Long Term Impact of Adeno-tonsillectomy on Immunity Against Respiratory Viral Infections; Evidence Deduced During COVID-19 Pandemic.

OBJECTIVES: To evaluate the risk of acquiring COVID-19 infection in patients who have undergone adeno-tonsillectomy (AT) as compared to their siblings. METHODS: In this bidirectional cohort control study, 36 cohorts, younger than 18 y, who underwent AT, and 27 controls (siblings of the enrolled cohorts, younger than 18 y) were recruited. Incidence of COVID-19 was analyzed by symptoms suggestive of COVID-19 infection, COVID-19 testing, and SARS-CoV-2 specific antibody measurement. RESULTS: In the cohort group, the overall COVID-19 positivity rate was 80.5% (n = 29/36) and symptomatic COVID-19 positivity rate was 68.9% (n = 20/29). Among the controls, the overall COVID-19 positivity rate was 44% (n = 12/27) and symptomatic COVID-19 positivity rate was 16% (n = 2/12). The cohorts had 1.8 times higher risk of contracting COVID-19 infection and the relative risk of symptomatic COVID-19 infections as compared to controls was 4.14. CONCLUSIONS: This pilot study indicates that adeno-tonsillectomy poses children at a significantly higher risk of COVID-19 infections and likely other viral upper respiratory tract infections.

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.

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

Efficacy of Bhramari pranayama and Om chanting on asthma control, quality of life, and airway inflammation in asthmatic children: an open-label randomized controlled trial.

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.

Knowledge, attitude, and practices among caregivers of children with Cystic Fibrosis.

BACKGROUND: Caregivers have crucial role in the care of the children with Cystic Fibrosis (CF), but there is limited knowledge about their knowledge, attitude, and practices (KAP) regarding chronic disease. This pilot study aimed to validate a self-developed KAP questionnaire for caregivers of young children with CF in India and determine factors associated with KAP. MATERIALS AND METHODS: A cross-sectional study was conducted among 95 caregivers of children with CF attending the specialty clinic of the pediatric outpatient department (OPD) in Northern India. Participants possessing certain characteristics such as willingness to participate and ability to understand Hindi or English language were enrolled in the study. Caregivers of children reported to the OPD with acute exacerbation requiring immediate hospitalization were excluded from the study. RESULTS: The self-developed KAP questionnaire had good content validity (CVI- 0.87-1.0) and internal consistency (Cronbach's α coefficient = 0.70, 0.71, 0.75 respectively). The majority of participants belonged to the Good KAP group (85.3%), while the remaining were in the Poor KAP group (14.7%). A χ2 test showed that KAP clusters vary significantly with sociodemographic variables like gender, marital status, educational status and monthly family income (p < .05). A weak negative correlation was found between knowledge and attitude scores in the Good KAP group (p < .001). Multiple linear regression analysis showed that the KAP of the caregivers was significantly influenced by knowledge related to clinical manifestation and complications, and attitude. CONCLUSION: All three sections of the KAP tool demonstrated good content validity and internal consistency. Caregivers had good knowledge, a positive attitude, and appropriate practices related to CF. However, targeted interventions are necessary to address specific areas for improvement, particularly for male caregivers with lower educational levels belonging to poor socioeconomic strata.

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.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Developing Standard Treatment Workflows-way to universal healthcare in India.

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80-90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC.

Serological profile of patients suspected with non-scrub typhus rickettsioses.

BACKGROUND: Rickettsial pathogens are Gram-negative, obligate intracellular bacteria. They are transmitted by arthropods and are responsible for a wide variety of disease, from minor to life-threatening, which have a global effect on human health. Limited data are available on the prevalence of rickettsial diseases from India, and the disease epidemiology is not fully described. This study aimed to diagnose non-scrub typhus rickettsioses including spotted fever and typhus group of Rickettsia in clinically suspected patients by using standard serological tests and recognition of common epidemiological conditions and clinical manifestations. METHODS: During the study period, a total of 700 patients of all ages with acute febrile illness were enrolled. Patients were screened for rickettsial infection using IgM Enzyme-linked immunosorbent assay (ELISA) and Immunofluorescence assay (IFA) was performed to confirm the ELISA positive results. The relevant demographic, clinical, and laboratory details of patients were documented and analyzed. RESULTS: Of 700 samples tested, 141 (20.2%) were found to be positive for IgM antibodies against rickettsioses using ELISA and IFA. SFGR was positive in 15 (2.2%), TGR was positive in 112 (16%) and 14 (2%) samples were positive for both groups. 20 (14.2%) patients required admission to the intensive care unit (ICU), and 24 (17%) in-hospital deaths occurred. CONCLUSIONS: The prevalence of rickettsioses in India appears to be underestimated; therefore, increased awareness and improved diagnostic testing could facilitate early detection of cases, pathogen-targeted appropriate treatment, and improved outcomes for patients. Despite the fact that Rickettsiae can be isolated or detected using molecular techniques in clinical specimens, serology still remains the most commonly used diagnostic method for rickettsioses around the world. Our study helps bridge the gap of limited data on Rickettsia in north India and could be useful for future epidemiological investigation of rickettsial diseases and outbreaks.

Microsporidia in HIV-Positive and HIV-Negative Pediatric Patients with Diarrhea at a Tertiary Care Hospital.

Background Human microsporidiosis presents as an important and rapidly emerging opportunistic infection. However, the exact burden of this infection especially in the pediatric population of Northern India remains unknown. In this study, we investigated the prevalence of microsporidia among human immunodeficiency virus (HIV)-positive and HIV-negative pediatric patients who presented with diarrhea. Methods A total of 263 children were recruited consisting of 98 HIV seropositive with diarrhea and 165 HIV seronegative but with diarrhea. Morning stool samples were collected and both direct and formol ether concentrated samples were examined for the presence of intestinal parasites. The modified acid-fast staining was done for coccidian parasites and trichrome stain for microsporidia detection. Further, the species were detected using a real-time polymerase chain reaction (PCR) targeting a conserved region of the small ribosomal subunit rRNA gene of Enterocytozoon bieneusi , Encephalitozoon hellem , Encephalitozoon intestinalis , and Encephalitozoon cuniculi . Results Overall, one or more parasites were detected in 52.04% (51/98) of HIV seropositive and 53.33% (88/165) of seronegative children ( p = 0.8391). However, coccidian parasites were detected in a significantly huge number of HIV seropositive children (21.43% [21/98]) as compared with HIV seronegative children (4.24% [7/165]). Microsporidial DNA could be detected in HIV seropositive with diarrhea children (17.35% [17/98]) by PCR. A significant correlation between low CD4 count (≤ 200/µL) and intestinal parasite positivity could be established. Conclusion Microsporidia is a significant cause of diarrhea in HIV seropositive pediatric patients and should be kept in mind as one of the differential diagnoses in such patients.

Childhood and Adolescent Sleep Awareness in Caregivers and Health Care Providers: A Community- and Hospital-Based Survey.

BACKGROUND: Sleep disorders are common in childhood and adolescence with mental and physical consequences needing appropriate intervention by caregivers and health care providers (HCPs). The objective of the study, conducted at a tertiary teaching hospital and public school in north India, was to develop validated questionnaires to evaluate childhood and adolescent sleep awareness in caregivers and HCPs. METHODS: The study participants (caregivers represented by parents of 2-18 year olds attending a public school and of those attending outpatient services at the study hospital and HCPs represented by medical interns and nursing graduates within 1 year of graduation) were enrolled after appropriate screening. RESULTS: Two separate questionnaires in English for caregivers (also translated in Hindi) and HCPs were applied on 313 caregivers and 175 HCPs (110 medical interns and 65 nursing graduates) and developed and validated with a Cronbach α of 0.73 and 0.74, respectively. The questionnaires covered three domains: sleep hygiene, sleep related health problems, and miscellaneous. Both group of respondents had >50% correct responses in sleep hygiene. The ĸ agreement between knowledge and practice of sleep hygiene in caregivers was 0.2. Poor response (<50% correct responses) was seen in sleep-related health problems in both groups of respondents implying knowledge deficit in various sleep disorders. The HCPs performed poorly on basic theoretical questions in miscellaneous domain. For consultation of sleep problems, most caregivers (48%) chose pediatricians. CONCLUSION: There is a need to strengthen undergraduate medical and nursing curriculum in sleep. Caregivers should be made aware of implications of unhealthy sleep.

Utility of Inferior Vena Cava Distensibility and Respiratory Variation in Peak Aortic Blood Flow Velocity to Predict Fluid Responsiveness in Children with Shock.

OBJECTIVES: To evaluate the sensitivity and specificity of inferior vena cava (IVC) distensibility index (∆IVC) and respiratory variation in peak aortic blood flow velocity (∆Vpeak) to predict fluid responsiveness in ventilated children with shock and to find out the best cut-off values for predicting fluid responsiveness. METHODS: In this prospective observational study, conducted in a pediatric ICU from January 2019 through May 2020, consecutive children aged 2 mo to 17 y with shock requiring fluid bolus were included. ∆IVC and ∆Vpeak were measured before and immediately after 10 ml/kg fluid bolus administration. ∆IVC and ∆Vpeak were compared between responders and non-responders, defined by a change in stroke volume index (SVI) of ≥10%. RESULTS: Thirty-seven ventilated children [26 (70.4%) boys] with median age of 60 (36, 108) mo were included. The median (IQR) ∆IVC was 21.7% (14.3, 30.9) and the median (IQR) ΔVpeak was 11.3% (7.2, 15.2). Twenty-three (62%) children were fluid responsive. The median (IQR) ∆IVC was higher in responders compared to non-responders [26% (16.9, 36.5) vs. 17.2% (8.4, 21.9); p = 0.018] and mean (SD) ΔVpeak was higher in responders [13.9% (6.1) vs. 8.4% (3.9), p = 0.004]. The prediction of fluid responsiveness with ΔIVC [ROC curve area 0.73 (0.56-0.9), p = 0.01] and ΔVpeak [ROC curve area 0.78 (0.63-0.94), p = 0.002] was similar. The best cut-off of ∆IVC to predict fluid responsiveness was 23% (sensitivity, 60.8%; specificity, 85.7%) and ΔVpeak was 11.3% (sensitivity, 74%; specificity, 86%). CONCLUSIONS: In this study, authors found that ∆IVC and ΔVpeak were good predictors of fluid responsiveness in ventilated children with shock.

Small molecule bio-signature in childhood intra-thoracic tuberculosis identified by metabolomics.

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.

Air pollution and its effects on emergency room visits in tertiary respiratory care centers in Delhi, India.

Environmental pollution has harmful effects on human health, particularly the respiratory system. We aimed to study the impact of daily ambient air pollution on daily emergency room visits for acute respiratory symptoms. This study was conducted in two tertiary respiratory care centres in Delhi, India. Daily counts of emergency room visits were collected. All patients attending the emergency room were screened for acute onset (less than 2 weeks) of respiratory symptoms and were recruited if they were staying in Delhi continuously for at least 4 weeks and having onset (≤2 weeks) of respiratory symptoms. Daily average air pollution data for the study period was obtained from four continuous ambient air quality monitoring stations. A total of 61,285 patients were screened and 11,424 were enrolled from June 2017 to February 2019. Cough and difficulty in breathing were most common respiratory symptoms. Poor air quality was observed during the months of October to December. Emergency room visits with acute respiratory symptoms significantly increased per standard deviation increase in PM10 from lag days 2-7. Increase in wheezing was primarily seen with increase in NO2. Pollutant levels have effect on acute respiratory symptoms and thus influence emergency room visits. *************************************************************** *Appendix Authors list Kamal Singhal,1 Kana Ram Jat,2 Karan Madan,3 Mohan P. George,4 Kalaivani Mani,5 Randeep Guleria,3 Ravindra Mohan Pandey,5 Rupinder Singh Dhaliwal,6 Rakesh Lodha,2 Varinder Singh1 1Department of Paediatrics, Lady Hardinge Medical College and associated Kalawati Saran Children's Hospital, New Delhi, India 2Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India 3Department of Pulmonary Medicine, Critical Care and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India 4Department of Environment, Delhi Pollution Control Committee, Kashmere Gate, New Delhi, India 5Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India 6Department of Non-communicable Diseases, Indian Council of Medical Research, New Delhi, India.

A Randomized Controlled Trial of Norepinephrine Plus Dobutamine Versus Epinephrine As First-Line Vasoactive Agents in Children With Fluid Refractory Cold Septic Shock.

Our objective was to compare norepinephrine plus dobutamine versus epinephrine as the first-line agent in children with fluid refractory cold septic shock. DESIGN: Open-label randomized controlled study. SETTING: A single-center PICU from North India. PATIENTS: Children 2 months to less than 18 years old with fluid refractory cold septic shock. INTERVENTIONS: In the intervention group, norepinephrine and dobutamine were started and in the control group, epinephrine was started as the first-line vasoactive agent. The primary outcome was the proportion attaining shock resolution (attaining all the therapeutic endpoints) at 1 hour of therapy. MEASUREMENTS AND MAIN RESULTS: We enrolled 67 children: 34 in the norepinephrine plus dobutamine group (intervention) and 33 in the epinephrine group (control). There was no difference in shock resolution at 1 hour (17.6% vs 9%; risk ratio [RR], 2.0; 95% CI, 0.54-7.35; p = 0.25), 6 hours (76.4% vs 54.5%; RR, 1.69; 95% CI, 0.92-3.13; p = 0.06), and 24 hours between the intervention and control groups, respectively. Children in the norepinephrine plus dobutamine group attained shock resolution earlier (measured from starting of vasoactive agents to attaining all the therapeutic endpoints) (hazard ratio, 1.84 [1.1-3.08]). The difference in 28-day mortality was not significant (23.5% vs 39.3% in the intervention and control groups, respectively [RR, 0.59; 95% CI, 0.28-1.25]). CONCLUSIONS: In children with fluid refractory cold septic shock, with use of norepinephrine plus dobutamine as first-line agents, the difference in the proportion of children attaining shock resolution at 1 hour between the groups was inconclusive. However, the time to shock resolution was earlier in the norepinephrine plus dobutamine group. Also, fewer children in the intervention group were refractory to treatment. Further studies powered to detect (or exclude) an important difference would be required to test this intervention.

Management of Dengue: An Updated Review.

Dengue is an important public health problem with a wide clinical spectrum. The World Health Organization classifies dengue into probable dengue, dengue with warning signs, and severe dengue. Severe dengue, characterized by plasma leakage, severe bleeding, or organ impairment, entails significant morbidity and mortality if not treated timely. There are no definitive curative medications for dengue; management is supportive. Judicious fluid resuscitation during the critical phase of dengue is the cornerstone of management. Crystalloids are the initial fluid of choice. Prophylactic platelet transfusion is not recommended. Organ involvement in severe dengue should be carefully looked for and managed. Secondary hemophagocytic lymphohistiocytosis is a potentially fatal complication of dengue that needs to be recognized, as specific management with steroids or intravenous immunoglobulin may improve outcomes. Several compounds with anti-dengue potential are being studied; no anti-dengue drug is available so far.