Nebulized vs IV Tranexamic Acid for Hemoptysis: A Pilot Randomized Controlled Trial.

BACKGROUND: Tranexamic acid (TA) is used to control bleeding in patients with hemoptysis. However, the effectiveness of the different routes of TA administration has not been studied. RESEARCH QUESTION: Does the nebulized route of TA administration reduce the amount of hemoptysis compared with the IV route in patients presenting to the ED with hemoptysis? STUDY DESIGN AND METHODS: This was a pragmatic, open-label, randomized, parallel, single-center, pilot trial of nebulized TA (500 mg tid) vs IV TA (500 mg tid) in adult patients presenting to the ED with active hemoptysis. The primary outcome was cessation of bleeding at 30 min. Secondary outcomes included amount of hemoptysis at 6, 12, and 24 h; interventional procedures; and side effects of TA. Patients who were hemodynamically unstable or requiring immediate interventional procedure or mechanical ventilation were excluded from the study. RESULTS: Of the 55 patients in each arm, hemoptysis cessation at 30 min following TA administration was significantly higher in the nebulization arm (n = 40) compared with the IV arm (n = 28): χ2 (1, n = 110) = 5.55; P = .0019. Also, hemoptysis amount was reduced significantly in the nebulization arm at all time periods of observation (P value at 30 min = .011, at 6 h = .002, 12 h = .0008, and at 24 h = .005). Fewer patients in the nebulization arm required bronchial artery embolization (13 vs 21; P = .024) and thereby had higher discharge rates from the ED (67.92% vs 39.02%; P = .005). Two patients in the nebulization arm had asymptomatic bronchoconstriction that resolved after short-acting beta-agonist nebulization. No patient discharged from the ED underwent any interventional procedure or revisited the ED with rebleed during the 72 h follow-up period. INTERPRETATION: Nebulized TA may be more efficacious than IV TA in reducing the amount of hemoptysis and need for ED interventional procedures. Future larger studies are needed to further explore the potential of nebulized TA compared with IV TA in patients with mild hemoptysis. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India; No.: CTRI/2019/05/019337; URL: http://ctri.nic.in/Clinicaltrials/advancesearchmain.php.

Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study.

BACKGROUND: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection. METHODS: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%. FINDINGS: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61). INTERPRETATION: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Post COVID-19 sequelae: A prospective observational study from Northern India.

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

Reasons for under-reporting of paraquat poisoning in India.

Background Paraquat is an inexpensive herbicide used in agriculture because it is easily available and the cost of labour for manual clearance of weeds is prohibitive. Paraquat is toxic to human beings and is also used for committing suicide. We studied the reasons for under-reporting of paraquat poisoning including those related to the training of doctors. Methods In this mixed-methods study, we describe a series of patients with paraquat poisoning. We recorded their demographic data, clinical features, treatment and outcome with an intention to explore the reason for an initial misdiagnosis. We also explored whether deficiencies in curricula contributed to the misdiagnosis. Results The patients of paraquat poisoning (n=28) were mostly young illiterate men driven by impulsive behaviour rather than chronic depression. Paraquat was consumed by patients from non-agricultural background as well, implying easy access to the poison. Many patients could not name the agent and so initial treatment was directed at organophosphorus poisoning. The diagnostic signs included paraquat tongue, renal failure and jaundice. Most of the casualty medical officers and residents were unfamiliar with the symptoms and signs of paraquat poisoning as was evident by their answers to the questionnaire. Knowledge of medical students about paraquat poisoning was not assessed in the theory examinations and viva. Conclusion Factors contributing to the limitation in establishing the diagnosis are illiteracy and ignorance of the patients, lack of specific signs and lack of training of medical officers in treating patients with paraquat poisoning.

Role of systemic corticosteroids in preventing hypoxia among patients with mild COVID-19: An observational study.

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.

Gargle lavage & saliva: Feasible & cheaper alternatives to nasal & throat swabs for diagnosis of COVID-19.

Background & objectives: In the present scenario, the most common sample for diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) is nasal and throat swab (NTS). Other sampling options such as gargle lavage have found limited application in clinical use mostly because of unavailability of an appropriate gargling liquid. This study was conducted to assess the stability of SARS-CoV-2 RNA in normal saline at 4°C that can serve as a gargling liquid as well as a transport medium. The study also looked at the agreement between NTS and gargle lavage/saliva for the detection of SARS-CoV-2. Methods: In 29 consecutive real-time RT-PCR (rRT-PCR) positive COVID-19 patients, paired NTS, gargle and saliva samples were taken. Samples were processed by rRT-PCR for the detection of SARS-CoV-2 RNA. To assess the SARS-CoV-2 RNA stability in normal saline, gargle lavage specimens were divided into two aliquots; one subset of the specimen was run within 4-6 h along with the routine samples (NTS and saliva) and the other subset was stored at 4°C and processed after 24-30 h. Agreement between cycle threshold (Ct) values from both the runs was compared using Bland-Altman (BA) analysis. Results: The positivity rates of rRT-PCR in NTS, saliva and gargle lavage samples were 82.7 (24/29), 79.3 (23/29) and 86.2 per cent (25/29), respectively. BA plot showed a good agreement between the Ct values of fresh and stored gargle samples, stipulating that there were no significant differences in the approximate viral load levels between the fresh and stored gargle lavage samples (bias: E gene -0.64, N gene -0.51, ORF gene -0.19). Interpretation & conclusions: Our study results show stability of SARS-CoV-2 RNA in the gargle samples collected using normal saline up to 24-30 h. Gargle lavage and saliva specimen collection are cost-effective and acceptable methods of sampling for the detection of SARS-CoV-2 RNA by rRT-PCR. These simplified, inexpensive and acceptable methods of specimen collection would reduce the cost and workload on healthcare workers for sample collection.

Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India.

Background & objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR). Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests. Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days. Interpretation & conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients.

Gargle lavage as a viable alternative to swab for detection of SARS-CoV-2.

BACKGROUND & OBJECTIVES: Nasopharyngeal and oropharyngeal swab (NPS and OPS) collection is widely accepted as the preferred method for obtaining respiratory samples. However, it has certain disadvantages which may be overcome by gargling. The primary objective of this study was to assess agreement between gargle lavage and swab as an appropriate respiratory sample for the detection of SARS-CoV-2. The secondary objective was to assess the patient acceptability of the two sampling methods. METHODS: It was a cross-sectional study done at a tertiary care hospital in New Delhi, India, on 50 confirmed COVID-19 patients. Paired swab (NPS and OPS) and gargle samples were taken within 72 h of their diagnosis. Samples were processed by reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2. Post-sample collection, a 10-point scale was administered to assess the level of discomfort with either of the collection methods. RESULTS: All gargle samples were positive and comparable to their corresponding swab samples irrespective of the symptoms and duration of illness. The cycle threshold (Ct) values for gargle samples were slightly higher but comparable to those of swabs. Bland-Altman plot showed good agreement between the two methods. Majority (72%) of the patients reported moderate-to-severe discomfort with swab collection in comparison to 24 per cent reporting only mild discomfort with gargle collection. INTERPRETATION & CONCLUSIONS: Our preliminary results show that the gargle lavage may be a viable alternative to swabs for sample collection for the detection of SARS-CoV-2. Adoption of gargle lavage for sample collection will have a significant impact as it will enable easy self-collection, relieve healthcare workers and also lead to substantial cost savings by reducing the need for swabs and personal protective equipment.

Hypereosinophilia with Multi-organ Dysfunction - A Diagnostic Conundrum.

Eosinophils are predominantly tissue-dwelling cells (spleen, lymph nodes, thymus, digestive tract) and counts <500/mm3 in the peripheral blood are considered to be normal. The functions of eosinophils are not completely understood, however there can be a significant rise in their levels in the peripheral blood and/or tissues in a variety of disease states. Hypereosinophilic syndromes (HES) are a group of disorders characterised by blood eosinophilia greater than 1500/mm3 on at least two occasions and eosinophilic infiltration and damage to multiple organs. Eosinophils on activation release substances that can lead to tissue damage. However, it is important to note that the degree of tissue damage is not directly proportional to the level of eosinophilia. A significant number of cases of HES are commonly missed and therefore a systematic approach is necessary for all such patients. Through our case, we have tried to summarise how to systematically approach a case of HES and manage it.