Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial.

BACKGROUND: Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. METHODS: This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is "definite or probable relapse" within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O'Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock's to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. DISCUSSION: This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.

Transport characteristics and predictors of mortality among neonates referred to a tertiary care centre in North India: a prospective observational study.

OBJECTIVE: The paucity of specialised care in the peripheral areas of developing countries necessitates the referral of sick neonates to higher centres. Organised interhospital transport services provided by a skilled and well-equipped team can significantly improve the outcome. The present study evaluated the transport characteristics and predictors of mortality among neonates referred to a tertiary care centre in North India. DESIGN: Prospective observational study. SETTINGS: Tertiary care teaching hospital in North India. PATIENTS: 1013 neonates referred from peripheral health units. MAIN OUTCOME MEASURES: Mortality among referred neonates on admission to our centre. RESULTS: Of the 1013 enrolled neonates, 83% were transferred through national ambulance services, 13.7% through private hospital ambulances and 3.3% through personal vehicles. Major transfer indications were prematurity (35%), requirement for ventilation (32%), birth asphyxia (28%) and hyperbilirubinaemia (19%). Hypothermia (32.5%, 330 of 1013), shock (19%, 192 of 1013) and requirement for immediate cardiorespiratory support (ICRS) (10.4%, 106 of 1013) on arrival were the major complications observed during transfer. A total of 305 (30.1%, N=1013) deaths occurred. Of these, 52% (n=160) died within 24 hours of arrival. On multivariate logistic analysis, unsupervised pregnancy (<4 antenatal visits; p=0.037), antenatal complications (p<0.001), prematurity ≤30 weeks (p=0.005), shock (p=0.001), hypothermia (p<0.001), requirement for ICRS on arrival (p<0.001), birth asphyxia (p=0.004), travel time >2 hours (p=0.005) and absence of trained staff during transfer (p<0.001) were found to be significant predictors of mortality. CONCLUSION: The present study depicts high mortality among infants referred to our centre. Adequate training of peripheral health personnel and availability of pre-referral stabilisation and dedicated interhospital transport teams for sick neonate transfers may prove valuable interventions for improved outcomes.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56-29.4% in pre-vaccine years to 34-12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.

Gastroenteritis in Haryana, India Post Introduction of Rotavirus Vaccine.

OBJECTIVE: To evaluate the epidemiology of rotavirus gastroenteritis in Haryana post-introduction of rotavirus vaccine. Expanded National rotavirus surveillance network in India reported high burden of rotavirus diarrhea in India. The Government of India introduced the monovalent rotavirus vaccine made in India by Bharat Biotech in the national immunization programme from 2016 onward along with oral polio vaccine (OPV) and Pentavalent vaccines. METHODS: A multi-centric, hospital-based surveillance study in the initial vaccine introducing states was started in a phased manner over a period of 3 y. PGIMS, Rohtak is a tertiary care center and was a part of the surveillance from 2016 to 2019. Children aged 0-59 mo admitted with acute gastroenteritis were enrolled into the surveillance and their stool samples were collected. Samples were tested at Christian Medical College (CMC), Vellore to detect rotavirus and reverse transcription-polymerase chain reaction (RT-PCR) was used for G and P typing. RESULTS: A total of 904 children were enrolled in the present surveillance over a period of 3 y starting 1st July 2016 to 30th June 2019. Stool samples were collected and analyzed for 827 children and out of them 141 samples were positive for rotavirus (17.1%). Maximum rotavirus positivity was observed during the winter months. Rotavirus positivity percentage was observed maximum in 12-23 mo age group. A declining trend was observed in rotavirus positivity from 22.8% in 2016 to 14.5% in 2019. Most common strains of rotavirus isolated were G3P[8] followed by G1P[8]. CONCLUSION: This study highlights that epidemiology of acute gastroenteritis among children less than 5 y of age in Haryana postintroduction of rotavirus vaccination in the state and the decline in rotavirus positivity from 22.8% in 2016 to 14.5% in 2019.

Epidemiology of Hospitalized Intussusception Cases from Northern States in India.

OBJECTIVE: To describe epidemiology of intussusception post-introduction of the rotavirus vaccine. METHODS: Hospital-based active surveillance system was set up in three tertiary care hospitals in Chandigarh and Haryana, India, to enroll children <2 y of age admitted with intussusception as per Brighton Collaboration Level-I criteria. The clinical characteristics, treatment modalities, seasonal trends, and outcome of the illness episodes were described. RESULTS: A total of 224 cases were reported. Majority were males (71%) and infants (69.5%). Number of intussusception was more in summer season. Location of intussusception was ileo-colic in 85% of the cases. Nearly 54% cases were treated conservatively and 46% needed surgical intervention. CONCLUSION: Surveillance data provided the epidemiological description of intussusception cases post-introduction of the rotavirus vaccine in northern India. This data could be used to assess the impact of vaccine and safety with a special focus on intussusception.

Rapid vs. Slow Rewarming for Management of Moderate to Severe Hypothermia in Low-Birth-Weight Pre-term Neonates-An Open Label Randomized Controlled Trial.

BACKGROUND: Evidence is lacking regarding the optimal method of rewarming hypothermic low-birth-weight (LBW) pre-term neonates. We aim to evaluate the effect of rapid vs. slow rewarming in the management of moderate to severe hypothermia in LBW pre-term neonates. METHODS: In this open label, randomized controlled trial, 100 LBW (<2.5 kg), pre-term (<37 weeks) neonates with moderate to severe hypothermia (<36°C) was randomized to two groups of 50 each and received either rapid (at >0.5°C/h) or slow (at ≤0.5°C/h) rewarming rate till normothermia. The primary outcome was stabilization score [TOPS (temperature, oxygenation, perfusion and saturation) and MSNS (modified sick neonatal score)] at baseline, 6 and 24 h and mortality until discharge. Other neonatal morbidities were assessed as secondary outcomes. RESULTS: Mean TOPS score and MSNS score at baseline, 6 and 24 h of admission as well as change in score from baseline were similar between the two groups. The median rewarming rate [interquartile range (IQR)] was higher in rapid rewarming group than in the slow rewarming group [5.05°C/h (3.54-7.71) vs. 0.71°C/h (0.60-0.90); p < 0.001]. The median rewarming time taken in rapid rewarming group was lesser compared with that in the slow rewarming group [0.31 h (IQR 0.13-0.75) vs. 2.05 h (IQR 1.11-3.03); p < 0.001]. Mortality in rapid rewarming and slow rewarming group was similar [7/50 vs. 5/50; OR 1.46 (0.43-4.97), p = 0.538]. CONCLUSION: Rapid rewarming was as effective and safe as slow rewarming in the management of moderate to severe hypothermia in LBW pre-term neonates with similar short-term neonatal outcomes. CTRI NUMBER: CTRI/2018/01/011187.

Enhancing Kangaroo Mother Care Uptake Through Implementation of an Education Protocol.

OBJECTIVES: Kangaroo mother care (KMC) uptake is low despite KMC being an evidence based tool to decrease neonatal mortality. It is important that local strategies be developed to enhance KMC usage. This study aimed to assess the effect of implementing an education protocol on the usage of KMC in the NICU and at home after discharge. METHODS: Preterm mother-infant dyads admitted to the NICU were enrolled prospectively. In initial 3 mo, baseline data on KMC usage in the unit and at home after discharge was collected. In the next three months, a KMC education protocol consisting of one-to-one counseling, education and sensitization of the mother and family members regarding benefits and procedure of KMC and focussed group discussions was implemented such that it became a unit work protocol. In the next 3 mo, data on KMC usage in the unit and at home after discharge was again collected and compared with the baseline data. RESULTS: Implementation of the education protocol resulted in earlier initiation of KMC (2.49 ± 0.67 vs. 4.65 ± 0.99 d, p < 0.05); increased duration of KMC (8 h/d vs. 3 h/d, p < 0.05); a higher proportion of eligible preterms receiving KMC during hospital stay (100% vs. 75%, p < 0.05) and at home (87% vs. 28%, p < 0.05) and KMC being provided more often by other family members (27.1% vs. 5.7%, p < 0.05). CONCLUSIONS: Implementation of a KMC education protocol resulted in improved KMC usage in the unit and at home 4 wk after discharge.

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Clinical profile and predictors of mortality among the referred neonates at a tertiary care centre in north India: a prospective observational study.

The National Family Health Survey (NFHS-4) shows encouraging improvement in infant and under-five mortality rates in India. However, the neonatal mortality rate (NMR) still remains high as India contributes to about one-fifth of global deaths. This prospective study was conducted from 15 January to 30 April 2016 to examine the clinical profile and predictors of mortality among referred neonates at our centre. Among 301 neonates, prematurity (40%) was the most common indication for referral followed by need for ventilation (38%) and birth asphyxia (28%). Approximately 73% neonates were referred within 24 h of birth. Ninety (29.9%) neonates died; of these, 63% died within 24 h of presentation. Prematurity, birth asphyxia, hypothermia, shock at presentation and extreme low birth weight were the most significant predictors of mortality. Adequate training of peripheral health personnel, dedicated teams for neonatal referral and strengthening of peripheral sick newborn care units (SNCUs) seem to be promising interventions for favourable outcome.

Longitudinally Extensive Transverse Myelitis (LETM) Following Varicella Infection in a 13-Year Immunocompetent Child.

Varicella infection in children is a common self-limited illness with neurological complications in less than 0.1% of cases. Longitudinally extensive transverse myelitis (LETM) is uncommon in children following infection with varicella-zoster virus. We describe a case of 13-yr immunocompetent girl with LETM following varicella infection shown a dramatic clinical response to a combination of acyclovir and pulse steroids.

Cognitive and Behavioral Profile of Treatment-Naïve Children Aged 6-14 Years with Neurocysticercosis from North India.

BACKGROUND: Neurocysticercosis (NCC) produces a progressive organic brain damage by altering brain function with alterations in memory, difficulties in learning, and behavioral changes. The present study was designed to compare the cognitive and behavioral profile of school-going children aged 6-14 years with newly diagnosed NCC with their age-matched controls. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted among children aged 6-14 years with newly (<7 days) diagnosed NCC. Age- and gender-matched typically developing children with minor illness attending outpatient facility served as control. Intelligence and behavioral assessment were performed using Malin's Intelligence Scale for Indian Children and Childhood Behavior Checklist (CBCL) (school age version CBCL/6-18). CBCL T-scores were computed and scores < 60 were considered as normal, 60-63 as borderline, and > 63 as clinical range. RESULTS: A total of 35 cases and 35 controls were enrolled. Baseline demographic characteristics were comparable between the two groups. Verbal intelligence quotient (IQ) scores were comparable between the cases (96.14 [10.23]) and controls (100.17 [10.89]) (P = 0.11). The behavioral assessment revealed normal T-scores (<60) in both the groups. CONCLUSIONS: The study revealed comparable IQ and normal behavioral profile of treatment-naïve children with recently diagnosed NCC to their age-matched peers. Further studies with larger sample size and longitudinal study design are required to evaluate the role of NCC on cognition and behavior in Indian children.

Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India.

BACKGROUND: Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models. METHODS: We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3 months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for 'months of intervention'. RESULTS: The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities. CONCLUSION: A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India. TRIAL REGISTRATION NUMBER: CTRI/2016/05/006963.

Unilateral Transient Watershed Cerebral Infarct in a 6-Year-Old Girl with Frequently Relapsing Nephrotic Syndrome.

Nephrotic syndrome is a prothrombotic state with predisposition to venous sinus thrombosis and arterial vascular stroke. Watershed infarcts in junction of arterial territory develop in hypotensive hypovolemic state. These border zone infarcts are usually bilateral in the absence of unilateral arterial stenosis or microembolism. We report a 6-year-girl of frequently relapsing nephrotic syndrome who developed sudden onset hemiparesis with aphasia. Magnetic resonance (MR) imaging brain revealed unilateral watershed infarct in territory between the major cerebral arterial vessels with evidence of restricted diffusion and normal vessel anatomy on MR angiography. This could possibly reflect asymmetric variant of posterior reversible encephalopathy syndrome that resolved with remission on steroids.

Pediatric Appropriate Evaluation Protocol for India (PAEP-India): Tool for Assessing Appropriateness of Pediatric Hospitalization.

OBJECTIVE: To develop and assess Pediatric Appropriateness Evaluation Protocol for India (PAEP-India) for inter-rater reliability and appropriateness of hospitalization. DESIGN: Cross-sectional study. SETTING: The available PAEP tools were reviewed and adapted for Indian context by ten experienced pediatricians following semi-Delphi process. Two PAEP-India tools; newborn (≤28 days) and children (>28 days-18 years) were developed. These PAEP-India tools were applied to cases to assess appropriateness of admission and inter-rater reliability between assessors. PARTICIPANTS: Two sets of case records were used: (i) 274 cases from five medical colleges in Delhi-NCR [≤28 days (n=51); >28 days to 18 years (n=223)]; (ii) 622 infants who were hospitalized in 146 health facilities and were part of a cohort (n= 30688) from two southern Indian states. INTERVENTIONS: Each case-record was evaluated by two pediatricians in a blinded manner using the appropriate PAEP-India tools, and 'admission criteria' were categorized as appropriate, inappropriate or indeterminate. OUTCOME MEASURES: The proportion of appropriate hospitalizations and inter-rater reliability between assessors (using kappa statistic) were estimated for the cases. RESULTS: 97.8% hospitalized cases from medical colleges were labelled as appropriate by both reviewers with inter-rater agreement of 98.9% (k=0.66). In the southerm Indian set of infants, both reviewers labelled 80.5% admissions as appropriate with inter-rater agreement of 96.1% (k= 0.89). CONCLUSIONS: PAEP-India (newborn and child) tools are simple, objective and applicable in diverse settings and highly reliable. These tools can potentially be used for deciding admission appropriateness and hospital stay and may be evaluated later for usefulness for cost reimbursements for insurance proposes.

Diagnosis of neonatal sepsis using 16S rRNA polymerase chain reaction.

The gold standard for detecting bacterial sepsis is blood culture. However, the sensitivity of blood culture is low and the results take 48-72 h. Molecular assays for the detection of bacterial DNA permit early detection of a bacterial cause as the turnaround time is 6-8 h. We undertook an evaluation of the performance of universal bacterial primer (16S rRNA) polymerase chain reaction (PCR) in the diagnosis of neonatal sepsis at a tertiary care medical college teaching hospital. 16S rRNA PCR was positive in all cases of blood culture proven sepsis. PCR revealed 95.6% sensitivity, 100% specificity, 100% positive predictive value and 91.2% negative predictive value and so appears to be a useful tool for the early diagnosis of bacterial neonatal sepsis.

Predictors for critical care admission among children presenting to emergency department with recurrent wheezing.

CONTEXT: Children with recurrent wheezing contribute to a significant burden of inpatient hospital admission in developing countries. However, many patients could be managed at home following a short observation period in emergency unit. AIM: This study aimed to determine the predictors of critical care admission in a population of children aged 6 months to 2 years attending pediatric emergency department (ED) for recurrent wheezing. SETTING AND DESIGN: This is a case-control study conducted in pediatric ED of a tertiary care center in North India. PATIENTS AND METHODS: Demographic and clinical details were recorded for children aged 6 months to 2 years who presented to ED for "recurrent wheezing" within 48 h of onset of symptoms. Those who were admitted to critical care unit were considered cases and those who were discharged within 6 h of stay at short observation units of ED were considered controls. STATISTICAL ANALYSIS: Logistic regression model was used to determine which of the various demographic and clinical factors best predicted the need for critical care admission. RESULTS: The cases (n = 58) had significantly higher number of emergency visits in the preceding 1 month (P = 0. 018), had more episodes of wheezing in the last 3 months (P = 0.025), had higher respiratory rate (P < 0.001), and had higher clinical severity score (P < 0.001) when compared to control (n = 58) group. Logistic regression model revealed incomplete immunization status of children (P = 0.005) to be a significant risk factor that determine the need for critical care admission. CONCLUSION: The present cross-sectional study with limited sample size revealed incomplete immunization status of children to be a significant risk factor that determined the need for critical care admission among children below 2 years of age presenting to ED with recurrent wheezing.

Congenital Giant Dysplastic Kidney Presenting as Respiratory Distress: A Case Report.

Multicystic dysplastic kidney (MCDK) is the most common form of renal cystic disease in children and is one of the most common causes of abdominal mass in infancy. Here in we are reporting a rare case of a large MCKD that caused respiratory compromise and the infant presented with respiratory distress.

A Case of Deep Vein Thrombosis and Intracranial Sinus Thrombosis: Possible rare complications of childhood abdominal tuberculosis.

Severe pulmonary tuberculosis (TB) complicated by deep vein thrombosis (DVT) in adults has been reported previously in the medical literature; however, childhood extrapulmonary TB complicated by DVT is rare. We report a 13-year-old girl who presented to the Department of Pediatrics at the Postgraduate Institute of Medical Sciences in Rohtak, India, in 2012 with abdominal TB complicated by DVT and intracranial sinus thrombosis. She was treated with a course of four antitubercular drugs and short-term anticoagulation therapy with a positive outcome over the next six months. To the best of the authors' knowledge, no previous reports have yet suggested a possible association between childhood TB and intracranial sinus thrombosis.