A randomised clinical trial of awake prone positioning in COVID-19 suspects with acute hypoxemic respiratory failure.

Background: Awake prone position (APP) has been reported to improve oxygenation in patients with COVID-19 disease and to reduce the requirement for invasive mechanical ventilation for patients requiring support with high flow nasal cannula. There is conflicting data for patients requiring lower-level oxygen support. Research question: Does APP reduce escalation of oxygen support in COVID-19 patients requiring supplementary oxygen?The primary outcome was defined as an escalation of oxygen support from simple supplementary oxygen (NP, HM, NRB) to NIV (CPAP or BiPAP), HFNC or IMV; OR from NIV (CPAP or BiPAP) or HFNC to IMV by day30. Study design: Two center, prospective, non-blind, randomised controlled trial. Patients with confirmed or suspected COVID-19 pneumonia requiring ≥ 5 liters/min oxygen to maintain saturations ≥ 94 % were randomised to either APP or control group. The APP group received a 3-h APP session three times per day for three days. Results: Between 9 May and July 13, 2021, 89 adults were screened and 61 enrolled, 31 to awake prone position and 30 controls. There was no difference in the primary outcome, 7 (22.6 %) patients randomised to APP and 9 (30.0 %) controls required escalation of oxygen support (OR 0.68 (0.22-2.14), P = 0.51). There were no differences in any secondary outcomes, in APP did not improve oxygenation. Interpretation: In COVID-19 patients, the use of APP did not prevent escalation of oxygen support from supplementary to invasive or non-invasive ventilation or improve patient respiratory physiology. Trial registration: NCT04853979 (clinicaltrials.gov).

Co-administration of Chrysin and Luteolin with Cisplatin and Topotecan Exhibits a Variable Therapeutic Value in Human Cancer Cells, HeLa.

Combinational treatment is a promising strategy for better cancer treatment outcomes. Chrysin and luteolin have demonstrated effective anticancer activity. Cisplatin and topotecan are commonly used for the treatment of human cancers. However, various side effects including drug resistance are an imperative restriction to use them as pharmacological therapy. Therefore, the aim was to use these agents in combination with flavones for better efficacy. In the present study, it was found that the combination of chrysin and cisplatin and luteolin and cisplatin significantly improved the anticancer effect as both the combinations showed synergistic interactions [combinational index (CI < 1)]. Remarkably, the combination of chrysin and luteolin with topotecan depicted the antagonistic interaction (CI > 1). Further, increased expression of the pro-apoptotic proteins Bax and caspase 8 and the inhibition of the antiapoptotic protein Bcl-2 were instituted in the synergistic doses (chrysin + cisplatin and luteolin + cisplatin), hence promoting apoptosis. Also, it was found that the synergistic combination inhibited the migration of HeLa cells by downregulation of metalloproteases and upregulation of TIMPs. However, there are no significant changes depicted in the antagonistic combinations which support their role in their antagonistic effects. Based on these results, it can be inferred that the two or more drug combinations need to be explored well for their interaction to enhance the therapeutic outcomes.

A cross-sectional study from Qatar on the effect of influenza vaccination on the severity of COVID-19.

To assess and compare the severity of corona virus disease 2019 (COVID-19) infection in patients with and without a history of influenza vaccination. In this cross-sectional study descriptive statistics were used to analyze COVID-19-related parameters, including demographics, comorbidities, and severity. Normally distributed data with mean, standard deviation, and 95% confidence interval (CI) were reported, while non-normally distributed data was presented with median and inter-quartile range. Categorical data was summarized using frequencies and percentages. Associations were assessed using Pearson Chi-square, Fisher Exact, t test, or Mann-Whitney U test. Univariate and multivariate logistic regression methods were used to evaluate the relationship between disease severity, clinical outcomes, influenza vaccination status, and other predictors. Significance was considered for p values < 0.05. Statistical analyses were done using SPSS V.27.0 (IBM Corp) and Epi Info (CDC) software. Between March 2020 and December 2020 before the availability of COVID-19 vaccination, 148,215 severe acute respiratory syndrome corona virus 2 positive patients were studied, with 3519 vaccinated against influenza, and 144,696 unvaccinated. After random sampling at 1:2 ratio, the final analysis included 3234 vaccinated and 5640 unvaccinated patients. The majority (95.4%) had mild or asymptomatic COVID-19, while 4.6% had severe or critical cases as defined by World Health Organization severity grading. Multivariate logistic regression analysis revealed that the vaccinated group had significantly less severe (adjusted odds ratio [OR] 0.683; 95% CI 0.513-0.911, P = .009) and critical (adjusted OR 0.345; 95% CI 0.145-0.822, P = .016) COVID-19 and were less likely to require oxygen therapy (adjusted OR 0.696; 95% CI 0.531-0.912, P = .009) after adjusting for confounders like age, gender and comorbidities. No significant differences in Intensive care unit admissions (adjusted OR 0.686; 95% CI 0.425-1.11, P = .122), mechanical ventilation (adjusted OR 0.631; 95% CI 0.308-1.295, P = .209) and mortality (adjusted OR 1.105; 95% CI 0.348-3.503, P = .866) were noted between the 2 groups. Influenza vaccination may significantly reduce the severity of COVID-19 but has no significant effect on intensive care unit admissions, mechanical ventilation and all- cause mortality.

A Prospective Cohort Study (OUTSTRIP-COVID) on Functional and Spirometry Outcomes in COVID-19 ICU Survivors at 3 Months.

Purpose: COVID-19 pandemic resulted in a significant number of critical care admissions secondary to severe pneumonia and acute respiratory distress syndrome. We evaluated the short-, medium- and long-term outcomes of lung function and quality of life in this prospective cohort study and reported the outcomes at 7 weeks and 3 months from discharge from intensive care unit. Methods: A prospective cohort study of ICU survivors with COVID-19 was conducted from August 2020 to May 2021 to evaluate baseline demographic and clinical variables as well as determine lung function, exercise capacity, and health-related quality of life (HRQOL) using spirometry and 6-minute walk test (6MWT) conducted in accordance with American Thoracic Society standards, and SF-36 (Rand), respectively. SF-36 is a generic 36 question standardized health survey. Descriptive and inferential statistics (alpha = 0.05) were used to analyse the data. Results: At baseline, 100 participants were enrolled in the study of whom 76 followed up at 3 months. Majority of the patients were male (83%), Asians (84%) and less than 60 years of age (91%). HRQOL showed significant improvement in all domains of SF-36, except in emotional wellbeing. Spirometry variables also showed significant improvement in all variables over time with greatest improvement in percentage predicted Forced expiratory volume 1 (79% vs 88% p < 0.001). 6MWT showed significant improvement in variables of walk distance, dyspnea, and fatigue with greatest improvement in change in oxygen saturation (3% vs 1.44% p < 0.001). Intubation status did not impact the changes in SF-36, spirometry or 6MWT variables. Conclusion: Our findings suggest that ICU survivors of COVID-19 have significant improvement in their lung function, exercise capacity and HRQOL within 3 months of ICU discharge regardless of intubation status.

Pre-procedural SARS-CoV-2 PCR testing in the pulmonary function laboratory at a tertiary government hospital in Qatar: A clinical audit.

BACKGROUND: Prior to pulmonary function testing (PFT), local and international recommendations advise pre-procedural screening. Pulmonary function tests generate aerosol droplets containing millions of viruses, significantly increasing the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission not only to the individuals in and around the PFT office, but also to subsequent patients who undergo the test later in the same room. METHODS: This clinical audit was carried out to establish the rate of positive pre-procedural SARS-CoV-2 PCR testing before a PFT. The data were obtained over a 6-week period from our ATS accredited pulmonary function laboratory at the Hamad General Hospital, Qatar (December 01, 2021, to January 10, 2022). The PFT laboratory was closed from January 10, 2022, till the date of this report (January 27, 2022) owing to an increase in COVID cases in the community in Qatar during the fourth wave. RESULTS: All the patients scheduled for PFT were asymptomatic of COVID-19. A total of 331 individuals were scheduled for PFT, and 221 PFTs were performed. There were 109 no-shows for both the PCR and the PFT. Between weeks 1 and 4, all the pre-procedural SARS-CoV-2 PCR tests were negative. The weekly average number of COVID-19 cases in Qatar increased from 157 per 100,000 population in week 1 to 2,918 in week 6.2 There was a similar trend in the pre-procedural SARS-CoV-2 PCR tests that increased and resulted in identifying 9 cases with positive SARS-CoV-2 PCR test over weeks 5 and 6 (Figure 1). CONCLUSION: As the number of documented positive SARS-CoV-2 PCR tests in the community grew, so did the pre-procedural COVID-19 PCR positivity and the number of no-shows. The large number of no-shows may indicate greater worry or concern about contracting COVID-19 when visiting the hospital amid peak community cases. Our findings further call into question the utility of routinely performing pre-procedural PCR screening in asymptomatic cases when the prevalence of COVID-19 is low in the local population. Perhaps, it is time to consider replacing this with on-the-spot quick antigen testing for more effective use of resources.

Clinical, Radiological, and Outcome Characteristics of Acute Pulmonary Embolism: A 5-year Experience from an Academic Tertiary Center.

BACKGROUND: Acute pulmonary embolism (PE) is a common and potentially life-threatening condition. This comprehensive study from a Gulf Cooperation Council (GCC) country aimed to evaluate the clinical, radiological, and outcome characteristics associated with acute PE. METHODS: This retrospective observational study analyzed data of patients with confirmed acute PE who were admitted to the largest academic tertiary center in the State of Qatar from January 1, 2014, to December 31, 2018. Data on the clinical presentation, radiologic, and echocardiographic findings, as well as outcomes were collected. RESULTS: A total of 436 patients were diagnosed with acute PE during the study period (male, 53%). Approximately 56% of the patients were < 50 years old at presentation, with a median age of 47 years. In approximately 69% of cases, the PE occurred outside the hospital. The main associated comorbidities were obesity (34.6%), hypertension (29.4%), and diabetes (25%). Immobilization (25.9%) and recent surgery (20.6%) were the most common risk factors. The most frequent presenting symptom was dyspnea (39.5%), and the most frequent signs were tachycardia (49.8%) and tachypnea (45%). Cardiac arrest was the initial presentation in 2.2% of cases. Chest X-ray findings were normal in 41%. On computed tomography pulmonary angiography (CTPA), 41.3% of the patients had segmental PE, 37.1% had central PE, and 64.1% had bilateral PE. The main electrocardiographic (ECG) abnormality was sinus tachycardia (98%). In patients who underwent echocardiography, right ventricular (RV) enlargement was the main echocardiographic finding (36.4%). Low-, intermediate-, and high-risk PE constituted 49.8%, 31.4%, and 18.8% of the cases, respectively. Thrombolysis was prescribed in 8.3% of the total and 24.4% of the high-risk PE cases. Complications of PE and its treatment (from admission up to 6 months post-discharge) included minor bleeding (14%), major bleeding (5%), PE recurrence (4.8%), and chronic thromboembolic pulmonary hypertension (CTEPH) (5%). A total of 15 (3.4%) patients died from PE. CONCLUSIONS: Acute PE can manifest with complex and variable clinical and radiological syndromes. Striking findings in this study are the younger age of acute PE occurrence and the low PE-related mortality rate.

Clinical Outcomes of COVID-19-Induced Acute Respiratory Distress Syndrome in Patients With Three Different Respiratory Support Modalities: A Retrospective Cohort Study.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute respiratory failure and acute respiratory distress syndrome (ARDS) had a considerable impact on intensive care utilization and resource optimization. Multiple modalities for respiratory support were implemented during the COVID-19 pandemic with the main concern of being able to identify those patients at high risk of rapidly progressive respiratory failure, whom the early initiation of invasive respiratory support would, in particular, affect the outcome in comparison to the noninvasive management strategy. Objectives In our cohort study, we describe demographic characteristics, respiratory support modalities, and their relation to patient outcomes. Method Patients 18 years of age and older who were admitted to a tertiary center COVID-19-dedicated medical intensive care unit (MICU) in Qatar between March 2020 and May 2020 with a confirmed diagnosis of COVID-19 pneumonia were included in this study. Patients were divided into invasive or noninvasive, and those who required invasive strategy were subdivided into the early intubation group (patients who were intubated within 72 hours of intensive care unit (ICU) admission) and the late intubation group (patients who were intubated after 72 hours from ICU admission). The primary outcome was ICU and hospital mortality, and the secondary effects were the length of stay and mortality determinants. Results A total of 686 patients were admitted to the medical intensive care unit (MICU) during the study period. There were 222 (32.4%), 131 (19.1%), and 333 (48.5%) patients in the early, late, and not intubated groups, respectively. Compared to the late intubated group, the early intubated group had a higher proportion of males. Diabetes (39.8%) was the most common comorbidity, followed by hypertension (HTN) (36%) and heart disease (9.8%). The 30-day ICU and hospital mortality were significantly higher in the late intubated group compared to the early intubated group (30.5% versus 15.8%, and 30% versus 16.2%). The median ICU and hospital stay days in the total sample were 8 (interquartile range (IQR): 5-14) and 19 (IQR: 14-25), respectively. The mean estimates of 30-day ICU survival times for early intubated, late intubated, and not intubated groups were 25.14 (95% confidence interval (CI): 23.71, 26.57), 23.35 (95% CI: 21.63, 25.07), and 29.91 (95% CI: 29.74, 30.09) respectively. Conclusions In our study, the COVID-19 ARDS patients who required early invasive ventilatory support and in whom the physiological parameter was more severe (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores) had a better outcome than the late intubation group. Age more than 60 years old, diabetes, hypertension, chronic kidney disease (CKD), and chronic liver disease (CLD) were the main predictor of mortality in total.

Hyperthyroidism precipitating cardiac arrest in a patient with Brugada pattern.

A 38-year-old man previously healthy suffered an out-of-hospital cardiac arrest; he was resuscitated successfully and admitted to the intensive care unit. His initial ECG suggested a Brugada pattern; other laboratory tests revealed low potassium level, low Thyroid Stimulating Hormone (TSH) and high FT4. He was started on carbimazole for hyperthyroidism, along with other supportive care. A comprehensive cardiac evaluation was done, including ajmaline and flecainide tests, results were inconclusive. An implantable cardioverter defibrillator device (ICD) was inserted to prevent such catastrophic events in the future. After discharge and on follow-up, our patient was doing well. His thyroid function test (TFT) was normal; moreover, a follow-up ICD interrogation did not record any arrhythmias. This case report highlighted asymptomatic hyperthyroidism as a precipitant for Brugada pattern resulting in sudden cardiac arrest.

A series of unfortunate events: Mind the windpipe.

Since we started seeing post-COVID pneumonia patients in our clinics, tracheo-laryngeal stenosis should be kept in mind as an important sequela of prolonged intubation (>7 days) particularly in those who are persistently symptomatic.

Epidemiological and Clinical Profiles of Patients with Acute Respiratory Distress Syndrome Admitted to Medical Intensive Care in Qatar: A Retrospective Analysis of the Data Registry for the Year 2015.

Background: Although acute respiratory distress syndrome (ARDS) is a common reason for admission to intensive care units, limited information is available about the epidemiological and clinical characteristics of these patients in Middle Eastern countries. Qatar is a high per capita income country with a large multinational expatriate population. Hamad General Hospital is our main tertiary referral center with the largest medical intensive care unit (MICU). Method: A retrospective cross-sectional study was conducted to extract data from the MICU registry for 101 patients aged >14 years who were admitted with ARDS from January 2015 to December 2015. Results: In 2015, a total of 101 (14.8%) of 682 patients admitted to MICU were diagnosed with ARDS. Males comprised 71.3% and females 28.7%. The mean age of the study population was 44.96 ± 17.97 years. Community-acquired bacterial and viral pneumonia were the most common reasons for ARDS. Crude mortality rate was 35%. The mean age of survivors was 42.09 ± 13.58 years compared with 50.36 ± 16.84 years of non-survivors (p = 0.008). Mortality was associated with increasing age, the Acute Physiologic Assessment and Chronic Health Evaluation II severity score, lower P/F ratio, higher Murray's score, higher PCO2, lower pH, and circulatory support with vasopressors. Preexisting comorbidities did not contribute to high mortality. No difference in mortality was noted with higher versus lower positive end expiratory pressure. The prone position was used in 8% of the cases. Twenty-seven (27%) patients had undergone salvage therapy with extracorporeal membrane oxygenation (ECMO) that resulted in a survival rate of 44%. ARDS was associated with acute renal failure requiring dialysis in 28.7% of the cases, pneumothoraces in 4%, ventilator-associated pneumonia in 7.9%, and central line-associated bloodstream infection in 2%. ARDS led to a prolonged length of stay compared with the average length of stay in MICU. Conclusion: Community-acquired bacterial and viral pneumonia were the most common causes of ARDS at our center. Critical care outcome correlated with the severity of the disease. ECMO was used as salvage therapy in our center.

Diagnostic value of bronchoalveolar lavage in the subset of patients with negative sputum/smear and mycobacterial culture and a suspicion of pulmonary tuberculosis.

BACKGROUND: The diagnostic value of bronchoalveolar lavage in patients with negative sputum/smear for tuberculous bacilli has been well studied. However, its value in the subset of patients with both negative sputum/smear and culture is seldom reported. METHODS: A retrospective study of patients referred for diagnostic bronchoscopy for the suspicion of pulmonary tuberculosis during the period from April 1st, 2015 to March 30th, 2016, and who had negative sputum/smear and culture for tuberculous bacilli. RESULTS: One hundred and ninety patients fulfilled the inclusion criteria. Bronchoalveolar lavage detected further 61/190 (32.1%) pulmonary tuberculosis cases. Bronchoalveolar lavage mycobacterial culture and polymerase chain reaction (positive in 60/190 (31.6%) and 58/190 (30.5%) of patients respectively) provided the highest diagnostic yield, whereas direct smear provided the lowest yield. Bronchoalveolar lavage had a sensitivity of 89.7%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 94.6%, and a test accuracy of 96.3% in suspected pulmonary tuberculosis cases with negative sputum/smear and culture. Positive bronchoalveolar lavage yield for tuberculosis was significantly associated with a positive QuantiFERON-TB Gold In-Tube test, positive purified protein derivative skin test, radiological evidence of upper zone abnormality and patient's origin being from the Indian subcontinent. CONCLUSION: Bronchoalveolar lavage should be pursued as a useful diagnostic tool for suspected pulmonary tuberculosis cases when sputum/smear and culture are negative. Its value is higher in the subset of patients with positive QuantiFERON-TB Gold In-Tube test, positive purified protein derivative skin test, upper zone abnormality on radiograph or being from the Indian subcontinent.

Medical thoracoscopy for exudative pleural effusion: an eight-year experience from a country with a young population.

BACKGROUND: With the exception of areas with high prevalence of tuberculosis, medical thoracoscopy is becoming the diagnostic modality of choice for exudative pleural effusions. The aims of this study were to determine the diagnostic yield and safety of medical thoracoscopy for exudative pleural effusions and ascertain the etiology of such effusions in Qatar. METHODS: This is a retrospective-descriptive study of 407 patients who underwent diagnostic medical thoracoscopy for exudative pleural effusions from January, 2008 till December, 2015 at the only tertiary referral center performing this procedure in Qatar. RESULTS: Tuberculosis was the most common etiology of exudative pleural effusions in Qatar accounting for 84.5% of all causes. Around 85% of patients were young males (mean age of 33 ± 12.1 years). The diagnostic yield of medical thoracoscopy for tuberculous pleural effusion was 91.4%. Malignant pleural effusions accounted for 5.2% of cases. Minor bleeding occurred in 1.2% of cases with no procedure-related mortality observed. CONCLUSION: Medical thoracoscopy is a very safe procedure. Tuberculous pleuritis is by far the most common etiology of exudative pleural effusions in Qatar. Closed needle biopsy is a worth consideration as an initial safe, easy and low-cost diagnostic modality for exudative pleural effusions in this country.

Effects of procalcitonin-guided treatment on antibiotic use and need for mechanical ventilation in patients with acute asthma exacerbation: Meta-analysis of randomized controlled trials.

OBJECTIVE: The primary outcome was to determine whether serum procalcitonin-guided antibiotic therapy can reduce antibiotic exposure in patients with an acute exacerbation of asthma presenting to the primary care facility or emergency department, or during hospital admission. The secondary outcome was the need for mechanical ventilation. METHODS: An extensive literature search was performed to identify randomized controlled clinical trials (published in English) that compared serum procalcitonin-guided antibiotic therapy versus antibiotic use according to physician's discretion for adult participants with mild, moderate, or severe acute asthma exacerbations. RESULTS: Four randomized controlled trials evaluating 457 patients were included in this meta-analysis, with significant homogeneity observed among these studies. Procalcitonin-based protocols decreased antibiotic prescriptions (relative risk 0.58, 95% confidence interval 0.50-0.67). The conclusion regarding the difference between the two groups in the need for mechanical ventilation (relative risk 1.10, 95% confidence interval 0.62-1.94) was guarded due to inadequate power and the potential for type II error. The overall quality of evidence was also limited by the lack of double-blinding. CONCLUSIONS: These data suggest a potential benefit for the use of serum procalcitonin in guiding antibiotic therapy in patients with an acute asthma exacerbation and advocates the need for more randomized controlled trials.

Diagnostic Delay among Adults with Pulmonary Tuberculosis in a High Gross Domestic Product Per Capita Country: Reasons and Magnitude of the Problem.

BACKGROUND: To determine the mean and median delays in pulmonary tuberculosis (PTB) diagnosis among adults in one of the world's highest gross domestic product per capita countries and identify patient and health system-related reasons for these delays. METHODS: This is a cross-sectional, face-to-face, prospective study of 100 subjects with confirmed PTB, conducted at main tuberculosis (TB) admitting facilities in Qatar. The mean and median diagnostic delays were measured. The Chi-square test with two-sided P < 0.05 was considered to determine the association between factors and diagnostic delay. RESULTS: The mean and median total diagnostic delays of PTB were 53 (95% confidence interval [CI] 42.61-63.59) and 30 (interquartile range; Q1-Q3, 15-60) days, respectively. The mean patient factor delay was 45.7 (95% CI 28.1-63.4) days, and the median was 30 (interquartile range; Q1-Q3, 15-60) days. The mean health system factor delay was 46.3 (95% CI 35.46-57.06) days, and the median was 30 (interquartile range; Q1-Q3, 18-60) days. The most common cause of patient factor delay was neglect of TB symptoms by patients (in 39% of cases), and for health-care system factor delay was a failure (mostly at general and private care levels) to suspect PTB by doctors (in 57% of cases). There were no significant associations between the presence of language barrier, patient occupation or nationality, and diagnostic delay. CONCLUSIONS: Despite a favorable comparison to other countries, there is a substantial delay in the diagnosis of PTB in Qatar. Relevant actions including health education on TB are required to minimize this delay.