5 research outputs found
Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study
Background: Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits the IL-6 receptor. Several randomized clinical trials have evaluated its safety and efficacy in patients with coronavirus disease 2019 (COVID-19), and these studies demonstrate conflicting results. Our study aimed to determine the association between tocilizumab treatment and microbial isolation and emergence of multidrug-resistant bacteria in critically ill patients with COVID-19. Methods: A multicenter retrospective cohort study was conducted at two tertiary government hospitals in Saudi Arabia. All critically ill patients admitted to intensive care units with a positive COVID-19 PCR test between March 1 and December 31, 2020, who met study criteria were included. Patients who received tocilizumab were compared to those who did not receive it. Results: A total of 738 patients who met our inclusion criteria were included in the analysis. Of these, 262 (35.5%) received tocilizumab, and 476 (64.5%) were included in the control group. Patients who received tocilizumab had higher odds for microbial isolation (OR 1.34; 95% CI 0.91–1.94, p = 0.13); however, the difference was not statistically significant. Development of resistant organisms (OR 1.00; 95% CI 0.51–1.98, p = 0.99) or detection of carbapenem-resistant Enterobacteriaceae (CRE) (OR 0.67; 95% CI 0.29–1.54, p = 0.34) was not statistically significant between the two groups. Conclusions: Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms. © 2021, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Drugs targeting the NO-sGC-cGMP pathway in the treatment of patients with COPD-associated pulmonary hypertension: a systematic review
BackgroundPulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD) is categorized as group 3 PH and is associated with increased mortality and morbidity. Currently, there are no approved therapies for those who have PH secondary to COPD due to conflicting evidence. Therefore, this systematic review aims to summarize the current evidence on the effectiveness of drugs targeting the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway on clinical outcomes among patients with COPD-associated PH.MethodsWe conducted a comprehensive search of electronic databases, including Embase, Medline, Cochrane, and Scopus, from inception to 1 February 2024. Studies investigating the efficacy of drugs targeting the NO-sGC-cGMP pathway on clinical outcomes in patients with COPD-associated PH were included. Exclusion criteria encompassed case reports, systematic reviews, review articles, conference abstracts with no full text, non-full-text articles, non-English manuscripts, opinion articles, and book chapters. Two distinct Cochrane risk-of-bias tools designed for randomized and non-randomized clinical trials were used to evaluate the risk of bias within the selected studies for inclusion.ResultsFourteen studies, comprising a total of 567 adult patients diagnosed with PH secondary to COPD, met the inclusion criteria and were included in this systematic review. Among these, nine studies reported significant improvements in clinical parameters related to pulmonary hemodynamics. Improvement in exercise capacity was observed in four out of seven studies. Three studies evaluated dyspnea severity and quality of life following treatment with agents targeting the NO-sGC-cGMP pathway. Of these, three demonstrated improvement in dyspnea severity while two reported enhancements in health-related quality of life. Substantial heterogeneity was evident regarding the potential of pharmacological agents targeting the NO-sGC-cGMP pathway to enhance gas exchange, lung function, and arterial oxygenation in COPD patients with concurrent PH.ConclusionThe short-term use of oral drugs targeting the NO-sGC-cGMP pathway, particularly sildenafil, demonstrates promising potential for enhancing pulmonary hemodynamics, exercise capacity, dyspnea severity, and health-related quality of life but not lung function and oxygenation status in adult patients with COPD-associated PH. Further double-blind, randomized, placebo-controlled trials are needed to assess the therapeutic benefits of agents targeting the NO-sGC-cGMP pathway, particularly inhaled therapies for managing PH due to COPD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, CRD42023453503
Predictors of sepsis, intensive care unit admission, and death in patients hospitalized for complicated skin and soft tissue infections: Retrospective study at a large tertiary-care center
Background: Complicated skin and soft tissue infections often lead to poor health outcomes, with necrotizing skin and soft tissue infections occurring in 70%–80% of hospitalized patients and a mortality rate typically exceeding 20%. The current study’s main objective was to identify early predictors of sepsis, intensive care unit admission, and mortality in hospitalized complicated skin and soft tissue infection patients. Methods: A retrospective review of records from 235 adult complicated skin and soft tissue infection patients admitted from 2012 to 2022 was conducted. Collected data included demographics, medical history, clinical presentation, treatment, and outcomes. Laboratory results were used to calculate the Laboratory Risk Indicator for Necrotizing Fasciitis score for diagnosing necrotizing fasciitis. Predictors of sepsis, intensive care unit admission, and death were identified using logistic regression analysis. Results: Of the 235 patients, 42.1% were wheelchair-bound or bedridden; 93.2% had diabetes, 76.2% had cardiovascular disease, and 33.6% had kidney disease. Necrotizing fasciitis criteria were met by 75% of patients. Sepsis was diagnosed in 27.7% of patients, while 30.6% required intensive care unit admission, and 20.4% did not survive hospital discharge. Low mean arterial pressure and vasopressor use were significant predictors of all three severe outcomes, with pre-existing kidney disease also a predictor of in-hospital death. The Glasgow Coma Scale predicted both intensive care unit admission and sepsis, but not death. Conclusions: Low mean arterial pressure, vasopressor use, and pre-existing kidney disease are key predictors of in-hospital death in patients hospitalized for complicated skin and soft tissue infection. The former two, and the patient’s Glasgow Coma Scale, also appear to predict both intensive care unit admission and sepsis
Drugs targeting the NO-sGC-cGMP pathway in the treatment of patients with COPD-associated pulmonary hypertension: a systematic review
Background: Pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD) is categorized as group 3 PH and is associated with increased mortality and morbidity. Currently, there are no approved therapies for those who have PH secondary to COPD due to conflicting evidence. Therefore, this systematic review aims to summarize the current evidence on the effectiveness of drugs targeting the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway on clinical outcomes among patients with COPD-associated PH.
Methods: We conducted a comprehensive search of electronic databases, including Embase, Medline, Cochrane, and Scopus, from inception to 1 February 2024. Studies investigating the efficacy of drugs targeting the NO-sGC-cGMP pathway on clinical outcomes in patients with COPD-associated PH were included. Exclusion criteria encompassed case reports, systematic reviews, review articles, conference abstracts with no full text, non-full-text articles, non-English manuscripts, opinion articles, and book chapters. Two distinct Cochrane risk-of-bias tools designed for randomized and non-randomized clinical trials were used to evaluate the risk of bias within the selected studies for inclusion.
Results: Fourteen studies, comprising a total of 567 adult patients diagnosed with PH secondary to COPD, met the inclusion criteria and were included in this systematic review. Among these, nine studies reported significant improvements in clinical parameters related to pulmonary hemodynamics. Improvement in exercise capacity was observed in four out of seven studies. Three studies evaluated dyspnea severity and quality of life following treatment with agents targeting the NO-sGC-cGMP pathway. Of these, three demonstrated improvement in dyspnea severity while two reported enhancements in health-related quality of life. Substantial heterogeneity was evident regarding the potential of pharmacological agents targeting the NO-sGC-cGMP pathway to enhance gas exchange, lung function, and arterial oxygenation in COPD patients with concurrent PH.
Conclusion: The short-term use of oral drugs targeting the NO-sGC-cGMP pathway, particularly sildenafil, demonstrates promising potential for enhancing pulmonary hemodynamics, exercise capacity, dyspnea severity, and health-related quality of life but not lung function and oxygenation status in adult patients with COPD-associated PH. Further double-blind, randomized, placebo-controlled trials are needed to assess the therapeutic benefits of agents targeting the NO-sGC-cGMP pathway, particularly inhaled therapies for managing PH due to COPD.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, CRD42023453503
Additional file 1 of Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study
Additional file 1: Table S1. Summary of demography, baseline characteristics, and co-existing illness
