Efficacy of vitamin D supplementation in asthmatic children with vitamin D deficiency: A randomized controlled trial (ESDAC trial).

BACKGROUND: Vitamin D supplementations for asthma control had shown inconsistent results. We aimed to study efficacy and safety of vitamin D supplementation in asthmatic children who were vitamin D deficient. METHODS: This double-blind, randomized controlled trial enrolled asthmatic children of 4-12 years of age who had 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL. The participants were randomized to receive either vitamin D orally 1000 IU/d for 9 months or similar-looking placebo. The primary outcomes were the proportion of children having the Childhood Asthma Control Test (CACT) score of ≥20 at the end of the treatment and adverse effects. RESULTS: The trial included 250 children (125 in each group) with a mean age of 8.1 ± 2.3 years and 180 boys. The baseline parameters were similar between the groups, including CACT score (21.7 ± 4.2 vs 21.9 ± 3.6, vitamin D vs placebo). At the end of the study, the proportion of asthmatic children who had CACT score ≥ 20 was similar between vitamin D and placebo group (93.6% vs 92.0%, P = .625). The number of exacerbations of asthma and side effect profile was also identical between the groups. 25(OH)D levels increased significantly in the vitamin D group (18.06 ± 7.11 vs 12.03 ± 5.98 ng/mL, P < .001). The results did not change when we did subgroup analysis for children with baseline CACT score < 20 and 25(OH)D levels at the end of the study ≥20 ng/mL. CONCLUSION: Vitamin D supplementation in asthmatic children with vitamin D deficiency did not improve control of asthma.

Nutritional Status of Children with Biliary Atresia and the Role of Portoenterostomy to Improve Nutrition.

BACKGROUND: Nutritional depletion and growth stunting are present in patients with biliary atresia; "normal" nutrient and vitamin supplementation fail to correct these deficiencies. Children with this condition form the largest group for possible liver transplantation in the future; hence, stress should be laid on close attention to their nutrition. METHODS: Twenty-five patients with biliary atresia as cases and 25 age-matched children as controls were enrolled in the study from November 2010 to June 2012. Preoperatively, patients underwent standard investigations and anthropometric measurement (weight, height, and head circumference) assessment. Nutritional status (assessed with standard growth chart) was compared with control population, and children were divided into poor nutritional status and good nutritional status. Kasai's portoenterostomy was performed in all patients, and comparison was done between preoperative nutritional status with postoperative status of children and also between hepatic iminodiacetic acid (HIDA) scan-positive (patent bilioenteric pathway) children with HIDA scan-negative children. Postoperatively, after 12 weeks, the same anthropometric measurements were taken again, growth velocity (GV) was assessed, and children were divided into poor, average, and good GV. RESULTS: Nutritional status of children with biliary atresia was significantly poor than that of control group. Postoperatively, children had better nutritional status than preoperative nutritional status, especially in HIDA scan-positive children. GV was also significantly better in those children in whom postoperative HIDA scan was positive. CONCLUSION: Children with biliary atresia have poor nutritional status in comparison to normal population and require multifaceted approach to achieve adequate nutrition. Establishment of a patent bilioenteric pathway in these children improves their nutritional status and GV.

Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells.

Zinc supplementation in cell culture has been shown to inhibit various viruses, like herpes simplex virus, rotavirus, severe acute respiratory syndrome (SARS) coronavirus, rhinovirus, and respiratory syncytial virus (RSV). However, whether zinc plays a direct antiviral role in viral infections and whether viruses have adopted strategies to modulate zinc homeostasis have not been investigated. Results from clinical trials of zinc supplementation in infections indicate that zinc supplementation may be beneficial in a pathogen- or disease-specific manner, further underscoring the importance of understanding the interaction between zinc homeostasis and virus infections at the molecular level. We investigated the effect of RSV infection on zinc homeostasis and show that RSV infection in lung epithelial cells leads to modulation of zinc homeostasis. The intracellular labile zinc pool increases upon RSV infection in a multiplicity of infection (MOI)-dependent fashion. Small interfering RNA (siRNA)-mediated knockdown of the ubiquitous zinc uptake transporter ZIP1 suggests that labile zinc levels are increased due to the increased uptake by RSV-infected cells as an antiviral response. Adding zinc to culture medium after RSV infection led to significant inhibition of RSV titers, whereas depletion of zinc by a zinc chelator, N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) led to an increase in RSV titers. The inhibitory effect of zinc was specific, as other divalent cations had no effect on RSV titers. Both RSV infection and zinc chelation by TPEN led to reactive oxygen species (ROS) induction, whereas addition of zinc blocked ROS induction. These results suggest a molecular link between RSV infection, zinc homeostasis, and oxidative-stress pathways and provide new insights for developing strategies to counter RSV infection.IMPORTANCE Zinc deficiency rates in developing countries range from 20 to 30%, and zinc supplementation trials have been shown to correct clinical manifestations attributed to zinc deficiency, but the outcomes in the case of respiratory infections have been inconsistent. We aimed at understanding the role of zinc homeostasis in respiratory syncytial virus (RSV) infection. Infection of lung epithelial cell lines or primary small-airway epithelial cells led to an increase in labile zinc pools, which was due to increased uptake of zinc. Zinc supplementation inhibited RSV replication, whereas zinc chelation had an opposing effect, leading to increases in RSV titers. Increases in labile zinc in RSV-infected cells coincided with induction of reactive oxygen species (ROS). Both zinc depletion and addition of exogenous ROS led to enhanced RSV infection, whereas addition of the antioxidant inhibited RSV, suggesting that zinc is part of an interplay between RSV-induced oxidative stress and the host response to maintain redox balance.

Current antibiotic use in the treatment of enteric fever in children.

Background & objectives: Antimicrobial resistance is a major challenge in the treatment of typhoid fever with limited choices left to empirically treat these patients. The present study was undertaken to determine the current practices of antibiotic use in children attending a tertiary care hospital in north India. Methods: This was a descriptive observational study in children suffering from enteric fever as per the case definition including clinical and laboratory parameters. The antibiotic audit in hospitalized children was measured as days of therapy per 1000 patient days and in outpatient department (OPD) as antibiotic prescription on the treatment card. Results: A total of 128 children with enteric fever were included in the study, of whom, 30 were hospitalized and 98 were treated from OPD. The mean duration of fever was 9.5 days at the time of presentation. Of these, 45 per cent were culture positive with Salmonella Typhi being aetiological agent in 68 per cent followed by S. Paratyphi A in 32 per cent. During hospitalization, the average length of stay was 10 days with mean duration of defervescence 6.4 days. Based on antimicrobial susceptibility ceftriaxone was given to 28 patients with mean duration of treatment being six days. An additional antibiotic was needed in six patients due to clinical non-response. In OPD, 79 patients were prescribed cefixime and additional antibiotic was needed in five during follow up visit. Interpretation & conclusions: Based on our findings, ceftriaxone and cefixime seemed to be the first line of antibiotic treatment for typhoid fever. Despite susceptibility, clinical non-response was seen in around 10 per cent of the patients who needed combinations of antibiotics.

Impact of HIV infection and highly active antiretroviral therapy (HAART) on B cell subpopulations in children.

B-cells play an important role in defending children against various infections. In view of scare data, we undertook this prospective cohort study to describe B cell compartment in HIV infected children (<5 years of age) and the effect of HAART on B cell subpopulations. HIV infected children (<5 years) from Pediatric HIV services of the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, were recruited (April 2012-December 2015). The enrolled HIV-1 infected children (n = 59) were followed up regularly for 12 months; healthy controls (n = 51) included HIV uninfected children with no major illness. Flow cytometry was performed on fresh EDTA-treated blood samples to characterize B cell subpopulations. In HIV-infected children, marked depletion of naive (P = 0.003), non-switched memory (P = 0.02), mature (P = 0.0005), resting memory (P < 0.0001) B cells, and expansion of double negative memory (P < 0.0001), activated memory (P < 0.0001) and tissue like memory (P < 0.0001) B cells were observed as compared to healthy controls. In children started on HAART, at the end of 12 months of therapy, frequencies of non-switched memory (P = 0.04), switched memory (P = 0.01), and resting memory (P = 0.003) B cells were lower; activated memory (P = 0.04), and tissue-like memory (P = 0.0001) B cells were still higher than healthy controls. HIV infection resulted in reduced memory B cells in HIV infected children. Following HAART, there was normalization of some B cell subpopulations. The study emphasizes the need of re-vaccination in HIV infected children to maintain the memory B cell pool and adequate humoral immune response against infections.

Efficacy of Oral Zinc Supplementation in Radiologically Confirmed Pneumonia: Secondary Analysis of a Randomized Controlled Trial.

Objective: To evaluate the effect of zinc as an adjuvant therapy in radiologically confirmed pneumonia in children 2-24 months of age. Patients and Methods: We analyzed data of 212 children with pneumonia for whom chest X-ray films were available at enrollment and at least two radiologists agreed on the diagnosis of pneumonia. We compared the time to recovery in the two groups (n = 121, zinc group and n = 91, placebo group) using a Cox proportional hazards regression model. Results: Time to recovery was similar in both groups [median interquartile range: zinc, 84 h (64, 140 h); placebo, 85 h (65, 140 h)]. The absolute risk reduction for treatment failure was 5.2% (95% confidence interval: -4.8, 15.1) with zinc supplementation. Conclusion: There was no significant beneficial effect of zinc on the duration of recovery or risk of treatment failure in children with radiologically confirmed pneumonia.

Current therapies for the treatment of multidrug-resistant tuberculosis in children in India.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a serious life threatening condition affecting children as well as adults worldwide. Timely diagnosis and effective treatment, both of which are complex in children, are the prerogatives for a favorable outcome. Areas covered: This review covers epidemiology, treatment regimen and duration, newer drugs and adverse events in children with MDR-TB. Special note has been made of epidemiology and principles of treatment followed in Indian children. Expert opinion: High index of suspicion is essential for diagnosing childhood MDR-TB. If there is high probability, a child can be diagnosed as presumptive MDR-TB and started on empiric treatment in consultation with experts. However, every effort should be made to confirm the diagnosis. Backbone of an effective MDR-TB regimen consists of four 2nd line anti-TB drugs plus pyrazinamide; duration being 18-24 months. The newer drugs delamanid and bedaquiline can be used in younger children if no other alternatives are available after consultation with experts. Wider availability of these drugs should be ensured for benefit to all concerned. More research is required for development of new and repurposed drugs to combat MDR-TB. Children need to be included in clinical trials for such life-saving drugs, so that nobody is denied the benefits.

Zinc Supplementation for One Year Among Children with Cystic Fibrosis Does Not Decrease Pulmonary Infection.

BACKGROUND: Children with cystic fibrosis may have a deficiency of micronutrients, including zinc, which may affect their susceptibility to infections. There is a paucity of data on zinc supplementation among children with cystic fibrosis. We hypothesized that a pharmacologic dose of zinc administered daily for 12 months would reduce the need for antibiotics by 50%. METHODS: This double-blind randomized placebo-controlled trial was conducted among children with cystic fibrosis to assess the effect of zinc supplementation on the need for antibiotics and pulmonary function tests. The children, age 5-15 y, of either sex, received either 30-mg zinc tablets or similar looking placebo tablets daily in addition to standard care. They were followed up every month for a period of 12 months and whenever they had pulmonary exacerbations. Their serum zinc was estimated at baseline and at 12 months of enrollment. During each visit, the children underwent a pulmonary function test and sputum culture. RESULTS: Of a total of 43 children screened, 40 were enrolled, and of them, 37 completed the study. The median (interquartile range) number of days of the administration of antibiotics over 12 months of follow-up among the children receiving zinc was 42 (14-97) d. In the placebo group, it was 38 (15-70) d (P = .79). There were no significant differences in the percent-of-predicted FEV1 or change in FEV1 values at 12 months (P = .44). The number of children in whose respiratory specimens Pseudomonas was isolated was similar for the 2 groups at different time intervals. The adverse events reported were similar in the 2 groups. CONCLUSION: We did not find any significant difference in the need for antibiotics, pulmonary function tests, hospitalization, colonization with Pseudomonas, or the need for antibiotics for children with cystic fibrosis receiving zinc supplementation of 30 mg/d.

High prevalence of primary drug resistance in children with intrathoracic tuberculosis in India.

BACKGROUND: Drug susceptibility testing (DST) of Mycobacterium tuberculosis (Mtb) isolates is crucial for the effective treatment of tuberculosis. Data on DST patterns in Mtb isolates in childhood tuberculosis are scanty. AIMS: To determine drug resistance patterns in Mtb isolates from a paediatric TB cohort in North India. METHODS: 403 children aged 6 months to14 year with probable intrathoracic tuberculosis were enrolled prospectively. All were treatment-naïve. 802 ambulatory-induced sputa (IS) and 787 gastric aspirate (GA) samples were cultured in BACTEC-MGIT960 system, and DST of the Mtb isolates was undertaken using the automated BACTEC-MGIT960 SIRE kit. RESULTS: Of the 403 children, 147 (36.4%) were culture-confirmed: 132 (89.8%) isolates were Mtb and 15 (10.2%) non-tuberculous mycobacteria (NTM). Five Mtb isolates were contaminated and the remaining 127 were subjected to in-vitro drug susceptibility testing against streptomycin, isoniazid, rifampicin and ethambutol. Twenty-six (20.47%) isolates were resistant to one or more drugs, seven (5.5%) were resistant to rifampicin singly or in combination, and 11 (8.7%) were resistant to isoniazid singly or in combination. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol was detected in four (3.1%), one (0.8%), four (3.1%) and two (1.6%), respectively. Five children (3.9%) had MDR-TB; 101 (79.9%) children had Mtb isolates which were sensitive to all four drugs. CONCLUSIONS: The rifampicin and isoniazid resistance rates were much higher than those in the adult TB population in India.

Vitamin D levels in Indian children with intrathoracic tuberculosis.

BACKGROUND & OBJECTIVES: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. METHODS: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. RESULTS: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (≥ 20 ng/ml). Levels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient ( p <0.05). INTERPRETATION & CONCLUSIONS: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did.

Effect of micronutrient supplementation on treatment outcomes in children with intrathoracic tuberculosis: a randomized controlled trial.

BACKGROUND: Micronutrients play an important role in immune function. To our knowledge, there have been no comprehensive studies on the role of micronutrient supplementation in children with tuberculosis. OBJECTIVE: We assessed the effect of micronutrient supplementation in children treated with antituberculosis therapy (ATT). DESIGN: A randomized, double-blind, placebo-controlled trial that used a 2 × 2 factorial design was undertaken at 2 teaching hospitals in Delhi. Children with newly diagnosed intrathoracic tuberculosis were enrolled, and they received ATT together with daily supplementation for 6 mo with either zinc alone, micronutrients without zinc, micronutrients in combination with zinc, or a placebo. Main outcomes were weight gain and an improvement in a chest X-ray (CXR) lesion assessed at 6 mo of treatment. RESULTS: A total of 403 children were enrolled and randomly assigned. A microbiological diagnosis of tuberculosis was confirmed in 179 children (44.4%). The median (95% CI) increase in weight-for-age z score at 6 mo was not significantly different between subjects who received micronutrients [0.75 (0.66, 0.84)] and those who did not receive micronutrients [0.76 (0.67, 0.85)] and between subjects who received zinc [0.76 (0.68, 0.85)] and those who did not receive zinc [0.75 (0.66, 0.83)]. An improvement in CXR was observed in 285 children, but there was no difference between those receiving zinc and no zinc or between those receiving micronutrients and no micronutrients after 6 mo of ATT. However, children who received micronutrients had a faster gain in height over 6 mo than did those who did not receive micronutrients (height-for-age z score Δ = 0.08; P = 0.014). CONCLUSIONS: Micronutrient supplementation did not modify the weight gain or clearance of lesions on CXR in children with intrathoracic tuberculosis. However, micronutrient supplementation during treatment may improve height gain in children with intrathoracic tuberculosis. This trial was registered at clinicaltrials.gov as NCT00801606.

Induction of resistant mutants of Salmonella enterica serotype Typhi under ciprofloxacin selective pressure.

BACKGROUND & OBJECTIVES: Infection with Salmonella enterica serovar Typhi (hereafter S. Typhi) is an important public health problem in India. There has been an increase in the number of reported clinical failures to ciprofloxacin treatment but the data on possible mechanism of failure are limited. One mechanism that has been widely reported and found associated with ciprofloxacin resistance, is the mutations in target genes in QRDR (quinolone resistance determining region). It is hypothesized that mutations in DNA gyrase or topoisomerase IV result in therapeutic failure under selective pressure of antibiotic while the patient is on treatment. We undertook in vitro sequential selection studies to expose the clinical isolates of S. Typhi to different concentration of ciprofloxacin to study the role of antibiotic selective pressure in the development of mutations in QRDR. METHODS: Total 26 clinical isolates were divided in to two parts: part I included six isolates obtained from three patients with relapse of enteric fever and part II included 20 isolates with different ciprofloxacin MIC levels. For in vitro induction of mutation experiment, five S. Typhi isolates were selected which included three NAS (nalidixic acid sensitive) and 2 NAR (nalidixic acid resistant) S. Typhi. These isolates were grown under increasing concentrations of ciprofloxacin and mutations acquired in QRDR of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) were investigated by sequencing. RESULTS: For the isolates included in the part I of the study, it was found that the MIC to ciprofloxacin increased in the isolates obtained during the relapse of enteric fever as compare to the first isolate. All isolates had single mutation in gyrA gene at S83 without additional mutation in the second isolate. In the second part of the study, the nine isolates with varying MICs to ciprofloxacin also had single mutation in gyrA gene at S83 and another six had triple mutations, two mutations in gyrA gene (at S83 and D87) and one mutation in parC gene (at S80). In in vitro induction of mutation experiment, all mutated isolates showed triple mutation (two mutation in gyrA and one in parC gene) while no mutations were found in wild isolates. INTERPRETATION & CONCLUSIONS: Upon exposure to the step-wise increased concentration of ciprofloxacin, isolates become more tolerant to the ciprofloxacin and showed 2-4 fold higher MICs without new mutation after 8 µg/ml. So the accumulation of mutations under continuous ciprofloxacin pressure and tolerance of the mutant isolates led to the clinical failure. These results also suggested that there could be another mechanism responsible for resistance.

Immunologic effect of zinc supplementation in HIV-infected children receiving highly active antiretroviral therapy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: We conducted this study to assess the immunologic effect of daily 20 mg zinc supplementation for 24 weeks in HIV-infected children older than 6 months receiving highly active antiretroviral therapy (ART). METHODS: Fifty-two HIV-infected children older than 6 months in whom ART was initiated were randomized to receive either 20 mg of zinc or placebo for a period of 24 weeks. Children underwent clinical examination, anthropometry, and laboratory evaluations: CD4% and count, viral load, and serum zinc level at baseline, 12 weeks, and 24 weeks. The primary outcome evaluated was CD4% value at the end of 12 and 24 weeks of study intervention in the enrolled children. RESULTS: Of 52 children enrolled, 49 completed the study. The median CD4% value rose from 10% to 23% at 12 weeks and to 24.5% at 24 weeks in the zinc group, whereas in the placebo group, the value rose from 11% to 20% at 12 weeks and to 22% at 24 weeks (P = 0.188 for comparison between the zinc and the placebo group at 12 wk and P = 0.3 for comparison at 24 wk). The median (interquartile range) log reductions in the viral load at 12 weeks in the 2 arms were similar at 12 (P = 0.84) and 24 weeks (P = 0.43). CONCLUSIONS: Supplementation of 20 mg zinc daily for 24 weeks did not have any statistically significant effect on the increase in CD4%, decrease in viral load, anthropometric indices, and morbidity profile in HIV-infected children started on ART.

Plasma exchange for hemolytic crisis and acute liver failure in Wilson disease.

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.

Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is a leading cause of death; in India, an estimated 370,000 children die of pneumonia each year. Zinc has multiple influences on the immune response to infections. Zinc supplementation has been shown to prevent diarrhea and pneumonia in children. However, zinc's therapeutic effect on respiratory infections is less clear. OBJECTIVE: We evaluated the role of zinc as an adjunct to antibiotics in the treatment of children hospitalized for severe or very severe pneumonia. DESIGN: In this randomized, double-blind, placebo-controlled trial, we enrolled 550 children aged 2-24 mo with severe or very severe pneumonia. Within each hospital and pneumonia-severity stratum, children were randomly assigned to receive zinc (20 mg elemental zinc/d) or a placebo in addition to antibiotics and supportive care. RESULTS: The time to recovery from severe or very severe pneumonia was similar in both groups (HR: 0.98; 95% CI: 0.82, 1.17). In the stratified analysis, zinc was shown to be efficacious in reducing the time to recovery in children with very severe pneumonia (HR: 1.52; 95% CI: 1.03, 2.23); however, the effect was no longer statistically significant after adjustment for differences in severely underweight children in the 2 groups. CONCLUSIONS: This study showed no overall benefit of the addition of zinc to antibiotics in reducing the time to recovery from pneumonia but showed a possible benefit of zinc supplementation in a subgroup of children with very severe pneumonia. Additional research is needed in specific subgroups such as children with very severe pneumonia. This trial was registered at http://www.controlled-trials.com as ISRCTN48954234.

Peripheral neuropathy in cystic fibrosis: a prevalence study.

BACKGROUND: Information on peripheral neuropathy in children with cystic fibrosis is scanty. The etiology can be multifactorial (micronutrient deficiency, chronic hypoxia, impaired glucose tolerance, immunological, vasculopathic, critical illness). METHODS: Forty five cystic fibrosis children aged 1-18 years on vitamin E supplementation for at least 6 months underwent detailed neurological examination, serum vitamin E, vitamin B12, folate, copper levels and detailed nerve conduction studies. RESULTS: The mean age of the study population was 8.35 years (±4.9 years) with 62.2% being males. Overall 22 out of 45 (48.88%,CI: 33.7-64.2) had electrophysiological evidence of peripheral neuropathy which was predominantly axonal (86.4%), sensory (50%), and polyneuropathy (95.45%). There was no significant association between status of serum micronutrients and electrophysiological evidence of peripheral neuropathy. CONCLUSION: Patients with cystic fibrosis have electrophysiological evidence of peripheral neuropathy (predominantly axonal, sensory and polyneuropathy). There is significant association of higher chronological age with occurrence of peripheral neuropathy.

Supportive care of a critically ill child.

The goal of pediatric intensive care is early identification, severity assessment and resuscitation of critical patients by utilizing standardized protocols. The primary or precipitating disorder should be the focus of attention and specific intervention. But in order to provide holistic care to a patient, due attention should also be rendered to supportive care. Monitoring of sick children in PICU is an essential part of management. Various monitoring technologies add to the clinical monitoring but cannot replace clinical monitoring. The treating team should follow a checklist to ensure all aspects of supportive care are taken care of in every patient. Due attention should be paid to glucose control, skin and eye care, oral hygiene, prevention of stress ulcer, care of various lines and catheters and prevention of nosocomial infections.

Status epilepticus.

Status epilepticus is a common neurological emergency in childhood and associated with significant morbidity and mortality. Status epilepticus (SE) has been defined as continuous seizure activity lasting more than 30 min or 2 or more seizures in this duration without gaining consciousness between them. However, the operational definition has brought the time down to 5 min. Management can be broadly divided into initial stabilization, seizure termination, and evaluation and treatment of the underlying cause. Diagnostic evaluation and seizure control should be achieved simultaneously to improve outcome. Seizure termination is achieved by pharmacotherapy. Benzodiazepines are the first line drugs for SE. Commonly used drugs include lorazepam, diazepam, and midazolam. In children without an IV access, buccal or nasal midazolam or rectal diazepam can be used. Phenytoin as a second line agent is usually indicated when seizure is not controlled after one or more doses of benzodiazepines. If the seizures continue to persist, valproate, phenobarbitone or levetiracetam is indicated. Midazolam infusion is useful in refractory status epilepticus. Thiopentone, propofol or high dose phenobarbitone are considered for treatment of refractory status epilepticus. Prolonged SE is associated with higher morbidity and mortality. Long term neurological sequelae include epilepsy, behavioural problems, cognitive decline, and focal neurologic deficits.