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Data are limited on the genetic profile of primary ciliary dyskinesia (PCD) from developing countries. Here, we report one of the first study on genetic profile of patients with suspected PCD from India. In this prospective cross-sectional study, we enrolled 162 children with suspected PCD. We recorded clinical features, relevant laboratory tests for PCD and performed whole exome sequencing (WES). We are reporting 67 patients here who had positive variant/s on WES. We had 117 variants in 40 genes among 67 patients. Among the 108 unique variants, 33 were categorized as pathogenic or likely pathogenic (P/LP). We had nine novel variants in out cohort. The 29 definite PCD cases, diagnosed by composite reference standards, had variants in 16 genes namely LRRC6/DNAAF11 (5), DNAH5 (3), CCDC39 (3), HYDIN (3), DNAH11 (2), CCDC40 (2), CCDC65 (2) and one each DNAAF3, DNAAF2, CFAP300, RPGR, CCDC103, CCDC114, SPAG1, DNAI1, and DNAH14. To conclude, we identified 108 unique variants in 40 genes among 67 patients. The common genes involved in definite cases of PCD in Indian patients were LRRC6, DNAH5, CCDC39, and HYDIN. Our findings suggest a need to develop a separate genetic panel for PCD in the Indian population.
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Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poorly, particularly in secondary DENV infection. To develop a highly sensitive NS1 ELISA, we generated a large repertoire of anti-DENV NS1 mouse mAbs (n = 95) that falls into 36 mAb classes based on binding specificities. The identified mAb pair, capable of efficiently detecting NS1 from four DENV serotypes in an immunoassay, was selected based on multiparametric analysis. The selected mAbs have subnanomolar affinities for NS1 with recognition sites outside the immunodominant wing domain. The assay was converted to an ELISA kit, which showed higher analytical sensitivity (3-fold to 83-fold) for NS1 from four DENV serotypes than commercial Platelia NS1 ELISA (Bio-Rad Laboratories). Compared to RT-PCR, the developed NS1 ELISA showed 78.57% (66 of 84) sensitivity, whereas Platelia NS1 ELISA showed a sensitivity of 60.71% (51 of 84). In a subgroup of RT-PCR-positive secondary dengue samples, our ELISA showed a sensitivity of 70.18% (40 of 57), whereas Platelia ELISA detected only 47.37% (27 of 57) samples. Furthermore, unlike Platelia ELISA, our test equally detected NS1 from four serotypes; Platelia ELISA performed poorly for the DENV-2 serotype, in which only 8 of 21 (38.10%) samples were detected compared with 17 of 21 (80.95%) in our ELISA. Moreover, our ELISA showed 100% specificity in 342 challenging dengue-negative samples. The large and diverse mAb repertoire generated against DENV NS1 and the appropriate selection of mAbs allowed us to establish an ELISA that can efficiently detect NS1 Ag even in secondary dengue and without serotype level bias.
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Antineoplásicos Inmunológicos , Virus del Dengue , Dengue , Animales , Ratones , Anticuerpos Monoclonales , Ensayo de Inmunoadsorción Enzimática , Epítopos Inmunodominantes , Dengue/diagnósticoRESUMEN
OBJECTIVES: To explore the efficacy of combination of Bhramari pranayama and om chanting as an adjunct to standard pharmacological treatment on asthma control, quality of life, pulmonary function, and airway inflammation in asthmatic children. METHODS: Children (n = 110; 8-15 years) with uncontrolled or partly controlled asthma were recruited from the Pediatric Chest Clinic of All India Institute of Medical Sciences, New Delhi. Eligible participants were randomized to either home-based online Bhramari pranayama and om chanting plus standard treatment (YI + ST) group, or standard treatment (ST) alone group. Primary outcome measures were 12-week change in level of asthma symptom control; asthma control questionnaire (ACQ) score, spirometry indices, impulse oscillometry parameters, and pediatric asthma quality of life questionnaire (PAQLQ) score. Secondary outcome was a change in fractional exhaled nitric oxide (FeNO) levels at 12 weeks. Beginning from the enrollment, every participant was evaluated at 0, 2, 6, and 12 weeks. RESULTS: After 12 weeks of intervention, higher proportion (68.2%) of children were found to have controlled asthma symptoms in the YI + ST group as compared to ST group (38.5%) according to per protocol analysis (p = 0.03). When compared to ST group, children in YI + ST group showed significantly lower ACQ score, higher PAQLQ score and reduced FeNO levels. No significant changes were observed for the lung function parameters. CONCLUSION: Children practicing Bhramari pranayama and om chanting for 12 weeks have better asthma symptom control, quality of life, and reduced airway inflammation than those taking standard pharmacotherapy alone.
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Asma , Niño , Humanos , Asma/diagnóstico , Inflamación/tratamiento farmacológico , Óxido Nítrico/análisis , Control de Calidad , Calidad de Vida , AdolescenteRESUMEN
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.
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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.
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Sepsis , Trombocitopenia , Niño , Humanos , Lactante , Estudios Retrospectivos , Estudios Prospectivos , Sepsis/diagnóstico , Fenotipo , Trombocitopenia/epidemiología , Trombocitopenia/complicaciones , Unidades de Cuidado Intensivo Pediátrico , India/epidemiologíaRESUMEN
BACKGROUND: Chest X-ray, the established standard of confirming endotracheal tube (ETT) position, has important drawbacks including radiation exposure. Point-of-care airway ultrasound, which has been insufficiently studied in children, can overcome these problems. MATERIALS AND METHODS: This was a prospective cross-sectional study done on children aged 2 months to 17 years undergoing intubation with cuffed ETT in the PICU. The ETT cuff was filled with saline and three ultrasonographic techniques were used- 1) Suprasternal (SS) method 2) Cricoid (CC) metho and 3) Tracheal ring (TR) method. Position of the ETT as determined by ultrasound and X-ray were compared. The main outcomes were sensitivity, specificity, and area under curve (AUC) for ultrasound-based methods vs. X-ray. For the TR method, concordance between the X-ray and ultrasound categories were taken. RESULTS: Total 62 patients were enrolled. The sensitivity and specificity of SS method were 71% (95% CI: 57-83%) and 100% (40-100%). The CC distance method had an AUC of 0.94 (95% CI: 0.86, 1.0). In the TR method, 98% of correct position on X-ray were correctly classified by USG. The agreement between X-ray and ultrasound categories with the cuff between the first and third tracheal rings, was very good [kappa (95% CI): 0.87 (0.70, 1.00), p ≤0.001)]. CONCLUSION: Bedside ultrasound is a good method to confirm ETT depth in children. The tracheal ring method had the best diagnostic accuracy and is easy to perform. The new method using cricoid cuff distance needs further validation in different ICU settings.
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Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.
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Sepsis , Choque Séptico , Humanos , Niño , Choque Séptico/mortalidad , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/etiología , Consenso , Sepsis/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Puntuaciones en la Disfunción de ÓrganosRESUMEN
Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3â¯049â¯699 in the development (including derivation and internal validation) set and 581â¯317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172â¯984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.
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Sepsis , Choque Séptico , Humanos , Niño , Choque Séptico/mortalidad , Insuficiencia Multiorgánica , Estudios Retrospectivos , Puntuaciones en la Disfunción de Órganos , Sepsis/complicaciones , Mortalidad HospitalariaRESUMEN
OBJECTIVE: ââThis study aimed to characterize the profile of myositis-specific and myositis-associated autoantibodies (MSAs/MAAs) in an Indian cohort of juvenile dermatomyositis (JDM) patients and correlate them with clinical features and outcomes. METHODS: Forty-three children diagnosed with JDM were enrolled for this observational study. Clinical details (presentation, course, and outcome) were noted in a predesigned proforma. Serum samples were tested for 16 MSAs/MAAs by line immunoassay. MSAs/MAAs were correlated with clinical features and outcome (defined as a complete clinical response [≥6 months' disease inactivity on medication] or complete remission [≥6 months' inactivity off all drugs]). RESULTS: Thirty-five subjects (81.4%) had at least 1 MSA/MAA detected. The most common antibodies were anti-NXP2 (n = 13, 30.2%), anti-TIF1γ (n = 10, 23.2%), and anti-MDA-5 (n = 8, 18.6%). No patient had anti-Ku, anti-Pm Scl-100, anti-PL-12, anti-EJ, anti-OJ, or anti-Ro52. Thirty-two patients (74.4%) attained a complete clinical response over a median follow-up duration of 14 months, among which 6 (13.9%) achieved complete remission over a median follow-up duration of 30 months. Anti-TIF1γ was associated with younger age at onset (≤3 years) (odds ratio [OR], 6.25; 95% confidence interval [CI], 1.15-34.12; p = 0.034) and disease flares after attaining complete response (OR, 10.18; 95% CI, 1.64-70.93; p = 0.013). Patients with anti-NXP2 had higher odds of severe muscular weakness (OR, 3.73; 95% CI, 0.95-14.59; p = 0.058) and truncal weakness (OR, 3.89; 95% CI, 0.97-15.64; p = 0.056). One child with anti-MDA-5 positivity had interstitial lung disease. We found no association between the MSA/MAA profile and the achievement of complete clinical response or remission. CONCLUSIONS: MSAs/MAAs were identified in 81% of children with JDM in our study, which is higher than most other studies. The most frequently observed antibodies displayed a pattern consistent with other studies. Anti-TIF1γ was associated with a younger age at onset and disease flares even after attaining a complete clinical response. Anti-NXP2 had higher odds of severe muscular weakness. These observations suggest consistency in certain phenotypic associations observed across geographic boundaries.
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Introduction: A pediatric intensive care unit (PICU) is a highly technological and fast-paced setting in a hospital. Objective: To explore the experiences of the parents in the critical care area of a selected tertiary care facility. Materials and methods: In a qualitative study, we interviewed 10 purposively selected parents of the children admitted to PICU using a pre-validated in-depth interview schedule. All parents, whose children were admitted to PICU for more than 5 days, who understood Hindi or English and were willing to participate in the study, were enrolled in the study. Parents of critically ill children having readmission to PICU or prolonged stay of more than 15 days and not accompanied by parents were excluded. Results: Parents had unmet needs, such as the need for information, counseling and education from the healthcare team (HCT) members, having trusting relationship with the HCT, and expecting receiving orientation of the routines and the protocols of PICU, and empathy from the various levels of PICU team. The majority of subjects expressed the desire to talk to a dedicated person for their queries. The parents had multiple feelings of distress, hopelessness, helplessness, guilt, and the fear of losing the child and used various coping strategies. Conclusion: Parents of critically ill children in the PICU have unmet needs. Healthcare team members should take initiative in relieving parental distress and improving their coping abilities. How to cite this article: Kichu S, Joshi P, Bhandari S, Lodha R, Jaykrishnan K. Experiences of the Parents of Children Admitted to PICU. Indian J Crit Care Med 2024;28(7):696-701.
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BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24â h post-dose (AUC0-24) and peak plasma concentration (C max) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0-24 and C max were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6)â h·mg·L-1), rifampicin (34.4 (95% CI 29.4-40.3)â h·mg·L-1), pyrazinamide (375.0 (95% CI 339.9-413.7)â h·mg·L-1) and ethambutol (8.0 (95% CI 6.4-10.0)â h·mg·L-1). Our multivariate models indicated that younger age (especially <2â years) and HIV-positive status were associated with lower AUC0-24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0-24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0-24 and slow acetylators had higher isoniazid AUC0-24 than intermediate acetylators. Determinants of C max were generally similar to those for AUC0-24. CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.
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Antituberculosos , Isoniazida , Niño , Adolescente , Humanos , Preescolar , Antituberculosos/uso terapéutico , Isoniazida/uso terapéutico , Pirazinamida/uso terapéutico , Etambutol/uso terapéutico , Rifampin/uso terapéuticoRESUMEN
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.
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Lesión Renal Aguda , Choque Séptico , Desequilibrio Hidroelectrolítico , Niño , Preescolar , Femenino , Humanos , Masculino , Soluciones Cristaloides , Fluidoterapia/efectos adversos , Fluidoterapia/métodos , Resucitación/métodos , Solución Salina , Choque Séptico/terapia , Desequilibrio Hidroelectrolítico/terapia , LactanteRESUMEN
The diagnosis of pediatric tuberculosis (TB) remains a major challenge, hence the evaluation of new tools for improved diagnostics is urgently required. We investigated the serum metabolic profile of children with culture-confirmed intra-thoracic TB (ITTB) (n = 23) and compared it with those of non-TB controls (NTCs) (n = 13) using proton NMR spectroscopy-based targeted and untargeted metabolomics approaches. In targeted metabolic profiling, five metabolites (histidine, glycerophosphocholine, creatine/phosphocreatine, acetate, and choline) differentiated TB children from NTCs. Additionally, seven discriminatory metabolites (N-α-acetyl-lysine, polyunsaturated fatty acids, phenylalanine, lysine, lipids, glutamate + glutamine, and dimethylglycine) were identified in untargeted metabolic profiling. The pathway analysis revealed alterations in six metabolic pathways. The altered metabolites were associated with impaired protein synthesis, hindered anti-inflammatory and cytoprotective mechanisms, abnormalities in energy generation processes and membrane metabolism, and deregulated fatty acid and lipid metabolisms in children with ITTB. The diagnostic significance of the classification models obtained from significantly distinguishing metabolites showed sensitivity, specificity, and area under the curve of 78.2%, 84.6%, and 0.86, respectively, in the targeted profiling and 92.3%, 100%, and 0.99, respectively, in the untargeted profiling. Our findings highlight detectable metabolic changes in childhood ITTB; however, further validation is warranted in a large cohort of the pediatric population.
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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.
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Asma , Humanos , Niño , Proteína C-Reactiva/análisis , Sistema Respiratorio , Inflamación , Biomarcadores , Óxido Nítrico/análisisRESUMEN
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.
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Asma Inducida por Ejercicio , Asma , Humanos , Niño , Asma/diagnóstico , Broncoconstricción , Oscilometría , Estudios Transversales , Pruebas de Provocación Bronquial , Prueba de Esfuerzo , Asma Inducida por Ejercicio/diagnósticoRESUMEN
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 beneï¬cial Biï¬dobacterium 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.
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Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a "Think globally, act locally" approach is required.
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Sepsis , Niño , Humanos , Sepsis/diagnóstico , Sepsis/terapia , Mortalidad Hospitalaria , Bases de Datos Factuales , Evaluación de Resultado en la Atención de SaludRESUMEN
Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.
Asunto(s)
Tuberculosis Extrapulmonar , Humanos , Estudios Retrospectivos , Riñón , Microscopía , ADNRESUMEN
A 11-year-old boy with acute myeloid leukemia was brought for treatment of severe acute respiratory infection in the National Capital Region, New Delhi, India. Avian influenza A(H5N1) infection was laboratory confirmed. Complete genome analysis indicated hemagglutinin gene clade 2.3.2.1a. We found the strain to be susceptible to amantadine and neuraminidase inhibitors.
Asunto(s)
Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Gripe Humana , Animales , Antivirales/farmacología , Aves , Niño , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , India , Subtipo H5N1 del Virus de la Influenza A/genética , Gripe Humana/diagnóstico , Gripe Humana/tratamiento farmacológico , Masculino , FilogeniaRESUMEN
OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.