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

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

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Infant Pulmonary Function Tests in Children with Airway Anomalies and Correlation with Bronchoscopy Findings.

OBJECTIVES: To evaluate the role infant pulmonary function tests (Tidal Breathing Flow Volume Loops, TBFVL) in children with airway anomalies and to correlate the TBFVL so obtained with bronchoscopy findings. METHODS: In this prospective cohort study, we enrolled children aged 0-2 years with airway anomalies and performed TBFVL and bronchoscopy. The primary outcome measure was graphic pattern of TBFVL in laryngomalacia. Secondary outcome measures were types of TBFVL results in various airway anomalies and controls. RESULTS: Out of 53 children enrolled, 28 (52.3%) had laryngomalacia. Pattern 3 (fluttering of inspiratory limb) was commonest TBFVL pattern in laryngomalacia. Among TBFVL parameters, the ratio of inspiratory time to expiratory time (Ti/Te) and tPTEF/tE was significantly high in children with isolated laryngomalacia compared to controls. At six months of follow-up, TBFVL pattern 1 (normal) became the commonest pattern. CONCLUSION: A particular type of airway anomaly may have a characteristic graphic pattern in TBFVL and TBFVL pattern may indicate improvement in airway anomalies in follow-up.

Management of the infant born to a mother with tuberculosis: a systematic review and consensus practice guideline.

Infants born to mothers with tuberculosis disease are at increased risk of developing tuberculosis disease themselves. We reviewed published studies and guidelines on the management of these infants to inform the development of a consensus practice guideline. We searched MEDLINE, CINAHL, and Cochrane Library from database inception to Dec 1, 2022, for original studies reporting the management and outcome of infants born to mothers with tuberculosis. Of the 521 published papers identified, only three met inclusion criteria and no evidence-based conclusions could be drawn from these studies, given their narrow scope, variable aims, descriptive nature, inconsistent data collection, and high attrition rates. We also assessed a collection of national and international guidelines to inform a consensus practice guideline developed by an international panel of experts from different epidemiological contexts. The 16 guidelines reviewed had consistent features to inform the expert consultation process. Two management algorithms were developed-one for infants born to mothers considered potentially infectious at the time of delivery and another for mothers not considered infectious at the time of delivery-with different guidance for high and low tuberculosis incidence settings. This systematic review and consensus practice guideline should facilitate more consistent clinical management, support the collection of better data, and encourage the development of more studies to improve evidence-based care.

B cell repertoire sequencing of HIV-1 pediatric elite-neutralizers identifies multiple broadly neutralizing antibody clonotypes.

Introduction: A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants. Methods: We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1. Results: BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330. Discussion: This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

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

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

Long-Term Outcomes of Survivors of COVID-19 with Moderate to Severe Infection and Children with Multisystem Inflammatory Syndrome or MIS-C.

The study aims to evaluate the long-term outcomes - functional, pulmonary and non-pulmonary (other organs) - in children hospitalized with COVID-19 infection or with Multisystem inflammatory syndrome (MIS-C) after 1-2 y of discharge. All children with moderate or severe COVID-19 or MIS-C were enrolled. Out of 45 enrolled subjects, 19.8% had COVID-19 infection and 82% had MIS-C. Four children (8.9%) had abnormal baseline echocardiography; two each with cardiac dysfunction and coronary dilatation. At baseline, 44% had moderate disability and 24% had mild disability as per Pediatric Cerebral Performance Category (PCPC). On follow-up, only 8.9% (n = 4) had mild and 2.2% (n = 1) had moderate disability as per the PCPC score. One child developed new onset tuberculosis of the bone. None had any pulmonary morbidities. Follow-up echocardiogram was also within normal limits for children with abnormal findings. Further studies in different populations (settings) are required to draw meaningful conclusions about long-term effects of COVID-19 on children.

Validation of a Clinical Tool to Predict Neurological Outcomes in Critically Ill Children-A Prospective Observational Study.

OBJECTIVES: To evaluate the performance of the empiric tool by Gupta et al. in predicting neurological outcomes in children admitted to the pediatric intensive care unit (PICU) and to evaluate the association of biomarkers S100B and NSE with neurological outcomes. METHODS: This prospective observational study was conducted in 163 critically ill children aged 2 mo to 17 y admitted to the PICU from June 2020 to July 2021. The authors used the prediction tool developed by Gupta et al.; the tool was applied at admission and at PICU discharge/death. Samples for NSE and S100B were collected at admission and discharge. The performance of the new tool was assessed through discrimination and calibration. Risk factors for "unfavorable outcomes" (decline in PCPC score by > 1) were evaluated by multivariate analysis. RESULTS: The PICU mortality was 28% (n = 45). When the tool developed by Gupta et al. was used at the time of admission, favorable neurological outcomes were predicted for 69% (112) children. The area under the curve for the new tool at admission was 0.72 and at discharge/death it was 0.99, and the calibration was excellent at both time points. Independent factors associated with unfavorable neurological outcomes were higher PCPC scores and organ failure. As the number of samples processed for NSE and S100B was less, statistical analysis was not attempted. CONCLUSIONS: The new tool by Gupta et al. has good discrimination, calibration, sensitivity, and specificity and can be used as a prediction tool. NSE and S100B are promising biomarkers and need further evaluation.

Development and Validation of a Weight Estimation Tool for Acutely Ill Children Who Cannot be Weighed.

OBJECTIVES: To develop and validate weight estimation tools using mid upper arm circumference (MUAC) and body length, and determine accuracy and precision of Broselow tape in children 6 mo to 15 y of age. METHODS: Data of 18,456 children aged 6 mo to 5 y and 1420 children aged 5 to 15 y were used to develop linear regression equations using length and MUAC to estimate weight. These were validated on prospectively enrolled populations of 276 and 312 children, respectively. Accuracy was measured by Bland-Altman bias, median percentage errors, and percentage of predicted weight within 10% of true weight. Broselow tape was tested on the validation population. RESULTS: Gender specific equations were developed which estimated weight within 10% of true weight in 69.9% (64.1-75.2%) and 65.7% (60.1-70.9%) of children aged 6 mo to 5 y, and 5 to 15 y, respectively. Broselow tape predicted weight within 10% of the true weight in 40.5% (34.7-46.6%) and 32.5% (26.7-38.7%) of children aged 6 mo to 5 y and 5 to 15 y, respectively. CONCLUSIONS: The model developed from MUAC and length accurately estimated weight in children aged 6 mo to 15 y, and is potentially useful during emergencies. The Broselow tape frequently overestimated weight in authors' setting.

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

OBJECTIVES: To explore the efficacy of combination of Bhramari pranayama and om chanting as an adjunct to standard pharmacological treatment on asthma control, quality of life, pulmonary function, and airway inflammation in asthmatic children. METHODS: Children (n = 110; 8-15 years) with uncontrolled or partly controlled asthma were recruited from the Pediatric Chest Clinic of All India Institute of Medical Sciences, New Delhi. Eligible participants were randomized to either home-based online Bhramari pranayama and om chanting plus standard treatment (YI + ST) group, or standard treatment (ST) alone group. Primary outcome measures were 12-week change in level of asthma symptom control; asthma control questionnaire (ACQ) score, spirometry indices, impulse oscillometry parameters, and pediatric asthma quality of life questionnaire (PAQLQ) score. Secondary outcome was a change in fractional exhaled nitric oxide (FeNO) levels at 12 weeks. Beginning from the enrollment, every participant was evaluated at 0, 2, 6, and 12 weeks. RESULTS: After 12 weeks of intervention, higher proportion (68.2%) of children were found to have controlled asthma symptoms in the YI + ST group as compared to ST group (38.5%) according to per protocol analysis (p = 0.03). When compared to ST group, children in YI + ST group showed significantly lower ACQ score, higher PAQLQ score and reduced FeNO levels. No significant changes were observed for the lung function parameters. CONCLUSION: Children practicing Bhramari pranayama and om chanting for 12 weeks have better asthma symptom control, quality of life, and reduced airway inflammation than those taking standard pharmacotherapy alone.

Prevalence of Metabolic Abnormalities and their Association with Asthma Symptom Control in Children.

OBJECTIVES: To determine the prevalence of insulin resistance (IR), dyslipidemia and metabolic syndrome (MS) in children with asthma, aged 10 to 15 y, and to determine if these metabolic abnormalities showed an association with asthma symptom control and lung function. METHODS: A cross-sectional study was conducted at a tertiary centre in north India. Consecutive children with physician diagnosed asthma were enrolled. Asthma symptom control over previous four weeks was assessed as per Global Initiative for Asthma (GINA) recommendations. Fasting plasma glucose, serum insulin and lipid levels were estimated. Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) was used as a marker of IR. Spirometry was performed for assessing lung function. RESULTS: Eighty-three children were enrolled. Median (IQR) age was 12.0 (11.0, 13.5) y and mean (SD) body mass index (BMI) Z score was -0.42 (1.0). Median (IQR) HOMA-IR was 1.65 (1.06, 2.39). Prevalence of IR was 42.3% (95% CI: 31.7-52.9%). Number of children with elevated triglycerides, total cholesterol, and low-density lipoprotein (LDL)-cholesterol was 4 (4.8%), 4 (4.8%) and 5 (6%), respectively. Sixty-seven (80.7%) children had low high-density lipoprotein (HDL)-cholesterol. Only one subject was found to have metabolic syndrome. Presence of IR and elevation in serum insulin and triglycerides were associated with poorer asthma control, independent of BMI. None of the metabolic parameters were associated with lung function, after adjusting for height. CONCLUSIONS: Among children with asthma, aged 10 to 15 y, the prevalence of IR was 42.3% (95% CI: 31.7-52.9%). Elevated serum insulin, triglycerides, and presence of IR were associated with poorer asthma control, after adjusting for BMI.

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

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

The Microbiome and Metabolome of the Gut of Children with Sepsis and Septic Shock.

BACKGROUND: There is limited understanding of alteration of gut microbiota and metabolome in children with sepsis/septic shock. METHODS: In this prospective observational study carried out in a pediatric intensive care unit of a tertiary care center from 2020 to 2022, patients aged <17 years with sepsis/septic shock and healthy children (HC) were enrolled. We characterized the gut bacterial compositions by metagenome sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. The primary outcome was to compare the gut microbiota and metabolome of children with sepsis/septic shock with that of HC. The Firmicutes/Bacteroidetes (F/B) ratio was compared between children with sepsis/septic shock and HC. Key secondary outcomes were to evaluate association of factors associated with a low F/B ratio in children with sepsis/septic shock. RESULTS: A total of 40 children (63% boys) (15 children with sepsis and septic shock and 10 healthy children) with a median (IQR) age of 5.5 (1.5, 10) years were enrolled. In the fecal microbiota, the α-diversity index including Shannon and Simpson indices of the sepsis/septic shock groups was significantly lower than that of the HC. The samples lacked beneficial Bifidobacterium spp. and were dominated by Bacteroides, Enterobacteriaceae, and Enterococcaceae. There was reduction in short-chain fatty acids (SCFAs) in patients with sepsis/septic shock as compared to healthy children. A lower F/B ratio (≤1.57) of the gut microbiota discriminated well between children with sepsis/septic shock and HC. Factors associated with lower F/B ratio were male gender, clinical GI dysfunction, elevated inflammatory markers, and higher organ failure scores. CONCLUSION: There were significant alterations in the gut microbiota and metabolome in children with sepsis/septic shock as compared to healthy children. Larger study is needed to confirm these exploratory findings and develop potential therapeutic targets that will improve outcomes in children with sepsis/septic shock.

MDCT and MRI in Bronchiectasis in Older Children and Young Adults - A Non-Inferiority Trial.

OBJECTIVES: To compare and evaluate the usefulness of magnetic resonance imaging (MRI) with computed tomography (CT) in bronchiectasis; to compare MRI and CT scores with pulmonary function tests (PFT) and to evaluate the role of Diffusion-weighted imaging (DWI) in bronchiectasis. METHODS: In this prospective study, 25 patients between 7-21 y of age with a clinical/radiological diagnosis of bronchiectasis underwent MDCT and MRI chest. MRI and CT scoring was performed using modified Bhalla-Helbich's score by two independent radiologists for all parameters. A final consensus score was recorded. The overall image quality of different MRI sequences to identify pathologies was also assessed. Appropriate statistical tests were used for inter-observer agreements, and correlation amongst CT and MRI; as well as CT, MRI and PFT. RESULTS: Strong agreement (ICC 0.80-0.95) between CT and MRI was seen for extent and severity of bronchiectasis, number of bullae, sacculation/abscess, emphysema, collapse/ consolidation, mucus plugging, and mosaic perfusion. Overall CT and MRI scores had perfect concordance (ICC 0.978). Statistically significant (p-value <0.01) intra-observer and inter-observer agreement for all CT and MRI score parameters were seen. A strong negative correlation was seen between total CT and MRI severity scores and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF) 25-75%. DWI MR, with an apparent diffusion coefficient (ADC) cut-off of 1.62 × 10-3 mm3/s had a sensitivity of 70% and specificity of 75% in detecting true mucus plugs. CONCLUSIONS: MRI with DWI can be considered as a radiation-free alternative in the diagnostic algorithm for assessment of lung changes in bronchiectasis, especially in follow-up.

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

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

GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis.

Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.

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

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