2 Clinical Pharmacologists, and 2 General Physicians) assessed and scored the 44 ADR-drug pairs. Agreement proportions between the rating pairs were evaluated as well individual/overall kappa statistics and intraclass correlation coefficients. We evaluated the weight of each of the 7 questions on the LAAT tool to ascertain its determinative role.Across 44 ADR-drug pairs, the overall median Fleiss kappa using the LAAT, and modified Hallas tools were 0.67 (interquartile range (IQR) 0.55, 0.76), 0.36 (IQR, 0.23-0.71) respectively. The overall percentage pairwise agreement with the LAAT and modified Hallas tools were 78.5%, and 62.2% respectively. Exact pairwise agreement occurred in 37 out of 44 (range 0.71-1), and 27 of 44 (0.53-0.77) ADR-drug pairs using the LAAT and modified Hallas tools respectively. Using the LAAT tool, the overall intraclass correlation coefficient was 0.68 (CI 0.55, 0.79), and 0.37 (CI 0.22, 0.53) with the modified Hallas tool.We report a higher proportion of "possible" and "definite" avoidability outcomes of adverse drug reactions compared with the modified Hallas, or that reported by developers of the LAAT tool. Although initially developed for research purposes, our report has suggested for the first time a potential applicability of this tool in clinical environment as well.

Acute lower respiratory tract infections in children.

Acute lower respiratory tract infection (ALRTI) is a common illness, but there have been relatively few studies of the bacterial etiology in developing countries. Nasopharyngeal aspirates of 70 children under 10 years of age with ALRTI were cultured for aerobic bacterial pathogens. Klebsiella pneumoniae was the commonest organism (32.2%) isolated followed by S. pneumoniae (10%), E. coli (10%), P. aeruginosa (5.7%), S. aureus (2.8%) and H. influenzae (1.4%). There were significantly more bacterial pathogens isolated in children <1 year of age (73.7%) than in those > 1 year of age (56.2%) (P=0.03). A shift in spectrum from Gram-positive cocci to Gram negative bacilli in ALRTI was observed in our study.

Adenosine deaminase and C-reactive protein in cerebrospinal fluid for differential diagnosis of tubercular meningitis in children.

Adenosine deaminase and C-reactive protein in CSF were assessed in 72 cases of Tubercular meningitis, 24 cases of partially treated pyogenic meningitis, 20 cases of Aseptic meningitis and 8 cases of febrile seizures. Mean Adenosine deaminase value was 12.12±3.13 IU/L for Tubercular meningitis group. It was significantly higher (p<0.001) as compared to partially treated pyogenic meningitis (5.39±2.70 IU/L) and aseptic meningitis (1.92±0.56 IU/L) groups. A combination of clinical criteria along with biochemical test of Adenosine deaminase and C-reactive protein in CSF increased the sensitivity of diagnosing Tubercular meningitis and differentiating it from other forms of meningitis at an early stage.

Pediatric Appropriate Evaluation Protocol for India (PAEP-India): Tool for Assessing Appropriateness of Pediatric Hospitalization.

OBJECTIVE: To develop and assess Pediatric Appropriateness Evaluation Protocol for India (PAEP-India) for inter-rater reliability and appropriateness of hospitalization. DESIGN: Cross-sectional study. SETTING: The available PAEP tools were reviewed and adapted for Indian context by ten experienced pediatricians following semi-Delphi process. Two PAEP-India tools; newborn (≤28 days) and children (>28 days-18 years) were developed. These PAEP-India tools were applied to cases to assess appropriateness of admission and inter-rater reliability between assessors. PARTICIPANTS: Two sets of case records were used: (i) 274 cases from five medical colleges in Delhi-NCR [≤28 days (n=51); >28 days to 18 years (n=223)]; (ii) 622 infants who were hospitalized in 146 health facilities and were part of a cohort (n= 30688) from two southern Indian states. INTERVENTIONS: Each case-record was evaluated by two pediatricians in a blinded manner using the appropriate PAEP-India tools, and 'admission criteria' were categorized as appropriate, inappropriate or indeterminate. OUTCOME MEASURES: The proportion of appropriate hospitalizations and inter-rater reliability between assessors (using kappa statistic) were estimated for the cases. RESULTS: 97.8% hospitalized cases from medical colleges were labelled as appropriate by both reviewers with inter-rater agreement of 98.9% (k=0.66). In the southerm Indian set of infants, both reviewers labelled 80.5% admissions as appropriate with inter-rater agreement of 96.1% (k= 0.89). CONCLUSIONS: PAEP-India (newborn and child) tools are simple, objective and applicable in diverse settings and highly reliable. These tools can potentially be used for deciding admission appropriateness and hospital stay and may be evaluated later for usefulness for cost reimbursements for insurance proposes.

Alpha-1 antitrypsin deficiency among Indian children with liver disorders.

AIMS: To determine the frequency of alpha-1 antitrypsin (AAT) deficiency in children with chronic liver disease (CLD) and neonatal cholestasis syndrome (NCS). METHODS: All children with NCS (n=23) or CLD (n=35) attending the Pediatric Gastroenterology Clinic between November 2003 and July 2005 were screened for AAT deficiency using phenotyping through isoelectric focusing of plasma. RESULTS: Of the 58 children studied, 57 had normal PiMM phenotype. One child with CLD had the M1E type of normal variant. None of the patients had the abnormal phenotype PiZZ. CONCLUSION: AAT deficiency is infrequent among children with CLD and NCS in our region.

Comparison of different diagnostic techniques in Plasmodium falciparum cerebral malaria.

BACKGROUND & OBJECTIVES: Plasmodium falciparum cerebral malaria remains a major health problem in India. The efficacy of treatment of cerebral malaria lies in its early diagnosis through rapid diagnostic methods. ParaSights-F test detects HRP-2 antigen secreted by parasitised red blood cells and quantitative buffy coat assay (QBC) is examination of buffy coat for the presence of malarial parasite stained with acridine orange. This study was performed to evaluate the effectiveness of ParaSight-F test and QBC assay as diagnostic methods in the patients of cerebral malaria. METHODS: Fifty clinically diagnosed patients of cerebral malaria were included in the study. ParaSight-F test, QBC and conventional blood smear examination was done. Patients who were in coma and there were no obvious features of bacterial or viral etiology were investigated for cerebral malaria by these diagnostic methods. RESULTS: ParaSight-F test, QBC and peripheral blood smears were examined. Patients were followed-up for signs of clinical recovery. ParaSight-F test was positive in 47 patients, QBC in 46 while blood smear examination was positive in 28 cases. INTERPRETATION & CONCLUSION: Sensitivity and specificity of ParaSight-F test were found to be 96.6 and 94% while QBC showed 97.8 and 100% respectively. ParaSight-F test and QBC were found to be novel methods for diagnosis of cerebral malaria especially in the cases where diagnosis can not be made by conventional blood smear examination due to low parasitaemia. These rapid diagnostic methods help in early therapeutic intervention.

Colonization of peripheral intravascular catheters with biofilm producing microbes: Evaluation of risk factors.

BACKGROUND: Biofilms often colonize catheters and contribute to catheter-related septicemia. However, predictors of catheter colonization by biofilms remain poorly defined. The aim of this study was to evaluate clinical factors that may be associated with biofilm colonization of catheters. MATERIALS AND METHODS: A total of 54 isolates colonizing the peripheral intravascular catheters (IVCs) were studied and their biofilm production ability was analyzed by the tube method and antimicrobial susceptibility was also done. A detailed clinical history and examination was done of each subject to know age, sex, duration of use of IVCs, site of IVCs, swelling/purulence around the IVCs, number of attempts to install the catheter, and duration of hospital stay. RESULTS: 44 (81.4%) out of 54 isolates colonizing the catheters showed biofilm formation. Biofilm formations were significantly associated with duration of hospital stay of more than 7 days [odds ratio (OR) = 6.6; 95% confidence interval (CI) = 1.3-34; P value (P) = 0.02], multiple attempts to install the catheter (OR=7; CI=1.5-31.8; P=0.01), and multidrug resistance (OR=9.5; CI=1.8 - 51.1: P=0.008). Klebsiella pneumoniae and Candida spp. comprised most of the biofilm-producing isolates. The overall susceptibility to antimicrobials was low among biofilm-producing compared to nonbiofilm-producing microbes. CONCLUSION: The results of this study suggest that evaluation of predictors of biofilm production is important in order to understand, prevent or manage biofilm colonization of IVCs.

Efficacy of tyndalized Lactobacillus acidophilus in acute diarrhea.

OBJECTIVE: A double-blind randomized controlled-trial was done to evaluate the efficacy of tyndalized Lactobacillus acidophilus in acute diarrhea. METHODS: All children from 6 months to 12 years with acute diarrhea were included. Lactobacillus acidophilus/placebo was given to the children for 3 days with ORS and feeds. Intake-output was recorded 4 hourly. Of the 98 children, 48 received lactobacillus and 50 the placebo. RESULTS: ORS consumed, frequency of stools, duration of diarrhea, time for rehydration, hospital stay, weight gain and IVF needed were comparable in the two study groups. There were 4 treatment failures in the lactobacillus group and none in the placebo group (OR 0.92, 95%CI 0.84-0.99). In the rotaviral diarrhea and in those who had diarrhea of less then 60 hours the difference did not reach statistical significance. CONCLUSION: There is no significant benefit of tyndalized Lactobacillus acidophilus in acute diarrhea.