Strengthening facility-based integrated emergency care services for time sensitive emergencies at all levels of healthcare in India: An implementation research study protocol.

BACKGROUND: The healthcare system in India is tiered and has primary, secondary and tertiary levels of facilities depending on the complexity and severity of health challenges at these facilities. Evidence suggests that emergency services in the country is fragmented. This study aims to identify the barriers and facilitators of emergency care delivery for patients with time-sensitive conditions, and develop and implement a contextually relevant model, and measure its impact using implementation research outcomes. METHODS: We will study 85 healthcare facilities across five zones of the country and focus on emergency care delivery for 11 time-sensitive conditions. This implementation research will include seven phases: the preparatory phase, formative assessment, co-design of Model "Zero", co-implementation, model optimization, end-line evaluation and consolidation phase. The "preparatory phase" will involve stakeholder meetings, approval from health authorities and the establishment of a research ecosystem. The "formative assessment" will include quantitative and qualitative evaluations of the existing healthcare facilities and personnel to identify gaps, barriers and facilitators of emergency care services for time-sensitive conditions. On the basis of the results of the formative assessment, context-specific implementation strategies will be developed through meetings with stakeholders, providers and experts. The "co-design of Model 'Zero'" phase will help develop the initial Model "Zero", which will be pilot tested on a small scale (co-implementation). In the "model optimization" phase, iterative feedback loops of meetings and testing various strategies will help develop and implement the final context-specific model. End-line evaluation will assess implementation research outcomes such as acceptability, adoption, fidelity and penetration. The consolidation phase will include planning for the sustenance of the interventions. DISCUSSION: In a country such as India, where resources are scarce, this study will identify the barriers and facilitators to delivering emergency care services for time-sensitive conditions across five varied zones of the country. Stakeholder and provider participation in developing consensus-based implementation strategies, along with iterative cycles of meetings and testing, will help adapt these strategies to local needs. This approach will ensure that the developed models are practical, feasible and tailored to the specific challenges and requirements of each region.

Mobile Direct Observed Therapy (MDOT) for Inhaler Therapy in Children With Newly Diagnosed Asthma: A Pilot Study.

OBJECTIVE: We aimed to assess the acceptability of Mobile Direct Observed Therapy (MDOT) amongst the parents/caregivers of children with asthma. METHODS: This open-label pilot randomized controlled trial enrolled newly diagnosed children aged 5-15 years with asthma, who were followed up telephonically for six weeks. Parents of children in the intervention arm were requested to record share a video of the metered dose inhaler with spacer (MDI-S) technique of their child on a mobile phone and share it through WhatsApp with investigator who then provided corrective measures as required by text/video message. The children in the control arm continued follow-up telephonically without exchange of any videos for six weeks. The primary outcome measures were the acceptability of MDOT and the effect of such interaction on the correctness of the MDI technique. Secondary outcome measures were the level of asthma control as per GINA guidelines and the caregivers' perception and feedback about MDOT. RESULTS: A total of 30 children were enrolled, 15 in each arm. Thirteen (86%) parents uploaded good-quality videos. The average number of incorrect steps decreased from 2.64 in the first video to 0.18 after the fourth video and nil after the fifth video in the MDOT group. At six weeks of follow-up, the average number of incorrect steps was significantly lower in the MDOT group compared to the control group (0 vs 2.9; P <0.0001). The proportion of children having controlled asthma was better in the MDOT group compared to controls (85% vs 70%) (P = 0.39). All parents liked MDOT. CONCLUSIONS: MDOT was well accepted by caregivers of children with astham and was helpful in improving the MDI-S technique.

Diagnostic accuracy of airway ultrasound in confirming the endotracheal tube depth in critically ill children.

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.

Prevalence and Clinical Implications of Autoantibodies in Juvenile Dermatomyositis: A Single-Center Experience From India.

OBJECTIVE: ​​This 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.

Experiences of the Parents of Children Admitted to PICU.

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.

Genetics of 67 patients of suspected primary ciliary dyskinesia from India.

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.

Approach to fever in children.

BACKGROUND: Fever in children is one of the most common reasons for outpatient visits as well as in-patient evaluation, often causing anxiety among parents and caregivers. Fever can be a standalone feature or be associated with other localising symptoms and signs like rash, lymphadenopathy, or any other organ system involvement with or without a focus of infection. The etiologies of fever vary depending on the clinical setting and epidemiology. India being a tropical country, sees a distinct spectrum of tropical infections. Physicians need to stay updated on the prevalent diseases in their region and the unique factors that may influence the clinical presentations and course of fever in the cohort of children they manage. The challenge lies in balancing the benefit of early treatment for severe diseases versus the harms of unnecessary investigations and treatment for self-resolving illnesses. OBJECTIVES: This review aims to provide a comprehensive overview of fever in children, covering its etiology, clinical features, and management strategies. This review offers an algorithmic approach to fever tailored to the Indian setting to guide physicians in identifying the disease based on clinical symptoms and signs, ordering essential laboratory investigations, and initiating appropriate management promptly. CONTENT: The review categorises fever into various segments like fever with localising signs like rash, lymphadenopathy, fever due to infection localised to a particular organ system, and fever without a focus including fever of unknown origin. It delves into the diverse etiological factors contributing to fever in each of these categories, encompassing infectious and non-infectious origins. It gives pointers to identify the etiology from history, examination, and confirm them with judicious use of diagnostic investigations with emphasis on identifying the red flag signs that require immediate attention, especially in vulnerable groups like neonates and young infants.

Risk Factors for Procedural Complications of Pediatric Flexible Bronchoscopy: Experience From a Tertiary Care Centre in Northern India.

We analyzed the records of 869 children who underwent flexible bronchoscopy. We found procedural complications in 6.7% (n = 59), with severe events in 3.2% (n = 28). Age < 1 y, recurrent respiratory papillomatosis, and finding lower airway malacia on bronchoscopy were identified as independent risk factors for developing complications with adjusted odds ratio (95% CI) of 2.6 (1.3, 4.9); P = 0.004; 5.4 (1.7, 17.6); P = 0.005 and 2.1 (1.1, 4.0); P = 0.031, respectively.

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.

Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis of Second-Line Anti-Tubercular Drugs in Indian Children with Multi-Drug Resistance.

OBJECTIVES: To conduct a thorough pharmacokinetic (PK) - pharmacodynamic (PD) analysis of second-line anti-tubercular therapy (ATT) in children diagnosed with multi-drug resistant tuberculosis (MDR-TB). METHODS: Twenty-seven children undergoing second-line ATT, including kanamycin (KM, n = 13), fluoroquinolones (FQs, n = 26), ethionamide (ETH, n = 20), para amino salicylic acid (PASA, n = 4), and cycloserine (CS, n = 15), were sampled at 0 (pre-dose), 1, 2, 3, and 4 h post-drug administration. Plasma drug levels were determined using a mass spectrometer and the collected dataset underwent non-compartmental PK analysis using PK solver ver2.0. PK/PD assessments involved individual drug simulation studies on 1000 subjects using Modviz Pop ver 1.0 in R-software. RESULTS: A total of 22 and 5 children were considered as responders and non-responders, respectively. Non-compartmental PK analysis revealed mean plasma drug levels of this study cohort attained the targeted maximum drug plasma concentration (Cmax). The ratio of Cmax /minimum inhibitory concentration (MIC) or the area under the curve (AUC)/MIC of the studied drugs had not shown a significant difference between responders and non-responders. Non-responders of ETH and ofloxacin had shown deviation from the derived dose-response profile for the simulated population. CONCLUSIONS: The management of MDR-TB with second-line ATT following national guidelines had cured the majority of the children (> 80%) who participated in the study. Inter-individual variability in few children from the targeted Cmax range suggests the need for future investigations on pharmacogenomic aspects of drug metabolism.

Infant Pulmonary Function Tests in Children with Airway Anomalies and Correlation with Bronchoscopy Findings.

OBJECTIVES: To evaluate the role infant pulmonary function tests (Tidal Breathing Flow Volume Loops, TBFVL) in children with airway anomalies and to correlate the TBFVL so obtained with bronchoscopy findings. METHODS: In this prospective cohort study, we enrolled children aged 0-2 years with airway anomalies and performed TBFVL and bronchoscopy. The primary outcome measure was graphic pattern of TBFVL in laryngomalacia. Secondary outcome measures were types of TBFVL results in various airway anomalies and controls. RESULTS: Out of 53 children enrolled, 28 (52.3%) had laryngomalacia. Pattern 3 (fluttering of inspiratory limb) was commonest TBFVL pattern in laryngomalacia. Among TBFVL parameters, the ratio of inspiratory time to expiratory time (Ti/Te) and tPTEF/tE was significantly high in children with isolated laryngomalacia compared to controls. At six months of follow-up, TBFVL pattern 1 (normal) became the commonest pattern. CONCLUSION: A particular type of airway anomaly may have a characteristic graphic pattern in TBFVL and TBFVL pattern may indicate improvement in airway anomalies in follow-up.

B cell repertoire sequencing of HIV-1 pediatric elite-neutralizers identifies multiple broadly neutralizing antibody clonotypes.

Introduction: A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants. Methods: We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1. Results: BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330. Discussion: This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

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.

Approach towards surveillance-based diagnosis of acute respiratory illness in India: Expert recommendations.

BACKGROUND: Emerging infectious diseases, often zoonotic, demand a collaborative "One-Health" surveillance approach due to human activities. The need for standardized diagnostic and surveillance algorithms is emphasized to address the difficulty in clinical differentiation and curb antimicrobial resistance. OBJECTIVE: The present recommendations are comprehensive diagnostic and surveillance algorithm for ARIs, developed by the Indian Council of Medical Research (ICMR), which aims to enhance early detection and treatment with improved surveillance. This algorithm shall be serving as a blueprint for respiratory infections landscape in the country and early detection of surge of respiratory infections in the country. CONTENT: The ICMR has risen up to the threat of emerging and re-emerging infections. Here, we seek to recommend a structured approach for diagnosing respiratory illnesses. The recommendations emphasize the significance of prioritizing respiratory pathogens based on factors such as the frequency of occurrence (seasonal or geographical), disease severity, ease of diagnosis and public health importance. The proposed surveillance-based diagnostic algorithm for ARI relies on a combination of gold-standard conventional methods, innovative serological and molecular techniques, as well as radiological approaches, which collectively contribute to the detection of various causative agents. The diagnostic part of the integrated algorithm can be dealt at the local microbiology laboratory of the healthcare facility with the few positive and negative specimens shipped to linked viral disease research laboratories (VRDLs) and other ICMR designated laboratories for genome characterisation, cluster identification and identification of novel agents.