Furosemide stress test to predict acute kidney injury progression in critically ill children.

BACKGROUND: Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. METHODS: Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. RESULTS: Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. CONCLUSIONS: Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.

Fluid resuscitation in children with severe infection and septic shock: a systematic review and meta-analysis.

This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups. CONCLUSIONS: The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children.Prospero registration: CRD42020209066. WHAT IS KNOWN: • Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children. WHAT IS NEW: • BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia.

Pediatric Sepsis Phenotypes and Outcome: 5-Year Retrospective Cohort Study in a Single Center in India (2017-2022).

OBJECTIVES: To describe mortality associated with different clinical phenotypes of sepsis in children. DESIGN: Retrospective study. SETTING: PICU of a tertiary care center in India from 2017 to 2022. PATIENTS: Six hundred twelve children (from 2 mo to 17 yr old) with a retrospectively applied diagnosis of sepsis using 2020 guidance. METHODS: The main outcome was mortality associated with sepsis subtypes. Other analyses included assessment of risk factors, requirement for organ support, and PICU resources used by sepsis phenotype. Clinical data were recorded on a predesigned proforma. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of the 612 children identified, there were 382 (62%) with sepsis but no multiple organ failure (NoMOF), 48 (8%) with thrombocytopenia-associated MOF (TAMOF), 140 (23%) with MOF without thrombocytopenia, and 40 (6.5%) with sequential MOF (SMOF). Mortality was higher in the SMOF (20/40 [50%]), MOF (62/140 [44%]) and TAMOF (20/48 [42%]) groups, compared with NoMOF group (82/382 [21%] [ p < 0.001]). The requirement for organ support and PICU resources was higher in all phenotypes with MOF as compared with those without MOF. On multivariable analysis elevated lactate and having MOF were associated with greater odds of mortality. CONCLUSIONS: In this single-center experience of sepsis in India, we found that sepsis phenotypes having MOF were associated with mortality and the requirement of PICU resources. Prospective studies in different regions of the world will help identify a classification of pediatric sepsis that is more widely applicable.

Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Role of high-sensitivity C-reactive protein (hs-CRP) in assessment of asthma control in children.

INTRODUCTION: Data are scarce on hs-CRP as a biomarker for airway inflammation in pediatric asthma. We aimed to examine correlation between hs-CRP and asthma control levels. METHODS: Children with physician-diagnosed asthma, ages 6-15 years, were enrolled. GINA-2016 criteria were used to assess the level of asthma control. The relationships between serum hs-CRP and each of asthma control measures (asthma control criteria, spirometry, impulse oscillometry, eosinophil counts and fractional exhaled nitric oxide (FeNO) were assessed. RESULTS: 150 asthmatic children were enrolled; 52 (35%) had well controlled asthma, 76 (51%), and 22 (14%) children had partly controlled and uncontrolled asthma, respectively. Median (IQR) values of hs-CRP were 0.47 (0.1, 1.67) mg/L in well controlled, 0.30 (0.1, 1.83) mg/L in partly controlled, and 2.74 (0.55, 3.74) mg/L in uncontrolled asthma (p = 0.029). Using receiver operator characteristic (ROC) curve analysis, area under the curve for hs-CRP (mg/L) to discriminate between uncontrolled and (controlled + partly controlled) asthma was 0.67 (95% CI 0.55, 0.80) and a cutoff 1.1 mg/L of serum hs-CRP level had a sensitivity of 68.1% with specificity of 67.97%. In two groups of hs-CRP (<3 mg/L) and hs-CRP (≥3 mg/L), high hs-CRP group had higher proportion of uncontrolled asthmatic children (p = 0.03). CONCLUSION: We observed higher serum hs-CRP values in children with uncontrolled asthma, suggesting its potential role as a biomarker of asthma control.

Impulse oscillometry (IOS) for detection of exercise induced bronchoconstriction in children with asthma ages 6-15 years.

OBJECTIVES: To determine the discriminatory value of various impulse oscillometry (IOS) parameters, and to find the cutoff value of the appropriate parameter for identifying exercise-induced bronchoconstriction (EIB) in children with asthma. METHODS: This cross-sectional study was conducted in India from October 2016 to March 2018 in children with asthma who were 6-15 years of age. One hundred and five children were enrolled and subjected to pre-exercise IOS and spirometry followed by free running treadmill test as an exercise challenge. All children could achieve minute ventilation >17.5-21 times of FEV1 during the exercise challenge test. Then, IOS and spirometry were performed at 10 ± 2, 20 ± 2, and 30 ± 2 min post-exercise challenge. EIB was defined as reduction of FEV1 ≥10% within 30 min of exercise. For purposes of analysis, the children were grouped into two categories: "EIB Present" or "EIB Absent". RESULTS: The prevalence of EIB in our study was 20.95% (n = 22). ΔR5max percentage within 30 min post-exercise (AUC 0.74; 95% CI: 0.64, 0.84) had the best discriminating capacity among all IOS parameters for identifying EIB. A cutoff value of 14.1% increase in R5 within 30 min post-exercise was obtained for detection of EIB (sensitivity-95.45%, specificity-50.6%, PPV-33.87% and NPV-97.67%). CONCLUSIONS: A percentage change in R5 with a cutoff value of 14.1% increase post-exercise had the best discriminatory capacity among all IOS parameters for detection of EIB in children with asthma. However, low positive predictive value (PPV) with high negative predictive value (NPV) made this cutoff value more apt to rule out EIB.

The Microbiome and Metabolome of the Gut of Children with Sepsis and Septic Shock.

BACKGROUND: There is limited understanding of alteration of gut microbiota and metabolome in children with sepsis/septic shock. METHODS: In this prospective observational study carried out in a pediatric intensive care unit of a tertiary care center from 2020 to 2022, patients aged <17 years with sepsis/septic shock and healthy children (HC) were enrolled. We characterized the gut bacterial compositions by metagenome sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. The primary outcome was to compare the gut microbiota and metabolome of children with sepsis/septic shock with that of HC. The Firmicutes/Bacteroidetes (F/B) ratio was compared between children with sepsis/septic shock and HC. Key secondary outcomes were to evaluate association of factors associated with a low F/B ratio in children with sepsis/septic shock. RESULTS: A total of 40 children (63% boys) (15 children with sepsis and septic shock and 10 healthy children) with a median (IQR) age of 5.5 (1.5, 10) years were enrolled. In the fecal microbiota, the α-diversity index including Shannon and Simpson indices of the sepsis/septic shock groups was significantly lower than that of the HC. The samples lacked beneficial Bifidobacterium spp. and were dominated by Bacteroides, Enterobacteriaceae, and Enterococcaceae. There was reduction in short-chain fatty acids (SCFAs) in patients with sepsis/septic shock as compared to healthy children. A lower F/B ratio (≤1.57) of the gut microbiota discriminated well between children with sepsis/septic shock and HC. Factors associated with lower F/B ratio were male gender, clinical GI dysfunction, elevated inflammatory markers, and higher organ failure scores. CONCLUSION: There were significant alterations in the gut microbiota and metabolome in children with sepsis/septic shock as compared to healthy children. Larger study is needed to confirm these exploratory findings and develop potential therapeutic targets that will improve outcomes in children with sepsis/septic shock.

Acute gastrointestinal injury in critically ill children: Impact on clinical outcome.

AIM: To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality. METHODS: In a prospective cohort study, critically ill children (1 month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated. RESULTS: Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR) = 2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR = 1.525, 95% CI: 1.142, 2.037) and haematological (OR = 1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR = 1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality. CONCLUSIONS: Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade.

Delayed Administration of Antibiotics Beyond the First Hour of Recognition Is Associated with Increased Mortality Rates in Children with Sepsis/Severe Sepsis and Septic Shock.

OBJECTIVE: To compare the risk of mortality and other clinical outcomes in children with sepsis, severe sepsis, or septic shock who received antibiotics within the first hour of recognition (early antibiotics group) with those who received antibiotics after the first hour (delayed antibiotics group). STUDY DESIGN: In this prospective cohort study, we enrolled children <17 years of age presenting to the pediatric emergency and diagnosed with sepsis or septic shock without prior antibiotic therapy. Primary outcome was mortality and the secondary outcomes were day 1 Pediatric Logistic Organ Dysfunction score, ventilator-free days, and hospital-free days. These outcomes were compared between the early and the delayed antibiotic groups. The reference point for defining early and delayed antibiotic groups was time 0, which was measured from the time the patient was diagnosed to have sepsis, severe sepsis, or septic shock to the time of administration of the first dose of antibiotics. RESULTS: About three-fourths (77%) of the 441 children enrolled had septic shock. A total of 241 (55%) and 200 (45%) children were in the delayed and early antibiotic groups, respectively. Children in the delayed group had significantly higher odds of mortality than those in the early group (29% vs 20%; aOR 1.83; 95% CI, 1.14-2.92; P = .01). The time to shock reversal was significantly shorter, and the ventilator-free days and hospital-free days were significantly greater, in the early antibiotic group. There was no difference between the groups with regard to any of the other clinical outcomes. CONCLUSIONS: Delayed administration of antibiotics beyond 1 hour of recognition was associated with higher mortality rates in children with sepsis, severe sepsis, and septic shock. Antibiotics should be administered within the first hour, along with other resuscitative measures, in these children.

COVID-19 with and without anosmia or dysgeusia: A case-control study.

Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID-19) pandemic begun. The objective of this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS-CoV-2 infection. All adult COVID-19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID-19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID-19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.09-0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99-0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5-37.6; p = .01) remained significant. In this retrospective study of COVID-19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.

Functional Outcomes at 1 Year After PICU Discharge in Critically Ill Children With Severe Sepsis.

OBJECTIVES: To evaluate the functional outcomes in critically ill children with severe sepsis using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale and to evaluate the risk factors for "worse outcomes." DESIGN: Prospective observational cohort study. SETTING: Tertiary care PICU from September 2017 to October 2019. PATIENTS: One hundred twenty-one children with severe sepsis, 2 months to 17 years old, admitted to PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores were recorded at admission, PICU discharge, at 3 months and 1 year after discharge. "New disability" was defined as Pediatric Overall Performance Category and Pediatric Cerebral Performance Category score change "from baseline score" by greater than or equal to 1 category. Risk factors for "worse outcomes" (defined as "death" or "new disability") were evaluated by univariate and multivariate analysis. At admission, 33% (n = 39) had mild to moderate "overall disability" (Pediatric Overall Performance Category) and 26% (n = 32) had mild to moderate "cognitive disability" (Pediatric Cerebral Performance Category). At PICU discharge (n = 89 children), 50.5% (n = 45) had "new disability" in overall function (Pediatric Overall Performance Category scores) and 28% (n = 25) had "new disability" in cognitive function (Pediatric Cerebral Performance Category scores). At 3 months follow-up (n = 85 children), "new disability" at PICU discharge improved in 65% (n = 28/43) and 50% (n = 12/24) of those with "overall disability" (Pediatric Overall Performance Category) and "cognitive disability" (Pediatric Cerebral Performance Category), respectively. At 1-year follow-up (n = 84 children), only 5% (n = 2/43) had residual "new disability" in overall function (Pediatric Overall Performance Category) and 14% (n = 3/21) had residual "new disability" in cognitive function. PICU mortality was 26% (n = 32). The proportion with "worse outcomes" was 64% (n = 77). Risk factors for worse outcomes on univariate analysis included higher Pediatric Index of Mortality-3 scores, day 1 pediatric Sequential Organ Failure Assessment score, receiving cardiopulmonary resuscitation during the ICU stay, and treatments received such as ventilation and Vasoactive-Inotrope Score. On multivariate analysis, only day 1 pediatric Sequential Organ Failure Assessment score and receiving cardiopulmonary resuscitation during the ICU stay were found to be statistically significant. CONCLUSIONS: Children with severe sepsis had significant "new onset" mild to moderate functional disability at PICU discharge, and most of these children recovered within 1 year after PICU discharge. Day 1 pediatric Sequential Organ Failure Assessment score and patient receiving cardiopulmonary resuscitation during the ICU stay were found to be the significant risk factors of "worse outcomes."

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.

Twenty-Four-Hour Esophageal pH Measurement in Mechanically Ventilated Children: A Prospective Cohort Study.

OBJECTIVES: To assess the prevalence of gastroesophageal reflux in mechanically ventilated children using 24-hour esophageal pH-metry and its role as a risk factor for ventilator-associated pneumonia. DESIGN: Prospective cohort study. SETTING: PICU of a tertiary care hospital from North India. PATIENTS: Mechanically ventilated children 1-15 years old in PICU from July 2015 to June 2017, excluding those receiving acid suppressants, known cases of gastroesophageal reflux disease, having upper gastrointestinal bleed. INTERVENTION: Demographic details, baseline investigations, diagnosis, treatment details, and Pediatric Risk of Mortality III score were recorded at enrollment. Gastroesophageal reflux was evaluated using 24-hour esophageal pH-metry. Children were followed up for 7 days or 48 hours after extubation for development of ventilator-associated pneumonia using Centers for Disease Control and Prevention criteria. Pathologic acidic gastroesophageal reflux was defined as fall in esophageal pH less than 4 for more than 4% of total time, whereas pathologic alkaline gastroesophageal reflux as rise in esophageal pH greater than 7 for more than 17% of total time. MEASUREMENTS AND MAIN RESULTS: Sixty-one children (median [interquartile range], age 73 mo [30-132 mo]; 44 boys [72%]) were enrolled. Median Pediatric Risk of Mortality III score was 10.0 (3-16). Median duration of ventilation was 6 days (3-9 d). Pathologic gastroesophageal reflux (acidic or alkaline) was present in 47 children (77%). Twelve children (19.7%) met criteria for pathologic acidic gastroesophageal reflux, whereas 44 children (72.1%) had pathologic alkaline gastroesophageal reflux; nine children (14.7%) had both pathologic acidic and alkaline gastroesophageal reflux. Of the enrolled children, 17 (27.9 %) developed ventilator-associated pneumonia. No patient had both pathologic acidic gastroesophageal reflux and ventilator-associated pneumonia. Of 17 children who developed ventilator-associated pneumonia, 12 (70.5%) had pathologic alkaline gastroesophageal reflux as compared to 32 children (72.7%) among the 44 children who did not develop ventilator-associated pneumonia (p = 0.87). CONCLUSIONS: The current study shows high incidence of gastroesophageal reflux on 24-hour esophageal pH-metry in mechanically ventilated children with medical diagnoses. The significance of this finding and its impact on ventilator-associated pneumonia and other ventilator-associated events need to be examined in larger studies.

Clinical Profile and Risk Factors for Severe Disease in 402 Children Hospitalized with SARS-CoV-2 from India: Collaborative Indian Pediatric COVID Study Group.

INTRODUCTION: There is a lack of large multicentric studies in children with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in children hospitalized with COVID-19 from India. METHODS: In this multicentric retrospective study, we retrieved data related to demographic details, clinical features, including the severity of disease, laboratory investigations and outcome. RESULTS: We included 402 children with a median (IQR) age of 7 (2-11) years. Fever was the most common symptom, present in 38.2% of children. About 44% had underlying comorbidity. The majority were asymptomatic (144, 35.8%) or mildly symptomatic (219, 54.5%). There were 39 (9.7%) moderate-severe cases and 13 (3.2%) deaths. The laboratory abnormalities included lymphopenia 25.4%, thrombocytopenia 22.1%, transaminitis 26.4%, low total serum protein 34.7%, low serum albumin 37.9% and low alkaline phosphatase 40%. Out of those who were tested, raised inflammatory markers were ferritin 58.9% (56/95), c-reactive protein 33.3% (41/123), procalcitonin 53.5% (46/86) and interleukin-6 (IL-6) 76%. The presence of fever, rash, vomiting, underlying comorbidity, increased total leucocyte count, thrombocytopenia, high urea, low total serum protein and raised c-reactive protein was factors associated with moderate to severe disease. CONCLUSION: Fever was the commonest symptom. We identified additional laboratory abnormalities, namely lymphopenia, low total serum protein and albumin and low alkaline phosphatase. The majority of the children were asymptomatic or mildly symptomatic. We found high urea and low total serum protein as risk factors for moderate to severe disease for the first time.

A Core Outcome Set for Pediatric Critical Care.

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Development of a novel outcome prediction score (PEDSS) for pediatric convulsive status epilepticus: A longitudinal observational study.

OBJECTIVE: The objectives of this study were to evaluate ENDIT score and develop a novel outcome prediction score for outcome of pediatric convulsive status epilepticus (CSE) at the hospital and 3 months postdischarge. METHODS: Children and adolescents aged 1 month to 14 years, presenting with CSE to a tertiary care teaching center in North India from January 2017 to March 2019, were screened for enrollment. In-hospital and 3-month postdischarge outcome were defined as poor if Pediatric Cerebral Performance Category Scale (PCPCS) score dropped by ≥2 levels. RESULTS: Overall, 61 patients were enrolled for final analysis after applying exclusion and inclusion criteria. The area under the receiver operating characteristic (ROC) curve for ENDIT score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge was 0.74 (95% confidence interval [CI] = 0.58-0.89), 0.7 (95% CI = 0.57-0.83), and 0.72 (95% CI = 0.6-0.82), respectively. Based on predictors in the present cohort that were significantly different between good and poor outcome cases at the hospital and 3 months postdischarge, a new six-point score named PEDSS (pre-status epilepticus PCPCS, background electroencephalographic abnormalities, drug refractoriness, semiology, and critical sickness) was developed. The area under ROC curves for PEDSS score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge were 0.93 (95% CI = 0.87-0.99), 0.8 (95% CI = 0.7-0.9), and 0.89 (95% CI = 0.8-0.96), respectively. The best cutoff PEDSS scores for predicting mortality and poor outcome at the hospital and at 3 months postdischarge were ≥4, ≥3, and ≥3, respectively. SIGNIFICANCE: The PEDSS score has high predictive accuracy for mortality and differentiating good from poor outcome at the hospital and 3 months postdischarge in pediatric CSE. Future studies should be planned to validate it in various geographical and health care settings and in adults.

COVID-19 infection outbreak among health care workers: perspective from a low-middle income country.

To the Editor, The new pandemic COVID -19 caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a global threat. So far, more than 11 million infections and more than five hundred thousand deaths have been reported worldwide. In India the number of cases as of 5th July, 2020 is 6,73,165 with 19,268 deaths. Health care workers (HCWs) have been the backbone of this pandemic since the very beginning...

Effect of Severe Vitamin D Deficiency at Admission on Shock Reversal in Children With Septic Shock: A Prospective Observational Study.

OBJECTIVES:: To evaluate the association of severe vitamin D deficiency with clinically important outcomes in children with septic shock. METHODS:: We enrolled children ≤17 years with septic shock prospectively over a period of 6 months. We estimated 25-hydroxyvitamin D [25 (OH) D] levels at admission and 72 hours. Severe deficiency was defined as serum 25 (OH) <10 ng/mL. We performed univariate and multivariate analysis to evaluate association with clinically important outcomes. RESULTS:: Forty-three children were enrolled in the study. The prevalence of severe vitamin D deficiency was 72% and 69% at admission and 72 hours, respectively. On univariate analysis, severe vitamin D deficiency at admission was associated with lower rates of shock reversal, 74% (23) versus 25% (3); relative risk (95% confidence interval [CI]): 2.9 (1.09-8.08), at 24 hours and greater need for fluid boluses (75 vs 59 mL/kg). On multivariate analysis, nonresolution of shock at 24 hours was significantly associated with severe vitamin D deficiency after adjusting for other key baseline and clinical variables, adjusted odds ratio (95% CI): 12 (2.01-87.01); 0.01. CONCLUSION:: The prevalence of severe vitamin D deficiency is high in children with septic shock admitted to pediatric intensive care unit. Severe vitamin D deficiency at admission seems to be associated with lower rates of shock reversal at 24 hours of ICU stay. Our study provides preliminary data for planning interventional studies in children with septic shock and severe vitamin D deficiency.