T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis.

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-ß)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.

Can cell-free DNA (cfDNA) in pleural lavage serve as a predictive and prognostic biomarker among surgically treated Stage I-III a nonsmall cell lung cancer (NSCLC)? A pilot study.

BACKGROUND AND OBJECTIVES: The role of cell-free DNA (cfDNA) in operable nonsmall cell lung cancer (NSCLC) is unclear. This study was aimed to evaluate the feasibility for identification of cfDNA in pleural lavage fluid and its correlation with plasma in resectable NSCLCs. METHODS: Consecutively resected NSCLCs were evaluated for cfDNA levels in preoperative plasma (PLS1), intraoperative pleural-lavage (PLV) and postoperative (at 1 month) plasma sample (PLS2). CfDNA was isolated and measured quantitatively by qPCR in a TaqMan probe-detection approach using the human ß-actin gene as the amplifying target. RESULTS: All (n = 34) except one were negative for malignant cells in PLV cytology. CfDNA could be isolated from all the three samples (PLS1, PLV, and PLS2) successfully in each patient. The median cfDNA levels in PLS1, PLV and PLS2 were 118 ng/mL (IQR 61-158), 167 ng/mL (IQR 59.9-179.9) and 103 ng/mL (IQR 66.5-125.4) respectively. The median follow-up was 34.1 months (IQR 25.2-41.6). A significant overall-survival (OS) and disease-free survival (DFS) were recorded for patients with cfDNA level cut-offs at 125, 170, and 100 ng/mL, respectively for PLS1, PLV, and PLS2. Patients with raised cfDNA in PLS1 (>125 ng/mL) and PLV (>170 ng/mL) had significantly poorer 2-year OS, p = 0.005 and p = 0.012, respectively. The hazards (OS) were also higher for those with raised cfDNA in PLV (HR = 5.779, 95% CI = 1.162-28.745, p = 0.032). PLV (>170 ng/mL) had increased pleural recurrences (p = 0.021) and correlated significantly with poorer DFS at 2-years (p = 0.001) with increased hazards (HR = 9.767, 95% CI = 2.098-45.451, p = 0.004). Multivariable analysis suggested higher cfDNA in PLV as a poor prognostic factor for both OS and DFS. CONCLUSIONS: Among patients with operable NSCLC, it is feasible to identify cfDNA in pleural lavage and correlate PLV cfDNA with pleural recurrences and outcomes.

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

INTRODUCTION: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.

Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches. METHODS: Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA. RESULTS: A total of six studies (five randomized trials and one case-control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65-2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects. CONCLUSION: Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.

Proposed quality indicators and recommended standard reporting items in performance of EBUS bronchoscopy: An official World Association for Bronchology and Interventional Pulmonology Expert Panel consensus statement.

BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.

Transfusion trigger in the critically ill with sepsis or septic shock: A prospective study.

Background & objectives: Current practice around transfusion trigger in critically ill sepsis patients is not clear. Moreover, any association of haemoglobin trigger and other transfusion parameters such as age of red blood cells (RBCs) at transfusion and number of units of RBCs transfused with mortality and other adverse outcomes need further assessment. Methods: In this prospective study, patients aged 18-70 yr and admitted to intensive care with a diagnosis of sepsis were included (n=108). Baseline demographic, clinical and laboratory parameters were noted and various transfusion data, i.e., haemoglobin trigger, number of units of RBCs and the age of RBCs were recorded. Following outcome data were collected: 28 and 90 day mortality, duration of mechanical ventilation, vasopressor therapy, intensive care unit (ICU) and hospital stay and requirement of renal replacement therapy. Results: Of the total 108 participants, 78 (72.2%) survived till 28 days and 66 (61.1%) survived till 90 days. Transfusion trigger was 6.9 (6.7-7.1) g/dl [median (interquartile range)]. On multivariable logistic regression analysis, acute physiology and chronic health evaluation (APACHE) II [adjusted odds ratio (aOR) (95% confidence interval {CI}): 0.86 (0.78, 0.96); P=0.005], cumulative fluid balance (CFB) [aOR (95% CI): 0.99 (0.99, 0.99); P=0.005] and admission platelet count [aOR (95% CI): 1.69 (1.01, 2.84); P=0.043] were the predictors of 28 day mortality [model area under the receiver operating characteristics (AUROC) 0.81]. APACHE II [aOR (95% CI): 0.88 (0.81, 0.97); P=0.013], CFB [a OR (95% CI): 0.99977 (0.99962, 0.99993); P=0.044] and transfusion trigger [aOR (95% CI): 3 (1.07, 8.34); P=0.035] were the predictors of 90 day mortality (model AUROC: 0.82). Interpretation & conclusions: In sepsis, patients admitted to the ICU, current practice suggests transfusion trigger is below 7 g/dl and it does not affect any adverse outcome including 28 day mortality.

Association of air pollution and coronavirus disease 2019 (COVID-19) in India.

The COVID-19 pandemic has affected the world, leading to significant morbidity and mortality. Various meteorological parameters are considered essential for the viability and transmission of the virus. Multiple reports from various parts of the world suggest a correlation between the disease spread and air pollution severity. This study was carried out to identify the relationship between meteorological parameters, air pollution, and COVID-19 in New Delhi, one of the worst-affected states in India. We studied air pollution and meteorological parameters in New Delhi, India. We obtained data about COVID-19 occurrence, meteorological parameters, and air pollution indicators from various sources from Apr 1, 2020, till Nov 12, 2020. We performed correlational analysis and employed autoregressive distributed lag models (ARDLM) for identifying the relationship between COVID-19 cases with air pollution and meteorological parameters. We found a significant impact of PM 2.5, PM 10, and meteorological parameters on COVID-19. There was a significant positive correlation between daily COVID-19 cases and COVID-19-related deaths with PM2.5 and PM10 levels. Increasing temperature and windspeed were associated with a reduction in the number of cases while increasing humidity was associated with increased cases. This study demonstrated a significant association of PM2.5 and PM10 with daily COVID-19 cases and COVID-19-related mortality. This knowledge will likely help us prepare well for the future and implement air pollution control measures for other airborne disease epidemics.

Leveraging multi-tier healthcare facility network simulations for capacity planning in a pandemic.

The COVID-19 pandemic has placed severe demands on healthcare facilities across the world, and in several countries, makeshift COVID-19 centres have been operationalised to handle patient overflow. In developing countries such as India, the public healthcare system (PHS) is organised as a hierarchical network with patient flows from lower-tier primary health centres (PHC) to mid-tier community health centres (CHC) and downstream to district hospitals (DH). In this study, we demonstrate how a network-based modelling and simulation approach utilising generic modelling principles can (a) quantify the extent to which the existing facilities in the PHS can effectively cope with the forecasted COVID-19 caseload; and (b) inform decisions on capacity at makeshift COVID-19 Care Centres (CCC) to handle patient overflows. We apply the approach to an empirical study of a local PHS comprising ten PHCs, three CHCs, one DH and one makeshift CCC. Our work demonstrates how the generic modelling approach finds extensive use in the development of simulations of multi-tier facility networks that may contain multiple instances of generic simulation models of facilities at each network tier. Further, our work demonstrates how multi-tier healthcare facility network simulations can be leveraged for capacity planning in health crises.

Efficacy of Intrabronchial Voriconazole Instillation for Inoperable Pulmonary Aspergilloma: A Pilot Randomized Controlled Trial.

BACKGROUND: Endobronchial administration of voriconazole is a potential therapeutic option for inoperable aspergilloma. OBJECTIVE: This study aimed to assess the efficacy of endobronchial instillation of voriconazole for inoperable pulmonary aspergilloma. METHOD: Patients with mild to moderate hemoptysis, due to inoperable aspergilloma, were randomized to receive either medical therapy (MT) alone or bronchoscopic instillation of voriconazole with MT and followed up till 3 months. The primary objective of this study was to compare the percentage of patients achieving reduction in the severity of hemoptysis assessed on visual analogue scale (VAS) in intervention and control arm at 3 months. RESULTS: This study included 60 patients (female = 47) with mean (SD) age of 40.6 (13.2) years who were randomized to receive either bronchoscopic instillation of voriconazole (n = 30) or MT alone (n = 30). At 3-month follow-up, the primary objective was achieved in 26/30 (86.7%) patients in intervention group as compared to 11/30 (36.7%) in the control group (p value <0.0001). The VAS score at 3 months was significantly lower in voriconazole group 13.9 (9.3) mm as compared to MT alone group 22.3 (11.5) mm, p value of 0.003. Bronchoscopic instillation of voriconazole was also associated with reduction in cough severity and size of the aspergilloma; however, there was no benefit of this therapy in terms of requirement of hospitalization and BAE. CONCLUSIONS: Our study shows that for nonoperable aspergilloma, bronchoscopic instillation of voriconazole is associated with reduction in the severity of hemoptysis. This therapy should be evaluated in large multi-center trials.

Geographic information system-based mapping of air pollution & emergency room visits of patients for acute respiratory symptoms in Delhi, India (March 2018-February 2019).

Background & objectives: Studies assessing the spatial and temporal association of ambient air pollution with emergency room visits of patients having acute respiratory symptoms in Delhi are lacking. Therefore, the present study explored the relationship between spatio-temporal variation of particulate matter (PM)2.5 concentrations and air quality index (AQI) with emergency room (ER) visits of patients having acute respiratory symptoms in Delhi using the geographic information system (GIS) approach. Methods: The daily number of ER visits of patients having acute respiratory symptoms (less than or equal to two weeks) was recorded from the ER of four hospitals of Delhi from March 2018 to February 2019. Daily outdoor PM2.5 concentrations and air quality index (AQI) were obtained from the Delhi Pollution Control Committee. Spatial distribution of patients with acute respiratory symptoms visiting ER, PM2.5 concentrations and AQI were mapped for three seasons of Delhi using ArcGIS software. Results: Of the 70,594 patients screened from ER, 18,063 eligible patients were enrolled in the study. Winter days had poor AQI compared to moderate and satisfactory AQI during summer and monsoon days, respectively. None of the days reported good AQI (<50). During winters, an increase in acute respiratory ER visits of patients was associated with higher PM2.5 concentrations in the highly polluted northwest region of Delhi. In contrast, a lower number of acute respiratory ER visits of patients were seen from the 'moderately polluted' south-west region of Delhi with relatively lower PM2.5 concentrations. Interpretation & conclusions: Acute respiratory ER visits of patients were related to regional PM2.5 concentrations and AQI that differed during the three seasons of Delhi. The present study provides support for identifying the hotspots and implementation of focused, intensive decentralized strategies to control ambient air pollution in worst-affected areas, in addition to the general city-wise strategies.

Evaluation of delays during diagnosis and management of lung cancer in India: A prospective observational study.

OBJECTIVE: The majority of lung cancers are diagnosed at an advanced stage; the reasons for which are variable and unclear. METHODS: Lung cancer patients were evaluated prospectively to quantify various timelines and establish reasons for delays. Timelines were defined as time intervals between symptom onset, first physician visit, first specialist visit, date of diagnosis and treatment. RESULTS: A total 410 patients were included, majority having advanced disease. The median period for a first visit to a physician was 30 days (interquartile range [IQR] 20-90), 50 days (IQR 20-110) for referral to our centre, 23 days (IQR 14-33) to reach diagnosis, and 24 days (IQR 14.5-34) to initiate treatment. Administration ofanti-tuberculosis treatment further delayed referral to specialist centre. Treatment delays were related to performance status, disease stage and treatment type. On multivariate analysis, education and histology affected diagnosis delay and treatment delay. Treatment delay was less in those who received targeted therapy compared to chemotherapy. Various time delays did not affect the overall survival. CONCLUSION: Poor education status and inappropriate anti-tubercular treatment were primary factors associated with longer diagnostic delays. Creating disease awareness and high clinical suspicion are essential to overcome these lacunae in lung cancer care.

Tuberculosis endemicity and BCG vaccination: Protection against COVID-19.

The coronavirus disease 2019 (COVID-19) has affected different countries in a differential manner. The host susceptibility and host factors are important parameters for this variability. This study aimed to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19. Available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 168 countries as of 19th September 2021was collected. Countries were divided into four cohorts based upon annual TB incidence and BCG coverage and COVID-19 incidence and case fatality rates were compared using the Kruskal-Wallis test. Countries with low TB incidence and low BCG coverage had the highest COVID-19 incidence per lac population. However, no significant difference was seen in COVID-19 cases fatality rate. Higher TB incidence and BCG coverage were associated with lesser incidence of COVID-19. This result paves the way for research into pathogenesis and host immune response in COVID-19.

Tocilizumab for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.

Pulmonary infections after renal transplantation: a prospective study from a tropical country.

Pulmonary infection is a leading cause of morbidity and mortality in renal transplant recipients. In a prospective study, we characterized their epidemiology in a tropical country with high infectious disease burden. Adult renal transplant recipients presenting with pulmonary infections from 2015 to 2017 were evaluated using a specific diagnostic algorithm. 102 pulmonary infections occurred in 88 patients. 32.3% infections presented in the first year, 31.4% between 1 and 5, and 36.3% beyond 5 years after transplantation. Microbiological diagnosis was established in 69.6%, and 102 microorganisms were identified. Bacterial infection (29.4%) was most common followed by tuberculosis (23.5%), fungal (20.6%), Pneumocystis jiroveci (10.8%), viral (8.8%), and nocardial (6.9%) infections. Tuberculosis(TB) and bacterial infections presented throughout the post-transplant period, while Pneumocystis (72.7%), cytomegalovirus (87.5%) and nocardia (85.7%) predominantly presented after >12 months. Fungal infections had a bimodal presentation, between 2 and 6 months (33.3%) and after 12 months (66.7%). Four patients had multi-drug resistant(MDR) TB. In 16.7% cases, plain radiograph was normal and infection was diagnosed by a computed tomography imaging. Mortality due to pulmonary infections was 22.7%. On multivariate Cox regression analysis, use of ATG (HR-2.39, 95% CI: 1.20-4.78, P = 0.013), fungal infection (HR-2.14, 95% CI: 1.19-3.84, P = 0.011) and need for mechanical ventilation (9.68, 95% CI: 1.34-69.82, P = 0.024) were significant predictors of mortality in our patients. To conclude, community-acquired and endemic pulmonary infections predominate with no specific timeline and opportunistic infections usually present late. Nocardiosis and MDR-TB are emerging challenges.

Yoga-An Alternative Form of Therapy in Patients with Blunt Chest Trauma: A Randomized Controlled Trial.

BACKGROUND: Yoga as alternative form of therapy has shown positive impact on pulmonary functions, exercise capacity, behavioral changes, and inflammation in non-trauma patients. However, the efficacy of Yoga has not been studied in chest trauma patients. METHODS: This randomized controlled trial was conducted at level-1 Trauma Centre. Isolated chest injury patients were randomized into either standard physiotherapy or Yogatherapy groups. Patients in physiotherapy group received conventional chest physiotherapy and Yogatherapy group received a set of Yogic exercises in addition to conventional chest physiotherapy. Primary outcome measure was changes in pulmonary function tests (PFT) at 4 weeks of discharge. Secondary outcomes were changes in quality of life (QoL), respiratory muscle strength and endurance, chest wall mobility, and levels of cytokines at 4 weeks. Data were analyzed using STATA v14.0. RESULTS: A total of 89 eligible patients were randomized to physiotherapy (n = 46) and Yoga therapy (n = 43) groups. Demographic characteristics were comparable in both the groups. There were statistically significant improvements in PFT in the Yogatherapy group compared with physiotherapy with an increase in Forced vital capacity (p = 0.02) and Forced expiratory volume (p = 0.01) at 4 weeks. In addition, there were significant improvement in physical component of QoL, respiratory muscle endurance (p = 0.003) and axillary cirtometry (p = 0.009) in the Yogatherapy group. However, no statistically significant difference in the trends of cytokine markers seen between the groups. CONCLUSION: Yoga was found to be effective in improving pulmonary functions and QoL in patients with chest trauma. (Trial registered at ctri.nic.in/clinicaltrials/login.php, numberREF/2016/05/011,287).

Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial.

INTRODUCTION: Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a repurposed agent for treating COVID-19. METHODS: In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population). RESULTS: Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred. CONCLUSIONS: In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.

Assessment of the impact and reorganization of interventional pulmonology services at a tertiary care centre during nationwide lockdown for COVID-19 pandemic.

COVID 19 pandemic has brought about a sea change in health care practices across the globe. All specialities have changed their way of working during the pandemic. In this study, we evaluated the impact of COVID-19 on the practice of interventional pulmonology at our centre. All interventional pulmonology procedures done during the three months after implementation of lockdown were evaluated retrospectively for patient demographics, clinical diagnosis, indication for procedure and diagnostic accuracy. The changes in practices, additional human resources requirement, the additional cost per procedure and impact on resident training were also assessed. Procedures done during the month of January 2020 were used as controls for comparison. Twenty-two flexible bronchoscopies (75.8%), four semirigid thoracoscopies (13.7%) and three EBUS-TBNAs (10.3%) were carried out during three month lockdown period as compared to 174 during January 2020. Twenty-three of the procedures were for the diagnostic indication (79%), and six were therapeutic (20.6%). The diagnostic yield in suspected neoplasm was 100% while for suspected infections was 58.3%. The percentage of independent procedures being done by residents reduced from 45.4% to 0%. The workforce required per procedure increased from 0.75 to 4-8, and the additional cost per procedure came out to be 135 USD. To conclude, COVID 19 has impacted the interventional pulmonology services in various ways and brought about a need to reorganize the services, while also thinking of innovative ideas to reduce cost without compromising patient safety.

Steroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

There is an urgent need for effective treatment modalities for coronavirus disease 2019 (COVID-19). Data for the use of steroids in COVID-19 is emerging. We conducted this systematic review and meta-analysis to estimate the effectiveness of steroid administration in mortality reduction due to COVID-19 compared to the control group. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of steroid therapy for COVID-19. An overall and subgroup (based upon the type of steroid) pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Six RCTs, including 7707 patients, were selected for review. Three trials reported 28-day mortality, and two trials reported 21-day mortality, and one trial reported in-hospital mortality. There were 730 deaths among 2837 participants in the steroid group while 1342 deaths among 4870 patients randomized to the control group (Odds ratio 0.76, 95% confidence interval 0.58-1.00, p=0.05). The effect was significant in patients on oxygen or mechanical ventilation. There was no difference in the various preparations and doses of the steroids. There was heterogeneity among the trials as the I2 value was 53%, with a p-value of 0.06. There was no indication of increased serious adverse events. This meta-analysis of RCTs demonstrated that the use of systemic corticosteroids is associated with a reduction in all-cause mortality in patients with COVID-19 on oxygen or mechanical ventilation.

Awake prone positioning in non-intubated patients for the management of hypoxemia in COVID-19: A systematic review and meta-analysis.

Coronavirus disease-2019 (COVID-19) may lead to hypoxemia, requiring intensive care in many patients. Awake prone positioning (PP) is reported to improve oxygenation and is a relatively safe modality. We performed a systematic review of the literature to evaluate the available evidence and performed meta-analysis of the effect of awake PP in non-intubated patients on improvement in oxygenation and reducing the need for intubation. We searched the PubMed and EMBASE databases to identify studies using awake PP as a therapeutic strategy in the management of COVID-19. Studies were included if they reported respiratory outcomes and included five or more subjects. The quality of individual studies was assessed by the Qualsyst tool. A meta-analysis was performed to estimate the proportion of patients requiring intubation. The degree of improvement in oxygenation parameters (PaO2: FiO2 or PaO2 or SpO2) was also calculated. Sixteen studies (seven prospective trials, three before-after studies, six retrospective series) were selected for review. The pooled proportion of patients who required mechanical ventilation was 0.25 (95% confidence interval (CI) 0.16-0.34). There was a significant improvement in PaO2: FiO2 ratio, PaO2, and SpO2 during awake PP. To conclude, there is limited evidence to support the efficacy of awake PP for the management of hypoxemia in COVID-19. Further RCTs are required to study the impact of awake PP on key parameters like avoidance of mechanical ventilation, length of stay, and mortality.

Secretion management in patients with ineffective airway clearance with non-invasive mechanical ventilation use: Expert guidance for clinical practice.

Non-invasive ventilation (NIV) is a mainstay of management of chronic respiratory failure in many disorders which are known to cause abnormal airway secretion clearance. Currently, there is no guidance regarding either the secretion handling during NIV use or the role of NIV in secretion management in these patients. The aim of this document was to provide an overview of the various techniques available in the management of respiratory secretions and their use in conjunction with NIV. Literature search was performed using the keywords, "(secretion OR secretions) AND (noninvasive ventilation OR NIV)" on PubMed and EMBASE. The search yielded 1681 and 509 titles from PubMed and EMBASE, respectively. After screening, 19 articles were included in this review. Suggestions of the expert panel were formulated by mutual consensus after reviewing the relevant literature. The draft of the expert panel's suggestions was circulated among all authors via electronic mail for comments. Any conflicts were resolved by mutual discussion to achieve agreement. The final document was approved by all. This document by the International Network for Airway Secretions Management in NIV describes various airway secretion clearance techniques. It provides the expert panel's suggestions for the use of these techniques in conjunction with NIV for patients with muco-obstructive and neuromuscular disorders.