NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

Comparing Transvaginal Ultrasound Measurements of Cervical Length to Bishop Score in Predicting Cesarean Section Following Induction of Labor: A Prospective Observational Study.

INTRODUCTION:  Bishop score (BS) has been used to see the favorability of the cervix for induction of labor (IOL), but it has limitations in today's diverse patient population. We aimed to assess the predictive value of transvaginal ultrasound (TVUS) measurements of cervical length (CL) compared to BS in determining the likelihood of cesarean section (CS) following IOL. METHODOLOGY: A prospective observational study was conducted on 120 women requiring IOL in a tertiary care hospital in central India. The inclusion criteria of the study were antenatal women more than 18 years of age, in need of IOL, having a singleton pregnancy with a gestational age of > 37 weeks as determined from the date of the last menstrual period and confirmed by sonographic measurements in the first trimester, presenting with a cephalic presentation, and having intact fetal membranes. Women with prior uterine scars and those unwilling to IOL were excluded from the study. TVUS was done just before induction. Statistical analyses were done to compare the predictive abilities of CL and BS for CS. RESULTS: The mean age and gestation period were 25.96 years and 39 weeks 3 days, respectively. The majority of the study population comprised multigravida (69, 57.5%), followed by primigravida (47, 39.2%), and grand multigravida (≥ G5) (4, 3.3%). Post-maturity (34, 28.3%), preeclampsia (21, 17.5%), and intrahepatic cholestasis of pregnancy (17, 14.2%) were common indications for induction. The overall CS rate was 35.8% (43/120). Women with CS had lower BS (3.60 vs. 4.70, P = 0.010) and higher CL (31.5 mm vs. 23.4 mm, P < 0.001). CL exhibited an area under the curve (AUC) of 0.857, outperforming BS (AUC = 0.643) in predicting CS. Using a CL cutoff of 26.5 mm yielded sensitivity (79.1%), specificity (81.8%), and overall accuracy (80.8%). CONCLUSIONS: TVUS measurement of CL (>26.5 mm) demonstrated superior predictive ability for CS following labor induction compared to BS (≤5). This study highlights the potential of CL measurement as an objective and reliable tool for optimizing decision-making in labor induction.

Study of secondary organic aerosol formation and aging using ambient air in an oxidation flow reactor during high pollution events over Delhi.

Secondary aerosols constitute a significant fraction of atmospheric aerosols, yet our understanding of their formation mechanism and fate is very limited. In this work, the secondary organic aerosol (SOA) formation and aging of ambient air of Delhi are studied using a potential aerosol mass (PAM) reactor, an oxidation flow reactor (OFR), coupled with aerosol chemical speciation monitor (ACSM), proton transfer reaction time of flight mass spectrometer (PTR-ToF-MS), and scanning mobility particle sizer with counter (SMPS + C). The setup mimics atmospheric aging of up to several days with the generation of OH radicals. Variations in primary volatile organic compounds (VOCs) and oxygenated volatile organic compounds (OVOCs) as a function of photochemical age were investigated. Primary VOCs such as benzene, toluene, xylene, trimethyl benzene, etc. decrease and OVOCs like formic acid, formaldehyde, acetone, ethanol, etc. increase substantially upon oxidation in OFR. The highest organic aerosol (OA) enhancement was observed for the 4.2 equivalent photochemical days of aging i.e., 1.84 times the ambient concentration, and net OA loss was observed at very high OH exposure, typically after 8.4 days of photochemical aging due to heterogeneous oxidation followed by fragmentation/evaporation. In ambient air, OA enhancement is highest during nighttime due to the high concentrations of precursor VOCs in the atmosphere. SMPS + C results demonstrated substantial new particle formation upon aging and decrement in preexisting aerosol mass. This is the first experimental study conducting an in-situ evaluation of potential SOA mass generated from the ambient aerosols in India.

Carbon conundrums: Geopolitical clashes and market mayhem in the race for sustainability.

This research presents an in-depth investigation into the dynamic correlation between geopolitical conflicts and carbon markets utilizing the Time-Varying Parameter Vector Autoregression (TVP-VAR) technique. The analysis focuses on the interconnectedness between the Geopolitical Risk Index Daily (GPRD) and vital carbon pricing instruments, specifically the Intercontinental Exchange Endex European Union Allowance (ECEFDC), KraneShares California Carbon Allowance Strat ETF (KCCAK), Shanghai Environment and Energy Exchange China Emission Allowances Online Transactions (SAXCEA), and S&P Global Ex-Japan LargeMidCap Carbon Efficient Index (SPGJ). The daily fluctuations were traced from May 2021 to July 2023. The analysis is divided into short- and long-term connectedness, with particular emphasis on the impact of the Russia-Ukraine conflict on the GPRD's spillover on carbon markets. The short-term connectedness (1-5 days) between GPRD and ECEFDC shows variability, fluctuating between 10% and 40%. Conversely, long-term connectedness exhibited a significant increase during the conflict, peaking at approximately 34% by mid-2022. The analysis of the Total Dynamic Connectedness (TCI) between the GPRD and the KCCAK indicates comparable magnitudes, although with minor initial discrepancies. The short-term connectedness of GPRD and KCCAK decreases from its peak of approximately 10% to approximately 1%. Conversely, long-term connectedness varies between approximately 32% and 2% from May 2022 onwards. The long-term connectedness between GPRD and SAXCEA revealed variable patterns, peaking at around 18% at the beginning of the sample period and rapidly reducing to around 1% within two months. The analysis of the connectedness between GPRD and the SPG) identifies intense fluctuations in both TCI and long-term connectedness. After an initial increase and decrease, these patterns rebound and experience another increase. This research provides significant insights into the complex dynamics of geopolitical conflicts and carbon markets, particularly the impact of the Russia-Ukraine conflict on carbon market behavior.

Environmental Factors Affecting Monoterpene Emissions from Terrestrial Vegetation.

Monoterpenes are volatile organic compounds that play important roles in atmospheric chemistry, plant physiology, communication, and defense. This review compiles the monoterpene emission flux data reported for different regions and plant species and highlights the role of abiotic environmental factors in controlling the emissions of biogenic monoterpenes and their emission fluxes for terrestrial plant species (including seasonal variations). Previous studies have demonstrated the role and importance of ambient air temperature and light in controlling monoterpene emissions, likely contributing to higher monoterpene emissions during the summer season in temperate regions. In addition to light and temperature dependence, other important environmental variables such as carbon dioxide (CO2), ozone (O3), soil moisture, and nutrient availability are also known to influence monoterpene emissions rates, but the information available is still limited. Throughout the paper, we identify knowledge gaps and provide recommendations for future studies.

Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation.

Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.

Effect of glucocorticoids on the development of COVID-19-associated pulmonary aspergillosis: A meta-analysis of 21 studies and 5174 patients.

COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.

CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation.

The transcription factor Interferon regulatory factor 8 (IRF8) is involved in maintaining B cell identity. However, how IRF8 regulates T cell independent B cell responses are not fully characterized. Here, an in vivo CRISPR/Cas9 system was optimized to generate Irf8-deficient murine B cells and used to determine the role of IRF8 in B cells responding to LPS stimulation. Irf8-deficient B cells more readily formed CD138+ plasmablasts in response to LPS with the principal dysregulation occurring at the activated B cell stage. Transcriptional profiling revealed an upregulation of plasma cell associated genes prematurely in activated B cells and a failure to repress the gene expression programs of IRF1 and IRF7 in Irf8-deficient cells. These data expand on the known roles of IRF8 in regulating B cell identity by preventing premature plasma cell formation and highlight how IRF8 helps evolve TLR responses away from the initial activation towards those driving humoral immunity.

The Design, Development, and Implementation of a Web-Enabled Informatics Platform to Enhance the Well-being of Individuals Aged 18-24 Years: Protocol for an Experimental Study.

BACKGROUND: Well-being is multidimensional, complex, and dynamic in nature. It is an amalgam of physical and mental health, essential for disease prevention and the promotion of a healthy life. OBJECTIVE: This study aims to explore the features that impact the well-being of individuals between 18 and 24 years of age in an Indian setting. It further aims to design, develop, and evaluate the usefulness and effectiveness of a web-based informatics platform or stand-alone intervention to enhance the well-being of individuals aged 18-24 years in an Indian setting. METHODS: This study follows a mixed method approach to identify factors influencing the well-being of individuals in the age group of 18-24 years in an Indian setting. The college-going students in this age group from the states of Uttarakhand (urban settings of Dehradun) and Uttar Pradesh (urban settings of Meerut) will be enrolled. They will be randomly allocated to the control and intervention groups. The participants in the intervention group will have access to the web-based well-being platform. RESULTS: This study will examine the factors that influence the well-being of individuals aged 18-24 years. It will also facilitate the design and development of the web-based platform or stand-alone intervention, which will enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. Furthermore, the results of this study will help generate a well-being index for individuals to plan tailored interventions. The 60 in-depth interviews have been conducted as of September 30, 2022. CONCLUSIONS: The study will help understand the factors that influence the well-being of individuals. The findings of this study will help in the design and development of the web-based platform or stand-alone intervention to enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38632.

Clinical characteristics of patients with diffuse alveolar hemorrhage diagnosed by cytological examination of 1000 bronchoalveolar lavage samples.

BACKGROUND AND AIM: Diffuse alveolar hemorrhage (DAH) is a life-threatening condition due to the extravasation of blood in the alveoli, resulting in hypoxemia and even acute respiratory distress syndrome. This study aimed to describe the clinico-radio-pathological profile of patients diagnosed with DAH and classify it into immune and nonimmune DAH. METHODS: This was a retrospective analytical study. Of a total of 1000 cases of bronchoalveolar lavage fluids (BALF) received for cytological examination, patients fulfilling the clinical, radiological, and laboratory details of cases satisfying the clinical and cytological criteria of DAH (n=47) were studied. RESULTS: The most common cause of immune DAH was ANCA-associated vasculitis (n=13, 27.6%), and that of nonimmune DAH was infections (n=10, 21.3%). Twenty-nine patients (61.7%) had hemoptysis. The most common radiological finding was ground-glass opacities (n=33, 70.2%). In univariate analysis, female sex, mean hemoglobin at admission, total leucocyte count (TLC), platelet count, and erythrocyte sedimentation rate (ESR) were significantly associated with immune-DAH. However, in multivariate analysis, female sex, higher TLC, high platelets, and high ESR were significantly associated with immune DAH. Patients were treated with corticosteroids (n=25, 46.3%), intravenous cyclophosphamide (n=12, 22.2%), plasma exchange (n=7, 13.0%), intravenous immunoglobulin (n=5, 9.3%) and rituximab (n=5, 9.3%). The overall mortality was 8.5% (n=4). CONCLUSIONS: DAH is a life-threatening syndrome that may be classified into immune and nonimmune DAH. Immune-DAH requires aggressive management, whereas nonimmune DAH cases respond best to conservative management.

Peripheral T helper subset profiling in idiopathic inflammatory myositis: Proof of concept.

INTRODUCTION: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation. METHODS: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany). RESULTS: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity. CONCLUSION: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM.

Development of an Artificial Intelligence-Guided Citizen-Centric Predictive Model for the Uptake of Maternal Health Services Among Pregnant Women Living in Urban Slum Settings in India: Protocol for a Cross-sectional Study With a Mixed Methods Design.

BACKGROUND: Pregnant women are considered a "high-risk" group with limited access to health facilities in urban slums in India. Barriers to using health services appropriately may lead to maternal and child mortality, morbidity, low birth weight, and children with stunted growth. With the increase in the use of artificial intelligence (AI) and machine learning in the health sector, we plan to develop a predictive model that can enable substantial uptake of maternal health services and improvements in adverse pregnancy health care outcomes from early diagnostics to treatment in urban slum settings. OBJECTIVE: The objective of our study is to develop and evaluate the AI-guided citizen-centric platform that will support the uptake of maternal health services among pregnant women seeking antenatal care living in urban slum settings. METHODS: We will conduct a cross-sectional study using a mixed methods approach to enroll 225 pregnant women aged 18-44 years, living in the urban slums of Delhi for more than 6 months, seeking antenatal care, and who have smartphones. Quantitative and qualitative data will be collected using an Open Data Kit Android-based tool. Variables gathered will include sociodemographics, clinical history, pregnancy history, dietary history, COVID-19 history, health care facility data, socioeconomic status, and pregnancy outcomes. All data gathered will be aggregated into a common database. We will use AI to predict the early at-risk pregnancy outcomes (in terms of the type of delivery method, term, and related complications) depending on the needs of the beneficiaries translating into effective service-delivery improvements in enhancing the use of maternal health services among pregnant women seeking antenatal care. The proposed research will help policy makers to prioritize resource planning, resource allocation, and the development of programs and policies to enhance maternal health outcomes. The academic research study has received ethical approval from the University Research Ethics Committee of Dehradun Institute of Technology (DIT) University, Dehradun, India. RESULTS: The study was approved by the University Research Ethics Committee of DIT University, Dehradun, on July 4, 2021. Enrollment of the eligible participants will begin by April 2022 followed by the development of the predictive model by October 2022 till January 2023. The proposed AI-guided citizen-centric tool will be designed, developed, implemented, and evaluated using principles of human-centered design that will help to predict early at-risk pregnancy outcomes. CONCLUSIONS: The proposed internet-enabled AI-guided prediction model will help identify the potential risk associated with pregnancies and enhance the uptake of maternal health services among those seeking antenatal care for safer deliveries. We will explore the scalability of the proposed platform up to different geographic locations for adoption for similar and other health conditions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/35452.

Role of T Lymphocyte Activation Profile in Predicting SARS-CoV-2 Severity: Experience from Tertiary Care Centre of North India.

Background: Immune dysregulation plays a key role in determining COVID-19 disease severity. We aimed to analyze the T cell activation profile in COVID - 19 cases and its predictive role in disease severity and outcome. Material & methods: This was a prospective observational pilot study from a tertiary care COVID-19 hospital. Peripheral blood samples obtained between the fifth and seventh day of COVID-19 illness, were subjected to lymphocyte subset analysis using multicolor flowcytometry using a single tube, 8 antibodies (CD45, CD19, CD3, CD4, CD8, CD38, HLADR, and CD56) analysis. Correlation between lymphocyte subset analysis and clinical profile was determined. Results: 26 patients including 11 with mild disease and 15 with severe disease were enrolled. The median age was 58 years (range: 33-81), with a male: female ratio of 1.36:1. Significant lymphopenia was observed in the severe group compared to the mild group (p < 0.02). The absolute numbers of CD3+, CD4+, CD8 + T cells, B cells, and NK cells were significantly reduced in the severe group as compared to the mild group (p < 0.05). In patients with severe disease, the proportion of CD8 + and CD4 + T cells were significantly higher than those in patients with mild disease (p = 0.0372). Using ROC analysis, a CD4:8 T cell ratio of ≥ 2.63 and an activated (CD38 + HLA-DR+) CD8 T cell proportion of > 15.85% of the total CD8 T cell population, significantly determined the severe disease category. Conclusions: Severe COVID-19 is associated with severe lymphopenia, altered CD4/CD8 ratio and markedly increased CD8 T cell activation profile. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01558-6.

Extensive Pulmonary Cryptococcosis as a Presentation in an Immunocompetent Young Male: A Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Finding.

A 42-year-old male presented with a dry cough, breathlessness, and fever. He underwent a computed tomography that revealed large consolidation in the right lung. Biopsy revealed Cryptococcus neoformans. He was on antifungal for 4 months with no clinicoradiological improvement. 18F- fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed consolidations in the right lung with multiple lung nodules. 18F-FDG PET/CT ascertains the diagnosis of residual fungal infection and rules out extrapulmonary involvement.

The current state of public health education in India: A scoping review.

With the creation of public health management cadre in the state, district, and block levels of India, there is a need for a comprehensive, synergistic education system to ensure efficient public health across the country. This scoping review, therefore, aims to examine the characteristics of public health education programs available in India's varied geographical and regional contexts. It examines 16 program-related descriptors across public health Doctoral, Masters, Bachelors, Post-graduate Diploma, and Diploma education programs offered. Data was retrieved through institutional websites. Results of our analysis showed 84 unique institutions in 20 states and 3 UTs currently offering 116 public health programs across India's 28 states and 8 UTs. Private and public institutes were 65% (n = 75) and 35% (n = 41) respectfully. The majority of universities mainly provided Masters of Public Health (n = 73, 63%) programs followed by Postgraduate Diploma (PGD) and Diploma (n = 17, 15%), BPHSc (n = 14, 12%), and Ph.D. (n = 12, 10%). The majority of Ph.D. programs in public health are offered in Maharashtra, Karnataka, and Haryana, while Masters in Public Health programs are offered highest in Karnataka, Bachelors in Public Health programs in Rajasthan, Post Graduate Diploma in Public Health program in Delhi, and Tamil Nadu had the most number of Diploma in Public Health programs. Thirty-one percent (n = 36) of the public health programs are offered across the south, 28% (n = 32) across the north, and 22% (n = 26) across the west Analyzed descriptors provide comprehensive information on program characteristics, mainly admission, format, and tuition fee. The review offers five suggestions to improve collaborative public health education and prepare a workforce with the skills, knowledge, and expertise to respond to the twentyfirst century's public health threats and challenges in India.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

New insights into development and mortality of COVID-19-associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.

Recent updates in diagnosis and management of drug-resistant tuberculosis in India: A paradigm shift and the way ahead during the COVID-19 crisis.

The recent guidelines on the Programmatic Management of Drug-Resistant Tuberculosis (DR-TB) in India (PMDT) have been released in March 2021 on World TB Day. The new guidelines have considered emerging diagnostic trends including TrueNat, Xpert Mtb/XDR, Next generation sequencing and evaluation for resistance to newer drugs including Bedaquiline (Bdq) and Delamanid. The emerging therapeutic trends include focus on oral shorter Bdq based regimen with phasing out injectables use. The replacement sequence of drugs for DR-TB have also been updated. Updated definitions for pre-XDR, XDR, culture conversion and default have also been added. These guidelines are a paradigm shift which will make treating DR-TB easier and more efficient especially during the ongoing COVID-19 pandemic crisis.

Impact of COVID-19 Pandemic Lockdown in Ambient Concentrations of Aromatic Volatile Organic Compounds in a Metropolitan City of Western India.

The real-time Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX) concentrations were measured in a metropolitan city of India during January to May of 2020 and 2014-2015-2018 to assess the impact of emission reduction during the COVID-19 lockdown. The total BTEX (∑BTEX) concentrations were 11.5 ± 9.0, 15.7 ± 16, 5.3 ± 5.0, 2.9 ± 2.0, and 0.93 ± 1.2 ppbv in January-May 2020, respectively. The evening rush hour peaks of BTEX during lockdown decreased by 4-5 times from the same period of years 2014-2015-2018. A significant decline in background concentrations suggests a regional-scale reduction in anthropogenic emissions. The contributions of ∑TEX compounds to ∑BTEX increased from 42% to 59% in winter to 64%-75% during the lockdown under hot summer conditions. While emission reductions dominated during the lockdown period, the meteorological and photochemical factors may also have contributed. Meteorological influence on actual observed BTEX data was removed by normalizing with ventilation coefficient (VC). The actual ambient air reductions of 85%-90% and VC-normalized reductions of 54%-88% of the BTEX concentrations during lockdown were estimated compared to those during the same period of 2014-2015-2018. The estimated changes using nighttime data, which take into account BTEX photooxidation removal, are ∼8% lower than the VC-normalized estimates using all data. These significant reductions in BTEX concentrations are consistent with the change in people's movement as inferred from mobility data during the lockdown. Although enforced, the significant decline in ambient BTEX levels during lockdown was a good change for the air quality. The study suggests a need for more effective science-based policies that consider local and regional factors.