Publications by authors named "Kapil Dev Soni"

86 Publications

Outcomes of Trauma Victims with Cardiac Arrest Who Survived to Intensive Care Unit Admission in a Level 1 Apex Indian Trauma Centre: A Retrospective Cohort Study.

Indian J Crit Care Med 2021 Dec;25(12):1408-1412

Department of Anaesthesiology, All India Institute of Medical Sciences, New Delhi, India.

Background And Aims: The prognosis of patients with cardiac arrest following trauma is poor. Our objectives were: (1) to determine outcomes of patients following in-hospital cardiac arrest posttrauma and admitted to the intensive care unit (ICU) and (2) to identify characteristics associated with in-hospital mortality.

Materials And Methods: This was a single-center retrospective analysis of patients admitted to ICU after resuscitation following in-hospital cardiac arrest between January 2017 and July 2018. Patients with isolated head injuries and multiple cardiac arrests were excluded. Bivariate analysis was done to determine a significant association between baseline characteristics and in-hospital mortality.

Results: A total of 37 patients were included. About 35.1% of trauma subjects survived hospital discharge. Bivariate analysis showed positive association between admission Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores with in-hospital mortality. Other characteristics, such as age, duration of cardiopulmonary resuscitation (CPR), and serum lactate levels on admission, were not associated with in-hospital mortality.

Conclusion: Despite being at lower survival following a cardiac arrest after trauma, approximately one-third of the patients survived hospital discharge. This implies that aggressive support of this population is not necessarily futile. Optimization of postresuscitation physiological factors and their impacts on outcomes for these patients need further studies.

How To Cite This Article: Soni KD, Rai N, Aggarwal R, Trikha A. Outcomes of Trauma Victims with Cardiac Arrest Who Survived to Intensive Care Unit Admission in a Level 1 Apex Indian Trauma Centre: A Retrospective Cohort Study. Indian J Crit Care Med 2021;25(12):1408-1412.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5005/jp-journals-10071-24057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693116PMC
December 2021

Acute critical care course for interns to develop competence.

Natl Med J India 2021 May-Jun;34(3):167-170

Department of Surgery, Wirral Teaching Hospitals, Birkenhead, Liverpool, UK.

Background All medical graduates must know how to stabilize and manage critically ill patients. A 2-day intensive course, called the acute critical care course (ACCC), was conducted to train interns in technical and non-technical skills for managing a patient whose condition is deteriorating. This analysis aims to assess the feasibility and effectiveness of ACCC for interns. Methods We developed and conducted the ACCC to train interns. It included lectures and skill stations. Twenty-four interns participated in the course. Immediate, post-course, quantitative and qualitative feedback was taken online. Qualitative information was also collected verbally and later by email. These data were analysed both quantitatively and qualitatively. Thematic analysis was used to identify, analyse and report the patterns of responses and behaviour. Results The average score for the utility of the course was 4.7 and for the skill stations it was 4.6 on a scale of 5. The qualitative analysis of the feedback emphasized the need for the course before the clinical posting and more skill-based modules rather than lectures. The interactive style of teaching and training in communication using role-play was appreciated. Few suggestions to improve the course were provided. Conclusions Implementing the ACCC needed simulation, interactive discussions, role-play, modified Pendleton's feedback, and reflective exercise that form the basis of a range of educational principles. The blended learning set of objectives of ACCC were the pillars for this successful internship training programme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.25259/NMJI_103_19DOI Listing
December 2021

Epidemiology and clinical characteristics of COVID- 19 patients requiring critical care in a Tertiary care teaching hospital.

J Anaesthesiol Clin Pharmacol 2021 Jul-Sep;37(3):366-370. Epub 2021 Oct 12.

Department of Anaesthesiology, Pain Medicine and Critical Care, JPNATC, AIIMS, New Delhi, India.

Background And Aims: We describe the epidemiological and clinical characteristics, and 28 day outcome of critically ill COVID-19 patients admitted to a tertiary care centre in India.

Material And Methods: We included 60 adult critically ill COVID-19 patients in this prospective observational study, admitted to the intensive care unit (ICU) after obtaining ethics committee approval and informed consent. Demographics, clinical data, and treatment outcome at 28 days were assessed.

Results: Demographic characteristics of the COVID-19 patients reveal that compared to the survivors, the non-survivors were significantly older [57.5 vs. 47.5 years], had more comorbid disease [Charlson's comorbidity index 4 vs. 2], higher Apache II scores [19 vs. 8.5], and had significantly higher percentage of smokers. Diabetes mellitus and hypertension were the most common comorbidities. Dyspnea, fever, and cough were the most common presenting symptoms. Total leucocyte count as well as blood lactate level were significantly higher in non-survivors. Around 47% patients had severe ARDS, and 60% patients required invasive mechanical ventilation. 28 day ICU mortality was 50%, with a mortality of 75% in patients receiving invasive mechanical ventilation. Mortality was higher in males than females (57% vs. 33%). Acute kidney injury and septic shock were the most common non-pulmonary complications during ICU stay. Incidence of liver dysfunction, septic shock, and vasopressor use was significantly higher in the non-survivors.

Conclusion: This study demonstrates a high 28 day mortality in severe COVID-19 patients. Further well designed prospective studies with larger sample size are needed to identify the risk factors associated with poor outcome in such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/joacp.JOACP_585_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562446PMC
October 2021

Predictors of in-hospital outcomes in patients with Cirrhosis and Coronavirus disease-2019.

J Clin Exp Hepatol 2021 Oct 29. Epub 2021 Oct 29.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background: Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported.

Aims: We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave.

Methods: In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n=221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes.

Results: The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P<0.001). The overall mortality was 90 (40.7%), highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves.

Conclusion: Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jceh.2021.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553413PMC
October 2021

An investigation to the prolonged requirement (>7 days) of vasopressors in cervical spinal cord injury patients-a retrospective analysis.

Spinal Cord Ser Cases 2021 11 2;7(1):96. Epub 2021 Nov 2.

Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India.

Study Design: Retrospective chart review.

Objectives: The primary aim was to identify the number of patients requiring vasopressors beyond the first week of cervical spinal cord injury (SCI). Secondary objectives were to note the type, duration and doses of vasopressors and any association between prolonged vasopressors use and outcome.

Setting: Neurosurgical intensive care of a tertiary trauma care centre.

Methods: After Ethical approval we retrospectively collected the data of patients of isolated cervical SCI admitted to neurosurgical intensive care from January to December 2017. Vasopressor requirement for sepsis or cardiac arrest was excluded.

Results: Out of 80 patients analysed, 54 (67.5%) received vasopressors. The prolonged requirement of vasopressors was observed in 77.7%. Our preferred agent was dopamine (64.8%). We found out that longer requirement (in days) of high dose of dopamine was associated with higher survival (p = 0.03).

Conclusion: Our results describe a significant portion of cervical SCI patients need ongoing vasopressor to maintain a mean arterial pressure >65 mm of Hg beyond first week. We observed patients who required longer duration of high dose dopamine had a higher chance of survival suggesting some unknown mechanism of high dose of dopamine. This is first such observation, further studies are needed to substantiate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41394-021-00459-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563917PMC
November 2021

Proteinaceous Lung With COVID-19: The Mimicker.

Cureus 2021 Sep 20;13(9):e18144. Epub 2021 Sep 20.

Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, New Delhi, IND.

Pulmonary alveolar proteinosis (PAP) is a syndrome, in which surfactants get deposited slowly in alveoli, blocking the airway exchange. PAP severity also varies from mild to severe, presenting with dyspnea, cough, hemoptysis with or without fever. The radiological findings are ground-glass opacities along with septal thickening (Crazy Paving), consolidations, and less commonly air bronchograms. COVID-19 is a viral infection caused by SARS COV2 primarily affecting the lungs and causing atypical viral pneumonia. The clinical picture of the disease varies from a milder form of fever, dry cough with or without expectoration, to severe disease-causing respiratory distress, pneumonia, acute respiratory distress syndrome (ARDS), and even death. Radiologically, the findings of COVID-19 are similar to PAP. So, PAP mimics the COVID-19, posing a differential challenge, though our patient was a known case of PAP. Therefore, for proper management of the disease, it is important to differentiate it from other pathologies. In this case report, we describe a patient who was a known case of autoimmune pulmonary alveolar proteinosis. She presented with acute exacerbation in the emergency department and tested positive for COVID-19. We followed a systematic approach consisting of clinical, laboratory, radiologic parameters to differentiate the cause of this exacerbation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.18144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529101PMC
September 2021

Efficacy of probiotics in the prevention of diarrhea in ventilated critically ill ICU patients: meta-analysis of randomized control trials: author's reply.

J Intensive Care 2021 Oct 15;9(1):61. Epub 2021 Oct 15.

Department of Laboratory Medicine, JPNA Trauma Center, AIIMS, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40560-021-00578-0DOI Listing
October 2021

Communication skills training through 'role play' in an acute critical care course.

Natl Med J India 2021 Mar-Apr;34(2):92-94

Wirral Teaching Hospitals, Core Surgical Training Merseyside, North West of England, University of Liverpool, Liverpool, UK.

Background: . Effective patient-doctor communication is a key component of patient-centred care, which is one of the six pillars of quality healthcare delivery. Structured and effective communication skills training for healthcare providers is the need of hour in medical education. We assessed the efficacy of role play and simulation in developing communication skills.

Methods: . As a key component of an acute critical care course (ACCC), communication skills are taught using role play models and simulation. Live feedback is critical in learning during this course as per the principles of adult learning (andragogy). Quantitative and qualitative data were collected to assess the efficacy of ACCC.

Results: . The 19th ACCC was introduced to interns at the All India Institute of Medical Sciences, New Delhi in December 2018. The teaching methodology and objective-oriented structured training in ACCC were much appreciated for training in human factors with emphasis on communication. A positive response was obtained from the candidates 3 weeks after they completed the course to assess whether interns are able to make use of this training in their day-to-day clinical practice amounting to a reliable evidence level of Kirkpatrick's 'return of investment'.

Conclusion: . The use of 'role play' to teach communication skills is effective and superior to lecture-based teaching. Further structured and interactive programmes in communication skills training will improve patient care, relatives' satisfaction and the image of medical profession.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0970-258X.326757DOI Listing
October 2021

Paranephric air in COVID-ARDS patient: an extension of pneumothorax.

Intensive Care Med 2022 Jan 30;48(1):118. Epub 2021 Aug 30.

Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-021-06511-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404757PMC
January 2022

Clinical Profile and Outcome of Critically Ill COVID-19 Patients With Malignancy Admitted in Intensive Care Unit of a Tertiary COVID Center, India.

Cureus 2021 Jul 22;13(7):e16553. Epub 2021 Jul 22.

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, IND.

Introduction There is a dearth of literature describing the clinical profile of coronavirus disease 2019 (COVID-19) in patients with malignancy. Patients with associated malignancy can have a more severe course of the disease. The aim was to study clinical course and outcome of critically ill patients admitted in ICU with associated malignancy. Methods The study was a single-center, retrospective, study conducted at a tertiary care hospital. Patients with active or recent malignancy on follow-up and with confirmed COVID-19 infection who were admitted to the Intensive care unit of COVID-19 dedicated hospital between November 1, 2020 to January 15, 2021 were included. Demographic data, clinical features, clinical course and outcome were retrieved from the hospital electronic medical records. Results A total of 24 patients with malignancy and COVID-19 were admitted to the ICU of COVID-19 center. There were 20 patients with solid organ malignancy and four patients with hematological malignancy. The most common malignancy was breast carcinoma in six (25 %) patients. Fifty percent of the patients were diagnosed with malignancy within the previous six months. Among the presenting symptoms, 13 (54.1%) patients presented with symptoms of severe acute respiratory infection (SARI), eight (33.3%) patients presented with altered sensorium, and three (12.5%) with pain abdomen. Regarding the severity of COVID-19, six (25%) patients had moderate COVID-19 and 18 (75%) had severe COVID-19. Out of 24 patients, six survived and 18 died, the mortality being 75%. The most common cause of death was sepsis with multiorgan dysfunction syndrome (MODS) in 10 (42.6 %) patients followed by severe acute respiratory distress syndrome (ARDS) and neurological cause in four (16.6 %) patients each. When survivors were compared with non-survivors, advanced age and presence of altered sensorium were more in non-survivors. Conclusion Severe COVID-19 and advanced malignancy is a sinister combination that has high mortality. These patients require close monitoring and aggressive care. Presence of altered sensorium and advanced age predicts poorer outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.16553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378308PMC
July 2021

Outcomes of Renal Trauma in Indian Urban Tertiary Healthcare Centres: A Multicentre Cohort Study.

World J Surg 2021 Dec 21;45(12):3567-3574. Epub 2021 Aug 21.

WHO Collaborating Centre for Research in Surgical Care Delivery in LMIC, Mumbai, India.

Background: Renal trauma is present in 0.5-5% of patients admitted for trauma. Advancements in radiologic imaging and minimal-invasive techniques have led to decreased need for surgical intervention. We used a large trauma cohort to characterise renal trauma patients, their management and outcomes.

Methods: We analysed "Towards Improved Trauma Care Outcomes in India" cohort from four urban tertiary public hospitals in India between 1st September 2013 and 31st December 2015. The data of patients with renal trauma were extracted using International Classification of Diseases 10 codes and analysed for demographic and clinical details.

Results: A total of 16,047 trauma patients were included in this cohort. Abdominal trauma comprised 1119 (7%) cases, of which 144 (13%) had renal trauma. Renal trauma was present in 1% of all the patients admitted for trauma. The mean age was 28 years (SD-14.7). A total of 119 (83%) patients were male. Majority (93%) were due to blunt injuries. Road traffic injuries were the most common mechanism (53%) followed by falls (29%). Most renal injuries (89%) were associated with other organ injuries. Seven of the 144 (5%) patients required nephrectomy. Three patients had grade V trauma; all underwent nephrectomy. The 30-day in-hospital mortality, in patients with renal trauma, was 17% (24/144).

Conclusion: Most renal trauma patients were managed nonoperatively. 89% of patients with renal trauma had concomitant injuries. The renal trauma profile from this large cohort may be generalisable to urban contexts in India and other low- and middle-income countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-021-06293-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572839PMC
December 2021

Coronavirus Disease-Associated Mucormycosis from a Tertiary Care Hospital in India: A Case Series.

Cureus 2021 Jul 3;13(7):e16152. Epub 2021 Jul 3.

Anaesthesiology, Critical Care and Pain Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND.

Background:  Coronavirus disease (COVID-19) remains a health concern with new challenges emerging as the pandemic progresses. The recent rise of opportunistic infections especially mucormycosis in COVID-19 patients is further complicating their outcomes. Mucormycosis is well known to infect patients with diabetes mellitus, malignancy, chemotherapy, and other immunocompromised conditions. The treatment of COVID-19 largely remains systemic steroids and other immunomodulators that add to the risk of invasive fungal infection.

Methodology: Here, we present a retrospective case series of 13 patients with individual clinical characteristics along with the demography and treatment details. The data were collected retrospectively in a single center that caters to a large population of COVID-19 patients with varying severity.

Results: Thirteen patients were presented with COVID-19 associated mucormycosis (CAM). The median age was higher in non-survivors (49.5 years), with a higher odds of death (23.8) in those with severe COVID, having overall mortality of 64.3%. Moreover, diabetes mellitus was present in 61.5% of patients with a mortality of 75%. About 11 (84.6%) patients had received prior steroids for COVID-19. The incidence of hyperglycemia at admission was equal among both survivors and non-survivors.

Conclusion: The prevalence of mucormycosis seems to be increasing among COVID-19 patients which may be associated with increased use of steroids, the possible immunocompromised state imposed by SARS-CoV-2, or co-existing conditions such as diabetes mellitus. The mortality of CAM is remarkably high and apart from preventive practices and rational use of immunomodulators, a high index of suspicion with early diagnosis would be key to survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.16152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329523PMC
July 2021

Imaging of Coronavirus Disease 2019 Infection From Head to Toe: A Primer for the Radiologist.

Curr Probl Diagn Radiol 2021 Nov-Dec;50(6):842-855. Epub 2021 Jul 5.

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Coronavirus Disease 2019 (COVID-19) disease has rapidly spread around the world after initial identification in Wuhan, China, in December 2019. Most common presentation is mild or asymptomatic disease, followed by pneumonia, and rarely- multiorgan failure and Acute Respiratory Distress Syndrome (ARDS). Knowledge about the pathophysiology, imaging and treatment of this novel virus is rapidly evolving due to ongoing worldwide research. Most common imaging modalities utilized during this pandemic are chest radiography and HRCT with findings of bilateral peripheral, mid and lower zone GGO and/or consolidation, vascular enlargement and crazy paving. HRCT is also useful for prognostication and follow-up of severely ill COVID-19 patients. Portable radiography allows follow-up of ICU patients & obviates the need of shifting critically ill patients and disinfection of CT room. As the pandemic has progressed, numerous neurologic manifestations have been described in COVID-19 including stroke, white matter hyperintensities and demyelination on MRI. Varying abdominal presentations have been described, which on imaging either show evidence of COVID-19 pneumonia in lung bases or show abdominal findings including bowel thickening and vascular thrombosis. Numerous thrombo-embolic and cardiovascular complications have also been described in COVID-19 including arterial and venous thrombosis, pulmonary embolism and myocarditis. It is imperative for radiologists to be aware of all the varied faces of this disease on imaging, as they may well be the first physician to suspect the disease. This article aims to review the multimodality imaging manifestations of COVID-19 disease in various organ systems from head to toe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1067/j.cpradiol.2021.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256677PMC
October 2021

Clinico-pathological features in fatal COVID-19 infection: a preliminary experience of a tertiary care center in North India using postmortem minimally invasive tissue sampling.

Expert Rev Respir Med 2021 10 24;15(10):1367-1375. Epub 2021 Jul 24.

Department of Medicine, AIIMS, New Delhi, India.

Objectives: To study the histopathology of patients dying of COVID-19 using post-mortem minimally invasive sampling techniques.

Methods: This was a single-center observational study conducted at JPNATC, AIIMS. Thirty-seven patients who died of COVID-19 were enrolled. Post-mortem percutaneous biopsies were taken from lung, heart, liver, kidney and stained with hematoxylin and eosin. Immunohistochemistry was performed using CD61 and CD163. SARS-CoV-2 virus was detected using IHC with primary antibodies.

Results: The mean age was 48.7 years and 59.5% were males. Lung histopathology showed diffuse alveolar damage in 78% patients. Associated bronchopneumonia was seen in 37.5% and scattered microthrombi in 21% patients. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of renal biopsies. Seventy-one percent of liver biopsies showed Kupffer cell hyperplasia and 27.5% showed submassive hepatic necrosis.

Conclusions: Predominant finding was diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase. Microvascular thrombi were rarely identified in any organ. Substantial hepatocyte necrosis, Kupffer cell hypertrophy, microvesicular, and macrovesicular steatosis unrelated to microvascular thrombi suggested that liver might be a primary target of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17476348.2021.1951708DOI Listing
October 2021

Changes in the behaviour of monocyte subsets in acute post-traumatic sepsis patients.

Mol Immunol 2021 08 1;136:65-72. Epub 2021 Jun 1.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Trauma remains a major public health problem worldwide, marked as the fourth leading cause of death among all diseases. Trauma patients who survived at initial stages in the Emergency Department (ED), have significantly higher chances of mortality due to sepsis associated complications in the ICU at the later stage. There is paucity of literature regarding the role of circulating monocytes subsets and development of sepsis complications following trauma haemorrhagic shock (THS). The study was conducted to investigate the circulating level of monocyte subsets (Classical, Inflammatory, and Patrolling) and its functions in patients with acute post-traumatic sepsis. A total 72, THS patients and 30 age matched healthy controls were recruited. Blood samples were collected at different time points on days 1, 7, and 14 to measure the serum levels of cytokines by Cytometric bead assay (CBA), for the immunophenotyping of monocytes subsets, and also for the cell sorting of monocytes subsets for the functional studies. The circulating levels of monocytes subsets were found to be significantly differs among THS patients, who developed sepsis when compared with others who did not. The levels of patrolling monocytes were elevated in THS patients who developed sepsis and showed negative correlation with Sequential organ failure assessment (SOFA) score on days 7 and 14. Classical monocytes responded strongly to bacterial TLR-agonist (LPS) and produced anti-inflammatory cytokines, whereas patrolling monocytes responded with viral TLR agonist TLR-7/8 (R848) and produced inflammatory cytokines in post-traumatic sepsis patients. In conclusion, this study shows disparity in the behaviour of monocytes subsets in patients with acute post-traumatic sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2021.04.005DOI Listing
August 2021

Estrogen as a Safe Therapeutic Adjunct in Reducing the Inflammatory Storm in Trauma Hemorrhagic Shock Patients.

Shock 2021 10;56(4):514-521

Department of Emergency Medicine, JPNATC, All India Institute of Medical Sciences, New Delhi, India.

Abstract: Trauma is a major cause of death and disability throughout the world. It is a leading cause of death with or without sepsis in about 50% of patients. Limited therapeutic options are available besides definitive care with a mortality benefit. Preclinical studies have demonstrated the mortality benefit of estrogen in trauma hemorrhagic shock (THS). Based on encouraging results from preclinical studies, we hypothesized that early administration of estrogen in male THS patients may reduce the inflammatory storm, prevent sepsis-associated problems, and subsequently reduce mortality. The authors studied the safety of early administration of estrogen as a therapeutic adjunct in the emergency department (ED) and its effects on the inflammatory storm, prevention of sepsis, and mortality during the intensive care unit stay. Forty THS patients were recruited. THS patients were divided into experimental and placebo control groups based on the estrogen administration in the ED. Serum levels of cytokines and immune cells were measured at different time points on days 0, 3, 7, and 14 in both groups of THS patients. The experimental group received intravenous estrogen (25 mg) at a single time point in the ED beside standard of care as per advanced trauma life support guidelines. Patients did not develop any major or minor adverse events and showed favorable clinical outcomes in the experimental group. The levels of T regulatory cells, monocytes, and systemic cytokines significantly reduced and showed a balanced inflammatory response in THS patients who received estrogen.In conclusion, this preliminary study showed that intravenous estrogen therapy is safe and reduced the inflammatory insult due to trauma hemorrhagic shock. It may protect THS patients from sepsis-associated complications. Future clinical trials are required to study the efficacy and mechanistic pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001779DOI Listing
October 2021

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

Indian J Med Res 2021 Jan & Feb;153(1 & 2):126-131

Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijmr.IJMR_3305_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184078PMC
April 2021

Donning N95 respirator masks during COVID-19 pandemic: look before you leap!

Braz J Anesthesiol 2021 May-Jun;71(3):302-303. Epub 2021 Mar 21.

Department of Critical & Intensive Care, JPN Apex Trauma centre, AIIMS, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bjane.2021.02.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981576PMC
June 2021

Associations of On-arrival Vital Signs with 24-hour In-hospital Mortality in Adult Trauma Patients Admitted to Four Public University Hospitals in Urban India: A Prospective Multi-Centre Cohort Study.

Injury 2021 May 26;52(5):1158-1163. Epub 2021 Feb 26.

Trauma Research group, WHO Collaborating Centre for Research in Surgical Care Delivery in LMICs, Mumbai, India; Affiliate, Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; Adjunct Professor (Research), School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia. Electronic address:

Introduction: In India, more than a million people die annually due to injuries. Identifying the patients at risk of early mortality (within 24 hour of hospital arrival) is essential for triage. A bilateral Government Australia-India Trauma System Collaboration generated a trauma registry in the context of India, which yielded a cohort of trauma patients for systematic observation and interventions. The aim of this study was to determine the independent association of on-arrival vital signs and Glasgow Coma Score (GCS) with 24-hour mortality among adult trauma patients admitted at four university public hospitals in urban India.

Methods: We performed an analysis of a prospective multicentre observational study of trauma patients across four urban public university hospitals in India, between April 2016 and February 2018. The primary outcome was 24-hour in-hospital mortality. We used logistic regression to determine mutually independent associations of the vital signs and GCS with 24-hour mortality.

Results: A total of 7497 adult patients (18 years and above) were included. The 24-hour mortality was 1.9%. In univariable logistic regression, Glasgow Coma Score (GCS) and the vital signs systolic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and peripheral capillary oxygen saturation (SpO2) had statistically significant associations with 24-hour mortality. These relationships held in multivariable analysis with hypotension (SBP<90mm Hg), tachycardia (HR>100bpm) and bradycardia (HR<60bpm), hypoxia (SpO2<90%), Tachypnoea (RR>20brpm) and severe (3-8) and moderate (9-12) GCS having strong association with 24-hour mortality. Notably, the patients with missing values for SBP, HR and RR also demonstrated higher odds of 24-hour mortality. The Injury Severity Scores (ISS) did not corelate with 24-hour mortality.

Conclusion: The routinely measured GCS and vital signs including SBP, HR, SpO2 and RR are independently associated with 24-hour in-hospital mortality in the context of university hospitals of urban India. These easily measured parameters in the emergency setting may help improve decision-making and guide further management in the trauma victims. A poor short-term prognosis was also observed in patients in whom these physiological variables were not recorded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.injury.2021.02.075DOI Listing
May 2021

Increase in optic nerve sheath diameter predicts early cerebral involvement in fat embolism syndrome.

Chin J Traumatol 2021 May 9;24(3):180-182. Epub 2021 Feb 9.

Department of Anaesthesiology, Critical Care and Pain Medicine, All India Institute of Medical Sciences, New Delhi, India.

Early diagnosis of cerebral fat embolism in a patient with contradiction to MRI is challenging. Here we report an interesting case, where the raised optic nerve sheath diameter helped us to predict the early cerebral involvement with fat emboli in a left femoral shaft fracture patient. MRI scan could not be performed due to the presence of a metallic implant in the patient from a previous surgery. He was later diagnosed as an atypical presentation of fat embolism syndrome. Optic nerve sheath monitoring also helped us to guide further management of the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjtee.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173580PMC
May 2021

Device associated infections at a trauma surgical center of India: Trend over eight years.

Indian J Med Microbiol 2021 Jan 4;39(1):15-18. Epub 2020 Nov 4.

Department of Orthopaedics, Chief, JPN Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background: Device-associated infections (DAIs) are an important cause of excessive stay and mortality in ICUs. Trauma patients are predisposed to acquire such infections due to various factors. The prevalence of HAIs is underreported from developing nations due to a lack of systematic surveillance. This study reports the rates and outcomes of DAIs at a dedicated Trauma Center in trauma patients and compares the rates with a previous pilot observation.

Methods: The study reports the finding of ongoing surveillance and the use of an indigenous software at a level-1 trauma center in India. Surveillance for ventilator-associated pneumonia, central line-associated bloodstream infections, and catheter-associated urinary tract infections was done based on standard definitions. The rates of HAIs and the profile of pathogens isolated from June 2010 to December 2018 were analyzed.

Results: A total of 7485 patients were included in the analysis, amounting to 68,715 patient days. The rates of VAP, CLABSI, and CA-UTI were respectively 12, 9.8 1st 8.5/1000 device days. There was a significant correlation between device days and the propensity to develop infections. Of the 1449 isolates recovered from cases of DAIs, Acinetobacter sp (28.2%) was the most common isolate, followed by Candida sp. A high rate of multi-resistance was observed.

Conclusion: Automated surveillance was easy and useful for data entry and analysis. Surveillance data should be used for implementing preventive programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijmmb.2020.10.015DOI Listing
January 2021

Artificial Intelligence-assisted chest X-ray assessment scheme for COVID-19.

Eur Radiol 2021 Aug 20;31(8):6039-6048. Epub 2021 Jan 20.

Indian Institute of Technology, Delhi, New Delhi, India.

Objectives: To study whether a trained convolutional neural network (CNN) can be of assistance to radiologists in differentiating Coronavirus disease (COVID)-positive from COVID-negative patients using chest X-ray (CXR) through an ambispective clinical study. To identify subgroups of patients where artificial intelligence (AI) can be of particular value and analyse what imaging features may have contributed to the performance of AI by means of visualisation techniques.

Methods: CXR of 487 patients were classified into [4] categories-normal, classical COVID, indeterminate, and non-COVID by consensus opinion of 2 radiologists. CXR which were classified as "normal" and "indeterminate" were then subjected to analysis by AI, and final categorisation provided as guided by prediction of the network. Precision and recall of the radiologist alone and radiologist assisted by AI were calculated in comparison to reverse transcriptase-polymerase chain reaction (RT-PCR) as the gold standard. Attention maps of the CNN were analysed to understand regions in the CXR important to the AI algorithm in making a prediction.

Results: The precision of radiologists improved from 65.9 to 81.9% and recall improved from 17.5 to 71.75 when assistance with AI was provided. AI showed 92% accuracy in classifying "normal" CXR into COVID or non-COVID. Analysis of attention maps revealed attention on the cardiac shadow in these "normal" radiographs.

Conclusion: This study shows how deployment of an AI algorithm can complement a human expert in the determination of COVID status. Analysis of the detected features suggests possible subtle cardiac changes, laying ground for further investigative studies into possible cardiac changes.

Key Points: • Through an ambispective clinical study, we show how assistance with an AI algorithm can improve recall (sensitivity) and precision (positive predictive value) of radiologists in assessing CXR for possible COVID in comparison to RT-PCR. • We show that AI achieves the best results in images classified as "normal" by radiologists. We conjecture that possible subtle cardiac in the CXR, imperceptible to the human eye, may have contributed to this prediction. • The reported results may pave the way for a human computer collaboration whereby the expert with some help from the AI algorithm achieves higher accuracy in predicting COVID status on CXR than previously thought possible when considering either alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07628-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816060PMC
August 2021

Crosstalk between T Helper Cell Subsets and Their Roles in Immunopathogenesis and Outcome of Polytrauma Patients.

Indian J Crit Care Med 2020 Nov;24(11):1037-1044

Department of Laboratory Medicine, JPNA Trauma Center, All India Institute of Medical Sciences, New Delhi, India.

Purpose: One of the leading causes of morbidity and early-age mortality across the globe is trauma. It disrupts immune system homeostasis and intensely affects the innate and adaptive immune responses, predisposing patients to posttrauma complications and poor outcomes. Most of the studies on posttrauma cellular immune response have been centered on the T helper-1-T helper-2 imbalances after trauma. This study was conducted to understand the role of circulating novel T helper cells in the acute posttraumatic period and clinical outcome of trauma patients.

Materials And Methods: Signature cytokines and transcription factors of circulating Th (T helper)-9, Th-17, Th-22, and regulatory T helper cells were studied using flowcytometry along with serum biomarkers in 49 patients with polytraumatic injuries admitted to a tertiary care hospital. The patients were followed up until their outcome. The results were correlated with their clinical outcomes.

Results: In patients who died, higher nTreg, iTreg, Tr1 (early-phase), and higher IRF4+Th-9, IL17+ Th-17, and RORγT+ Th-17 (mid-phase) were seen. However, by the late phase, only RORγT+ Th-17 remained higher. Serum IL-6 and PCT were found to be consistently higher. In survivors, higher Th-3 (early phase), Th-22 (mid-phase), and IRF4+Th-9, IL17+ Th-17, nTreg, Th-3 (late phase) were observed to have played a protective role. Serum IL-2, IL-4, IL-17A and IL-22 were significantly higher in survivors.

Conclusion: Different T helper subsets were observed to be playing pathogenic and protective roles in different phases of trauma and could be used for early prognostication and make way for noninvasive management of critically injured trauma patients by immunomodulation.

How To Cite This Article: Khurana S, Bhardwaj N, Kumar S, Sagar S, Pal R, Soni KD, Crosstalk between T Helper Cell Subsets and Their Roles in Immunopathogenesis and Outcome of Polytrauma Patients. Indian J Crit Care Med 2020;24(11):1037-1044.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5005/jp-journals-10071-23577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751033PMC
November 2020

Does in-hospital trauma mortality in urban Indian academic centres differ between "office-hours" and "after-hours"?

J Crit Care 2021 04 17;62:31-37. Epub 2020 Nov 17.

Trauma Research Group, WHO Collaborating Centre for Research in Surgical Care Delivery in LMICs, Mumbai, India; Dept of Global Public Health, Karolinska Institutet, Stockholm, Sweden; School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia. Electronic address:

Introduction: Trauma services within hospitals may vary considerably at different times across a 24 h period. The variable services may negatively affect the outcome of trauma victims. The current investigation aims to study the effect of arrival time of major trauma patients on mortality and morbidity.

Method: Retrospective analysis of the Australia-India Trauma Systems Collaboration (AITSC) registry established in four public university teaching centres in India Based on hospital arrival time, patients were grouped into "Office-hours" and "After-hours". Outcome parameters were compared between the above groups.

Results: 5536 (68.4%) patients presented "after-hours" (AO) and 2561 (31.6%) during "office-hours" (OH). The in-hospital mortality for "after-hours" and "office-hours" presentations were 12.1% and 11.6% respectively. On unadjusted analysis, there was no statistical difference in the odds of survival for OH versus AH presentations. (OR,1.05, 95% CI 0.9-1.2). Adjusting for potential prognostic factors (injury severity, presence of shock on arrival, referral status, sex, or extremes of age), there was no statistically significant odds of survival for OH versus AH presentations (OR,1.02, 95%CI 0.9-1.2).ICU length of stay and duration of mechanical ventilation was longer in the AH group.

Conclusion: The in-hospital mortality did not differ between trauma patients who arrived during "after-hours" compared to '"office-hours".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcrc.2020.11.009DOI Listing
April 2021

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

Indian J Med Res 2020 Oct 31. Epub 2020 Oct 31.

Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijmr.IJMR_3305_20DOI Listing
October 2020

Fast tracking intensive care units and operation rooms during the COVID-19 pandemic in resource limited settings.

J Anaesthesiol Clin Pharmacol 2020 Aug 31;36(Suppl 1):S7-S14. Epub 2020 Jul 31.

Department of Anaesthesiology, Pain Medicine and Critical Care, AIIMS, New Delhi, India.

The ongoing pandemic of COVID-19 has affected more than 43 million people all over the world with about 280000 deaths worldwide at the time of writing this article The outcome of this pandemic is impossible to predict at the present time as the numbers of both, infected patients and those dying of the disease are increasing on a daily basis. China, Italy, France, Spain, Germany, United Kingdom, and USA are the worst affected countries. All these countries have robust health care systems but despite this there has been a huge shortage of health care facilities especially intensive care beds in these countries. A country like India has different challenges as far as medical care during this pandemic is concerned. The need of the hour is to improve the health care system as a whole. In the present pandemic this involves setting up of patients screening facilities for the disease, enhancing the number of hospital beds, setting up of dedicated high dependency units, intensive care units and operation theatres for COVID positive patients. The present article describes in brief the way this can be done in a short time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/joacp.JOACP_262_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574016PMC
August 2020

An Analysis of 30-Day in-Hospital Trauma Mortality in Four Urban University Hospitals Using the Australia India Trauma Registry.

World J Surg 2021 Feb 21;45(2):380-389. Epub 2020 Oct 21.

Trauma Research Group, WHO Collaborating Centre for Research in Surgical Care Delivery in LMICs, Mumbai, India.

Background: India has one-sixth (16%) of the world's population but more than one-fifth (21%) of the world's injury mortality. A trauma registry established by the Australia India Trauma Systems Collaboration (AITSC) Project was utilized to study 30-day in-hospital trauma mortality at high-volume Indian hospitals.

Methods: The AITSC Project collected data prospectively between April 2016 and March 2018 at four Indian university hospitals in New Delhi, Mumbai, and Ahmedabad. Patients admitted with an injury mechanism of road or rail-related injury, fall, assault, or burns were included. The associations between demographic, physiological on-admission vitals, and process-of-care parameters with early (0-24 h), delayed (1-7 days), and late (8-30 days) in-hospital trauma mortality were analyzed.

Results: Of 9354 patients in the AITSC registry, 8606 were subjected to analysis. The 30-day mortality was 12.4% among all trauma victims. Early (24-h) mortality was 1.9%, delayed (1-7 days) mortality was 7.3%, and late (8-30 days) mortality was 3.2%. Abnormal physiological parameters such as a low SBP, SpO2, and GCS and high HR and RR were observed among non-survivors. Early initiation of trauma assessment and monitoring on arrival was an important process of care indicator for predicting 30-day survival.

Conclusions: One in ten admitted trauma patients (12.4%) died in urban trauma centers in India. More than half of the trauma deaths were delayed, beyond 24 h but within one week following injury. On-admission physiological vital signs remain a valid predictor of early 24-h trauma mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-020-05805-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773616PMC
February 2021

Efficacy of probiotics in the prevention of VAP in critically ill ICU patients: an updated systematic review and meta-analysis of randomized control trials.

J Intensive Care 2020 15;8:81. Epub 2020 Oct 15.

Department of Laboratory Medicine, JPNA Trauma Center, AIIMS, New Delhi, 110029 India.

Introduction: Ventilator-associated pneumonia (VAP) is reported as the second most common nosocomial infection among critically ill patients with the incidence ranging from 2 to 16 episodes per 1000 ventilator days. The use of probiotics has been shown to have a promising effect in many RCTs. Our systematic review and meta-analysis were thus planned to determine the effect of probiotic use in critically ill ventilated adult patients on the incidence of VAP, length of hospital stay, length of ICU stay, duration of mechanical ventilation, the incidence of diarrhea, and the incidence of oropharyngeal colonization and in-hospital mortality.

Methodology: Systematic search of various databases (such as Embase, Cochrane, and Pubmed), published journals, clinical trials, and abstracts of the various major conferences were made to obtain the RCTs which compare probiotics with placebo for VAP prevention. The results were expressed as risk ratios or mean differences. Data synthesis was done using statistical software - Review Manager (RevMan) Version 5.4 (The Cochrane Collaboration, 2020).

Results: Nine studies met our inclusion criterion and were included in the meta-analysis. The incidence of VAP (risk ratio: 0.70, CI 0.56, 0.88; = 0.002; = 37%), duration of mechanical ventilation (mean difference -3.75, CI -6.93, -0.58; 0.02; = 96%), length of ICU stay (mean difference -4.20, CI -6.73, -1.66; = 0.001; = 84%) and in-hospital mortality (OR 0.73, CI 0.54, 0.98; = 0.04; = 0%) in the probiotic group was significantly lower than that in the control group. Probiotic administration was not associated with a statistically significant reduction in length of hospital stay (MD -1.94, CI -7.17, 3.28; = 0.47; = 88%), incidence of oro-pharyngeal colonization (OR 0.59, CI 0.33, 1.04; = 0.07; = 69%), and incidence of diarrhea (OR 0.59, CI 0.34, 1.03; = 0.06; = 38%).

Discussion: Our meta-analysis shows that probiotic administration has a promising role in lowering the incidence of VAP, the duration of mechanical ventilation, length of ICU stay, and in-hospital mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40560-020-00487-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561245PMC
October 2020
-->