A pragmatic calibration of the ROX index to predict outcome of nasal high-flow therapy in India.

PURPOSE: Identifying thresholds at which the ROX index would satisfactorily predict HFNC failure across heterogenous resourced contexts is necessary for clinical use. METHODS: Patients ≥18 years admitted to 30 diverse ICUs across 10 states in India who required HFNC for respiratory support were retrospectively included in this study. Patient data and hourly ROX indices were then analyzed and contextualized to clinical outcomes as well as with ROX index thresholds in other regions of the world. MEASUREMENTS AND MAIN RESULTS: Among the 614 patients included, 276 (44.9%) required respiratory escalation. Pneumonia was the most common diagnosis on admission. Receiver operating characteristic curve analysis revealed that a baseline ROX score of 7.86 was similar to 4.88 in other populations which was confirmed by Kaplan-Mier curves (hazard ratio,3.58 (2.72-4.69, p < 0.001)). ROX scores at 11.84 or 5.89 had roles in screening and confirming HFNC failure. The index performed poorly in a subset of patients who died without respiratory escalation. The ROX index was most predictive in the initial hours of ICU admission and a longer duration of HFNC was associated with more severe outcomes. CONCLUSIONS: When optimally calibrated this index can using a method that can reliably predict the risk of HFNC failure among ICU patients from diverse settings.

A Proof-of-Concept Model for Implementing a "Smart-NICU" to Improve Infant Mortality.

Low- and middle-income countries face limited critical care capacity due to constraints in staffing, resources, and technology. "Smart ICUs" that integrate telehealth to augment care delivery, communication, and data integration have the potential to bridge these gaps and reduce preventable morbidity and mortality. While their efficacy has been well validated in adult populations, applications of Smart-ICU services in the neonatal population have not been studied. Neonatal intensive care units (NICUs) in India using a common Smart-NICU platform, developed by CloudPhysician, utilize a hub-and-spokes framework along with locally designed technology to facilitate remote patient care in collaboration with local health systems. In this article, we investigate the operational characteristics and performance outcomes for Smart-NICU deployment from the 18 NICUs and 214 beds deployed to date. These findings highlight the potential impact of Smart-NICUs and establish generalizable principles for implementation in low-resource settings.

Risk factors for renal scarring and clinical morbidity in children with high-grade and low-grade primary vesicoureteral reflux.

INTRODUCTION: Primary vesicoureteral reflux (VUR) is associated with urinary tract infections (UTIs) and renal damage. However, the importance of early diagnosis of VUR has been questioned. Moreover, most studies have few patients with high-grade VUR. Hence, we retrospectively analyzed a large cohort of patients with primary high-grade and low-grade VUR and assessed risk factors for renal damage and clinical morbidity. MATERIAL AND METHODS: We included patients (<18 years) at diagnosis with low-grade (1-3) or high-grade (4-5) primary VUR and noted their clinical history and presence of hypertension, low eGFR (<60ml/in/1.73 m2), renal scarring (focal or generalised) and reduced differential renal function (DRF; <45%). Risk factors were assessed (in patients and renal units) by logistic regression and generalised estimating equation. RESULTS: Of 399 primary VUR patients, 255 (64%) had high-grade VUR. Indications for voiding cystourethrogram were recurrent UTI (38%), first UTI (28%) and antenatal hydronephrosis (17%). At diagnosis, 252 (65%) had renal scars (focal in 170 [44%], generalised in 82 [21%]), and 188 (47%) had reduced DRF. High-grade VUR patients were more likely than low-grade VUR patients to have renal scarring (75% vs. 49%, p < 0.01), low eGFR (23% vs. 13%, p = 0.04) and significant hypertension (26% vs. 13%, p = 0.02). High-grade VUR was associated with generalised scars (odds ratio [OR] 11, p < 0.001), focal scars (OR 3.1, p < 0.001) and reduced DRF (OR 2.3, p < 0.001) shown in the table. Male sex was a risk factor for generalised scars (OR 2.3, p = 0.005). Focal scars were associated with recurrent UTIs (OR = 1.8, p = 0.004) and reduced DRF (OR 1.4, p = 0.027). Patients with multiple focal scars were diagnosed at an older age (2 years [1,4] than those with single scars (1.5 years [1,4] or no scars (1 year [0, 3]), p = 0.04). DISCUSSION: The prevalence of renal damage and clinical morbidity at VUR diagnosis was higher than other studies. High-grade VUR patients had a greater prevalence of renal damage, low eGFR and hypertension than low-grade VUR patients and was a risk factor for focal scars, generalised scars and reduced DRF. Focal scars were independently associated with recurrent UTI. Those with multiple scars were diagnosed later than those with single scars or no scars. CONCLUSIONS: High-grade VUR was associated with renal damage and clinical morbidity. Our study highlights the importance of diagnosing VUR early to identify patients who may warrant long-term follow-up and intervention to minimize morbidity.

The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis.

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes.

BACKGROUND: India is endemic for enteric fever, and it is not known whether the variations in clinical manifestations between patients are due to host, environmental or pathogen factors.Blood culture surveillance was conducted at St. John's Medical College Hospital, Bangalore, between July 2016 and June 2017. Clinical, laboratory and demographic data were collected from each case, and bacterial isolates were subjected to whole genome sequencing. Comparative analysis between adults and paediatric patients was carried out to ascertain differences between adult and paediatric disease. RESULTS: Among the 113 cases of blood culture-confirmed enteric fever, young adults (16-30 years) and children < 15 years accounted for 47% and 37% of cases, respectively. Anaemia on presentation was seen in 46% of cases, and 19% had an abnormal leucocyte count on presentation. The majority received treatment as inpatients (70%), and among these, adults had a significantly longer duration of admission when compared with children (p = 0.002). There were atypical presentations including arthritis, acute haemolysis and a case of repeated typhoid infection with two separate S. Typhi genotypes. There was no association between infecting genotype/serovar and treatment status (outpatient vs inpatient), month of isolation, duration of admission, patient age (adult or child), antimicrobial susceptibility, Widal positivity or haematologic parameters. CONCLUSIONS: Amidst the many public health concerns of South India, enteric fever continues to contribute substantially to hospital burden with non-specific as well as uncommon clinical features in both paediatric and adult populations likely driven by host and environmental factors. Robust clinical surveillance as well monitoring of pathogen population structure is required to inform treatment and preventive strategies.

Persistent circulation of a fluoroquinolone-resistant Salmonella enterica Typhi clone in the Indian subcontinent.

BACKGROUND: The molecular structure of circulating enteric fever pathogens was studied using hospital-based genomic surveillance in a tertiary care referral centre in South India as a first genomic surveillance study, to our knowledge, of blood culture-confirmed enteric fever in the region. METHODS: Blood culture surveillance was conducted at St John's Medical College Hospital, Bengaluru, between July 2016 and June 2017. The bacterial isolates collected were linked to demographic variables of patients and subjected to WGS. The resulting pathogen genomic data were also globally contextualized to gauge possible phylogeographical patterns. RESULTS: Hospital-based genomic surveillance for enteric fever in Bengaluru, India, identified 101 Salmonella enterica Typhi and 14 S. Paratyphi A in a 1 year period. Ninety-six percent of isolates displayed non-susceptibility to fluoroquinolones. WGS showed the dominant pathogen was S. Typhi genotype 4.3.1.2 (H58 lineage II). A fluoroquinolone-resistant triple-mutant clone of S. Typhi 4.3.1.2 previously associated with gatifloxacin treatment failure in Nepal was implicated in 18% of enteric fever cases, indicating ongoing inter-regional circulation. CONCLUSIONS: Enteric fever in South India continues to be a major public health issue and is strongly associated with antimicrobial resistance. Robust microbiological surveillance is necessary to direct appropriate treatment and preventive strategies. Of particular concern is the emergence and expansion of the highly fluoroquinolone-resistant triple-mutant S. Typhi clone and its ongoing inter- and intra-country transmission in South Asia, which highlights the need for regional coordination of intervention strategies, including vaccination and longer-term strategies such as improvements to support hygiene and sanitation.