Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.

Enteritis: a window to the diagnosis of systemic lupus erythematosus in an adolescent girl: case report.

BACKGROUND: Enteritis is one of the rare systemic manifestations in childhood-onset systemic lupus erythematosus and its diagnosis is very challenging. This is a rare case of an adolescent girl with recurrent non-specific gastro-intestinal symptoms which were later diagnosed to be owing to lupus enteritis, the only presenting manifestation of an active flare. CASE REPORT: A 15-year-old girl was admitted with recurrent episodes of abdominal pain, vomiting and loose stools. She had diffuse abdominal tenderness. Abdominal ultrasonography demonstrated moderate ascites. A contrast-enhanced abdominal computerised tomography scan revealed thickening of the small bowel wall. On colonoscopy, there were rectal erosions, and microscopic examination of the biopsy specimens demonstrated mild inflammation. Non-specific enteritis was diagnosed and she was given antibiotics and supportive care. She was re-admitted 6months later with abdominal pain. An abdominal contrast-enhanced computerised tomography scan revealed thickening of the bowel wall and the target sign and comb sign in the small intestine. The anti-nuclear antibody was positive. Renal biopsy demonstrated grade 2 lupus nephritis. Lupus enteritis was diagnosed and the case satisfied the 2019 EULAR-ACR criteria and SLICC criteria. She was treated with methylprednisolone, cyclophosphamide and hydroxychloroquine. She improved with treatment and has remained asymptomatic during follow-up. CONCLUSION: This case emphasises the need for healthcare providers to be alert to the possibility of lupus enteritis. It also highlights the importance of close follow-up of cases who have non-specific gastro-intestinal symptoms. Lupus enteritis should be considered in the differential diagnosis of recurrent non-specific gastro-intestinal symptoms in children, especially adolescents, to ensure timely diagnosis and treatment.Abbreviations: ACR American College of Rheumatology; ANA anti-nuclear antibody; CRP: C-reactive protein; CT: computerised tomography; CECT: contrast-enhanced computerised tomography; EULAR: European League Against Rheumatism; GI: gastro-intestinal; LE: lupus enteritis; SLE systemic lupus erythematosis; SLICC: Systemic Lupus International Collaborating Clinics; SLEDAI: SLE disease activity index.

A Study of the Clinical Profile and Respiratory Index of Severity in Children (RISC) Score in Infants Admitted With Acute Respiratory Infections at a Tertiary Care Hospital.

Background Pneumonia is a major infectious cause of mortality in young children worldwide. The Respiratory Index of Severity in Children (RISC) score was designed with the intent to provide an objective mean to quantify the severity of lower respiratory tract infection in young children based on their risk of mortality. Knowledge about the clinical profile of acute respiratory infections and the scoring system predicting the risk of mortality helps in modifying treatment strategies. This study was undertaken at a resource-limited, tertiary-care public hospital in southern India with the objectives of describing the clinical profile of infants admitted with acute respiratory infections and determining the association of the RISC score with mortality. Method This was a retrospective observational study conducted over six months. Case records of infants admitted with acute respiratory infections were reviewed. The socio-demographic and clinical details of each case were recorded. The RISC score was calculated using clinical parameters which included the history of refusal of feeds, oxygen saturation lower than 90%, chest in-drawing, wheezing, and low weight-for-age. The maximum score was six. Descriptive data was represented using mean, standard deviation, and percentage or proportion. The association between any two categorical variables was analyzed using the chi-square test. The differences between any two continuous variables were analyzed using the independent sample t-test. A p-value of < 0.05 was considered statistically significant. Results A total of 75 infants were admitted with a diagnosis of acute respiratory infection during the study period. Of these, 68 were included in the study. The mean age of infants was 6.69 ± 3.96 months; 58.8% were male, 41 (60%) were exclusively breastfed, and 51 (75%) were up-to-date immunized. Twenty (29.4%) infants had a history of exposure to indoor smoke. The majority (67.6%) had pneumonia. Nine (13.2%) were mechanically ventilated. The mean duration of hospital stay was 8.16 ± 5.45 days. Sixty-three (92.64%) infants recovered and there were five deaths. The presence of less than 90% oxygen saturation (p-value=0.004), a diagnosis of severe pneumonia (p-value <0.001), and the need for mechanical ventilation (p-value <0.001) were significantly associated with mortality. A statistically significant (p-value=0.001) association was observed between the RISC score and mortality. Conclusions Addressable factors like the absence of exclusive breastfeeding, partial-immunization status, exposure to indoor smoke, and malnutrition were observed in infants with acute respiratory infections, which reinforces the importance of protective and preventive strategies for the control of pneumonia. The RISC score was observed to be beneficial in predicting mortality in an infant with acute respiratory infection. Triaging and early identification of infants at risk of mortality using this score could be very helpful in initiating timely treatment to reduce mortality, especially in resource-limited settings.

Quality Improvement Study With Low-Cost Strategies to Reduce Neonatal Admission Hypothermia.

Background Admission hypothermia is still an underappreciated major challenge for new-born survival in low-resource settings. The WHO recommends skin-to-skin contact as the simplest and safest way for maintaining the body temperature even during transportation. Quality improvement initiatives for hospitalised new-borns have shown benefits like a reduction in neonatal morbidity and mortality. This study was undertaken in a resource-constrained public hospital in southern India with an aim to reduce neonatal hypothermia at admission to <20%. Method It was a prospective, quality improvement study undertaken over 20 weeks. All neonates born in the selected delivery room (DR), requiring transportation to the neonatal intensive care unit, were included. The primary outcome indicators were the mean axillary temperature of neonates measured upon arrival at the neonatal intensive care unit and the percentage of neonates with hypothermia at admission. Improving the thermoregulatory practices and ambient DR temperature to >25˚C, transportation by the kangaroo method, and a portable infant warmer (PIW) were implemented in three successive Plan-Do-Study-Act (PDSA) cycles. Result In the third PDSA cycle, the mean admission temperature (36.51˚C ±0.82) was significantly (p<0.0001) higher when compared with the baseline phase (35.41˚C ±1.09), and there was a significant (p<0.001) reduction in hypothermia (33.33%). The aim was achieved in the last two weeks of the third cycle with a reduction in hypothermia to 17.6%. Conclusion Implementation of appropriate thermoregulatory practices and low-cost strategies like the kangaroo method and PIW using quality improvement methodology significantly reduced admission hypothermia.

Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probable in 55 (63%), and possible in 16 (18%). IgM detection in CSF had a sensitivity of 93% and specificity of 82% compared with PCR. Our findings suggest scrub typhus as an emerging common treatable cause of AES in children in southern India and highlight the importance of routine testing for scrub typhus in diagnostic algorithms. Our results also suggest the potential promise of IgM screening of CSF for diagnosis of AES resulting from scrub typhus.

CoRe study: COVID-19 and remdesivir: An insight into the current health planning and policy.

Introduction: The ongoing coronavirus disease-2019 (COVID-19) pandemic has witnessed rampant use of the repurposed drug, remdesivir, despite its conflicting evidence and rapidly changing guidelines. Methods: A cross-sectional, country-wide, questionnaire-based, electronic survey was conducted among the healthcare professionals involved in COVID-19 management from April 18 to May 18, 2021. Results: Out of 231 responses, 185 were included. Significantly, greater knowledge of trials was reported by the frontline healthcare professionals compared to those who are not involved in COVID-19 care. Medicine practitioners and pulmonologists expressed greater willingness to continue remdesivir (Odds ratio (OR) 5.329, 95% Confidence interval (CI) 2.31-12.291 and 5.063, 95% CI 1.414-18.129, respectively). The rationale attributed was personal experience, current guidelines, non-availability of any alternate antiviral drug, expert recommendations, and local hospital policy either alone (20%, 8.1%, 5.9%, 2.7%, and 2.2%, respectively) or in combination (46.5%, 39.5%, 29.2%, 21.1%, and 15.7%, respectively). Awareness of evidence and knowledge of landmark studies made no statistically significant impact on clinical decision-making. Improved clinical outcomes were reported by 10/22 (45.4%) practitioners who used remdesivir for unconventional indications. Conclusion: The study throws critical insights into the current perspectives of doctors on remdesivir in clinical management and its potential impact on current health planning strategies.

Ochoa Syndrome - Neurogenic Bladder with an Inverted Smile.

Ochoa or urofacial syndrome is a rare autosomal recessive syndrome with around 150 cases reported in the medical literature comprising of neurogenic bladder and facial abnormalities, culminating in obstructive uropathy and chronic kidney disease. We report a 5-year-old boy presenting to us with Stage IV chronic kidney disease with bilateral hydroureteronephrosis secondary to chronic urinary incontinence. His peculiar facial expression with a grimace while smiling suggested the diagnosis of Ochoa syndrome. He was managed conservatively for neurogenic bladder and is under follow-up. We wish to highlight this unique syndrome and the simplicity in making this syndromic diagnosis, just by appreciating abnormal facial expressions.

Early congenital syphilis: missed opportunities in a mother owing to many problems during pregnancy - a case report.

Untreated syphilis in pregnancy can result in an adverse outcome for the fetus. A multigravida woman with a previously poor obstetric history of early neonatal death, abortion and stillbirth was admitted in labour in the 7th month of pregnancy. On admission, syphilis screening with the qualitative rapid plasma reagin (RPR) test was negative. The infant had macules on the chest, abdomen and extremities, desquamating bullous skin lesions on the palms and soles, bilateral cataracts, an enlarged liver and spleen, anaemia, thrombocytopenia and conjugated hyperbilirubinaemia. A quantitative RPR test in the infant was positive in a 1:64 dilution and was subsequently positive in the mother in a 1:16 dilution after congenital syphilis was diagnosed. The mother later reported the father's high-risk behaviour and her previous visits to healthcare facilities for genital ulcers. The quantitative RPR test in the father was positive in a 1:32 dilution, and the parents and infant were treated for syphilis. The case demonstrates the importance of timely identification of high-risk pregnant women, early screening, repetition of the non-treponemal test on diluted serum when a routine screening test is negative, proper advice from the laboratory regarding selection of the most appropriate tests, and screening with the treponemal test first (reverse) algorithm utilising an automated enzyme immunoassay/chemiluminescence assay for the initial screening in high-risk cases, even in resource-limited settings to prevent a missed diagnosis.Abbreviations: ANC, antenatal care; BPG, benzathine penicillin G; CS, congenital syphilis; CSF, cerebrospinal fluid; CIA, chemiluminescence assay; EIA, enzyme immunoassay; HIC: high-income countries; IgM, immunoglobulin M; LMIC, low- and middle-income countries; MTCT: mother-to-child transmission; NTT, non-treponemal test; POC, point of care; RPR, rapid plasma reagin; RST, rapid syphilis test; STI, sexually transmitted infections; TT, treponemal test; TPHA, Treponema pallidum haemagglutination assay; VDRL, venereal disease research laboratory; WHO, World Health Organization.

Exploring the Skin Mycobiome in Very Preterm babies during the early neonatal period in a Neonatal Intensive Care Unit of India.

The neonatal skin microbiome consists of all the genomes and genetic products of micro-organisms harbouring the skin of babies. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. Our study was conducted to explore the neonatal skin fungal microbiome of very preterm neonates admitted to Neonatal Intensive Care Unit at a tertiary health care setting using Next Generation Sequencing of the18S rRNA gene. The most abundant genera found in 22/30 samples were Candida followed by Bipolaris & Cladosporium on the skin microbiome of these neonates. The presence of these fungi, whether just as commensals or as potential pathogens, is currently under research, owing to the risk of early exposure and incidence of infection right from birth.

Mycobacterium Species on the Cutaneous Microbiome of Very Preterm Neonates.

The neonatal skin microbiome consists of all the genomes and genetic products of microorganisms harboring on an infant's skin. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. This study was conducted to understand the neonatal skin microbiome of very preterm neonates (under 32 weeks) admitted to the Neonatal Intensive Care Unit(NICU) at a tertiary healthcare setting before and after kangaroo mother care (KMC), using next-generation sequencing (NGS). Skin swabs were collected on two different occasions and analyzed using the NGS technique after amplification via polymerase chain reaction. The results showed relative abundance for Mycobacterium tuberculosis in 83.33% and 66.67% (p = 0.29) and Mycobacteroides abscessus in 100% and 93.33% (p = 0.30) of the very preterm neonates on the skin microbiome before and after KMC, respectively as an incidental finding. The mere presence of these bacilli as commensals or as potential pathogens is alarming due to the risk of early exposure and incidence of tuberculosis from birth. These findings, in our view, are the first findings to be established in such a setting.

A phase III randomized, open-label, non-inferiority clinical trial comparing liquid and lyophilized formulations of oral live attenuated human rotavirus vaccine (HRV) in Indian infants.

The human rotavirus vaccine (HRV; Rotarix, GSK) is available as liquid (Liq) and lyophilized (Lyo) formulations, but only Lyo HRV is licensed in India. In this phase III, randomized, open-label trial (NCT02141204), healthy Indian infants aged 6-10 weeks received 2 doses (1 month apart) of either Liq HRV or Lyo HRV. Non-inferiority of Liq HRV compared to Lyo HRV was assessed in terms of geometric mean concentrations (GMCs) of anti-RV immunoglobulin A (IgA), 1-month post-second dose (primary objective). Reactogenicity/safety were also evaluated. Seroconversion was defined as anti-RV IgA antibody concentration ≥20 units [U]/mL in initially seronegative infants (anti-RV IgA antibody concentration <20 U/mL) or ≥2-fold increase compared with pre-vaccination concentration in initially seropositive infants. Of the 451 enrolled infants, 381 (189 in Liq HRV and 192 in Lyo HRV group) were included in the per-protocol set. The GMC ratio (Liq HRV/Lyo HRV) was 0.93 (95% confidence interval [CI]: 0.65-1.34), with the lower limit of the 95% CI reaching ≥0.5, the pre-specified statistical margin for non-inferiority. In the Liq HRV and Lyo HRV groups, 42.9% and 44.3% (baseline) and 71.4% and 73.4% (1-month post-second dose) of infants had anti-RV IgA antibody concentration ≥20 U/mL, and overall seroconversion rates were 54.5% and 50.0%. Incidences of solicited and unsolicited adverse events were similar between groups and no vaccine-related serious adverse events were reported. Liq HRV was non-inferior to Lyo HRV in terms of antibody GMCs and showed similar reactogenicity/safety profiles, supporting the use of Liq HRV in Indian infants.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus is the most common cause of acute gastronenteritis and contributes to the high number of hospitalizations and deaths in young children worldwide.Vaccination against rotavirus has led to a significant decrease in rotavirus-related infections.The human rotavirus vaccine Rotarix (GSK) is currently used as a liquid or lyophilized formulation.In clinical trials conducted in European and North American infants, the liquid vaccine showed ability to induce immune response and safety comparable to the lyophilized formulation.Only the lyophilized vaccine is currently marketed in india.What is new?We compared the 2-dose liquid and lyophilized human rotavirus vaccines in indian infants in a phase III clinical trial:The ability to induce immune response for thw liquid formulation was not inferior to that observed for the lyophilized vaccine.The safety profiles of the 2 formulations were comparable.Why is this important?This study shows that the liquid human rotavirus vaccine can be administrated to infants from india.

Acute Leukoencephalopathy with Restricted Diffusion in an Infant with Severe COVID-19 and Dengue Coinfection Progressing to West Syndrome.

COVID-19 pandemic is increasingly being recognized in infants and some develop cytokine storm mediated tissue damage. We report 5-month-old infant presenting with fever, refusal of feeds, developing altered sensorium and convulsions during the hospital course, tested positive for SARS-CoV2 RT-PCR in second week of illness. Her serology was also Dengue positive. She had features of cytokine storm and her MRI Brain suggested acute demyelinating encephalomyelitis (ADEM). She was treated with high-dose methylprednisolone followed oral prednisolone, under antibiotics cover. Infant improved gradually over 3 weeks duration following a stormy hospital course. On follow-up, infant showed delayed motor milestones with epileptic spasms and hysparrhthymia on EEG, progressing to develop secondary West syndrome. Features of acute encephalopathy, hypercytokinemia and restricted diffusion on DWI-MRI, with post-encephalopathic epilepsy, pointed to a differential of ADEM-acute leukoencephalopathy with restricted diffusion (ALERD) as the primary diagnosis; establishing ALERD as a possible neurological complication of COVID-19 infection in infants. Timeline of events. There is a demonstrable fall in the inflammatory markers with clinical improvement following the start of intravenous methylprednisolone. Epileptic spasms and developmental delay with hypsarrhthymia noted on follow-up, suggestive of secondary West syndrome.

Decreasing antibiotic over-use by implementation of an antibiotic stewardship programme in preterm neonates in resource limited settings - a quality improvement initiative.

BACKGROUND: Antibiotics play a critical role in neonatal sepsis but excessive use is associated with adverse outcomes and the current prescribing rates of antibiotics are unacceptably high. AIM: To reduce antibiotic over-use in preterm neonates by implementing an antibiotic stewardship programme using a quality improvement (QI) initiative. METHODS: This study was conducted at a neonatal intensive care unit in a resource-limited setting. The reasons for antibiotic over-use were analysed and an antibiotic stewardship programme was implemented by using a QI initiative. The duration of the QI was a 1-month baseline phase followed by 3 months of implementation which was undertaken in the form of Plan-Do-Study-Act (P-D-S-A) cycles. The sustainment phase was observed for 2 months. All neonates admitted to the preterm unit were included. The outcome measure was the antibiotic usage expressed as days of therapy (DOT)/1000 patient days. RESULTS: In the baseline phase, DOT/1000 patient days was 1464 which fell to 706, 511, and 442 DOT/1000 patient days, respectively, over 3 months, resulting in a 65% reduction in antibiotic usage. This was achieved by a combination of efforts directed towards defining the conditions for no antibiotics, revising existing antibiotic policy, stopping orders at 48 hours, de-escalation to the narrowest spectrum antibiotic, stopping prophylactic antifungal agents and limited use of broad-spectrum antibiotics. The results were achieved without an increase in culture-positive sepsis or mortality. CONCLUSIONS: Implementation of a tailored antibiotic stewardship programme through a QI initiative was effective and safe in reducing antibiotic use in preterm neonates in a resource-limited setting. ABBREVIATIONS: AIIMS, All India Institute of Medical Sciences; DOT, days of therapy; HIC, high-income countries; ICMR, Indian Council of Medical Research; LMIC, low- to middle-income countries; LOS, late-onset sepsis; NICU, neonatal intensive care unit; NNF, National Neonatology Forum; P-D-S-A, plan-do-study-act; QI, quality improvement; SNCU, Special newborn care unit.

Quality improvement initiative to improve the duration of kangaroo mother care for twin preterm neonates born at a tertiary care hospital in resource-limited settings.

AIM: Kangaroo mother care (KMC) can be challenging in multiple births and more so in resource-limited settings. This study aims at increasing the mean duration of KMC with early initiation in twin preterm neonates born at a tertiary care hospital using a quality improvement (QI) initiative. METHODS: Barriers for poor KMC practice in twin preterm neonates born at the tertiary care hospital were analysed and baseline data were collected over a period of 4 months using a predesigned proforma. A QI team was formed and suggested solutions were prioritised through focus group discussions in the form of Plan-Do-Study-Act (P-D-S-A) cycles. Each cycle was of one-month duration and three cycles were implemented, followed by the sustenance phase studied at 1-month post-implementation. RESULTS: There were a total of 238 twin deliveries in the study period, of which 169 twin pairs were included in the study. At the end of implementation, the average day of initiation of KMC improved from 8th to 3rd day of life and the duration of KMC increased significantly from an average of 2.70 h/infant/day to 7.88 h/infant/day. CONCLUSION: This QI project focused on the improvement of KMC practice in twin preterm neonates in a tertiary care hospital where results were achieved with maximal utilisation of available hospital resources and low-cost interventions. This study design is generalizable to other hospitals in resource-limited settings where family participatory care can be strengthened to overcome the challenges of KMC in multiple births.

Newborn Screening for Five Conditions in a Tertiary Care Government Hospital in Bengaluru, South India-Three Years Experience.

PURPOSE: Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU). METHODS: The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47 623 livebirths during this period out of which 41 027 babies were screened (coverage-86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests. RESULTS: G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%. CONCLUSION: The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.

Absent pulmonary valve: a case with rare presentation treated with bioprosthetic valve replacement.

Congenital absence of the pulmonary valve is a rare congenital cardiac malformation, usually seen in association with tetralogy of Fallot. Patients generally present early in life with respiratory distress or recurrent respiratory tract infections, failure to thrive, cyanosis, infective endocarditis, or heart failure. Isolated absent pulmonary valve is quite rare and may be discovered in older age-group as in our patient, a nine-year-old male child who presented with atypical symptoms of exertional chest pain. Unusual echocardiographic features in this case include intact ventricular septum and prominent trabeculations of the right ventricle. Surgical implantation of a bioprosthetic valve was followed by hemodynamic and symptomatic improvement.