PURPOSE: Inhaled nitric oxide (iNO) is a potent vasodilator that has been studied as a treatment for acute respiratory distress syndrome (ARDS).However, clinical trials have not been able to demonstrate a survival benefit, and its use in clinical practice has been relegated to "rescue" or "bridging" therapy in refractory hypoxemia.However, it's early use prior to endotracheal intubation and invasive mechanical ventilation for patients with ARDS has not been investigated.As a result of the COVID-19 pandemic causing resource constraints, as well as the potential anti-viral effects of iNO, our center had a significant number of patients who were treated with iNO prior to intubation, often in combination with a high-flow nasal cannula (HFNC) system.Given this large cohort, we aimed to explore whether pre-intubation iNO resulted in any improved clinical outcomes among patients with COVID-19 induced hypoxic respiratory failure.METHODS: This is a descriptive study of patients admitted with COVID-19 pneumonia at a single tertiary care center.The COVID-19 population was surveyed to gather data on iNO delivered via a high-flow nasal cannula (HFNC).We collected information on patient demographics, co-morbidities, iNO treatment, need for intubation, ABG values, patient labs, hospital length of stay, and mortality.Patients were divided into two groups based on the timing of iNO initiation: group 1 -"postintubation" (i.e.iNO started on the same day as or after endotracheal intubation and mechanical ventilation) and group 2 -"preintubation" (i.e.iNO started at least 1 day prior to endotracheal intubation, if any). RESULTS:We had a total of 45 COVID-19 patients (group 1, n¼20 [44.4%] vs group2, n¼25 [65.6%]) who had iNO use.Age and gender were similar between the groups.On comparing the two groups (group 1 vs group 2), iNO was started at a median of 1(IQR, 1-6) day vs 2(IQR, 1-3) days from hospital admission.The number of Ventilation-free days (VFD) was 6.7 [mean(x)] in group 1 as opposed to 4.7 (x) in group 2. The total length of mechanical ventilation (days) was 17.8(x) vs 11.6 (x) in group 1 vs group 2. The mean hospital length of stay from the beginning of iNO treatment until discharge or death was 23.5 vs 17.2 days, with 11 deaths (55%) vs 7 deaths (28%) in group 1 vs group 2, respectively.Severity of illness as indicated by the mean SOFA score was higher in group 1 (7.8) than in group 2 (3.3). CONCLUSIONS:The use of iNO prior to intubation among patients with COVID-19 hypoxic respiratory failure appears to be safe and comparable on important clinical outcomes, including the duration of mechanical ventilation, hospital length of stay, and possibly mortality.This suggests that a formal prospective investigation on the earlier pre-intubation use of iNO for patients affected by ARDS is warranted.CLINICAL IMPLICATIONS: This study suggests that pre-intubation use of iNO in COVID patients with hypoxemic respiratory failure is feasible and that a formal prospective clinical trial is warranted.
The present study was carried out to determine the seroprevalence and risk factors associated with caprine brucellosis in Punjab, India. A total of 277 serum samples collected randomly from goats were tested by RBPT, MAT, STAT and i-ELISA. Out of 277 sera samples, 31 (11.19%), 44(15.88%), 49(17.68) and 52 (18.77%) samples were positive by RBPT, MAT, STAT and i-ELISA. Overall prevalence was 18.7%. The seroprevalence was found significantly (p<0.05) higher in females, non-descript breeds, animals in age group of 3-5 years, mixed flock, animals bred on farm, unorganized rearing system and animals kept in unhygienic conditions. Further analysis was done using multivariate logistic regression model to assess the association between the potential individual and management risk factors at p≤0.01 at 5% level. Upon odds ratio analysis, parity, breeding practices, flock type, contact with other herd and lack of disinfection were considered the major risk factors associated with spread of brucellosis in animals.
Abstract Background Ketamine, a dissociative anesthetic, induces remission of depression by antagonizing glutaminergic NMDA receptors. Ketamine has been used previously in outpatient setting for treatment-resistant depression, but we showcase its utility in depression management at the Intensive Care Unit (ICU). Research Question Can ketamine be used for depression treatment in ICU patients? Study Design and Methods A retrospective chart review of ICU patients was done at a tertiary center from 2018 to 2021, to assess the ketamine usage. Among the patients reviewed, ketamine was used for depression in 12, and for analgesia & sedation in 2322 patients. Ketamine was administered in doses of 0.5mg/kg & 0.75mg/kg for depression. Each course consisted of 3 doses of ketamine administered over 3 days. 7 in 12 patients received a single course of ketamine. The rest received 3-4 courses 1 week apart. Results Ketamine was found to improve mood and affect in most of the patients with depression. 11 in 12 patients had a positive response with better sleep. It has a major advantage over conventional anti-depressants since it takes only a few hours to induce remission. Patients who refused to eat and follow treatment protocol, and who would otherwise succumb to death if not for the rapid remission of depression, were administered ketamine. Conclusion A major drawback of ketamine is that the duration of remission is short, with the response lasting only up to 7 days after a single dose. Hence, all the patients in our study were weaned off ketamine with a supporting antidepressant. Ketamine has been documented to cause cardio-neurotoxicity; however, only one patient had worsening lethargy in our study. To conclude, ketamine has a monumental benefit in treating depression in the ICU. Although our study was associated with positive outcomes, there is a need for prospective studies with long-term follow-up assessments.
Background: Mistrust of medical and public authorities and the media in the Black community may exacerbate their COVID-19 related stress, perceptions, safety behaviors, inflammatory biomarkers and poor sleep quality. We examined this hypothesis in a sample of underserved Black adults. Methods: Black adults (n=67) recruited from a clinical setting completed assessments of medical mistrust, trust in public authorities and the media as well as a scale to assess COVID-19 related stress, perceptions, and safety behaviors. Inflammation levels were measured using C-Reactive Protein levels derived from a blood assay. Sleep Quality was indicated using apnea hypopnea index (AHI) and REM generated by a home sleep assessment tool (Itamar WatchPAT200). The association between feelings of mistrust with COVID-19 related outcomes were examined using bivariate correlations. Results: The study sample were 66% female and had a mean age of 56.1 (SD=5.1) years. Overall, participants endorsed high levels of mistrust in medical and public authorities, high levels of COVID-related stress, and low engagement in safety behaviors (see Table 1). Higher levels of medical mistrust were associated with a lower belief that reducing the number of people met in a day (r= -.258;p<.05) and avoiding public transportation (r= -.259;p<.05), would reduce the risk of contracting COVID-19. Lower levels of trust in public authorities were associated with higher levels of AHI (r= -.312;p<.05), and less REM sleep (r= .444;p<.01). Lower levels of media trust were associated with higher levels of inflammation (CRP;r= -.368;p<.05) and AHI (r= -.413;p<.05). Discussion: Mistrust of medical, public authority, and media entities in the context of COVID- 19 was high in this small clinical sample. Higher levels of medical mistrust was particularly relevant to lower endorsement of important COVID-19 protective behaviors. Lower levels of trust in public authorities and media were more relevant to poorer sleep quality and greater inflammation. Rebuilding trust of these entities among under-resourced populations may be critical to forestalling the COVID-19 pandemic. Word Count: 347/400.
113 Background: Bevacizumab (BVZ), a recombinant humanized monoclonal IgG antibody, is commonly used as first- and second-line adjuvant therapy in metastatic colorectal cancer. Recent guidelines have shown that a combination of three cytotoxic drug regimens FOLFOX (fluorouracil, leucovorin and oxaliplatin) along with BVZ is regarded as one of the first-line options. As we see an upward trend in using BVZ; it is crucial to analyze the side effects and potential toxicities. A frequent adverse effect with BVZ is hypertension. The prevailing hypothesis for the mechanism of BVZ induced hypertension is an increase in vascular tone due to the inhibition of VEGF-mediated vasodilation. A persistent elevation of arterial blood pressure is generally asymptomatic, but unmanaged hypertension can lead to cardiovascular complications, encephalopathy, and subarachnoid hemorrhage. Therefore, this meta-analysis aims to evaluate and assess the risk of BVZ induced hypertension. Methods: Our search included articles from PubMed, EMBASE, Web of Science, and Cochrane Library from 1980 to March 2022. Randomized controlled trials and clinical trials with BVZ as an add-on therapy mentioning cardiovascular side effects were included. Full analysis control group included various guideline directed chemotherapies and the subgroup analysis control group focused on FOLFOX therapy. A random-effects model was used with Review Manager, and a P value < 0.05 was considered significant. Results: We included a total of 17,807 patients in our study with an average age of 65 years. Analysis pooled from 19 RCTs showed that the odds of hypertension (Grade 3 or more) in patients treated with BVZ were about four times higher than the control group (OR 3.82, 95% CI 3.35-4.36, p-value < 0.00001, I2 = 78%). In a subgroup analysis, BVZ was compared with FOLFOX group, with odds of hypertension (Grade 3 or more) in BVZ group being about five times higher than in FOLFOX group (OR 5.24, 95% CI 4.06-6.77, p-value < 0.00001, I2 = 58%). Conclusions: Our meta-analysis demonstrates a significant cardiovascular risk of Bevacizumab when added to the standard regime for advanced colorectal cancer treatment. When BVZ was used as an add-on therapy to FOLFOX regimens for colorectal cancer, it was associated with about five times higher odds of developing hypertension (Grade 3 or more) in the treatment group with BVZ. Previous RCTs have demonstrated that BVZ add-on therapy to the standard regime is safe and without significant risk of toxicity. Our findings are important as they give vital information in assessing the risk-benefit ratio of adding BVZ, especially in a population with vascular comorbidities. Now that we have established the statistical significance of hypertensive risk with BVZ, it will be interesting to see how these events can be prevented in patients treated for metastatic colorectal cancer. Dedicated RCTs are needed to confirm these findings.
Introduction: Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN. Methods: English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models. Results: Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1). Conclusion: In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.
Rationale: Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory illness resulting from infection by SARS-CoV2. COVID-19 in its severe state results in respiratory failure requiring mechanical ventilation. Usual reasons for mechanical ventilation are a combination of hypoxemia and ventilatory failure resulting in hypercapnia. It has been shown in acute respiratory distress syndrome (ARDS) that dead space fraction predicts mortality. In the wake of COVID-19, there has been postulation that the respiratory failure resulting from this disease might be different from ARDS. In this study, we propose that the dead space fraction can predict mortality in patients with COVID- 19 respiratory failure requiring mechanical ventilation.Methods: This is a retrospective study in which 42 mechanically ventilated patients' dead space at day 0, day 1, and day 3 were calculated. Dead space was estimated using Penn State estimates, rearranged Weir, and alveolar ventilation equation as was validated by Beitler et al. The two cohorts (alive and deceased) were compared using Chi-squared tests for categorical variables and 2-sample t-tests for continuous variables.Results: Of the 42 mechanically ventilated patients, majority (n=25, 60%) died. The demographics of the two cohorts were similar except for older age (68 vs. 56.47) and the presence of CKD (32% vs. 0%) which are both statistically higher in the deceased cohort. Dead space ventilation on day 3 of mechanical ventilation was found to predict 28-day mortality with a p-value of 0.045. The mean dead space on day 3 was statistically significantly different in the deceased cohort in contrast to the alive cohort (60.64 vs. 50.82). Fluid balance at day 3, D-dimer at day 0, and 1, Ferritin at day 0,1, and 3, Lactate dehydrogenase at day 0,1, and 3, were higher in the deceased cohort. Absolute lymphocyte count on day 3 was lower in the deceased group.Conclusion: Our study shows that higher dead space fraction is associated with higher 28-day mortality as has been previously shown in prior ARDS study. This study strengthens the data supporting dead space as a predictor of mortality in mechanically ventilated patients. It also raises several questions regarding the reason for elevated inflammatory markers as is seen here. Are these elevated inflammatory markers signals of progressive vasculopathy induced by the viral infection? Or are they elevated as a result of cytokine storm-like reaction in response to the act of intubation? These are questions we hope to answer as we continue further analysis of this patient population.
