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.

Efficacy of Rifaximin in Patients With Abdominal Bloating or Distension: A Systematic Review and Meta-analysis.

BACKGROUND: Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID). METHODS: We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy. RESULTS: A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01). CONCLUSIONS: Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID.

Global Burden of Chronic Obstructive Pulmonary Disease Through 2050.

Importance: Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies assessed the global current-day prevalence of COPD, but to better facilitate resource planning and intervention development, long-term projections are needed. Objective: To assess the global burden of COPD through 2050, considering COPD risk factors. Design, Setting, and Participants: In this modeling study, historical data on COPD prevalence was extracted from a recent meta-analysis on 2019 global COPD prevalence, and 2010 to 2018 historical prevalence was estimated using random-effects meta-analytical models. COPD risk factor data were obtained from the Global Burden of Disease database. Main Outcomes and Measures: To project global COPD prevalence to 2050, generalized additive models were developed, including smoking prevalence, indoor and outdoor air pollution, and development indices as predictors, and stratified by age, sex, and World Bank region. Results: The models estimated that the number of COPD cases globally among those aged 25 years and older will increase by 23% from 2020 to 2050, approaching 600 million patients with COPD globally by 2050. Growth in the burden of COPD was projected to be the largest among women and in low- and middle-income regions. The number of female cases was projected to increase by 47.1% (vs a 9.4% increase for males), and the number of cases in low- and middle-income regions was expected to be more than double that of high-income regions by 2050. Conclusions and Relevance: In this modeling study of future COPD burden, projections indicated that COPD would continue to affect hundreds of millions of people globally, with disproportionate growth among females and in low-middle income regions through 2050. Further research, prevention, and advocacy are needed to address these issues so that adequate preparation and resource allocation can take place.

Evaluation of kit-based loop-mediated isothermal amplification (TB-LAMP) assay in the diagnosis of tubercular lymphadenitis.

Background: The rapid and accurate diagnosis of tubercular lymphadenitis remains a challenging task today. The World Health Organization (WHO) endorsed the LoopAMP MTBC kit (TB-LAMP) as a replacement for sputum smear microscopy in the diagnosis of pulmonary tuberculosis (PTB). However, no prospective diagnostic accuracy study of TB-LAMP for tubercular lymphadenitis in adults has been performed yet. The current study evaluated the diagnostic performance of TB-LAMP in tubercular lymphadenitis (LNTB). Methods: In a prospective observational study conducted at a tertiary care hospital in India, 90 subjects (age >18 years) suspected of LNTB were recruited consecutively and followed up for 6 months between January 2019 and December 2020. Samples were processed for microscopy, culture, GeneXpert, histopathology and TB-LAMP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TB-LAMP against the composite reference standard (CRS) and culture were determined. Results: TB-LAMP showed a sensitivity of 83.78 % (95 % CI, 73.76-90.47) and a specificity of 81.25 % (95 % CI, 56.99-93.41), respectively, against the CRS. The PPV and NPV were 95.38 % (95 % CI, 87.29-98.42) and 52.00 % (95 % CI, 33.50-69.97), respectively. TB-LAMP showed a sensitivity of 88.89 % (95 % CI, 71.94-96.15) and a specificity of 36.17 % (95 % CI, 23.97-50.46), respectively, against culture. The PPV and NPV were 44.44 % (95 % CI, 32-57.62) and 85 % (95 % CI, 63.96-94.76), respectively. Conclusion: TB-LAMP can be used instead of conventional microscopy for the diagnosis of TB in lymph node specimens at primary healthcare centres. It provides rapid and cost-effective diagnosis of LNTB in resource-limited settings due to good sensitivity and NPV.

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.

Central Line-Associated Bloodstream Infections: Effect of Patient and Pathogen Factors on Outcome.

Introduction: Patients on central lines are often having multiple morbidities, and invasive devices provide a niche for biofilm formation, which makes central line-associated bloodstream infections (CLABSIs), a serious concern in health-care settings, as the infections difficult to treat. In this study, we evaluated the common bacteria causing CLABSI, and various patient and pathogen factors affecting the clinical outcome. Methods: In the prospective observational study, patients diagnosed with CLABSI were recruited. Extensive clinical, microbiological, and other laboratory workup was done, and observations were recorded. Congo red agar method, tube test, and microtiter plate assay were used for eliciting the biofilm-forming attributes of the bacterial pathogens. Results: Klebsiella pneumoniae was responsible for 48% of CLABSI, followed by Coagulase-negative Staphylococci (16%) and Staphylococcus aureus and Acinetobacter baumannii (12% each). Fifty-six percent of the isolates produced biofilms. The median (interquartile range) duration of hospital stay till death or discharge was 30 (20, 43) days. The all-cause mortality was 44%. Patients having a deranged liver function on the day of diagnosis (P value for total bilirubin 0.001 and for aspartate transaminase 0.02), and those infected with multidrug-resistant organisms (P value = 0.04) had significantly poor prognosis. The difference in the demographic, clinical, laboratory profile, and outcome of patients infected with biofilm producers and nonproducers was not found to be statistically significant. Conclusion: The study throws light on various host and pathogen factors determining the cause and outcome of CLABSI patients. To the best of our knowledge, this is the first study trying to decipher the role of biofilm formation in the virulence of pathogens and the prognosis of CLABSI.

Cardiopulmonary Outcomes in Covid-19 Patients Discharged From a Tertiary Care Center: A Prospective Study.

To determine the cardiopulmonary changes in the survivors of acute COVID-19 infection at 3-6 month and 6-12 month. We followed up 53 patients out of which 28 (52%) had mild COVID-19 and 25 (48%) had severe COVID-19. The first follow-up was between 3 month after diagnosis up to 6 month and second follow-up between 6 and 12 month from the date of diagnosis of acute COVID-19. They were monitored using vital parameters, pulmonary function tests, echocardiography and a chest computed tomography (CT) scan. We found improvement in diffusing capacity for carbon monoxide (DLCO) with a median of 52% of predicted and 80% of predicted at the first and second follow-up, respectively. There was improvement in the CTSS in severe group from 22 (18-24) to 12 (10-18; p-0.001). Multivariable logistic regression revealed increased odds of past severe disease with higher CTSS at follow-up (OR-1.7 [CI 1.14-2.77]; P = 0.01). Correlation was found between CTSS and DLCO at second follow-up (r2 = 0.36; p < 0.01). Most of patients recovered from COVID-19 but a subgroup of patients continued to have persistent radiological and pulmonary function abnormalities necessitating a structured follow-up.

Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses.

RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2',3'-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses.

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial.

BACKGROUND: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. METHODS: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. RESULTS: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. CONCLUSIONS: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. TRIAL REGISTRATION: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Survival of Persons Living With HIV/AIDS: A Multicentric Study From India.

BACKGROUND: It has been more than 17 years since the introduction of free ART in India. At this point, it would be prudent to look at the factors associated with the survival of persons living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLHA) who are already enrolled in the ART program. METHODS: PLHAs enrolled from antiretroviral therapy (ART) centers located in three different cities in India - Delhi, Pune and Kolkata, and were followed up at six monthly intervals monitoring the WHO stage, CD4 counts, complete blood counts, and liver and kidney function tests, for a duration of three years. RESULTS AND DISCUSSION: The incidence of mortality among HIV/AIDS patients on ART was 5.0 per 1000 patient-years (21/1410, 1.4%). Age at initiation of ART, being above 35 years, was the only significant predictor of mortality (log-rank p = 0.018). Multivariable analysis showed a significant association of an unfavourable outcome (defined as mortality or development of opportunistic infection during follow-up) with male gender (adjusted odds ratio (AOR) = 5.26, p = <0.01) and being unmarried at ART initiation (AOR = 1.39, p = 0.005). CONCLUSION: The survival of PLHA with good adherence to ART is independent of the WHO stage or CD4 counts at the initiation of ART. Initiation of ART after 35 years of age was a significant predictor of mortality.

Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses.

RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small library of innate immune agonists targeting pathogen recognition receptors, including TLRs, STING, NOD, Dectin and cytosolic DNA or RNA sensors. We observed that TLR3, STING, TLR8 and Dectin-1 ligands inhibited arboviruses, Chikungunya virus (CHIKV), West Nile virus (WNV) and Zika virus, to varying degrees. Cyclic dinucleotide (CDN) STING agonists, such as cAIMP, diABZI, and 2',3'-cGAMP, and Dectin-1 agonist scleroglucan, demonstrated the most potent, broad-spectrum antiviral function. Comparative transcriptome analysis revealed that CHIKV-infected cells had larger number of differentially expressed genes than of WNV and ZIKV. Furthermore, gene expression analysis showed that cAIMP treatment rescued cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provided protection against CHIKV in a CHIKV-arthritis mouse model. Cardioprotective effects of synthetic STING ligands against CHIKV, WNV, SARS-CoV-2 and enterovirus D68 (EV-D68) infections were demonstrated using human cardiomyocytes. Interestingly, the direct-acting antiviral drug remdesivir, a nucleoside analogue, was not effective against CHIKV and WNV, but exhibited potent antiviral effects against SARS-CoV-2, RSV (respiratory syncytial virus), and EV-D68. Our study identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses, which can be rapidly deployed to prevent or mitigate future pandemics.

Ultrasonography of the neck in patients with obstructive sleep apnea.

INTRODUCTION: In resource-limited settings, obstructive sleep apnea (OSA) often goes undiagnosed as polysomnography (PSG) is expensive, time-consuming, and not readily available. Imaging studies of upper airway have been tried as alternatives to PSG to screen for OSA. However, racial differences in upper airway anatomy preclude generalizability of such studies. We sought to test the hypothesis that ultrasonography (USG), an inexpensive, readily available tool to study soft tissue structures of the upper airway, would have predictive value for OSA in South Asian people. METHODS: Adult patients with sleep-related complaints suspicious for OSA were taken for overnight PSG. After the PSG, consecutive patients with and without OSA were studied with submental ultrasonography to measure tongue base thickness (TBT) and lateral pharyngeal wall thickness (LPWT). RESULTS: Among 50 patients with OSA and 25 controls, mean age was 43.9 ± 11.4 years, and 39 were men. Patients with OSA had higher TBT (6.77 ± 0.63 cm vs 6.34 ± 0.54 cm, P value = 0.004) and higher LPWT (2.47 ± 0.60 cm vs 2.12 ± 0.26 cm, P value = 0.006) compared to patients without OSA. On multivariate analysis, TBT, LPWT, and neck circumference were identified as independent factors associated with OSA. These variables could identify patients with severe OSA with a sensitivity of 72% and a specificity of 76%. CONCLUSION: Patients with OSA have higher tongue base thickness and lateral pharyngeal wall thickness proportionate to the severity of the disease, independent of BMI and neck circumference. These findings suggest that sub-mental ultrasonography may be useful to identify patients with severe OSA in resource-limited settings.

Applications of Gas Discharge Visualization Imaging in Health and Disease: A Systematic Review.

Context: Gas discharge visualization (GDV) works on the principle of the Kirlian effect. It's a noninvasive, quick, and safe biometric tool to investigate the psychophysiological state of an individual, with the potential to identify deviations from the healthy functioning of humans at early stages. Objective: The study intended to systematically document the scientific evidence pertaining to the use of GDV devices in human health and disease conditions. Design: The research team performed a systematic search for studies on GDV on research databases such as Google Scholar, PubMed, and PsychINFO, using the following inclusion criteria: (1) experimental studies dealing with a GDV device, (2) studies dealing with human participants related to health and disease, and (3) studies published in the English language. The study excluded: (1) review articles, (2) case studies, (3) letter to editors, (4) studies with unclear methodology, and (5) studies published before the year 2000. Setting: The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bengaluru, India. Results: After filtering, the research team obtained 108 publications that dealt with the application of a GDV device in human participants. Based on the selection criteria, 42 studies were included in the review. These 42 studies included eight randomized controlled trials (RCTs), five nonrandomized controlled studies, 17 cross-sectional studies, 10 single-group pre-post studies, and two correlational studies. Conclusions: More studies with a robust methodology are needed to make definitive conclusions. The literature reveals that the GDV technique has the potential to provide early diagnosis and screening, especially in disorders of the endocrine and immune systems. It might also be used to assess wellness in healthy subjects and monitor the effects of interventions, such as yoga-including pranayama and meditation, acupuncture, qigong, music therapy, and massage on the human energy system. Future studies should focus on the validation of GDV imaging in clinical settings.

In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics.

New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron's spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.

Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial.

INTRODUCTION: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. METHODS: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. RESULTS: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection. CONCLUSIONS: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. CLINICAL TRIALS REGISTRY: Clinical Trials Registry India (CTRI/2020/07/026668).

The Bacillus Calmette­Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters.

A study on the effect of mobile phone use on sleep.

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Prevalence of Long COVID-19 and its Impact on Quality of Life Among Outpatients With Mild COVID-19 Disease at Tertiary Care Center in North India.

Literature is lacking on the spectrum of symptoms of long COVID-19 (defined as symptoms persisting beyond 28 days of diagnosis) and its impact on quality of life. This single-center, cross-sectional study included mild COVID-19 cases as determined by a positive real-time reverse transcription polymerase chain reaction test. Patients were contacted at least 28 days after diagnosis and were interviewed telephonically using semi-structured questionnaires for duration of symptoms, fatigue using Fatigue Severity Scale (FSS) and quality of life using the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). A total of 251 COVID-19 patients were included; of which 169 (67.3%) were males. The mean age of the patients was 35.8 years (SD = 12.5). The prevalence of long COVID-19 was 28.2% (n = 71, 95% CI: 23.0-34.2). The most common symptoms involved the musculoskeletal system (12.7%), upper respiratory tract (7.6%), and fatigue among 17 (6.8%) patients. Patients with long COVID-19 had significantly higher FSS score and lower WHOQOL-BREF score compared to the patients without long COVID-19 (<28 days).

Prevalence, time trends and treatment practices of asthma in India: the Global Asthma Network study.

Objective: The objective of this subanalysis of data from centres across urban areas in India of the Global Asthma Network (GAN) was to study 1) the prevalence of symptoms of asthma in children and adults, 2) the change in prevalence of asthma and its trigger factors since the International Study of Asthma and Allergies in Childhood (ISAAC), and 3) current asthma treatment practice. Methods: In this cross-sectional, multicentre, school-based and self-administered questionnaire, responses from children aged 6-7 years and 13-14 years, and their respective parents, were analysed. Results: The GAN Phase I study included 20 084 children in the 6-7-year age group, 25 887 children in the 13-14-year age group and 81 296 parents. The prevalence of wheeze in the previous 12 months was 3.16%, 3.63% and 3.30% in the three groups, respectively. In comparison to the ISAAC studies, there was a significant reduction in the prevalence of current wheeze (p<0.001). Bivariate analysis revealed a significant reduction in the prevalence of trigger factors. Almost 82% of current wheezers and 70% of subjects with symptoms of severe asthma were not clinically diagnosed as having asthma. The daily use of inhaled corticosteroids (ICS) was less than 2.5% in subjects with current wheeze and those with symptoms of severe asthma but less than 1% used daily ICS when asthma remained undiagnosed. Conclusion: The prevalence of current wheeze and its causal factors showed a significant reduction compared to previous ISAAC studies. Among subjects with current wheeze and symptoms of severe asthma, the problem of under-diagnosis and under-treatment was widespread.