Threshold of Inotropic Score and Vasoactive-Inotropic Score for Predicting Mortality in Pediatric Septic Shock.

OBJECTIVE: To determine the threshold of the inotropic score (IS) and vasoactive-inotropic score (VIS) for predicting mortality in pediatric septic shock. METHOD: This retrospective cohort study included children aged 1 mo to 13 y with septic shock, requiring vasoactive medication. The area under curve receiver operating characteristic (AUROC) was calculated using mean IS and mean VIS to predict PICU mortality, and Youden index cut points were generated. Sensitivity, specificity, and binary regression analysis were performed. RESULTS: A total of 176 patients were enrolled (survivor, n = 72, 41% and nonsurvivor, n = 104, 59%). For predicting the PICU mortality, AUROC (95% CI) of IS was 0.80 (0.74-0.86) [sensitivity of 88.5 (80.7-94) and specificity of 58.3 (46.1-69.8)] and AUROC of VIS was 0.88 (0.82-0.92) [sensitivity of 83.7 (75.1-90.2) and specificity of 80.6 (69.5-89)]. The respective cutoff scores of IS and VIS were 28 and 42.5. On regression analysis (adjusted odds ratio, 95% CI), illness severity (PRISM-III) (1.12, 1.05-1.12), worst lactate value (1.31, 1.08-1.58), IS (> 28) (3.98, 1.24-12.80), and VIS (> 42.5) (4.66, 1.57-13.87) independently predicted the PICU mortality (r2 = 0.625). CONCLUSION: Threshold of inotropic score (> 28) and vasoactive-inotropic score (> 42.5) were independently associated with PICU mortality. In addition to IS and VIS, severity and worst lactate value independently predicted septic shock mortality in PICU.

Modified Schwartz formula and 99mTc-DTPA plasma clearance methods to calculate glomerular filtration rate in critically ill children.

BACKGROUND: Studies comparing the modified Schwartz formula with measured GFR (m-GFR) are lacking in critically ill children. METHODS: This prospective cohort study enrolled children aged 1 month to 12 years, within 24 h of admission. m-GFR measured by technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) and calculated by Russell's two-sample slope-intercept method. Serum creatinine was estimated by modified Jaffe method and estimated GFR (e-GFR) calculated by modified Schwartz formula. The primary outcome was to find agreement between the two methods. Bias, precision, and accuracy were calculated. Secondary outcomes were the incidence of AKI (by p-RIFLE criteria) and the difference between the two methods to diagnose AKI. RESULTS: A total of 208 pairs were analyzed. e-GFR showed good agreement with m-GFR with a mean bias of -4.37 ml/min/1.73 m2 and precision (SD of bias) of 33.07, 95% limit of agreement -69.18 to 60.45, and intraclass correlation of 74% (95%CI 66-80%, P < 0.001). e-GFR underestimated m-GFR by 19.8% (95% CI 7.9-31.7%). Accuracy of e-GFR values within 10%, 20%, and 30% of m-GFR were 68.3%, 72.6%, and 78.8%, respectively. Incidence of AKI within 24 h was 60.1% by e-GFR and 54.3% by m-GFR (kappa 0.569, P < 0.001; sensitivity of 85.8%, 95%CI (78-91.7%). CONCLUSIONS: The modified Schwartz formula shows good agreement with 99mTc-labeled DTPA double plasma sample clearance method for calculating GFR in critically ill children aged 1 month to 12 years. The underestimation of GFR should be kept in mind while applying the formula at the bedside in PICU. TRIAL REGISTRATION: Protocol accessible at Clinical Trial Registry of India (CTRI) www.ctri.nic.in . (Trial Registered Prospectively and Registration No. CTRI/2017/10/010014) ([Registered on: 06/10/2017] Trial Registered Prospectively.) (Title "Measured glomerular filtration rate using Diethylenetriaminepentaacetic acid (DTPA) renal scan versus estimated glomerular filtration rate using modified Schwartz formula in critically ill children: A prospective observational, analytical study."). A higher resolution version of the Graphical abstract is available as Supplementary information.

Prospective Cohort Study on Cumulative Fluid Balance and Outcome in Critically Ill Children Using a Restrictive Fluid Protocol.

OBJECTIVE: To study the association of cumulative fluid balance and clinical outcomes in a pediatric intensive care unit (PICU) practicing restrictive fluid protocol. METHODS: In this prospective cohort study, children aged less than 13 y admitted for more than 48 h were screened. Children with unstable hemodynamics throughout the stay were excluded. Fluid balance was calculated by percentage fluid overload (%FO) for the first 7 d. Patients were divided into positive fluid and negative fluid balance groups. The primary outcome was all-cause 28-d mortality. RESULTS: A total of 888 patients (positive fluid balance group = 531, negative fluid balance group = 357) were analyzed. Mean (SD) cumulative %FO was 1.52 (0.67) vs. -1.18 (0.71), p = < 0.001, and minimum and maximum cumulative %FO were -3.0% and 3.1%, respectively. There was no significant difference in all-cause 28-d mortality between the two groups (n = 104/531, 19.6% vs. n = 60/357, 16.8%, RR = 1.17, 95% CI 0.87 to 1.55; p = 0.29). There was no difference in organ dysfunction [mean (SD) sequential organ failure assessment (SOFA) score 3.3 (0.7) vs. 3.3 (0.6)], acute kidney injury (65% vs. 63.6%), need for renal replacement therapy (14% vs. 13%), and duration of ventilation (median, IQR 4, 2-6 vs. 4, 2-6 d). Longer stay in PICU (5, 3-9 vs. 4, 3-7 d; p = 0.014) and in hospital (8, 5-11 vs. 7, 4-10 d; p = 0.007) were noted in the positive fluid balance group. CONCLUSION: Cumulative fluid balance within 3% using restrictive fluid protocol was not associated with a significant difference in PICU mortality and morbidity.

Early Goal-Directed Therapy With and Without Intermittent Superior Vena Cava Oxygen Saturation Monitoring in Pediatric Septic Shock: A Randomized Controlled Trial.

OBJECTIVE: To compare early goal-directed therapy (EGDT) 'with' and 'without' intermittent superior vena cava oxygen saturation (ScvO2) monitoring in pediatric septic shock. DESIGN: Open label randomized controlled trial. SETTING: Pediatric intensive care unit in a tertiary care center. PARTICIPANTS: Children aged 1 month to 12 year with septic shock. INTERVENTION: Patients not responding to fluid resuscitation (up to 40 mL/kg) were randomized to EGDT 'with' (n=59) and 'without' (n=61) ScvO2 groups. Resuscitation was guided by ScvO2 monitoring at 1-hour, 3-hour, and later on six-hourly in the 'with' ScvO2 group, and by clinical variables in the 'without' ScvO2 group. OUTCOME: Primary outcome was all-cause 28-day mortality. Secondary outcomes were time to and proportion of patients achieving therapeutic endpoints (at 6 hours and PICU stay), need for organ supports, new organ dysfunction (at 24 hours and PICU stay), and length of PICU and hospital stay. RESULTS: The study was stopped after interim analysis due to lower mortality in the intervention group. There was significantly lower all-cause 28-day mortality in EDGT with ScvO2 than without ScvO2 group [37.3% vs. 57.5%, adjusted hazard ratio 0.57, 95%CI 0.33 to 0.97, P=0.04]. Therapeutic endpoints were achieved early in 'with' ScvO2 group [mean (SD) 3.6 (1.6) vs. 4.2 (1.6) h, P=0.03]. Organ dysfunction by sequential organ assessment score during PICU stay was lower in 'with' ScvO2 group [median (IQR) 5 (2,11) vs. 8 (3,13); P=0.03]. There was no significant difference in other secondary outcomes. CONCLUSIONS: EGDT with intermittent ScvO2 monitoring was associated with reduced mortality and improved organ dysfunction in pediatric septic shock.

A Prospective Cohort Study on Serum Sodium and Clinical Outcome in Pediatric Nontraumatic Coma.

OBJECTIVE: To study the serum sodium level and clinical outcome in pediatric nontraumatic coma. METHODS: A prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from September 2015 to June 2016. Children aged < 13 y with nontraumatic coma [modified-Glasgow Coma Scale (m-GCS) score ≤ 8 or fall of ≥ 3 from baseline within 24 h of admission] were included. Children who received intravenous fluids for > 24 h, those with developmental delay, or died within 24 h of admission were excluded. The serum sodium profile (mEq/L) in the first 72 h and clinical outcome [mortality, length of stay in mechanical ventilation, PICU, and hospital] were studied. RESULTS: Eighty patients [Died n = 26 and Survived n = 54] were enrolled. Median [interquartile range (IQR)] age and m-GCS were 21 (4-78) mo and 9 (7-11), respectively. The mean [standard deviation (SD)] Pediatric Risk of Mortality-III (PRISM-III) was 17.7 (4). The most common etiology was acute central nervous system (CNS) infections (30%, n = 24) followed by an intracranial bleed (11.3%, n = 9). Mean (Standard error, SE) sodium levels and fluctuation of serum sodium from baseline up to 72 h were similar between nonsurvivors and survivors [140.8 (1.3) vs. 139.6 (0.8), p = 0.421] and [1.2 (0.3) vs. 0.8 (0.2), p = 0.307], respectively. On multivariate analysis, the need for vasoactive therapy was an independent predictor of mortality [adjusted odds ratio = 20.78, 95% CI 4.24-101.85, p = < 0.001, R2 = 0.62]. CONCLUSION: Mean serum sodium within normal range and fluctuation of serum sodium of 0.8 to 1.2 mEq/L over 72 h was not associated with poor outcomes in pediatric nontraumatic coma. Vasoactive therapy was an independent predictor of mortality.

Prospective Inverse Probability of Treatment-Weighting Analysis of the Clinical Outcome of Red Blood Cell Transfusion Practice in Critically Ill Children.

OBJECTIVE: To study the clinical outcomes of red blood cell (RBC) transfusion practices in critically ill children. METHOD: This prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from March-2015 to January-2018. Inverse probability of treatment weighting (IPTW) using propensity score analysis was used. Children aged 1 mo to 12 y admitted to the PICU were screened. Patients were classified into 'transfused' and 'nontransfused', based on whether they received a transfusion or not. Patients with hematological malignancies, or immunosuppressant drugs, or those who received repeated transfusions, or received transfusion before admission, or died within 24 h were excluded. The primary outcome was all-cause 28 d mortality. Secondary outcomes were new-onset organ dysfunction, mechanical ventilation duration, and length of PICU and hospital stay. RESULTS: A total of 1014 patients [transfused = 277; nontransfused = 737) were included. In IPTW analysis, the risk of all-cause 28 d mortality was 53% higher in transfused than nontransfused patients [hazard ratio = 1.53, 95% CI: 1.18-1.98, p = 0.001 by Log-rank test]. Organ dysfunction was higher in transfused than nontransfused patients [3.8% vs. 1.3%, hazard ratio = 3.0, 95% CI: 1.40-6.48, p = 0.005]. The risk of staying in the mechanical ventilation was similar in both groups [hazard ratio = 1.03, 95% CI: 0.86-1.23, p = 0.756]. The risk of extended stay in the PICU and hospital was 16% and 21% higher in transfused than nontransfused patients [hazard ratio = 1.16, 95% CI: 1.03-1.30; p = 0.005; and 1.21, 95% CI: 1.08-1.36; p = 0.001], respectively. CONCLUSION: Red blood cell transfusion was independently associated with higher all-cause 28 d mortality and morbidities in critically ill children.

Trial of Furosemide to Prevent Acute Kidney Injury in Critically Ill Children: A Double-Blind, Randomized, Controlled Trial.

OBJECTIVE: To study whether furosemide infusion in early-onset acute kidney injury (AKI) in critically ill children would be associated with a reduced proportion of patients progressing to the higher stage (Injury or Failure) as compared to placebo. METHOD: A double-blind, placebo-controlled, randomized pilot trial was conducted. The authors enrolled children aged 1-mo (corrected) to 12-y, who were diagnosed with AKI ("risk" stage) using pediatric-Risk, Injury, Failure, Loss, End stage kidney disease (p-RIFLE) criteria, and achieved immediate resuscitation goals within 24 h of admission. Participants received either furosemide (0.05 to 0.4 mg/kg/h) or placebo (5%-dextrose) infusion. The primary outcome was the proportion of patients progressing to a higher stage (injury or failure). Secondary outcomes were (i) need for renal replacement therapy, (ii) the effect on neutrophil gelatinase-associated lipocalin (urine and blood), (iii) fluid balance, (iv) adverse effects, (v) time to achieve renal recovery, (vi) duration of hospital stay and mechanical ventilation, and (vii) all-cause 28-d mortality. RESULTS: The trial was stopped for futility, and data were analyzed on an intention-to-treat basis (furosemide-group: n = 38; placebo-group: n = 37). No significant difference was noted in the progression of AKI to a higher stage between furosemide and placebo groups (10.5% vs. 21.6%; relative risk = 0.49, 95% CI 0.16 to 1.48) (p = 0.22). There were no differences in the secondary outcomes between the study groups. All-cause 28-d mortality was similar between the groups (10.5% vs. 10.8%). No trial-related severe adverse events occurred. CONCLUSIONS: Furosemide infusion in early-onset AKI did not reduce the progression to a higher stage of AKI. A future trial with large sample size is warranted.

Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To compare the efficacy of insulin infusion of 0.05 Unit/kg/hour vs 0.1 Unit/kg/hour in the management of pediatric diabetic ketoacidosis (DKA). DESIGN: Randomized, double-blind controlled clinical trial. SUBJECT: Pediatric critical care division of a tertiary care hospital from October, 2014 to July, 2018. PARTICIPANTS: Children aged 12 years or younger with a diagnosis of DKA. Children with septic shock and those who had received insulin before enrollment were excluded. INTERVENTION: Low-dose (0.05 Unit/kg/hour) vs. Standard-dose (0.1 Unit/kg/hour) insulin infusion. OUTCOME MEASURES: The primary endpoint was time for resolution of DKA (pH ≥7.3, bicarbonate ≥15 mEq/L, beta-hydroxybutyrate <1 mmol/L). Secondary outcomes were the rate of fall in blood glucose until 250 mg/dL or less and the rate of complications (hypokalemia, hypoglycemia, and cerebral edema). RESULTS: Sixty patients were analyzed on an intention-to-treat basis (Low-dose group: n=30; Standard-dose group: n=30). Mean (SD) time taken for the resolution of ketoacidosis was similar in both groups [22 (12) vs 23 (18.5) hours; P=0.92]. The adjusted hazard ratio (95% CI) of the resolution of ketoacidosis was lower in the low-dose group [0.40 (0.19 to 0.85); P=0.017]. Mean (SD) rate of blood glucose decrease until 250 mg/dL or less reached [56 (41) vs 64 (65) mg/dL/hour; P=0.41] and time to achieve the target [4.2 (3.1) vs 4.8 (3.3) hours; P=0.44] were similar in both groups. Hypokalemia [30% vs 43.3%; P=0.28] and hypoglycemia [3.3% vs 13.3%; P=0.35] were lower in low-dose group. No child had cerebral edema, and no mortality occurred. CONCLUSIONS: Time for resolution of ketoacidosis was similar in the low-dose and standard-dose insulin with a lower rate of therapy-related complications in the low-dose group. Hence, low-dose insulin infusion can be a safer approach in the management of pediatric DKA.

Epinephrine Plus Vasopressin vs Epinephrine Plus Placebo in Pediatric Intensive Care Unit Cardiopulmonary Resuscitation: A Randomized Double Blind Controlled Clinical Trial.

OBJECTIVE: To compare the efficacy of epinephrine plus vasopressin vs epinephrine plus placebo in the pediatric intensive care unit (PICU) cardiopulmonary resuscitation (CPR). DESIGN: Randomized, double-blind controlled clinical trial. SETTING: PICU in a tertiary care institute from February, 2019 to May, 2020. PARTICIPANTS: Children aged one month to 13 years who required CPR during PICU stay. Patients in whom vascular access was not available or return of spontaneous circulation (ROSC) was achieved by defibrillation without epinephrine were excluded. INTERVENTION: Patients were randomized to receive vasopressin 0.1 mL per kg (=0.8 unit per kg) or placebo (0.1 mL per kg normal saline) in addition to epinephrine (1:10000) 0.1 mL per kg. The drugs were given as bolus doses every three minutes until the ROSC or up to a maximum of five doses, whichever was earlier. OUTCOME MEASURE: The primary outcome was the proportion of patients who achieved ROSC. The secondary outcomes were survival rate and functional status (at 24-hour, PICU, hospital, and 90-day post-discharge), need for organ supports, length of stay (PICU and hospital), and adverse effect(s) of the study drugs. RESULTS: 90 patients (epinephrine plus vasopressin group, n=45 and epinephrine plus placebo group, n=45) were analyzed on intention-to-treat basis. There was no significant difference in the primary outcome between epinephrine plus vasopressin (n=25, 55.5%) and epinephrine plus placebo groups (n=24, 53.3%) (Relative risk 1.04, 95% CI 0.71 to 1.52). There was no significant difference in survival rate at 24-hour (n=7, 15.6% vs. n=8, 17.8%), at PICU, hospital, and 90-day post-discharge (n=1, 2.2% vs n=1, 2.2%). There was no difference in other secondary outcomes. No trial drug-related serious adverse events were observed. CONCLUSIONS: A combination of epinephrine plus vasopressin did not improve the rate of return of spontaneous circulation in the pediatric intensive care unit cardiopulmonary resuscitation as compared with epinephrine plus placebo.

Use of Honey Versus Standard Care for Hospital-Acquired Pressure Injury in Critically Ill Children: A Multicenter Randomized Controlled Trial.

OBJECTIVES: To examine if the use of honey (medicated) for dressing is superior to standard care in terms of time to complete wound healing in stages 1-3 of pressure injuries in children admitted to the PICU. DESIGN: Multicenter, open-label, parallel-group, randomized trial. SETTING: Tertiary-care PICU from August 2017 to January 2019. PATIENTS: Critically ill children, 2 months to 17 years old, who developed pressure injury (stages 1-3) were included; those on more than two inotropes or with signs of acute wound infection or wounds with greater than 5 cm diameter or known allergy to honey were excluded. INTERVENTIONS: Children were randomized to receive either medicated honey dressing or standard (routine) wound care for the management of their pressure injury. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the time to complete wound healing. Manuka or active Leptospermum honey dressing/gel was used in the intervention group. Enrolled children were followed up until death or discharge from the hospital. A total of 99 children were enrolled: 51 in the intervention group and 48 in the standard care group. Baseline characteristics, including the nutritional status, were comparable between the groups. The most common sites of injury were bony prominences at face mask contact points. The median time to complete healing was 7 days (95% CI, 6-7 d) versus 9 days (7-10 d) in the intervention and standard care groups, respectively (p = 0.002; log-rank test). At any random time, children in the intervention group were about 1.9-fold more likely to have their pressure injury completely healed than those in the standard care group (hazard ratio 1.86; 95% CI, 1.21-2.87). There were no allergic reactions or secondary wound infections in the intervention group. CONCLUSIONS: The use of medicated honey dressings decreased the time to wound healing in critically ill children with pressure injuries. There were no allergic reactions or secondary bacterial infections in any of these children.

Retrospective Hospital-Based Cohort Study on Risk Factors of Poor Outcome in Pediatric Snake Envenomation.

BACKGROUND AND OBJECTIVES: Among Southeast Asian countries, India has reported the highest mortality due to snakebite envenomation. To identify the risk factors of poor outcome (mortality/mechanical ventilation/renal replacement therapy-RRT) in pediatric snakebite envenomation. METHOD: Case records of children aged less than 13 years with snakebite envenomation admitted between June 2009 and July 2015 were reviewed retrospectively. Medical records of the patient died within 6 h, those required RRT before administration of antisnake venom (ASV), and those with unknown bites were excluded. RESULTS: A total of 308 patients were included. One hundred eighty (58.4%) had hemotoxic, and 128 (41.6%) had neuroparalytic envenomation. Median (interquartile range) bite to ASV time was 3 (2-6) h. Seventy-five (24.4%) patients received ASV within 6 h of bite. Poor outcomes occurred in 128 (41.6%), and 36 (11.7%) patients died. On binary logistic analysis (adjusted odds ratio, 95% confidence interval), age ≤5 years (2.97, 1.28-6.90), walking (6.15, 2.88-13.17), playing (3.36, 1.64-6.88), no tourniquet (2.39, 1.25-4.57), time to ASV more than 6 h (2.71, 1.45-5.06), fang marks (2.22, 1.21-4.07), neurotoxic envenomation (3.01, 1.11-8.13) and additional ASV dose (8.41, 2.99-23.60) were independently predicted the poor outcome (Hosmer and Lemeshow goodness of fit model p = 0.135; overall percentage of the model is 72.2% and R-square = 0.28). CONCLUSION: Age below 5 years, activity at/after the bite (playing/walking), no tourniquet, a longer bite to ASV time, presence of fang marks, neurotoxic envenomation and need for additional ASV dose were independent predictors of poor outcome in pediatric snakebite envenomation.

Evaluation of LAMP for detection of Shigella from stool samples in children.

BACKGROUND: To assess the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for the detection of Shigella from stool samples from children. METHODS: Consecutive stool samples from children aged <13 years old who presented with acute watery diarrhoea or dysentery to the Department of Paediatrics were collected and processed in the Department of Microbiology. All the stool samples were subjected to culture, conventional PCR and LAMP. Genomic sequencing was performed for samples that were positive by LAMP but negative by both culture and conventional PCR. The LAMP results were compared to those from culture and to a composite reference standard based on culture and conventional PCR. RESULTS: Amongst the 374 stool samples tested, 291 samples were positive by LAMP and 213 were positive by the composite reference standard. The sensitivity of LAMP was 100 % (98.3-100 %) and its specificity was 51.6 % (43.6-59.5 %) with a disease prevalence of 57 %. The sensitivity and specificity of LAMP improved to 99.3 % (94.2-100) and 98.2 % (94.5-99.9), respectively, using latent class analysis, while assuming that genomic sequencing has perfect specificity. DISCUSSION: The authors have standardized the LAMP procedure for direct application to clinical stool samples. LAMP is a sensitive and specific method for the diagnosis of Shigella from stool samples of children as compared to both culture and conventional PCR.

Comparison of Phenytoin, Valproate and Levetiracetam in Pediatric Convulsive Status Epilepticus: A Randomized Double-blind Controlled Clinical Trial.

OBJECTIVE: To compare the efficacy of phenytoin, valproate, and levetiracetam in the management of pediatric convulsive status epilepticus. DESIGN: Randomized double-blind controlled clinical trial. SETTING: Pediatric critical care division in a tertiary care institute from June, 2016 to December, 2018. PARTICIPANTS: 110 children aged three month to 12 year with convulsive status epilepticus. INTERVENTION: Patients not responding to 0.1 mg/kg intravenous lorazepam were randomly assigned (1:1:1) to receive 20 mg/kg of phenytoin (n=35) or valproate (n=35) or levetiracetam (n=32) over 20 minutes. Patients with nonconvulsive status epilepticus, recent hemorrhage, platelet count less than 50,000 or International normalized ratio (INR) more than 2, head injury or neurosurgery in the past one-month, liver or kidney disease, suspected or known neurometabolic or mitochondrial disorders or structural malformations, and allergy to study drugs; and those who were already on any one of the study drugs for more than one month or had received one of the study drugs for current episode, were excluded. OUTCOME MEASURE: The primary outcome was the proportion of patients that achieved control of convulsive status epilepticus at the end of 15 minutes after completion of the study drug infusion. Secondary outcomes were time to control of seizure, rate of adverse events, and the requirement of additional drugs to control seizure, length of ventilation, hospital stay, and functional status after three months (Glasgow Outcome Scale). RESULTS: The study was stopped after the planned mid-interim analysis for futility. Intention to treat analysis was done. There was no difference in primary outcome in phenytoin (31/35, 89%), valproate (29/35, 83%), and levetiracetam (30/32, 94%) (P=0.38) groups. There were no differences between the groups for secondary outcomes. One patient in the phenytoin group had a fluid-responsive shock, and one patient in the valproate group died due to encephalopathy and refractory shock. CONCLUSIONS: Phenytoin, valproate, and levetiracetam were equally effective in controlling pediatric convulsive status epilepticus.

Assessment of global DNA methylation in children with tuberculosis disease.

Background: Studying DNA methylation changes in disease condition provides the basis of disease pathogenesis or host immune response to infection. Evidences suggest that pathogen-mediated DNA methylation changes influences the expression pattern of genes contributing to disease condition to avert host immune response. Hence, we attempted to study the association between tubercle bacilli-mediated global DNA methylation changes in children with tuberculosis (TB) disease and healthy controls. Methods: Forty-three children diagnosed with TB and 33 healthy children were enrolled in this study. ELISA-based global DNA methylation quantification was performed to measure the changes in percentage of global genomic DNA methylation level. Results: Highly significant difference in global DNA methylation level was found between cases and controls and median global DNA methylation level was 6.25% (interquartile range [IQR] 2.5%-10%) in cases and 25% (IQR, 12.5%-25%) in controls (P < 0.001). Significant difference was found in GeneXpert-positive cases (P < 0.01). Receiver operating curve analysis showed that area under curve 0.81 for the total study population and 0.76 for GeneXpert-positive cases. Conclusion: The results show the significant difference in global DNA methylation level in children with TB disease that can serve as a potential biomarker in early diagnosis of TB disease. Measuring global DNA methylation level, however, not an accurate or sensitive diagnostic method but evaluating active demethylation at genome-wide level can be used to monitor disease progression and treatment efficacy.

Second Dose of Scorpion Antivenom in Children with Indian Red Scorpion (Mesobuthus tamulus) Sting Envenomation.

OBJECTIVE: To study the effect of the second dose of scorpion antivenom in children with non-resolving or worsening scorpion sting envenomation. METHODS: 72 children aged ≤12 years with scorpion sting envenomation grade 2 and above were enrolled. 61 received the first dose of three vials of antivenom at admission (group A). Children with persistent/worsening envenomation at 6 hours received the second dose (group B). The time required for resolution of autonomic symptoms, myocardial dysfunction, predictors of the second dose and side effects were studied. RESULTS: The mean time taken for resolution of autonomic symptoms were similar in GroupA and B (4.1 vs. 5.3 hours, P=0.452), and of myocardial dysfunction was shorter in Group A (10.8 vs. 37.6 hours, P=0.019). On regression analysis, abnormal echocardiography at admission was found to be a significant predictor of the second dose (OR=27.6, 95% CI, 4.7-162.5; P=<0.001). CONCLUSION: Children with severe scorpion sting envenomation with abnormal echocardiography may require a higher dose of scorpion antivenom.

Basidiobolomycosis complicated by hydronephrosis and a perinephric abscess presenting as a hypertensive emergency in a 7-year-old boy.

A 7-year-old boy presented with a chronic, indurated, tender left thigh swelling in association with a hypertensive emergency. He had a bilateral moderate degree of hydronephrosis and a left perinephric abscess, and MRI features of posterior reversible encephalopathy syndrome. Histopathological examination of the biopsy specimen demonstrated eosinophilic fasciitis with filamentous fungi. Basidiobolus ranarum was isolated from the culture. The fungus was also isolated from a perinephric fluid aspirate. Computerised tomography of the abdomen demonstrated features consistent with fungal invasion of the pelvic floor muscles and urinary bladder, leading to bilateral hydronephrosis. He required multiple antihypertensive drug therapy and was treated with intravenous amphotericin B, oral itraconazole and potassium iodide. Antihypertensive agents were discontinued after 2 weeks of antifungal therapy. At 6-months follow-up, the hydronephrosis had resolved completely. Perinephric abscess associated with basidiobolomycosis has not been reported previously.

Comparative Effect of Divided Doses of Adult Solid and Liquid Oral Formulations of Antiepileptic Drugs in the Management of Pediatric Epilepsy.

OBJECTIVE: To compare the differences in the efficacy and safety of the commonly prescribed AEDs in the management of epilepsy in children when using divided doses of adult solid oral formulations (DDSF) with the liquid oral formulations (LFs). MATERIALS AND METHODS: Patients who had one or more seizures per month and prescribed with DDSF were recruited. Initially the patients were continued on DDSF for 4 months following which they were switched over to LF for the subsequent 4 months. Seizure frequencies and adverse drug effects (ADRs) were recorded every month for 8 months and plasma AED levels were estimated at the end of 4th and 8th months. RESULTS: A total of 200 patients completed the study protocol. The median seizure frequencies per month with DDSF and LF were: partial seizures (20.5, 9.0; P < 0.001), generalized tonic-clonic seizures (6.5, 2.0; P < 0.001), myoclonic seizures (58.5, 29.0; P < 0.001). Mean plasma drug levels ± SD (µg/ml) with DDSF and LF were: sodium valproate (48.2 ± 13.7, 69.1 ± 16.3; P < 0.001), phenytoin sodium (5.0 ± 2.4, 12.8 ± 3.8; P < 0.001), carbamazepine (4.5 ± 2.0, 11.5 ± 4.8; P < 0.001) and phenobarbitone (14.1 ± 5.2, 25.4 ± 12.3, P < 0.001). The incidence of treatment emergent ADRs was poor scholastic performance (25.5%), behavioral problems and dizziness/sedation (21.0%), somnolence/sleep disorders (19.5%). CONCLUSION: Patients treated with LF had better seizure control and optimal therapeutic drug levels and less adverse effects when compared to DDSF.