Publications by authors named "Rakesh Lodha"

369 Publications

Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study.

Lancet Infect Dis 2021 Nov 23. Epub 2021 Nov 23.

Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India.

Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.

Methods: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%.

Findings: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61).

Interpretation: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.

Funding: None.

Translation: For the Hindi translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00674-5DOI Listing
November 2021

Predictors of mortality in children with cystic fibrosis in India.

Pediatr Pulmonol 2021 Nov 26. Epub 2021 Nov 26.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, New Delhi, India.

Background: There is a lack of studies on cystic fibrosis (CF) outcomes in children from developing countries like India. Identifying risk factors for mortality may help identify the high-risk group and plan policy management of such patients. We aimed to determine the factors associated with mortality among Indian children with CF.

Methods: In this retrospective study, we extracted demography, clinical features, laboratory and outcome data from medical records of children with CF. Bivariate and multivariate analysis was performed to identify variables associated with mortality.

Results: We enrolled 178 children, and there were 32 (18.0%) deaths. Median (IQR) z-score for body mass index (BMI) at last follow up was -1.5 (-2.7, -0.2) and -2.5 (-4.0, -1.6), p-value 0.039, in survived and deceased group respectively. Mean (SD) of % predicted of FEV1/FVC and FEV1 25-75 at the time of diagnosis in survived versus diseased group was 94.7 (24.1) versus 81.5 (19.1), p-value 0.063 and 56.1 (38.9) versus 45.7 (29.9), p-value 0.347, respectively. Significant factors associated with mortality included history of neonatal complications; hazard ratio (HR): 8.5 (95% confidence interval [CI]: 3.0-23.9, p < 0.001), low Z-scores for BMI at the time of diagnosis; HR: 7.1 (95% CI: 2.3-22.0, p < 0.001), FEV1/FVC at the time of diagnosis; HR: 5.1 (95% CI: 1.65-15.4, p < 0.004), and FEV1 25-75; HR: 3.6 (95% CI: 1.1-11.8, p = 0.03).

Conclusions: Factors associated with increased mortality risk included neonatal complications, low BMI, and lower pulmonary function test results. Low BMI and low PFT indices can be improved upon by timely treatment of respiratory infections, better nutrition, early diagnosis, and treatment. A newborn screening program may help in early diagnosis and identification of the neonatal problem of CF.
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http://dx.doi.org/10.1002/ppul.25766DOI Listing
November 2021

Acute Severe Hypertension in Children: An Ongoing Search for Therapeutic Agent of Choice.

Indian J Pediatr 2021 Nov 25. Epub 2021 Nov 25.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-04036-5DOI Listing
November 2021

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

J Paediatr Child Health 2021 Nov 9. Epub 2021 Nov 9.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Aim: To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality.

Methods: In a prospective cohort study, critically ill children (1 month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated.

Results: Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR) = 2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR = 1.525, 95% CI: 1.142, 2.037) and haematological (OR = 1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR = 1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality.

Conclusions: Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade.
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http://dx.doi.org/10.1111/jpc.15804DOI Listing
November 2021

Identification and characterization of novel infection associated transcripts in macrophages.

RNA Biol 2021 Nov 8:1-8. Epub 2021 Nov 8.

Department of Cardio- Respiratory Disease Biology, CSIR Institute of Genomics and Integrative Biology, Mathura Road, New Delhi-110025, India.

By analysis of lncRNA expression profiles of macrophages in response to (Mtb) infection, we identified novel highly expressed transcripts, unique in encompassing a protein coding transcript- Cytidine Monophosphate Kinase 2 (CMPK2) and a previously identified lncRNA- Negative Regulator of Interferon Response (NRIR). While these transcripts (TILT1, 2,3 - LR4 and nfection induced ong ranscript) are induced by virulent Mtb as well as lipopolysaccharide (LPS) early, lack of/delayed expression in non-viable Mtb/BCG infected cells, respectively, suggest an important role in macrophage responses. The elevated expression by 3 hr in response to fast growing bacteria further emphasizes the importance of these RNAs in the macrophage infection response. Overall, we provide evidence for the presence of multiple transcripts that form a part of the early infection response programme of macrophages. IFN: Interferon; NRIR: negative regulator of interferon response; CMPK2: cytidine/ uridine monophosphate kinase; LPS: lipopolysaccharide; LAM: Lipoarabinomannan; PIMs: Phosphatidylinositol Mannosides; TILT1, 2,3: LR4 and nfection induced ong ranscript; TLR4: Toll-like receptor 4; Mtb: ; BCG: BCG; MDMs: human monocyte derived macrophages.
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http://dx.doi.org/10.1080/15476286.2021.1989217DOI Listing
November 2021

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia.

J Glob Health 2021 9;11:04062. Epub 2021 Oct 9.

Centre d'Infectiologie Charles Mérieux, Antanarivo, Madagascar.

Background: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores.

Methods: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules.

Results: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73).

Conclusions: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.
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http://dx.doi.org/10.7189/jogh.11.04062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542381PMC
November 2021

Outcomes of multisystem inflammatory syndrome in children temporally related to COVID-19: a longitudinal study.

Rheumatol Int 2021 Oct 19. Epub 2021 Oct 19.

All India Institute of Medical Sciences, New Delhi, India.

To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5-18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.
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http://dx.doi.org/10.1007/s00296-021-05030-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524205PMC
October 2021

Dengue virus replication enhances labile zinc pools by modulation of ZIP8.

Cell Microbiol 2021 Oct 7:e13395. Epub 2021 Oct 7.

Clinical and Cellular Virology lab, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India.

Zinc-dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life-cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV-inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA-mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection. TAKE AWAYS: Dengue virus utilises cellular zinc homeostasis during replication of its RNA. ZIP8 upregulates free zinc levels during dengue virus replication. Enhanced viremia associates with elevated intracellular free zinc in dengue.
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http://dx.doi.org/10.1111/cmi.13395DOI Listing
October 2021

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce.

Crit Care Med 2021 Oct 6. Epub 2021 Oct 6.

Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada. Pediatric and Neonatal ICU, University Children`s Hospital Zurich, Zurich, Switzerland, and Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia. KEMRI Wellcome Trust Research Program, Nairobi, Kenya. Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa. Department of Paediatrics, Verona University Hospital, Verona, Italy. Department of Clinical Infection Microbiology and Immunology, University of Liverpool Institute of Infection, Veterinary and Ecological Sciences, Liverpool, United Kingdom. Children's Hospital of Philadelphia, Philadelphia, PA. International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, and The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, PA. Paediatric Intensive Care Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. Departments of Emergency Medicine and Pediatrics, University of California San Diego School of Medicine, La Jolla, CA. Department of Pediatrics, University of British Columbia and British Columbia Children's Hospital, Vancouver, BC, Canada. All India Institute of Medical Sciences, Delhi, India. St. Mary's Hospital, Imperial College Healthcare NHS Trust, and Imperial College London, London, United Kingdom. Associação de Medicina Intensiva Brasileira, São Paulo, Brazil. University College London Great Ormond Street Institute of Child Health, London, United Kingdom. Departments of Anesthesia and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada. Departments of Pediatrics and Emergency Medicine, University of Colorado School of Medicine, Aurora, CO. Departments of Pediatrics, Hospital Sírio-Libanês and Hospital Universitário da Universidade de São Paulo, São Paolo, Brazil. Pediatric Intensive Care, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA. University of British Columbia, Vancouver, BC, Canada. Mbarara University of Science and Technology, Mbarara, Uganda. Department of Pediatrics, University of Florida, Gainesville, FL. Ann & Robert H. Lurie Children's Hospital and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Lurie Children's Pediatric Research & Evidence Synthesis Center (PRECIISE): A JBI Affiliated Group, Chicago, IL.

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.
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http://dx.doi.org/10.1097/CCM.0000000000005294DOI Listing
October 2021

Immunophenotyping and Transcriptional Profiling of Human Plasmablasts in Dengue.

J Virol 2021 Nov 15;95(23):e0061021. Epub 2021 Sep 15.

ICGEB-Emory Vaccine Center, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

Plasmablasts represent a specialized class of antibody-secreting effector B cells that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections such as dengue or Ebola that cause hemorrhagic fever. To gain a detailed understanding of human plasmablast responses beyond antibody expression, here, we performed immunophenotyping and RNA sequencing (RNA-seq) analysis of the plasmablasts from dengue febrile children in India. We found that plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues, including skin, mucosa, and intestine, and upregulated the expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated the expression of receptors for several B-cell prosurvival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock than in patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody-dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.
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http://dx.doi.org/10.1128/JVI.00610-21DOI Listing
November 2021

Childhood Intra-Thoracic Tuberculosis Clinical Presentation Determines Yield of Laboratory Diagnostic Assays.

Front Pediatr 2021 25;9:667726. Epub 2021 Aug 25.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Diagnosis of intra-thoracic tuberculosis (ITTB) in children is difficult due to the paucibacillary nature of the disease, the challenge in collecting appropriate specimens, and the low sensitivity of smear microscopy and culture. Culture and Xpert MTB/RIF provide higher diagnostic yield in presumptive TB in adults than in children. Current study was designed to understand poor yield of diagnostic assays in children. Children with presumptive ITTB were subjected to gastric aspirates and induced sputum twice. Samples were tested by Ziehl-Neelsen stain, Xpert MTB/RIF-assay, and MGIT-960 culture. Subjects were grouped as Confirmed, Unconfirmed, and Unlikely TB, and classified as progressive primary disease (PPD, lung parenchymal lesion), and primary pulmonary complex (PPC, hilar lymphadenopathy) on chest X-ray. Of children with culture-positive TB 51/394 (12.9%), culture-negative TB 305 (77.4%), and unlikely TB 38 (9.6%), 9 (2.3%) were smear positive, while 95 (24.1%) were Xpert-MTB/RIF positive. Xpert-MTB/RIF detected 40/51 culture confirmed cases (sensitivity 78.4% and NPV 96.3%). Culture was positive in more children presenting as PPD ( < 0.04). In culture-negative TB group, Xpert positivity was seen in 31% of those with PPD and 11.9% in those with PPC ( < 0.001). Xpert-MTB/RIF improved diagnosis by 2-fold and increased detection of MDR-TB. Both liquid culture and Xpert-MTB/RIF gave higher yield in children with lung parenchymal lesions. Children with hilar lymphadenopathy without active lung parenchymal lesions had poor diagnostic yield even with sensitive nucleic acid amplification tests, due to paucibacillary/localized disease, suggesting possible utility of invasively collected samples in early diagnosis and treatment.
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http://dx.doi.org/10.3389/fped.2021.667726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425475PMC
August 2021

Clinical Profile of Children With Cystic Fibrosis Surviving Through Adolescence and Beyond.

Indian Pediatr 2021 Sep 4. Epub 2021 Sep 4.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.

Objective: To document morbidities in adolescents with cystic fibrosis from India.

Methods: Details of children with cystic fibrosis surviving beyond 15 years of age were extracted from hospital records, and analyzed.

Results: 43 children [Median (IQR) age 18.7 (17, 20.6) years, were enrolled. Median (IQR) body mass index was 15.82 (13.5, 19.05) kg/m2. Pseudomonas species were isolated from respiratory specimens of 34 (79%) adolescents. Allergic bronchopulmonary aspergillosis (ABPA) and Cystic fibrosis related diabetes (CFRD) were seen in 12 (28%) and 11 (26%) patients, respectively. Conjugated hyperbilirubinemia and distal intestinal obstruction syndrome (DIOS) were diagnosed in 15 (35%) and 6 (14%) children, respectively. Pseudomonas species colonization (P=0.04) and multiple pulmonary exacerbation in last one year (P=0.0002) were significant predictors of FEV1%.

Conclusion: Malnutrition, Chronic airway colonization, ABPA, CFRD, conjugated hyperbilirubinemia, DIOS are morbidities observed in adolescents with CF in India. The data support the need for early screening of CF associated morbidities.
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September 2021

Physical Growth and Its Determinants in Indian Children with Down Syndrome, from 3 Months to 5 Years of Age.

Indian J Pediatr 2021 Aug 19. Epub 2021 Aug 19.

Departments of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

Objective: To compare the growth of Indian children with Down syndrome (DS), with typically developing Indian children. The effect of comorbidities on their physical growth was also evaluated, so that factors affecting growth can be identified early and timely interventions be planned.

Methods: A cross-sectional study was conducted at the All India Institute of Medical Sciences, New Delhi from June 2015 to June 2017. Children with karyotype-proven DS within age group of 3 mo to 5 y were enrolled as study subjects. Children with DS having mosaic karyotype were excluded. Anthropometry and associated comorbidities were assessed.

Results: Hundred and eight children with DS were enrolled, mean WHO z scores were-WAZ: -2.31 (SD 1.44), HAZ: -2.51 (SD 1.47), BAZ: -1.07 (SD 1.8), and HCZ: -2.79 (SD 1.21). Congenital heart disease (in 44.5% children), hypothyroidism (in 27.7%), and anemia (in 50%) were the common comorbidities. Growth parameters of children with and without any comorbidity were significantly different, mean WHO z scores were WAZ -2.61 vs. -1.09 (p = 0.005), HAZ -2.43 vs. -2.41 (p = 0.3), BAZ -1.49 vs. -0.38 (p = 0.001), and HCZ -3.13 vs. -2.33 (p = 0.001).

Conclusion: Growth of Indian children with DS is significantly less compared to normally growing children. Weight was affected maximum during infancy, length was more affected as the age progressed, head circumference was affected similarly in all age groups, whereas BMI showed almost progressive increase with age. Children with severe heart disease had significantly lower BMI whereas children with treated hypothyroidism had better growth. There is a need for a large longitudinal study on Indian children with DS to construct Indian DS-specific growth charts.
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http://dx.doi.org/10.1007/s12098-021-03864-9DOI Listing
August 2021

The impact of pediatric tracheostomy on the quality of life of caregivers.

Int J Pediatr Otorhinolaryngol 2021 Oct 27;149:110854. Epub 2021 Jul 27.

Department of Otolaryngology, Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.

Objective: Pediatric tracheostomy is a challenge in otolaryngology practice and it is associated with greater morbidity and mortality than in adults; hence, constant vigilance by the designated family caregiver is critical. This study was designed to assess the impact of on quality of life of caregivers in a homecare setting as a result of the presence of child with a tracheostomy.

Methods: This was a combined retrospective and prospective cohort study with caregivers of children younger than 16 years who had undergone a tracheostomy, had been discharged home with a tracheostomy tube and completed 6 months of domiciliary tracheostomy care. The consenting primary caregivers were assessed for their quality of life based on the PedsQL v 4.0 questionnaires across various domains.

Results: We identified the primary caregivers of 85 children who had undergone a tracheostomy during the study period. The children's median age was 3.5 years (range, 9 months to 14 years). The mean caregiver health-related quality of life (HRQOL) score was 59.3, the mean family functioning score was 62.8, and the mean total family impact score was 54.7 with relative deficits seen in caregiver's social functioning (56.9) and emotional functioning (53.2). Good or average quality of physical and social function was seen among 74 % and 65 % of caregivers respectively while only 55 % were reported having good or average emotional function. Emotional disturbance, interfering with everyday family activities, and sleep disturbance were the major concerns among caregivers.

Conclusion: The biopsychosocial consequences of caring for a child with a tracheostomy are profound for the family, affecting the quality of life of caregivers and adding to the emotional and social burden of the child's family.
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http://dx.doi.org/10.1016/j.ijporl.2021.110854DOI Listing
October 2021

Strengthening sepsis care at a tertiary care teaching hospital in New Delhi, India.

BMJ Open Qual 2021 07;10(Suppl 1)

Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Failure of early identification of sepsis in the emergency department (ED) leads to significant delays in antibiotic administration which adversely affects patient outcomes.

Aim: The primary objective of our Quality Improvement (QI) project was to reduce the door-to-antibiotic time (DTAT) by 30% from the preintervention in patients with suspected sepsis. Secondary objectives were to increase the blood culture collection rate by 30% from preintervention, investigate the predictors of improving DTAT and study the effect of these interventions on 24-hour in-hospital mortality.

Methods: This QI project was conducted in the ED of a tertiary care teaching hospital of North India; the ED receives approximately 400 patients per day. Adult patients with suspected sepsis presenting to our ED were included in the study, between January 2019 and December 2020. The study was divided into three phases; preintervention phase (100 patients), intervention phase (100 patients) and postintervention phase (93 patients). DTAT and blood cultures prior to antibiotic administration was recorded for all patients. Blood culture yield and 24-hour in-hospital mortality were also recorded using standard data templates. Change ideas planned by the Sepsis QI Team were implemented after conducting plan-do-study-act cycles.

Results: The median DTAT reduced from 155 min in preintervention phase to 78 min in postintervention phase. Drawing of blood cultures prior to antibiotic administration improved by 67%. Application of novel screening tool at triage was found to be an independent predictor of reduced DTAT.

Conclusion: Our QI project identified the existing lacunae in implementation of the sepsis bundle which were dealt with in a stepwise manner. The sepsis screening tool and on-site training improved care of patients with sepsis. A similar approach can be used to deal with complex quality issues in other high-volume low-resource settings.
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http://dx.doi.org/10.1136/bmjoq-2020-001335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336124PMC
July 2021

Dexmedetomidine vs Midazolam for Sedation in Mechanically Ventilated Children: Few Concerns: Authors' Reply.

Indian Pediatr 2021 07;58(7):690

Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, AIIMS, New Delhi.

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July 2021

Unexplained to Unexpected: Cytokine Levels Unravel the Mystery and Help Attain Closure in Sudden Unexpected Death in Children.

Indian J Pediatr 2021 09 8;88(9):855-856. Epub 2021 Jul 8.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-03869-4DOI Listing
September 2021

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

J Trop Pediatr 2021 07;67(3)

Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubli, Karnataka 580021, India.

Introduction: There is a lack of large multicentric studies in children with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in children hospitalized with COVID-19 from India.

Methods: In this multicentric retrospective study, we retrieved data related to demographic details, clinical features, including the severity of disease, laboratory investigations and outcome.

Results: We included 402 children with a median (IQR) age of 7 (2-11) years. Fever was the most common symptom, present in 38.2% of children. About 44% had underlying comorbidity. The majority were asymptomatic (144, 35.8%) or mildly symptomatic (219, 54.5%). There were 39 (9.7%) moderate-severe cases and 13 (3.2%) deaths. The laboratory abnormalities included lymphopenia 25.4%, thrombocytopenia 22.1%, transaminitis 26.4%, low total serum protein 34.7%, low serum albumin 37.9% and low alkaline phosphatase 40%. Out of those who were tested, raised inflammatory markers were ferritin 58.9% (56/95), c-reactive protein 33.3% (41/123), procalcitonin 53.5% (46/86) and interleukin-6 (IL-6) 76%. The presence of fever, rash, vomiting, underlying comorbidity, increased total leucocyte count, thrombocytopenia, high urea, low total serum protein and raised c-reactive protein was factors associated with moderate to severe disease.

Conclusion: Fever was the commonest symptom. We identified additional laboratory abnormalities, namely lymphopenia, low total serum protein and albumin and low alkaline phosphatase. The majority of the children were asymptomatic or mildly symptomatic. We found high urea and low total serum protein as risk factors for moderate to severe disease for the first time.
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http://dx.doi.org/10.1093/tropej/fmab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344837PMC
July 2021

Second COVID-19 Surge: Challenges and Handling.

Indian J Pediatr 2021 06;88(6):531-533

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-03787-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096887PMC
June 2021

Feasibility of Pediatric Non-Invasive Respiratory Support in Low and Middle-Income Countries.

Indian Pediatr 2021 May 3. Epub 2021 May 3.

Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Dr Rakesh Lodha, Professor, Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, Ansari Nagar, New Delhi,110 029, India.

Non-Invasive respiratory support can be viewed as mechanical respiratory support without endotracheal intubation and it includes Continuous Positive Airway Pressure, Bi-Level Positive Airway Pressure, High Flow Nasal Cannula, and Non-invasive Positive Pressure Ventilation. Over past few years, non-invasive respiratory support is getting more popular across pediatric intensive care units for acute respiratory failure as well as for long-term ventilation support at home. It reduces the need for invasive mechanical ventilation, decreases the risk of nosocomial pneumonia as well as mortality in selected pediatric and adult population. Unfortunately, majority of available studies on non-invasive respiratory support have been conducted in high-income countries, which are different from low- and middle-income countries (LMICs) in terms of resources, man-power, and the disease profile. Hence, we need to consider disease profile, severity on admission to ICU or ward, availability of age-appropriate equipment, ability of health care professionals to manage patients on non-invasive respiratory support, and cost-benefit ratio. In view of the relatively high cost of equipment, there is a need to innovate to develop indigenous kits/ devices with available resources in LMICs to reduce the cost and potentially benefit health system. In this review, we highlight the role of non-invasive respiratory support in different clinical conditions, practical problems encountered in LMICs setting, and few indigenous techniques to provide non-invasive respiratory support.
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May 2021

Chikungunya-specific IgG and neutralizing antibody responses in natural infection of Chikungunya virus in children from India.

Arch Virol 2021 Jul 27;166(7):1913-1920. Epub 2021 Apr 27.

Department of Pediatrics, All India Institute of Medical sciences, New Delhi, 110029, India.

Chikungunya virus (CHIKV) infection is endemic in many different countries. CHIKV outbreaks are emerging in new areas and re-emerging in previously exposed geographical regions, thus making it a significant public health concern. CHIKV infections are often clinically inapparent, especially in children, which poses a challenge to testing and evaluating any vaccine. During CHIKV infection, CHIKV-specific antibodies are produced, and some of these antibodies can neutralize viruses released from infected cells before they can enter uninfected cells. In this study, we evaluated IgG binding and neutralizing antibody responses in paired serum samples from CHIKV-infected children and those with other febrile illness, using a recombinant truncated E2 protein and whole CHIKV particles as test antigens. Antibody detection using the truncated E2 protein showed a significant overlap between CHIKV-infected subjects and those with other febrile illnesses. This overlap was greater when binding antibody titers were determined using fixed CHIKV particles as the test antigen. Acute- and convalescent-phase sera collected from children after CHIKV infection showed significant differences in their neutralizing capacity. The neutralizing and binding antibody response showed a significant positive correlation. We detected IgG antibodies in most cases during the acute phase of infection. This was observed at two different geographical locations, one of which is not considered highly endemic. Conventional wisdom would suggest this to be a marker of re-infection (secondary infection). However, dissenting opinions have been voiced in other viral diseases (such as Ebola) where studies have detected IgG in acute illness. In the absence of any significant body of work documenting secondary CHIKV infections, we believe further work is needed to understand the early IgG response that we observed.
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http://dx.doi.org/10.1007/s00705-021-05049-3DOI Listing
July 2021

Oxidative stress specifically inhibits replication of dengue virus.

J Gen Virol 2021 04;102(4)

Clinical and Cellular Virology lab, Infection and Immunology, Translational Health Science and Technology Institute, Faridabad, Haryana, India.

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (HO) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.
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http://dx.doi.org/10.1099/jgv.0.001596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611606PMC
April 2021

Effects of ambient air pollution on emergency room visits of children for acute respiratory symptoms in Delhi, India.

Environ Sci Pollut Res Int 2021 Sep 21;28(33):45853-45866. Epub 2021 Apr 21.

Indian Council of Medical Research, New Delhi, 110029, India.

The present study explored the association between daily ambient air pollution and daily emergency room (ER) visits due to acute respiratory symptoms in children of Delhi. The daily counts of ER visits (ERV) of children (≤15 years) having acute respiratory symptoms were obtained from two hospitals of Delhi for 21 months. Simultaneously, data on daily concentrations of particulate matter (PM and PM), nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO), and ozone (O) and weather variables were provided by the Delhi Pollution Control Committee. K-means clustering with time-series approach and multi-pollutant generalized additive models with Poisson link function was used to estimate the 0-6-day lagged change in daily ER visits with the change in multiple pollutants levels. Out of 1,32,029 children screened, 19,120 eligible children having acute respiratory symptoms for ≤2 weeks and residing in Delhi for the past 4 weeks were enrolled. There was a 29% and 21% increase in ERVs among children on high and moderate level pollution cluster days, respectively, compared to low pollution cluster days on the same day and previous 1-6 days of exposure to air pollutants. There was percentage increase (95% CI) 1.50% (0.76, 2.25) in ERVs for acute respiratory symptoms for 10 μg/m increase of NO on previous day 1, 46.78% (21.01, 78.05) for 10 μg/m of CO on previous day 3, and 13.15% (9.95, 16.45) for 10 μg/m of SO on same day of exposure. An increase in the daily ER visits of children for acute respiratory symptoms was observed after increase in daily ambient air pollution levels in Delhi.
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http://dx.doi.org/10.1007/s11356-021-13600-7DOI Listing
September 2021

Study Designs: Diagnostic Studies.

Indian Pediatr 2021 Apr 20. Epub 2021 Apr 20.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Dr Rakesh Lodha, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029, India.

Diagnostic tests are evolving with betterment of technology, quest for patient safety with less invasive medicine, and evolution of new diseases. It is important to assess diagnostic accuracy of a new test, and clinical impact of introduction of new test on outcomes and cost. A diagnostic study is planned for the index test based on place of new test in diagnostic pathway (screening, triage, diagnostic or add-on test) and established information of the test. A reference standard is used to classify population into diseased and healthy, and the discriminating ability of index test is measured. A sample size is calculated for expected sensitivity/specificity, margin of error and prevalence of disease in population. For dichotomous outcomes, sensitivity, specificity, predictive values and likelihood ratio are used to describe diagnostic accuracy. Efforts should be made to avoid common forms of bias including spectrum bias and partial verification bias, and blinding of observers should preferably be done.
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April 2021

Cystic Lung Disease in Tuberculosis.

Indian J Pediatr 2021 07 17;88(7):734-735. Epub 2021 Apr 17.

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-03751-3DOI Listing
July 2021

Congenital Lung Malformations: Experience From a Tertiary Care Center in India.

Indian Pediatr 2021 02;58(2):129-133

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Background: There are limited data on congenital lung malformations (CLM) and their clinical course from developing countries.

Methods: A 10-year retrospective chart review of records of children with CLM attending pediatric chest clinic at an Indian tertiary care center was conducted.

Results: Among the 48 children (24 boys) included in the review, the malformations included congenital lung ypoplasia/agenesis in 24 (50%), cystic pulmonary airway malformation in 9 (19%), bronchogenic/foregut cyst in 8 (18%), and congenital lobar emphysema in 4 (9%). Median (IQR) age at symptom onset and diagnosis were 1.5 (0.4,9.5) and 24 (3,62) months, respectively. Median (IQR) weight for age for age z-score at presentation was -2.4 (-1.4,-3.4). More than a third (37.5%) children underwent surgical removal of resectable lesions at median (IQR) age of 14 (6,42) months. 14 (27%) children had associated congenital heart disease. Median duration of follow-up was 13 months. In children with lung hypoplasia, median (IQR) number of hospitalizations in follow-up were significantly less than that prior to diagnosis 0 (0,0) vs 1(0,2) (P=0.001). Median (IQR) numbers of hospitalizations in follow up were significantly less than that of prior to surgical resection 0 (0,0) vs 1(1,1) (P=0.016) in children with CPAM.

Conclusion: Lung hypoplasia was the most common congenital lung malformation in our setup. Detection of malformation during antenatal period was poor. Age of diagnosis and surgical intervention is often delayed. Regular follow up and definitive and/or supportive management decreased the morbidity.
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February 2021

Dexmedetomidine vs Midazolam for Sedation in Mechanically Ventilated Children: A Randomized Controlled Trial.

Indian Pediatr 2021 02;58(2):117-122

Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Dr Rakesh Lodha, Professor, Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India.

Background: There is a paucity of data on use of dexmedetomidine as a sedative agent in mechanically ventilated children.

Objectives: To compare the efficacy of dexmedetomidine and midazolam for sedation in mechanically ventilated children aged 1 month - 15 years. Secondary objectives were to compare the need for top-up doses of fentanyl and paralytic agents, duration of mechanical ventilation, ICU stay and hospital stay, and adverse events.

Design: Open label, non-inferiority, randomized controlled trial.

Setting: PICU of a tertiary care teaching hospital in India.

Patients: Consecutive children aged 1 month to 15 years who were mechanically ventilated.

Intervention: Children were randomized to either dexmedeto-midine or midazolam and the doses were titrated to maintain target sedation score of 4 or 5 as measured by Penn State Children Hospital Sedation algorithm.

Outcome: The percentage of time spent in level 4 or 5 of Penn State Children Hospital sedation algorithm for ventilated children.

Results: 49 children were randomized (24 to 'midazolam group' and 25 to 'dexmedetomidine group'). There was no difference in the percentage of time spent in the targeted sedation between the groups [midazolam 67.3% (18.8) vs. dexmedetomidine 56.3 %. (28.6); P=0.12]. The absolute difference in the percentage of time spent was -10.9% [SE (95% CI) 7.05: (-25.15 to 3.25)]. The lower end of 95% CI for the difference breached the non-inferiority limit of -20%. Number of fentanyl boluses, duration of mechanical ventilation, ICU stay, and hospital stay were similar. Four (17.4%) children in dexmedetomidine group developed persistent bradycardia.

Conclusion: Non-inferiority of dexmedetomidine compared to midazolam for sedation in children on mechanical ventilation could not be established.
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February 2021

A public health approach for deciding policy on infant feeding and mother-infant contact in the context of COVID-19.

Lancet Glob Health 2021 04 22;9(4):e552-e557. Epub 2021 Feb 22.

International Center for Equity in Health, Federal University of Pelotas, Pelotas, Brazil.

The COVID-19 pandemic has raised concern about the possibility and effects of mother-infant transmission of SARS-CoV-2 through breastfeeding and close contact. The insufficient available evidence has resulted in differing recommendations by health professional associations and national health authorities. We present an approach for deciding public health policy on infant feeding and mother-infant contact in the context of COVID-19, or for future emerging viruses, that balances the risks that are associated with viral infection against child survival, lifelong health, and development, and also maternal health. Using the Lives Saved Tool, we used available data to show how different public health approaches might affect infant mortality. Based on existing evidence, including population and survival estimates, the number of infant deaths in low-income and middle-income countries due to COVID-19 (2020-21) might range between 1800 and 2800. By contrast, if mothers with confirmed SARS-CoV-2 infection are recommended to separate from their newborn babies and avoid or stop breastfeeding, additional deaths among infants would range between 188 000 and 273 000.
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http://dx.doi.org/10.1016/S2214-109X(20)30538-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906661PMC
April 2021

Improving the Detection of Phlebitis in Hospitalized Children.

Indian J Pediatr 2021 04 20;88(4):328-329. Epub 2021 Feb 20.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-03703-xDOI Listing
April 2021
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