To investigate the statistical measures of the performance of 2 interventions: a) early sepsis id... more To investigate the statistical measures of the performance of 2 interventions: a) early sepsis identification by a computerized sepsis "sniffer" algorithm (CSSA) in the emergency department (ED) and b) human decision to activate a multidisciplinary early resuscitation sepsis and shock response team (SSRT). This study used a prospective and historical cohort study design to evaluate the performance of two interventions. A computerized sepsis sniffer algorithm (CSSA) to aid in early diagnosis and a multidisciplinary sepsis and shock response team (SSRT) to improve patient care by increasing compliance with Surviving Sepsis Campaign (SSC) bundles. The CSSA yielded a sensitivity of 100% (95% CI, 99.13-100%) and a specificity of 96.2% (95% CI, 95.55-96.45%) to identifying sepsis in the ED (Table 1). The SSRT resource was activated appropriately in 34.1% (86/252) of patients meeting severe sepsis or septic shock criteria; the SSRT was inappropriately activated only three times i...
Introduction: Animal studies demonstrate sleep disturbance can negatively affect host immunologic... more Introduction: Animal studies demonstrate sleep disturbance can negatively affect host immunologic defenses and lead to bacteremia and death. However, whether obstructive sleep apnea (OSA) could impact the incidence and outcomes of sepsis in humans is unknown. We planned a pilot prospective observational study to explore whether OSA might affect sepsis severity and sepsis related outcomes. Methods: We identified 74 subjects with sepsis admitted to a tertiary academic center (September 2013 to March 2014).Subjects were excluded if patients had an otherwise terminal illness or received palliative care. We analyzed for whether clinically documented OSA would influence sepsis severity and related outcomes, including the need for mechanical ventilation (MV), development of acute respiratory distress syndrome (ARDS), and hospital mortality. Both univariate as well as multivariate analyses were performed. Results: The mean age and standard deviation (+/SD) was 68 years +/17;and 59% were male. In all, 47% met criteria for severe sepsis (evidence of organ dysfunction or lactic acidosis) and 47% for septic shock (volume refractory requiring pressors) ;with a mean APACHE IV of 28 +/5.9. OSA was present in 12%.In univariate analyses, OSA was significantly associated with body mass index (BMI), but not with sex, age, APACHEIV, sepsis severity, need for MV,ICU admission, ARDS, length of stay, or hospital mortality. In multivariate analyses, OSA was not independently predictive of sepsis severity or related outcomes, even after adjusting for age, sex, race/ethnicity, BMI, APACHE IV score. Further exploratory analysis of subjects with "untreated" OSA was limited by the unexpectedly high adherence (78%) of OSA patients to nocturnal noninvasive positive pressure ventilation prehospital. Conclusions: In this pilot observational study, we found no significant effect of OSA on sepsis severity or sepsis related outcomes, including ARDS and death. This may be confounded by a high treatment adherence rate and limited sample size. Future investigations exploring any potential link between OSA and sepsis should consider OSA severity and treatment adherence
SESSION TITLE: Sepsis SESSION TYPE: Original Investigation Slide PRESENTED ON: Monday, October 26... more SESSION TITLE: Sepsis SESSION TYPE: Original Investigation Slide PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM PURPOSE: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT. METHODS: Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period. RESULTS: There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation. CONCLUSIONS: There is a room for improvement in rates of SSRT activations. Utilization of CCS was related to the clinical severity of SS/S, therefore timely and appropriate care could be delayed when SSRT is not timely activated. Despite this, systematic approach to early recognition and management of SS/S patients with SSRT improved the compliance with standard care measures and overall mortality. CLINICAL IMPLICATIONS: Implementation of automated electronic alerts followed by systematic assessment and early intervention will improve compliance with the standard of care measures and outcomes of patients with severe sepsis and septic shock. DISCLOSURE: The following authors have nothing to disclose: Pablo Moreno Franco, Vikas Bansal, Muhammad Asif Mangi, Emir Festic No Product/Research Disclosure Information
To systematically review all available studies on inhaled corticosteroid use and incident pneumon... more To systematically review all available studies on inhaled corticosteroid use and incident pneumonia in asthma patients. We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers' web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies. Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0....
Polyarteritis Nodosa (PAN) is a vasculitis of unknown origin that affects the medium and small ar... more Polyarteritis Nodosa (PAN) is a vasculitis of unknown origin that affects the medium and small arteries of our organ system. Isolated Polyarteritis Nodosa is a rare condition that may be due to modulation of local immune reaction by exposure to certain local triggering agent without any systemic immune reaction. Symptomatic PAN confined to the testis in hepatitis B infection is extremely rare and not reported frequently. We report a case of isolated testicular PAN in hepatitis B infection with chronic unilateral testicular pain and successfully treated by interferon α, systemic steroid and cyclophosphamide for 7 month.
1 Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with ... more 1 Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the Fio 2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome. (Crit Care Med 2017; XX:00–00)
Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They h... more Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They have been associated with increased risk of pneumonia but not with increased pneumonia-associated or overall mortality.
Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic.
Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35–1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39–2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia -case-fatality: RR 0.91; 95% CI 0.52–1.59, p = 0.74; and OR 0.72; 95% CI 0.59–0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85–1.05, p=0.31; and OR 0.79; 95% CI 0.65–0.97, p=0.02, respectively.
Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.
Objective. Inhaled corticosteroids and inhaled beta agonists were shown to decrease the lung inju... more Objective. Inhaled corticosteroids and inhaled beta agonists were shown to decrease the lung injury in animal models. We investigated the association of pre-hospital use of inhaled corticosteroids and inhaled beta agonists with the incidence of Acute Respiratory Distress Syndrome (ARDS) in a population based cohort of hospitalized patients.
Material and methods. Retrospective cohort study of adult patients from Olmsted County, Minnesota admitted to the hospital with at least one predisposing condition for ARDS from 2001-2008. The association with pre-hospital use of inhaled corticosteroids and inhaled beta agonists was evaluated using univariate and multivariate analyses. Primary outcome was ARDS and secondary outcome was hospital mortality.
Results. Out of 2429 hospitalized adult patients with at least one risk factor for ARDS, 10.5% of those taking and 14% of those not taking inhaled corticosteroids developed ARDS (OR 0.72; 0.53-0.97; p<0.03). Inhaled beta agonists showed similar unadjusted protective effect; 9.7% of users and 14.4% of non-users developed ARDS (OR 0.64; 0.48-0.86; p=0.003). After adjusting for risk factors, comorbidities and severity of illness in the multiple logistic regression model, use of inhaled beta agonists, but not inhaled corticosteroids, remained independently associated with decreased risk of ARDS (OR 0.48; 0.31-0.72; p<0.001 versus 0.87; 0.57-1.29; p=0.49). The estimated protective effects were more pronounced among patients with pneumonia compared to those without pneumonia.
Conclusion. Prehospital use of inhaled beta agonists but not inhaled corticosteroids was significantly associated with decreased incidence of ARDS among hospitalized patients at risk, once adjusted for baseline characteristics, predisposing and comorbid conditions, as well as severity of illness.
Objectives: To systematically review all available studies on inhaled corticosteroid use and inci... more Objectives: To systematically review all available studies on inhaled corticosteroid use and incident pneumonia in asthma patients.
Methods: We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies.
Results: Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0.57to 0.95, p=0.02. On the contrary, observational studies showed summed odds ratio of 1.97; 95% CI 1.87to 2.07, p<0.0001, I²=0%, suggesting increased risk of pneumonia with use of inhaled corticosteroids in asthma patients.
Conclusions: Inhaled corticosteroids are associated with decreased risk of incident pneumonia in patients with asthma based on meta-analysis of available randomized trials. Although observational studies in similar patients suggested higher risk of pneumonia, the inherent methodological limitations confer lower grade of confidence in these studies.
Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been validated as... more Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO2/FiO2 measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO2/FiO2. The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO2/FiO2 values. Median SpO2/FiO2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO2/FiO2 and ARDS (P ≤ .001). The SpO2/FiO2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO2/FiO2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO2/FiO2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO2/FiO2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. Conclusions: The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.
Objective: To address clinical concern regarding the use of inhaled corticosteroids (ICSs) and th... more Objective: To address clinical concern regarding the use of inhaled corticosteroids (ICSs) and the risk for pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma. Patients and Methods: A multicentered prospective cohort of patients admitted to the hospital from March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was determined in a multiple logistic regression model. Results: Of the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P<.001). After adjusting in the logistic regression model, prehospital ICS use was not significantly associated with pneumonia in the whole cohort (OR, 1.20; 95% CI, 0.93-1.53; P¼.162), among the subset of 589 patients with COPD (OR, 1.40; 95% CI, 0.95-2.09; P¼.093), among the 440 patients with asthma (OR, 1.07; 95% CI, 0.61-1.87; P¼.81), nor among the remaining 4629 patients without COPD or asthma (OR, 1.32; 95% CI, 0.88-1.97; P¼.179). Conclusion: When adjusted for multiple confounding variables, ICS use was not substantially associated with an increased risk for pneumonia requiring admission in our cohort.
Learning Objectives: The current strategies for timely identification of patients at risk for asp... more Learning Objectives: The current strategies for timely identification of patients at risk for aspiration are limited. With increasing numbers of hospitals adopting electronic medical records, electronic search algorithms in hospitalized patients are becoming useful tools to expedite data abstraction and clinical research with a goal to improve timely recognition of clinical syndromes and related clinical outcomes.
Objective: To develop and validate a computable phenotype to identify aspiration in hospitalized patients. Hypothesis: The automated electronic search algorithm will feasible, reliable and it outperform ICD-9 code-based search for aspiration detection.
Methods: The study cohort consisted of 256,333 (older than 18 years and with prior research authorization) patients hospitalized at Mayo Clinic in Rochester, MN between January 1, 2006 and December 31, 2014. We randomly assigned 100 patients for a derivation cohort, where several iterations of a free-text electronic search (computable phenotype) were performed. Subsequently, the iterated automated search algorithm was validated on an independent cohort of 100 patients. The sensitivity and specificity of the automated digital algorithm were compared to the International Classification of Diseases-9 (ICD-9) codes for aspiration, and manual chart review served as a reference.
Results: In the derivation cohort, computable phenotype achieved sensitivity and specificity of 100% and 97.1%, while ICD-9 code-based search achieved sensitivity and specificity of 83.9% and 84.1%, respectively. In the validation cohort, computable phenotype achieved sensitivity and specificity of 100% and 95%, while ICD-9 code-based search achieved sensitivity and specificity 87.5% and 93.3%, respectively.
Conclusions: A computable phenotype for nosocomial aspiration in the form of automated electronic search is feasible, reliable and it outperforms ICD-9 code-based search for aspiration detection.
RATIONALE: Despite numerous past clinical trials, no pharmacological therapy has improved outcome... more RATIONALE: Despite numerous past clinical trials, no pharmacological therapy has improved outcomes of ARDS. Therefore, the paradigm has recently shifted to earlier treatment to prevent ARDS. Treatment with inhaled corticosteroids and beta agonists prior to onset of ARDS has several potential benefits. Besides established anti-inflammatory and enhanced alveolar fluid clearance functions, direct delivery to the target organ allows potential therapeutic benefits with less adverse systemic effects. Early treatment prior to the onset of ARDS may also allow more efficient drug delivery and provide more clinically relevant benefit by preventing acute respiratory failure.
METHODS: This was a double-blind, multicenter, randomized clinical trial of adults admitted through the emergency department at high-risk for ARDS (Lung Injury Prediction Score ≥ 4 and acute hypoxemia). Patients received combined aerosolized budesonide (0.5 mg) and formoterol (2 mg) vs. placebo (normal saline) twice daily for 5 days. The primary outcome was change in oxygen saturation to fraction of inspired oxygen (S/F) ratio from baseline to day 5, analyzed as both a longitudinal continuous variable by mixed effects model and a trichotomous variable (> 20% decrease, no change, or >20% increase). Secondary outcomes included rate of progression to ARDS, ICU and hospital length of stay, and need for invasive mechanical ventilation.
RESULTS: We enrolled 59 patients between September 2013 and June 2015. Patients in the treatment group were older (70±15 vs. 57±13) but less likely to have shock (10% vs. 47%) at enrollment. Median time from emergency department presentation to first study drug was < 9 hours. The longitudinal increase in S/F ratio over the treatment period was greater in the treatment group (p < 0.01) and independent of age and shock, although the absolute change in S/F from baseline was not significant (p=0.20). S/F ratio as a trichotomous variable improved significantly in the treatment group (p=0.01), in which no patient had a decline in S/F ratio. Also, ARDS developed in 7 placebo patients and no treated patients. Placebo patients were more likely to need ICU admission and mechanical ventilation, and longer ICU and hospital lengths of stay.
CONCLUSIONS: This trial establishes the feasibility of inhaled budesonide and formoterol in patients at high-risk for ARDS. Treated patients demonstrated improved oxygenation, lower rates of acute respiratory failure and ARDS, and a shorter hospital length of stay. This is the first prevention trial to suggest efficacy of the intervention for prevention/amelioration of ARDS.
SESSION TITLE: Sepsis
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October ... more SESSION TITLE: Sepsis
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM
PURPOSE: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT.
METHODS: Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period.
RESULTS: There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation.
CONCLUSIONS: There is a room for improvement in rates of SSRT activations. Utilization of CCS was related to the clinical severity of SS/S, therefore timely and appropriate care could be delayed when SSRT is not timely activated. Despite this, systematic approach to early recognition and management of SS/S patients with SSRT improved the compliance with standard care measures and overall mortality.
CLINICAL IMPLICATIONS: Implementation of automated electronic alerts followed by systematic assessment and early intervention will improve compliance with the standard of care measures and outcomes of patients with severe sepsis and septic shock.
DISCLOSURE: The following authors have nothing to disclose: Pablo Moreno Franco, Vikas Bansal, Muhammad Asif Mangi, Emir Festic
Introduction:
Animal studies demonstrate sleep disturbance can negatively affect host immunologic... more Introduction: Animal studies demonstrate sleep disturbance can negatively affect host immunologic defenses and lead to bacteremia and death. However, whether obstructive sleep apnea (OSA) could impact the incidence and outcomes of sepsis in humans is unknown. We planned a pilot prospective observational study to explore whether OSA might affect sepsis severity and sepsis related outcomes.
Methods: We identified 74 subjects with sepsis admitted to a tertiary academic center (September 2013 to March 2014).Subjects were excluded if patients had an otherwise terminal illness or received palliative care. We analyzed for whether clinically documented OSA would influence sepsis severity and related outcomes, including the need for mechanical ventilation (MV), development of acute respiratory distress syndrome (ARDS), and hospital mortality. Both univariate as well as multivariate analyses were performed.
Results: The mean age and standard deviation (+/SD) was 68 years +/17;and 59% were male. In all, 47% met criteria for severe sepsis (evidence of organ dysfunction or lactic acidosis) and 47% for septic shock (volume refractory requiring pressors) ;with a mean APACHE IV of 28 +/5.9. OSA was present in 12%.In univariate analyses, OSA was significantly associated with body mass index (BMI), but not with sex, age, APACHEIV, sepsis severity, need for MV,ICU admission, ARDS, length of stay, or hospital mortality. In multivariate analyses, OSA was not independently predictive of sepsis severity or related outcomes, even after adjusting for age, sex, race/ethnicity, BMI, APACHE IV score. Further exploratory analysis of subjects with "untreated" OSA was limited by the unexpectedly high adherence (78%) of OSA patients to nocturnal noninvasive positive pressure ventilation prehospital.
Conclusions: In this pilot observational study, we found no significant effect of OSA on sepsis severity or sepsis related outcomes, including ARDS and death. This may be confounded by a high treatment adherence rate and limited sample size. Future investigations exploring any potential link between OSA and sepsis should consider OSA severity and treatment adherence
Introduction:
Scoring systems in ICU were introduced almost 30 years ago with the goal of using p... more Introduction: Scoring systems in ICU were introduced almost 30 years ago with the goal of using physiologic data available at ICU admission to predict individual patient outcomes. Later, the Emergency Medicine developed scoring systems for triage ED patient. However, there is limited experience with scoring systems in the ED. Therefore, we plan to perform a systematic review on this. We hypothesized that the scoring systems used in ED would have a low ability to assess severity in critically ill patient at admission.
Methods: We conducted an extensive literature search using PubMed, Medline, EMBASE and the Cochrane Library, according to the PRISMA guidelines, on scoring systems used to assess severity in patients at admission. The primary endpoints were hospital mortality. The ability to identify patients at risk (discriminatory power) and agreement between observed and predicted outcome (calibration) along with the method of derivation and validation (application on a new cohort) were extracted.
Results: We identified 1,871 articles. Out of them 16 were included. Studies derived for only a single or few diagnoses were excluded.11 systems used vital signs as variables,2 used vital signs and blood test and 2 relied on blood tests.15 systems derived using regression analysis.7 included patients admitted to MAU,7 in ED,1 included patient transported to hospital by helicopter and 1 included patient who activated EMS. Discriminatory power was specified for 14 of the scoring systems and was acceptable or better in 10 of these. The calibration was only specified for 6 scoring systems. In none of these studies impact analysis or interobserver reliability were analyzed.
Conclusions: None of the 16 scoring systems are perfect, all have some flaws.Both the HOTEL and the SCS score were good in both discriminatory power and calibration but not externally validated. The REMS showed an acceptable discriminatory power but poor calibration. More research is needed especially external validation and impact analyses before the use of scoring systems can be fully implemented to the risk assessment of critically ill patients in ED admission.
Objective: Chronic cough defined as cough that persists for >8 weeks, effects up to 30% of the po... more Objective: Chronic cough defined as cough that persists for >8 weeks, effects up to 30% of the population and significantly impairs quality of life; with physical, psychological and social consequences (1,2). Moreover, the frequency of coughing episodes directly correlates with quality of life (3). Episodes of coughing have been shown to temporally associate with gastro-esophageal reflux events, irrespective of the presence of other concomitant conditions contributing to cough, such as nasal disease and/or asthma (4). How reflux in cough relates to cough-specific quality of life remains unclear.
Methods: We retrospectively identified consecutive patients who were referred for evaluation of a chronic cough at our specialist Chronic Cough Clinic, Mayo Clinic, Florida, and who had undergone ambulatory 24-h impedance/pH recording and completed the validated Cough-Specific Quality of Life Questionnaire (CSQLQ) (5).
Results: 79 patients had undergone 24-h impedance/pH (aged 63 ± 12 years (mean ± SD); 56 (71%) female) and completed the CSQLQ, of whom 25 (32%) were on acid suppressants. The mean total number of reflux events was 53 ± 25, with 13 (29%) patients having evidence of pathological reflux. The mean numbers of acid and nonacid reflux events were 28 ± 25 and 25 ± 19, respectively. A weak correlation was found between cough specific QoL and the number of reflux events (r = 0.20,p = 0.073), which appeared to be driven by a relationship between cough-specific QoL and the number of non-acid reflux (r = 0.29, p = 0.009) rather than acid reflux (r = 0.016, p = 0.892) events. There was no correlation between cough-specific QoL and the percentage of time pH <4 (r = 0.107, p = 0.352). In a multivariate analysis including age, sex, use of acid suppressants during the test, percentage of time pH <4 in the proximal/distal esophagus, together with the total number of acid and non-acid events; only sex and the number of non-acid reflux events were significantly predictive of the subject’s cough-specific QoL. On average, an increase in non-acid reflux events of 10 per 24-h worsened the cough-specific QoL 2.1 points.
Conclusion: Cough-specific quality of life worsens with increasing numbers of reflux events, particularly nonacid reflux events but not the percentage of time pH <4. Further studies are required using acoustic cough recording to determine whether this association between the number of reflux events and cough-specific QoL, is related to a worsening in the actual cough frequency.
INTRODUCTION
Inhaled Corticosteroids (ICS) are currently recommended for use in patients with sev... more INTRODUCTION Inhaled Corticosteroids (ICS) are currently recommended for use in patients with severe COPD and those with frequent exacerbations. The TORCH study and several other trials have shown increased incidence of pneumonia among patients using ICS. These trials have relied on unadjusted adverse event-reports of pneumonia frequently without any radiologic confirmation. Despite increased incidence of pneumonia, they have not demonstrated increased pneumonia-associated or overall mortality. This meta-analysis was done to affirm the increased risk of pneumonia and then better define whether ICS use affected unadjusted pneumonia-associated and overall mortality. METHODS Study designs consisting of randomized controlled trials or observational studies (cohort or case control) involving COPD patients, using ICS and a comparison arm lacking ICS and reporting the outcome of interest were considered for enrollment. We searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analyses of included RCTs and observational studies on the topic. RESULTS We identified 38 studies, 29 randomized controlled and 9 observational. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35-1.93, I =37%, p<0.001; as well as in observational studies: OR 1.89; 95% CI 1.39-2.59, I =99%, 2 2 p<0.001. Six estimable randomized trials showed no difference in pneumonia-associated mortality, RR 0.91; 95% CI 0.52-1.59, p=0.74, I2 =0% whereas 7 estimable observational studies showed a decrease in pneumonia associated mortality, OR 0.72; 95% CI 0.59-0.88, I =74%, 2 p=0.001, Similarly, 29 estimable randomized trials estimated no difference in unadjusted risk of overall mortality, RR 0.95; 95% CI 0.85-1.05, I = 0%, p=0.31, whereas 6 estimable observational studies found a decrease in overall mortality in the ICS group, OR 0.79; 95% CI 2 0.65-0.97, I =83%, p=0.02. 2 DISCUSSION Despite significantly increased unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia-associated and overall mortality was found not to be different in randomized controlled trials. However, observational studies showed significantly decreased unadjusted risk of pneumonia-associated and overall mortality, although there was high heterogeneity among these studies. Previous observations have indicated a combined immunosuppressive effect and potent anti-inflammatory effect of ICS. ICS predisposes COPD patients to an increased risk of incident pneumonia but conversely appears to have a counterbalancing beneficial effect on mortality resulting in no net change, or possibly a slight improvement in mortality.
Introduction: As asthma is a chronic inflammatory disease of the airway, affected patients usual... more Introduction: As asthma is a chronic inflammatory disease of the airway, affected patients usually require long-term anti-inflammatory therapy. Inhaled corticosteroids (ICS) are recommended as the first-line treatment for the persistent disease; however, their routine use might raise certain safety concerns. Although an increased risk of pneumonia have been established in patients with COPD on chronic ICS, it is not clear whether this risk pertains to asthma patients, as well.
Methods: We performed a comprehensive literature search from January 1, 1993, through March 31, 2014, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries (GlaxoSmithKline and AstraZeneca) with the clinical trial filters using multiple search terms with no language restrictions. We included all studies that compared patients 14 years of age and older on ICS and not on ICS relative to the risk of incident pneumonia (community
acquired, lower respiratory tract infection, non-tuberculous mycobacterial pneumonia). We then summarized individual study estimates into two random-effect meta-analyses, one including randomized controlled trials (RCTs) and another one including observational studies (OBS).
Results: There were total of 12 studies, 7 RCTs including total of 10,585 and 5 OBS including total of 44,127 participants. There was no heterogeneity in RCTs and summarized estimated effect of ICS was protective of pneumonia; OR 0.75 (0.57-0.99. p=0.05). On the contrary, OBS showed moderate heterogeneity (I2 =48%) with resulting summed OR of 1.94 (1.42-2.65, p<0.0001), suggesting increased risk of pneumonia with
use of ICS in asthma patients. However, OBS had lower grade of confidence compared to RCTs. Conclusions: ICS may carry protective effect or at the very least do not have increased risk of incident pneumonia in patients with asthma, based on our meta-analysis of available RCTs. While observational studies suggested higher risk of pneumonia in similar patients, the observed heterogeneity and inherent methodological limitations conferred lower grade of confidence in these studies.
To investigate the statistical measures of the performance of 2 interventions: a) early sepsis id... more To investigate the statistical measures of the performance of 2 interventions: a) early sepsis identification by a computerized sepsis "sniffer" algorithm (CSSA) in the emergency department (ED) and b) human decision to activate a multidisciplinary early resuscitation sepsis and shock response team (SSRT). This study used a prospective and historical cohort study design to evaluate the performance of two interventions. A computerized sepsis sniffer algorithm (CSSA) to aid in early diagnosis and a multidisciplinary sepsis and shock response team (SSRT) to improve patient care by increasing compliance with Surviving Sepsis Campaign (SSC) bundles. The CSSA yielded a sensitivity of 100% (95% CI, 99.13-100%) and a specificity of 96.2% (95% CI, 95.55-96.45%) to identifying sepsis in the ED (Table 1). The SSRT resource was activated appropriately in 34.1% (86/252) of patients meeting severe sepsis or septic shock criteria; the SSRT was inappropriately activated only three times i...
Introduction: Animal studies demonstrate sleep disturbance can negatively affect host immunologic... more Introduction: Animal studies demonstrate sleep disturbance can negatively affect host immunologic defenses and lead to bacteremia and death. However, whether obstructive sleep apnea (OSA) could impact the incidence and outcomes of sepsis in humans is unknown. We planned a pilot prospective observational study to explore whether OSA might affect sepsis severity and sepsis related outcomes. Methods: We identified 74 subjects with sepsis admitted to a tertiary academic center (September 2013 to March 2014).Subjects were excluded if patients had an otherwise terminal illness or received palliative care. We analyzed for whether clinically documented OSA would influence sepsis severity and related outcomes, including the need for mechanical ventilation (MV), development of acute respiratory distress syndrome (ARDS), and hospital mortality. Both univariate as well as multivariate analyses were performed. Results: The mean age and standard deviation (+/SD) was 68 years +/17;and 59% were male. In all, 47% met criteria for severe sepsis (evidence of organ dysfunction or lactic acidosis) and 47% for septic shock (volume refractory requiring pressors) ;with a mean APACHE IV of 28 +/5.9. OSA was present in 12%.In univariate analyses, OSA was significantly associated with body mass index (BMI), but not with sex, age, APACHEIV, sepsis severity, need for MV,ICU admission, ARDS, length of stay, or hospital mortality. In multivariate analyses, OSA was not independently predictive of sepsis severity or related outcomes, even after adjusting for age, sex, race/ethnicity, BMI, APACHE IV score. Further exploratory analysis of subjects with &quot;untreated&quot; OSA was limited by the unexpectedly high adherence (78%) of OSA patients to nocturnal noninvasive positive pressure ventilation prehospital. Conclusions: In this pilot observational study, we found no significant effect of OSA on sepsis severity or sepsis related outcomes, including ARDS and death. This may be confounded by a high treatment adherence rate and limited sample size. Future investigations exploring any potential link between OSA and sepsis should consider OSA severity and treatment adherence
SESSION TITLE: Sepsis SESSION TYPE: Original Investigation Slide PRESENTED ON: Monday, October 26... more SESSION TITLE: Sepsis SESSION TYPE: Original Investigation Slide PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM PURPOSE: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT. METHODS: Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period. RESULTS: There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation. CONCLUSIONS: There is a room for improvement in rates of SSRT activations. Utilization of CCS was related to the clinical severity of SS/S, therefore timely and appropriate care could be delayed when SSRT is not timely activated. Despite this, systematic approach to early recognition and management of SS/S patients with SSRT improved the compliance with standard care measures and overall mortality. CLINICAL IMPLICATIONS: Implementation of automated electronic alerts followed by systematic assessment and early intervention will improve compliance with the standard of care measures and outcomes of patients with severe sepsis and septic shock. DISCLOSURE: The following authors have nothing to disclose: Pablo Moreno Franco, Vikas Bansal, Muhammad Asif Mangi, Emir Festic No Product/Research Disclosure Information
To systematically review all available studies on inhaled corticosteroid use and incident pneumon... more To systematically review all available studies on inhaled corticosteroid use and incident pneumonia in asthma patients. We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers' web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies. Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0....
Polyarteritis Nodosa (PAN) is a vasculitis of unknown origin that affects the medium and small ar... more Polyarteritis Nodosa (PAN) is a vasculitis of unknown origin that affects the medium and small arteries of our organ system. Isolated Polyarteritis Nodosa is a rare condition that may be due to modulation of local immune reaction by exposure to certain local triggering agent without any systemic immune reaction. Symptomatic PAN confined to the testis in hepatitis B infection is extremely rare and not reported frequently. We report a case of isolated testicular PAN in hepatitis B infection with chronic unilateral testicular pain and successfully treated by interferon α, systemic steroid and cyclophosphamide for 7 month.
1 Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with ... more 1 Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the Fio 2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome. (Crit Care Med 2017; XX:00–00)
Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They h... more Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They have been associated with increased risk of pneumonia but not with increased pneumonia-associated or overall mortality.
Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic.
Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35–1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39–2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia -case-fatality: RR 0.91; 95% CI 0.52–1.59, p = 0.74; and OR 0.72; 95% CI 0.59–0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85–1.05, p=0.31; and OR 0.79; 95% CI 0.65–0.97, p=0.02, respectively.
Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.
Objective. Inhaled corticosteroids and inhaled beta agonists were shown to decrease the lung inju... more Objective. Inhaled corticosteroids and inhaled beta agonists were shown to decrease the lung injury in animal models. We investigated the association of pre-hospital use of inhaled corticosteroids and inhaled beta agonists with the incidence of Acute Respiratory Distress Syndrome (ARDS) in a population based cohort of hospitalized patients.
Material and methods. Retrospective cohort study of adult patients from Olmsted County, Minnesota admitted to the hospital with at least one predisposing condition for ARDS from 2001-2008. The association with pre-hospital use of inhaled corticosteroids and inhaled beta agonists was evaluated using univariate and multivariate analyses. Primary outcome was ARDS and secondary outcome was hospital mortality.
Results. Out of 2429 hospitalized adult patients with at least one risk factor for ARDS, 10.5% of those taking and 14% of those not taking inhaled corticosteroids developed ARDS (OR 0.72; 0.53-0.97; p<0.03). Inhaled beta agonists showed similar unadjusted protective effect; 9.7% of users and 14.4% of non-users developed ARDS (OR 0.64; 0.48-0.86; p=0.003). After adjusting for risk factors, comorbidities and severity of illness in the multiple logistic regression model, use of inhaled beta agonists, but not inhaled corticosteroids, remained independently associated with decreased risk of ARDS (OR 0.48; 0.31-0.72; p<0.001 versus 0.87; 0.57-1.29; p=0.49). The estimated protective effects were more pronounced among patients with pneumonia compared to those without pneumonia.
Conclusion. Prehospital use of inhaled beta agonists but not inhaled corticosteroids was significantly associated with decreased incidence of ARDS among hospitalized patients at risk, once adjusted for baseline characteristics, predisposing and comorbid conditions, as well as severity of illness.
Objectives: To systematically review all available studies on inhaled corticosteroid use and inci... more Objectives: To systematically review all available studies on inhaled corticosteroid use and incident pneumonia in asthma patients.
Methods: We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies.
Results: Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0.57to 0.95, p=0.02. On the contrary, observational studies showed summed odds ratio of 1.97; 95% CI 1.87to 2.07, p<0.0001, I²=0%, suggesting increased risk of pneumonia with use of inhaled corticosteroids in asthma patients.
Conclusions: Inhaled corticosteroids are associated with decreased risk of incident pneumonia in patients with asthma based on meta-analysis of available randomized trials. Although observational studies in similar patients suggested higher risk of pneumonia, the inherent methodological limitations confer lower grade of confidence in these studies.
Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been validated as... more Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO2/FiO2 measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO2/FiO2. The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO2/FiO2 values. Median SpO2/FiO2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO2/FiO2 and ARDS (P ≤ .001). The SpO2/FiO2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO2/FiO2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO2/FiO2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO2/FiO2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. Conclusions: The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.
Objective: To address clinical concern regarding the use of inhaled corticosteroids (ICSs) and th... more Objective: To address clinical concern regarding the use of inhaled corticosteroids (ICSs) and the risk for pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma. Patients and Methods: A multicentered prospective cohort of patients admitted to the hospital from March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was determined in a multiple logistic regression model. Results: Of the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P<.001). After adjusting in the logistic regression model, prehospital ICS use was not significantly associated with pneumonia in the whole cohort (OR, 1.20; 95% CI, 0.93-1.53; P¼.162), among the subset of 589 patients with COPD (OR, 1.40; 95% CI, 0.95-2.09; P¼.093), among the 440 patients with asthma (OR, 1.07; 95% CI, 0.61-1.87; P¼.81), nor among the remaining 4629 patients without COPD or asthma (OR, 1.32; 95% CI, 0.88-1.97; P¼.179). Conclusion: When adjusted for multiple confounding variables, ICS use was not substantially associated with an increased risk for pneumonia requiring admission in our cohort.
Learning Objectives: The current strategies for timely identification of patients at risk for asp... more Learning Objectives: The current strategies for timely identification of patients at risk for aspiration are limited. With increasing numbers of hospitals adopting electronic medical records, electronic search algorithms in hospitalized patients are becoming useful tools to expedite data abstraction and clinical research with a goal to improve timely recognition of clinical syndromes and related clinical outcomes.
Objective: To develop and validate a computable phenotype to identify aspiration in hospitalized patients. Hypothesis: The automated electronic search algorithm will feasible, reliable and it outperform ICD-9 code-based search for aspiration detection.
Methods: The study cohort consisted of 256,333 (older than 18 years and with prior research authorization) patients hospitalized at Mayo Clinic in Rochester, MN between January 1, 2006 and December 31, 2014. We randomly assigned 100 patients for a derivation cohort, where several iterations of a free-text electronic search (computable phenotype) were performed. Subsequently, the iterated automated search algorithm was validated on an independent cohort of 100 patients. The sensitivity and specificity of the automated digital algorithm were compared to the International Classification of Diseases-9 (ICD-9) codes for aspiration, and manual chart review served as a reference.
Results: In the derivation cohort, computable phenotype achieved sensitivity and specificity of 100% and 97.1%, while ICD-9 code-based search achieved sensitivity and specificity of 83.9% and 84.1%, respectively. In the validation cohort, computable phenotype achieved sensitivity and specificity of 100% and 95%, while ICD-9 code-based search achieved sensitivity and specificity 87.5% and 93.3%, respectively.
Conclusions: A computable phenotype for nosocomial aspiration in the form of automated electronic search is feasible, reliable and it outperforms ICD-9 code-based search for aspiration detection.
RATIONALE: Despite numerous past clinical trials, no pharmacological therapy has improved outcome... more RATIONALE: Despite numerous past clinical trials, no pharmacological therapy has improved outcomes of ARDS. Therefore, the paradigm has recently shifted to earlier treatment to prevent ARDS. Treatment with inhaled corticosteroids and beta agonists prior to onset of ARDS has several potential benefits. Besides established anti-inflammatory and enhanced alveolar fluid clearance functions, direct delivery to the target organ allows potential therapeutic benefits with less adverse systemic effects. Early treatment prior to the onset of ARDS may also allow more efficient drug delivery and provide more clinically relevant benefit by preventing acute respiratory failure.
METHODS: This was a double-blind, multicenter, randomized clinical trial of adults admitted through the emergency department at high-risk for ARDS (Lung Injury Prediction Score ≥ 4 and acute hypoxemia). Patients received combined aerosolized budesonide (0.5 mg) and formoterol (2 mg) vs. placebo (normal saline) twice daily for 5 days. The primary outcome was change in oxygen saturation to fraction of inspired oxygen (S/F) ratio from baseline to day 5, analyzed as both a longitudinal continuous variable by mixed effects model and a trichotomous variable (> 20% decrease, no change, or >20% increase). Secondary outcomes included rate of progression to ARDS, ICU and hospital length of stay, and need for invasive mechanical ventilation.
RESULTS: We enrolled 59 patients between September 2013 and June 2015. Patients in the treatment group were older (70±15 vs. 57±13) but less likely to have shock (10% vs. 47%) at enrollment. Median time from emergency department presentation to first study drug was < 9 hours. The longitudinal increase in S/F ratio over the treatment period was greater in the treatment group (p < 0.01) and independent of age and shock, although the absolute change in S/F from baseline was not significant (p=0.20). S/F ratio as a trichotomous variable improved significantly in the treatment group (p=0.01), in which no patient had a decline in S/F ratio. Also, ARDS developed in 7 placebo patients and no treated patients. Placebo patients were more likely to need ICU admission and mechanical ventilation, and longer ICU and hospital lengths of stay.
CONCLUSIONS: This trial establishes the feasibility of inhaled budesonide and formoterol in patients at high-risk for ARDS. Treated patients demonstrated improved oxygenation, lower rates of acute respiratory failure and ARDS, and a shorter hospital length of stay. This is the first prevention trial to suggest efficacy of the intervention for prevention/amelioration of ARDS.
SESSION TITLE: Sepsis
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October ... more SESSION TITLE: Sepsis
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM
PURPOSE: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT.
METHODS: Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period.
RESULTS: There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation.
CONCLUSIONS: There is a room for improvement in rates of SSRT activations. Utilization of CCS was related to the clinical severity of SS/S, therefore timely and appropriate care could be delayed when SSRT is not timely activated. Despite this, systematic approach to early recognition and management of SS/S patients with SSRT improved the compliance with standard care measures and overall mortality.
CLINICAL IMPLICATIONS: Implementation of automated electronic alerts followed by systematic assessment and early intervention will improve compliance with the standard of care measures and outcomes of patients with severe sepsis and septic shock.
DISCLOSURE: The following authors have nothing to disclose: Pablo Moreno Franco, Vikas Bansal, Muhammad Asif Mangi, Emir Festic
Introduction:
Animal studies demonstrate sleep disturbance can negatively affect host immunologic... more Introduction: Animal studies demonstrate sleep disturbance can negatively affect host immunologic defenses and lead to bacteremia and death. However, whether obstructive sleep apnea (OSA) could impact the incidence and outcomes of sepsis in humans is unknown. We planned a pilot prospective observational study to explore whether OSA might affect sepsis severity and sepsis related outcomes.
Methods: We identified 74 subjects with sepsis admitted to a tertiary academic center (September 2013 to March 2014).Subjects were excluded if patients had an otherwise terminal illness or received palliative care. We analyzed for whether clinically documented OSA would influence sepsis severity and related outcomes, including the need for mechanical ventilation (MV), development of acute respiratory distress syndrome (ARDS), and hospital mortality. Both univariate as well as multivariate analyses were performed.
Results: The mean age and standard deviation (+/SD) was 68 years +/17;and 59% were male. In all, 47% met criteria for severe sepsis (evidence of organ dysfunction or lactic acidosis) and 47% for septic shock (volume refractory requiring pressors) ;with a mean APACHE IV of 28 +/5.9. OSA was present in 12%.In univariate analyses, OSA was significantly associated with body mass index (BMI), but not with sex, age, APACHEIV, sepsis severity, need for MV,ICU admission, ARDS, length of stay, or hospital mortality. In multivariate analyses, OSA was not independently predictive of sepsis severity or related outcomes, even after adjusting for age, sex, race/ethnicity, BMI, APACHE IV score. Further exploratory analysis of subjects with "untreated" OSA was limited by the unexpectedly high adherence (78%) of OSA patients to nocturnal noninvasive positive pressure ventilation prehospital.
Conclusions: In this pilot observational study, we found no significant effect of OSA on sepsis severity or sepsis related outcomes, including ARDS and death. This may be confounded by a high treatment adherence rate and limited sample size. Future investigations exploring any potential link between OSA and sepsis should consider OSA severity and treatment adherence
Introduction:
Scoring systems in ICU were introduced almost 30 years ago with the goal of using p... more Introduction: Scoring systems in ICU were introduced almost 30 years ago with the goal of using physiologic data available at ICU admission to predict individual patient outcomes. Later, the Emergency Medicine developed scoring systems for triage ED patient. However, there is limited experience with scoring systems in the ED. Therefore, we plan to perform a systematic review on this. We hypothesized that the scoring systems used in ED would have a low ability to assess severity in critically ill patient at admission.
Methods: We conducted an extensive literature search using PubMed, Medline, EMBASE and the Cochrane Library, according to the PRISMA guidelines, on scoring systems used to assess severity in patients at admission. The primary endpoints were hospital mortality. The ability to identify patients at risk (discriminatory power) and agreement between observed and predicted outcome (calibration) along with the method of derivation and validation (application on a new cohort) were extracted.
Results: We identified 1,871 articles. Out of them 16 were included. Studies derived for only a single or few diagnoses were excluded.11 systems used vital signs as variables,2 used vital signs and blood test and 2 relied on blood tests.15 systems derived using regression analysis.7 included patients admitted to MAU,7 in ED,1 included patient transported to hospital by helicopter and 1 included patient who activated EMS. Discriminatory power was specified for 14 of the scoring systems and was acceptable or better in 10 of these. The calibration was only specified for 6 scoring systems. In none of these studies impact analysis or interobserver reliability were analyzed.
Conclusions: None of the 16 scoring systems are perfect, all have some flaws.Both the HOTEL and the SCS score were good in both discriminatory power and calibration but not externally validated. The REMS showed an acceptable discriminatory power but poor calibration. More research is needed especially external validation and impact analyses before the use of scoring systems can be fully implemented to the risk assessment of critically ill patients in ED admission.
Objective: Chronic cough defined as cough that persists for >8 weeks, effects up to 30% of the po... more Objective: Chronic cough defined as cough that persists for >8 weeks, effects up to 30% of the population and significantly impairs quality of life; with physical, psychological and social consequences (1,2). Moreover, the frequency of coughing episodes directly correlates with quality of life (3). Episodes of coughing have been shown to temporally associate with gastro-esophageal reflux events, irrespective of the presence of other concomitant conditions contributing to cough, such as nasal disease and/or asthma (4). How reflux in cough relates to cough-specific quality of life remains unclear.
Methods: We retrospectively identified consecutive patients who were referred for evaluation of a chronic cough at our specialist Chronic Cough Clinic, Mayo Clinic, Florida, and who had undergone ambulatory 24-h impedance/pH recording and completed the validated Cough-Specific Quality of Life Questionnaire (CSQLQ) (5).
Results: 79 patients had undergone 24-h impedance/pH (aged 63 ± 12 years (mean ± SD); 56 (71%) female) and completed the CSQLQ, of whom 25 (32%) were on acid suppressants. The mean total number of reflux events was 53 ± 25, with 13 (29%) patients having evidence of pathological reflux. The mean numbers of acid and nonacid reflux events were 28 ± 25 and 25 ± 19, respectively. A weak correlation was found between cough specific QoL and the number of reflux events (r = 0.20,p = 0.073), which appeared to be driven by a relationship between cough-specific QoL and the number of non-acid reflux (r = 0.29, p = 0.009) rather than acid reflux (r = 0.016, p = 0.892) events. There was no correlation between cough-specific QoL and the percentage of time pH <4 (r = 0.107, p = 0.352). In a multivariate analysis including age, sex, use of acid suppressants during the test, percentage of time pH <4 in the proximal/distal esophagus, together with the total number of acid and non-acid events; only sex and the number of non-acid reflux events were significantly predictive of the subject’s cough-specific QoL. On average, an increase in non-acid reflux events of 10 per 24-h worsened the cough-specific QoL 2.1 points.
Conclusion: Cough-specific quality of life worsens with increasing numbers of reflux events, particularly nonacid reflux events but not the percentage of time pH <4. Further studies are required using acoustic cough recording to determine whether this association between the number of reflux events and cough-specific QoL, is related to a worsening in the actual cough frequency.
INTRODUCTION
Inhaled Corticosteroids (ICS) are currently recommended for use in patients with sev... more INTRODUCTION Inhaled Corticosteroids (ICS) are currently recommended for use in patients with severe COPD and those with frequent exacerbations. The TORCH study and several other trials have shown increased incidence of pneumonia among patients using ICS. These trials have relied on unadjusted adverse event-reports of pneumonia frequently without any radiologic confirmation. Despite increased incidence of pneumonia, they have not demonstrated increased pneumonia-associated or overall mortality. This meta-analysis was done to affirm the increased risk of pneumonia and then better define whether ICS use affected unadjusted pneumonia-associated and overall mortality. METHODS Study designs consisting of randomized controlled trials or observational studies (cohort or case control) involving COPD patients, using ICS and a comparison arm lacking ICS and reporting the outcome of interest were considered for enrollment. We searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analyses of included RCTs and observational studies on the topic. RESULTS We identified 38 studies, 29 randomized controlled and 9 observational. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35-1.93, I =37%, p<0.001; as well as in observational studies: OR 1.89; 95% CI 1.39-2.59, I =99%, 2 2 p<0.001. Six estimable randomized trials showed no difference in pneumonia-associated mortality, RR 0.91; 95% CI 0.52-1.59, p=0.74, I2 =0% whereas 7 estimable observational studies showed a decrease in pneumonia associated mortality, OR 0.72; 95% CI 0.59-0.88, I =74%, 2 p=0.001, Similarly, 29 estimable randomized trials estimated no difference in unadjusted risk of overall mortality, RR 0.95; 95% CI 0.85-1.05, I = 0%, p=0.31, whereas 6 estimable observational studies found a decrease in overall mortality in the ICS group, OR 0.79; 95% CI 2 0.65-0.97, I =83%, p=0.02. 2 DISCUSSION Despite significantly increased unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia-associated and overall mortality was found not to be different in randomized controlled trials. However, observational studies showed significantly decreased unadjusted risk of pneumonia-associated and overall mortality, although there was high heterogeneity among these studies. Previous observations have indicated a combined immunosuppressive effect and potent anti-inflammatory effect of ICS. ICS predisposes COPD patients to an increased risk of incident pneumonia but conversely appears to have a counterbalancing beneficial effect on mortality resulting in no net change, or possibly a slight improvement in mortality.
Introduction: As asthma is a chronic inflammatory disease of the airway, affected patients usual... more Introduction: As asthma is a chronic inflammatory disease of the airway, affected patients usually require long-term anti-inflammatory therapy. Inhaled corticosteroids (ICS) are recommended as the first-line treatment for the persistent disease; however, their routine use might raise certain safety concerns. Although an increased risk of pneumonia have been established in patients with COPD on chronic ICS, it is not clear whether this risk pertains to asthma patients, as well.
Methods: We performed a comprehensive literature search from January 1, 1993, through March 31, 2014, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries (GlaxoSmithKline and AstraZeneca) with the clinical trial filters using multiple search terms with no language restrictions. We included all studies that compared patients 14 years of age and older on ICS and not on ICS relative to the risk of incident pneumonia (community
acquired, lower respiratory tract infection, non-tuberculous mycobacterial pneumonia). We then summarized individual study estimates into two random-effect meta-analyses, one including randomized controlled trials (RCTs) and another one including observational studies (OBS).
Results: There were total of 12 studies, 7 RCTs including total of 10,585 and 5 OBS including total of 44,127 participants. There was no heterogeneity in RCTs and summarized estimated effect of ICS was protective of pneumonia; OR 0.75 (0.57-0.99. p=0.05). On the contrary, OBS showed moderate heterogeneity (I2 =48%) with resulting summed OR of 1.94 (1.42-2.65, p<0.0001), suggesting increased risk of pneumonia with
use of ICS in asthma patients. However, OBS had lower grade of confidence compared to RCTs. Conclusions: ICS may carry protective effect or at the very least do not have increased risk of incident pneumonia in patients with asthma, based on our meta-analysis of available RCTs. While observational studies suggested higher risk of pneumonia in similar patients, the observed heterogeneity and inherent methodological limitations conferred lower grade of confidence in these studies.
ABSTRACT Learning Objectives: Several severity scores have been proposed for predicting sepsis se... more ABSTRACT Learning Objectives: Several severity scores have been proposed for predicting sepsis severity. We conducted a systematic review to check the characteristics of sepsis-specific severity scores.
Methods: MEDLINE, EMBASE, SCOPUS and web of science databases were searched for the articles published from July 1983 to June 2013 by using following terms or their combination - Sepsis Grading, Sepsis Severity score, APACHE, SAPS, OSF, MODS, SOFA, MEDS, MPM, REM score and PIRO staging system. This yielded 1999 articles. Retrospective, prospective, comparative studies and RCTs involving adult patients in ED or ICU with diagnosis of severe sepsis/septic shock were included for further review, there by excluding 1003 articles. Of the remaining 996 articles, those using only non-sepsis specific severity scores like APACHE, SOFA and SAPS were further excluded. Remaining 226 articles were then reviewed. Those using single mortality predictors in sepsis like procalcitonin, lactic acid, cardiac index, gene polymorphisms, lipid levels, vitamin D and other biomarkers (interleukins, cardiac markers) were excluded. All the articles with scores using invasive monitoring techniques and evaluating sepsis severity in specific population were also excluded, leaving 6 articles for final review.
Results: All 6 articles used PIRO, MEDS, NEWS, mottling score, MSOF or MEWS as the primary score for determining sepsis severity with primary end-point being long-term mortality. Four (67%) articles described retrospectively conducted studies. Range of total number of included patients was 60–2628. Median (IQR) age of included subjects was 65.5 (61–72). One study (17%) used only physical examination, 2 studies (33%) used only vitals and 3 studies (50%) used a combination of both with laboratory data and imaging to determine sepsis severity. All studies were found to be focusing on mortality, rather than predicting sepsis severity.
Conclusions: There is a lack of a sepsis-specific severity score which could predict sepsis severity using combination of vitals, physical examination and basic laboratory data collected during first 6 hours of presentation.
Introduction: Focused echocardiograms (echos) performed by intensivists are essential in providin... more Introduction: Focused echocardiograms (echos) performed by intensivists are essential in providing standard of care to critically ill patients. Previous studies identified very good agreement in results of focused echos performed by intensivists and standard echos performed by cardiology. However, in highly dynamic care of critically ill patients, difference in results on consecutively performed echos by intensivists or cardiology may be reflective of underlying dynamic changes in cardiac function rather than mere disagreements in interpretations of underlying static cardiac function. Methods: Retrospective analysis of all critically ill patients in a multidisciplinary ICU of a tertiary academic medical center who had echos performed by intensivist and cardiology within 48 hours regardless of sequence. We analyzed agreement in interpretation of the left ventricular (LV), right venricular (RV) function, presence and characteristics of pericardial effusion (PE), assesment of inferior vena cava (IVC) diameter and the presence of respiratory variation. Results: There were 38 ICU patients who had intensivist and cardiology performed echos within 48 hours. Twenty (53%) were female, mean age was 63 (SD 15), and mean APACHE IV was 77 (27). In 31 patients (82%), first echo performed was by intensivist, on average 17 (14) hours before echo performed by cardiology. Overall, agreements in interpretation of LV, RV and PE were seen in 24 (63%), 25 (65%), and 33 (87%), respectively. Agreement on IVC was present in only 5 patients (13%), as this part of echo was not documented in 31 patients (82%) by cardiology and 2 patients (5%) by intensivist. In a subgroup of 31 patients who had first echo done by intensivist, agreements in interpretation of LV, RV and PE were seen in 19 (61%), 23 (74%), and 28 (90%), respectively. In cases of agreements on LV and RV, the mean differences in time between intensivist and cardiology were 16 (15) and 14 (13) hours, respectively. In cases of disagreements on LV and RV, the mean differences in time between intensivist and cardiology were 20 (13) and 24 (14) hours, respectively. Once cases who lacked specific interpretation were excluded, agreement between intensivist and cardiology on LV, RV and PE was seen in 66% (19/29), 77% (23/30), and 93% (28/30) of cases when first echo was done by intensivist, versus 83% (5/6), 40% (2/5), and 83% (5/6) of cases when first echo was done by cardiology, respectively. Conclusions: Although the sample size is relatively small, the results suggest that observed differences in echo interpretation between intensivists and cardiology are at least partially related to the difference in time when echos are performed. It appeared that RV function was particularly prone to the dynamic changes and different interpretations as the consequence.
ABSTRACT Background: Chronic cough defined as cough that persists for > 8 weeks, effects up to 30... more ABSTRACT Background: Chronic cough defined as cough that persists for > 8 weeks, effects up to 30%
of the population and significantly impairs quality of life; with physical, psychological and
social consequences (1, 2). Moreover, the frequency of coughing episodes directly correlates
with quality of life (3). Episodes of coughing have been shown to temporally associate with
gastro-esophageal reflux events, irrespective of the presence of other concomitant conditions
contributing to cough, such as nasal disease and/or asthma (4). How reflux in cough relates
to cough-specific quality of life remains unclear. Methods: We retrospectively identified
consecutive patients who were referred for evaluation of a chronic cough at our specialist
Chronic Cough Clinic, Mayo Clinic, Jacksonville, and who had undergone ambulatory 24-
hr impedance/pH recording and completed the validated Cough-Specific Quality of Life
Questionnaire (CSQLQ) (5). Results: Seventy nine patients had undergone 24-hr impedance/
pH [aged 63 +12 yrs (mean + SD); 56 (71%) female] and completed the CSQLQ, of whom
25 (32%) were on acid-suppressant medications. The mean total number of reflux events
was 53 + 25, with 13 (29%) patients having evidence of pathologic reflux. The mean number
of acid and non-acid reflux events were 28 + 25 and 25 + 19, respectively. A weak correlation
was found between cough-specific quality of life (QoL) and the number of reflux events (r=
0.20, p=0.073, Pearson's correlation), which appeared to be driven by a relationship between
cough-specific QoL and the number of non-acid reflux (r=0.29, p=0.009) rather than acid
reflux (r=-0.016, p=0.892) events. There was no correlation between cough-specific QoL
and the percentage of time pH<4 (r=0.107, p=0.352). In a multivariate analysis including
age, sex, use of acid suppressants during the test, percentage of time pH<4 in the proximal/
distal esophagus, together with the total number of acid and non-acid events; only sex and
the number of non-acid reflux events were significantly predictive of the subject's coughspecific
QoL. On average, an increase in non-acid reflux events of 10 per 24-hrs worsened
the cough-specific QoL 2.1 points. Conclusion: Cough-specific quality of life worsens with
increased numbers of reflux events, particularly non-acid reflux events but not the percentage
of time pH<4. Further studies are required using acoustic cough recording to determine
whether this association between the number of reflux events and cough-specific QOL, is
related to a worsening in the actual cough frequency. Refs: (1)French et al. Arch Intern Med
1998; 158: 1657-61; (2) Morice et al. Thorax 2006; 61(suppl 1): 11-24; (3) Decalmer et
al. Thorax 2007; 62: 329-334; (4) Smith et al. Gastroenterology 2010; 139: 754-762; (5)
French et al. Chest 2002; 121: 1123-1131.
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Papers by VIKAS BANSAL
Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic.
Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35–1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39–2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia -case-fatality: RR 0.91; 95% CI 0.52–1.59, p = 0.74; and OR 0.72; 95% CI 0.59–0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85–1.05, p=0.31; and OR 0.79; 95% CI 0.65–0.97, p=0.02, respectively.
Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.
Material and methods. Retrospective cohort study of adult patients from Olmsted County, Minnesota admitted to the hospital with at least one predisposing condition for ARDS from 2001-2008. The association with pre-hospital use of inhaled corticosteroids and inhaled beta agonists was evaluated using univariate and multivariate analyses. Primary outcome was ARDS and secondary outcome was hospital mortality.
Results. Out of 2429 hospitalized adult patients with at least one risk factor for ARDS, 10.5% of those taking and 14% of those not taking inhaled corticosteroids developed ARDS (OR 0.72; 0.53-0.97; p<0.03). Inhaled beta agonists showed similar unadjusted protective effect; 9.7% of users and 14.4% of non-users developed ARDS (OR 0.64; 0.48-0.86; p=0.003). After adjusting for risk factors, comorbidities and severity of illness in the multiple logistic regression model, use of inhaled beta agonists, but not inhaled corticosteroids, remained independently associated with decreased risk of ARDS (OR 0.48; 0.31-0.72; p<0.001 versus 0.87; 0.57-1.29; p=0.49). The estimated protective effects were more pronounced among patients with pneumonia compared to those without pneumonia.
Conclusion. Prehospital use of inhaled beta agonists but not inhaled corticosteroids was significantly associated with decreased incidence of ARDS among hospitalized patients at risk, once adjusted for baseline characteristics, predisposing and comorbid conditions, as well as severity of illness.
Methods: We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies.
Results: Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0.57to 0.95, p=0.02. On the contrary, observational studies showed summed odds ratio of 1.97; 95% CI 1.87to 2.07, p<0.0001, I²=0%, suggesting increased risk of pneumonia with use of inhaled corticosteroids in asthma patients.
Conclusions: Inhaled corticosteroids are associated with decreased risk of incident pneumonia in patients with asthma based on meta-analysis of available randomized trials. Although observational studies in similar patients suggested higher risk of pneumonia, the inherent methodological limitations confer lower grade of confidence in these studies.
Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO2/FiO2. The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death.
Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO2/FiO2 values. Median SpO2/FiO2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO2/FiO2 and ARDS (P ≤ .001). The SpO2/FiO2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO2/FiO2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO2/FiO2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO2/FiO2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively.
Conclusions: The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.
pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma.
Patients and Methods: A multicentered prospective cohort of patients admitted to the hospital from
March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory
distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among
patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was
determined in a multiple logistic regression model.
Results: Of the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia
requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs
vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P<.001). After adjusting in the
logistic regression model, prehospital ICS use was not significantly associated with pneumonia in the
whole cohort (OR, 1.20; 95% CI, 0.93-1.53; P¼.162), among the subset of 589 patients with COPD (OR,
1.40; 95% CI, 0.95-2.09; P¼.093), among the 440 patients with asthma (OR, 1.07; 95% CI, 0.61-1.87;
P¼.81), nor among the remaining 4629 patients without COPD or asthma (OR, 1.32; 95% CI, 0.88-1.97;
P¼.179).
Conclusion: When adjusted for multiple confounding variables, ICS use was not substantially associated
with an increased risk for pneumonia requiring admission in our cohort.
Conference Presentations by VIKAS BANSAL
Objective: To develop and validate a computable phenotype to identify aspiration in hospitalized patients. Hypothesis: The automated electronic search algorithm will feasible, reliable and it outperform ICD-9 code-based search for aspiration detection.
Methods: The study cohort consisted of 256,333 (older than 18 years and with prior research authorization) patients hospitalized at Mayo Clinic in Rochester, MN between January 1, 2006 and December 31, 2014. We randomly assigned 100 patients for a derivation cohort, where several iterations of a free-text electronic search (computable phenotype) were performed. Subsequently, the iterated automated search algorithm was validated on an independent cohort of 100 patients. The sensitivity and specificity of the automated digital algorithm were compared to the International Classification of Diseases-9 (ICD-9) codes for aspiration, and manual chart review served as a reference.
Results: In the derivation cohort, computable phenotype achieved sensitivity and specificity of 100% and 97.1%, while ICD-9 code-based search achieved sensitivity and specificity of 83.9% and 84.1%, respectively. In the validation cohort, computable phenotype achieved sensitivity and specificity of 100% and 95%, while ICD-9 code-based search achieved sensitivity and specificity 87.5% and 93.3%, respectively.
Conclusions: A computable phenotype for nosocomial aspiration in the form of automated electronic search is feasible, reliable and it outperforms ICD-9 code-based search for aspiration detection.
METHODS: This was a double-blind, multicenter, randomized clinical trial of adults admitted through the emergency department at high-risk for ARDS (Lung Injury Prediction Score ≥ 4 and acute hypoxemia). Patients received combined aerosolized budesonide (0.5 mg) and formoterol (2 mg) vs. placebo (normal saline) twice daily for 5 days. The primary outcome was change in oxygen saturation to fraction of inspired oxygen (S/F) ratio from baseline to day 5, analyzed as both a longitudinal continuous variable by mixed effects model and a trichotomous variable (> 20% decrease, no change, or >20% increase). Secondary outcomes included rate of progression to ARDS, ICU and hospital length of stay, and need for invasive mechanical ventilation.
RESULTS: We enrolled 59 patients between September 2013 and June 2015. Patients in the treatment group were older (70±15 vs. 57±13) but less likely to have shock (10% vs. 47%) at enrollment. Median time from emergency department presentation to first study drug was < 9 hours. The longitudinal increase in S/F ratio over the treatment period was greater in the treatment group (p < 0.01) and independent of age and shock, although the absolute change in S/F from baseline was not significant (p=0.20). S/F ratio as a trichotomous variable improved significantly in the treatment group (p=0.01), in which no patient had a decline in S/F ratio. Also, ARDS developed in 7 placebo patients and no treated patients. Placebo patients were more likely to need ICU admission and mechanical ventilation, and longer ICU and hospital lengths of stay.
CONCLUSIONS: This trial establishes the feasibility of inhaled budesonide and formoterol in patients at high-risk for ARDS. Treated patients demonstrated improved oxygenation, lower rates of acute respiratory failure and ARDS, and a shorter hospital length of stay. This is the first prevention trial to suggest efficacy of the intervention for prevention/amelioration of ARDS.
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM
PURPOSE: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT.
METHODS: Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period.
RESULTS: There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation.
CONCLUSIONS: There is a room for improvement in rates of SSRT activations. Utilization of CCS was related to the clinical severity of SS/S, therefore timely and appropriate care could be delayed when SSRT is not timely activated. Despite this, systematic approach to early recognition and management of SS/S patients with SSRT improved the compliance with standard care measures and overall mortality.
CLINICAL IMPLICATIONS: Implementation of automated electronic alerts followed by systematic assessment and early intervention will improve compliance with the standard of care measures and outcomes of patients with severe sepsis and septic shock.
DISCLOSURE: The following authors have nothing to disclose: Pablo Moreno Franco, Vikas Bansal, Muhammad Asif Mangi, Emir Festic
No Product/Research Disclosure Information
Animal studies demonstrate sleep disturbance can negatively affect host immunologic defenses and lead to bacteremia and death. However, whether obstructive sleep apnea (OSA) could impact the incidence and outcomes of sepsis in humans is unknown. We planned a pilot prospective observational study to explore whether OSA might affect sepsis severity and sepsis related outcomes.
Methods:
We identified 74 subjects with sepsis admitted to a tertiary academic center (September 2013 to March 2014).Subjects were excluded if patients had an otherwise terminal illness or received palliative care. We analyzed for whether clinically documented OSA would influence sepsis severity and related outcomes, including the need for mechanical ventilation (MV), development of acute respiratory distress syndrome (ARDS), and hospital mortality. Both univariate as well as multivariate analyses were performed.
Results:
The mean age and standard deviation (+/SD) was 68 years +/17;and 59% were male. In all, 47% met criteria for severe sepsis (evidence of organ dysfunction or lactic acidosis) and 47% for septic shock (volume refractory requiring pressors) ;with a mean APACHE IV of 28 +/5.9. OSA was present in 12%.In univariate analyses, OSA was significantly associated with body mass index (BMI), but not with sex, age, APACHEIV, sepsis severity, need for MV,ICU admission, ARDS, length of stay, or hospital mortality. In multivariate analyses, OSA was not independently predictive of sepsis severity or related outcomes, even after adjusting for age, sex, race/ethnicity, BMI, APACHE IV score. Further exploratory analysis of subjects with "untreated" OSA was limited by the unexpectedly high adherence (78%) of OSA patients to nocturnal noninvasive positive pressure ventilation prehospital.
Conclusions:
In this pilot observational study, we found no significant effect of OSA on sepsis severity or sepsis related outcomes, including ARDS and death. This may be confounded by a high treatment adherence rate and limited sample size. Future investigations exploring any potential link between OSA and sepsis should consider OSA severity and treatment adherence
Scoring systems in ICU were introduced almost 30 years ago with the goal of using physiologic data available at ICU admission to predict individual patient outcomes. Later, the Emergency Medicine developed scoring systems for triage ED patient. However, there is limited experience with scoring systems in the ED. Therefore, we plan to perform a systematic review on this. We hypothesized that the scoring systems used in ED would have a low ability to assess severity in critically ill patient at admission.
Methods:
We conducted an extensive literature search using PubMed, Medline, EMBASE and the Cochrane Library, according to the PRISMA guidelines, on scoring systems used to assess severity in patients at admission. The primary endpoints were hospital mortality. The ability to identify patients at risk (discriminatory power) and agreement between observed and predicted outcome (calibration) along with the method of derivation and validation (application on a new cohort) were extracted.
Results:
We identified 1,871 articles. Out of them 16 were included. Studies derived for only a single or few diagnoses were excluded.11 systems used vital signs as variables,2 used vital signs and blood test and 2 relied on blood tests.15 systems derived using regression analysis.7 included patients admitted to MAU,7 in ED,1 included patient transported to hospital by helicopter and 1 included patient who activated EMS. Discriminatory power was specified for 14 of the scoring systems and was acceptable or better in 10 of these. The calibration was only specified for 6 scoring systems. In none of these studies impact analysis or interobserver reliability were analyzed.
Conclusions:
None of the 16 scoring systems are perfect, all have some flaws.Both the HOTEL and the SCS score were good in both discriminatory power and calibration but not externally validated. The REMS showed an acceptable discriminatory power but poor calibration. More research is needed especially external validation and impact analyses before the use of scoring systems can be fully implemented to the risk assessment of critically ill patients in ED admission.
Methods: We retrospectively identified consecutive patients who were referred for evaluation of a chronic cough at our specialist Chronic Cough Clinic, Mayo Clinic, Florida, and who had undergone ambulatory 24-h impedance/pH recording and completed the validated Cough-Specific Quality of Life Questionnaire (CSQLQ) (5).
Results: 79 patients had undergone 24-h impedance/pH (aged 63 ± 12 years (mean ± SD); 56 (71%) female) and completed the CSQLQ, of whom 25 (32%) were on acid suppressants. The mean total number of reflux events was 53 ± 25, with 13 (29%) patients having evidence of pathological reflux. The mean numbers of acid and nonacid reflux events were 28 ± 25 and 25 ± 19, respectively. A weak correlation was found between cough specific QoL and the number of reflux events (r = 0.20,p = 0.073), which appeared to be driven by a relationship between cough-specific QoL and the number of non-acid reflux (r = 0.29, p = 0.009) rather than acid reflux (r = 0.016, p = 0.892) events. There was no correlation between cough-specific QoL and the percentage of time pH <4 (r = 0.107, p = 0.352). In a multivariate analysis including age, sex, use of acid suppressants during the test, percentage of time pH <4 in the proximal/distal esophagus, together with the total number of acid and non-acid events; only sex and the number of non-acid reflux events were significantly predictive of the subject’s cough-specific QoL. On average, an increase in non-acid reflux events of 10 per 24-h worsened the cough-specific QoL 2.1 points.
Conclusion: Cough-specific quality of life worsens with increasing numbers of reflux events, particularly nonacid reflux events but not the percentage of time pH <4. Further studies are required using acoustic cough recording to determine whether this association between the number of reflux events and cough-specific QoL, is related to a worsening in the actual cough frequency.
Refs: (1) Arch Intern Med 1998; 581657, (2) Thorax 2006; 6111, (3) Thorax 2007; 62:329, (4) Gastroenterology 2010;139:754, (5) Chest 2002;121:1123.
Inhaled Corticosteroids (ICS) are currently recommended for use in patients with severe COPD and those with frequent exacerbations. The
TORCH study and several other trials have shown increased incidence of pneumonia among patients using ICS. These trials have relied on
unadjusted adverse event-reports of pneumonia frequently without any radiologic confirmation. Despite increased incidence of
pneumonia, they have not demonstrated increased pneumonia-associated or overall mortality. This meta-analysis was done to affirm the
increased risk of pneumonia and then better define whether ICS use affected unadjusted pneumonia-associated and overall mortality.
METHODS
Study designs consisting of randomized controlled trials or observational studies (cohort or case control) involving COPD patients, using
ICS and a comparison arm lacking ICS and reporting the outcome of interest were considered for enrollment. We searched for potentially
relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994
to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic
review and meta-analyses of included RCTs and observational studies on the topic.
RESULTS
We identified 38 studies, 29 randomized controlled and 9 observational. The estimated unadjusted risk of pneumonia was increased in
randomized trials: RR 1.61; 95% CI 1.35-1.93, I =37%, p<0.001; as well as in observational studies: OR 1.89; 95% CI 1.39-2.59, I =99%, 2 2
p<0.001. Six estimable randomized trials showed no difference in pneumonia-associated mortality, RR 0.91; 95% CI 0.52-1.59, p=0.74, I2
=0% whereas 7 estimable observational studies showed a decrease in pneumonia associated mortality, OR 0.72; 95% CI 0.59-0.88, I =74%, 2
p=0.001, Similarly, 29 estimable randomized trials estimated no difference in unadjusted risk of overall mortality, RR 0.95; 95% CI 0.85-1.05,
I = 0%, p=0.31, whereas 6 estimable observational studies found a decrease in overall mortality in the ICS group, OR 0.79; 95% CI 2
0.65-0.97, I =83%, p=0.02. 2
DISCUSSION
Despite significantly increased unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia-associated and
overall mortality was found not to be different in randomized controlled trials. However, observational studies showed significantly
decreased unadjusted risk of pneumonia-associated and overall mortality, although there was high heterogeneity among these studies.
Previous observations have indicated a combined immunosuppressive effect and potent anti-inflammatory effect of ICS. ICS predisposes
COPD patients to an increased risk of incident pneumonia but conversely appears to have a counterbalancing beneficial effect on
mortality resulting in no net change, or possibly a slight improvement in mortality.
Methods: We performed a comprehensive literature search from January 1, 1993, through March 31, 2014, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries (GlaxoSmithKline and AstraZeneca) with the clinical trial filters using multiple search terms with no language restrictions. We included all studies that compared patients 14 years of age and older on ICS and not on ICS relative to the risk of incident pneumonia (community
acquired, lower respiratory tract infection, non-tuberculous mycobacterial pneumonia). We then summarized individual study estimates into two random-effect meta-analyses, one including randomized controlled trials (RCTs) and another one including observational studies (OBS).
Results: There were total of 12 studies, 7 RCTs including total of 10,585 and 5 OBS including total of 44,127 participants. There was no heterogeneity in RCTs and summarized estimated effect of ICS was protective of pneumonia; OR 0.75 (0.57-0.99. p=0.05). On the contrary, OBS showed moderate heterogeneity (I2 =48%) with resulting summed OR of 1.94 (1.42-2.65, p<0.0001), suggesting increased risk of pneumonia with
use of ICS in asthma patients. However, OBS had lower grade of confidence compared to RCTs. Conclusions: ICS may carry protective effect or at the very least do not have increased risk of incident pneumonia in patients with asthma, based on our meta-analysis of available RCTs. While observational studies suggested higher risk of pneumonia in similar patients, the observed heterogeneity and inherent methodological limitations conferred lower grade of confidence in these studies.
Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic.
Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35–1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39–2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia -case-fatality: RR 0.91; 95% CI 0.52–1.59, p = 0.74; and OR 0.72; 95% CI 0.59–0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85–1.05, p=0.31; and OR 0.79; 95% CI 0.65–0.97, p=0.02, respectively.
Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.
Material and methods. Retrospective cohort study of adult patients from Olmsted County, Minnesota admitted to the hospital with at least one predisposing condition for ARDS from 2001-2008. The association with pre-hospital use of inhaled corticosteroids and inhaled beta agonists was evaluated using univariate and multivariate analyses. Primary outcome was ARDS and secondary outcome was hospital mortality.
Results. Out of 2429 hospitalized adult patients with at least one risk factor for ARDS, 10.5% of those taking and 14% of those not taking inhaled corticosteroids developed ARDS (OR 0.72; 0.53-0.97; p<0.03). Inhaled beta agonists showed similar unadjusted protective effect; 9.7% of users and 14.4% of non-users developed ARDS (OR 0.64; 0.48-0.86; p=0.003). After adjusting for risk factors, comorbidities and severity of illness in the multiple logistic regression model, use of inhaled beta agonists, but not inhaled corticosteroids, remained independently associated with decreased risk of ARDS (OR 0.48; 0.31-0.72; p<0.001 versus 0.87; 0.57-1.29; p=0.49). The estimated protective effects were more pronounced among patients with pneumonia compared to those without pneumonia.
Conclusion. Prehospital use of inhaled beta agonists but not inhaled corticosteroids was significantly associated with decreased incidence of ARDS among hospitalized patients at risk, once adjusted for baseline characteristics, predisposing and comorbid conditions, as well as severity of illness.
Methods: We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies.
Results: Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0.57to 0.95, p=0.02. On the contrary, observational studies showed summed odds ratio of 1.97; 95% CI 1.87to 2.07, p<0.0001, I²=0%, suggesting increased risk of pneumonia with use of inhaled corticosteroids in asthma patients.
Conclusions: Inhaled corticosteroids are associated with decreased risk of incident pneumonia in patients with asthma based on meta-analysis of available randomized trials. Although observational studies in similar patients suggested higher risk of pneumonia, the inherent methodological limitations confer lower grade of confidence in these studies.
Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO2/FiO2. The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death.
Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO2/FiO2 values. Median SpO2/FiO2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO2/FiO2 and ARDS (P ≤ .001). The SpO2/FiO2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO2/FiO2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO2/FiO2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO2/FiO2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively.
Conclusions: The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.
pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma.
Patients and Methods: A multicentered prospective cohort of patients admitted to the hospital from
March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory
distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among
patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was
determined in a multiple logistic regression model.
Results: Of the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia
requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs
vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P<.001). After adjusting in the
logistic regression model, prehospital ICS use was not significantly associated with pneumonia in the
whole cohort (OR, 1.20; 95% CI, 0.93-1.53; P¼.162), among the subset of 589 patients with COPD (OR,
1.40; 95% CI, 0.95-2.09; P¼.093), among the 440 patients with asthma (OR, 1.07; 95% CI, 0.61-1.87;
P¼.81), nor among the remaining 4629 patients without COPD or asthma (OR, 1.32; 95% CI, 0.88-1.97;
P¼.179).
Conclusion: When adjusted for multiple confounding variables, ICS use was not substantially associated
with an increased risk for pneumonia requiring admission in our cohort.
Objective: To develop and validate a computable phenotype to identify aspiration in hospitalized patients. Hypothesis: The automated electronic search algorithm will feasible, reliable and it outperform ICD-9 code-based search for aspiration detection.
Methods: The study cohort consisted of 256,333 (older than 18 years and with prior research authorization) patients hospitalized at Mayo Clinic in Rochester, MN between January 1, 2006 and December 31, 2014. We randomly assigned 100 patients for a derivation cohort, where several iterations of a free-text electronic search (computable phenotype) were performed. Subsequently, the iterated automated search algorithm was validated on an independent cohort of 100 patients. The sensitivity and specificity of the automated digital algorithm were compared to the International Classification of Diseases-9 (ICD-9) codes for aspiration, and manual chart review served as a reference.
Results: In the derivation cohort, computable phenotype achieved sensitivity and specificity of 100% and 97.1%, while ICD-9 code-based search achieved sensitivity and specificity of 83.9% and 84.1%, respectively. In the validation cohort, computable phenotype achieved sensitivity and specificity of 100% and 95%, while ICD-9 code-based search achieved sensitivity and specificity 87.5% and 93.3%, respectively.
Conclusions: A computable phenotype for nosocomial aspiration in the form of automated electronic search is feasible, reliable and it outperforms ICD-9 code-based search for aspiration detection.
METHODS: This was a double-blind, multicenter, randomized clinical trial of adults admitted through the emergency department at high-risk for ARDS (Lung Injury Prediction Score ≥ 4 and acute hypoxemia). Patients received combined aerosolized budesonide (0.5 mg) and formoterol (2 mg) vs. placebo (normal saline) twice daily for 5 days. The primary outcome was change in oxygen saturation to fraction of inspired oxygen (S/F) ratio from baseline to day 5, analyzed as both a longitudinal continuous variable by mixed effects model and a trichotomous variable (> 20% decrease, no change, or >20% increase). Secondary outcomes included rate of progression to ARDS, ICU and hospital length of stay, and need for invasive mechanical ventilation.
RESULTS: We enrolled 59 patients between September 2013 and June 2015. Patients in the treatment group were older (70±15 vs. 57±13) but less likely to have shock (10% vs. 47%) at enrollment. Median time from emergency department presentation to first study drug was < 9 hours. The longitudinal increase in S/F ratio over the treatment period was greater in the treatment group (p < 0.01) and independent of age and shock, although the absolute change in S/F from baseline was not significant (p=0.20). S/F ratio as a trichotomous variable improved significantly in the treatment group (p=0.01), in which no patient had a decline in S/F ratio. Also, ARDS developed in 7 placebo patients and no treated patients. Placebo patients were more likely to need ICU admission and mechanical ventilation, and longer ICU and hospital lengths of stay.
CONCLUSIONS: This trial establishes the feasibility of inhaled budesonide and formoterol in patients at high-risk for ARDS. Treated patients demonstrated improved oxygenation, lower rates of acute respiratory failure and ARDS, and a shorter hospital length of stay. This is the first prevention trial to suggest efficacy of the intervention for prevention/amelioration of ARDS.
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM
PURPOSE: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT.
METHODS: Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period.
RESULTS: There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation.
CONCLUSIONS: There is a room for improvement in rates of SSRT activations. Utilization of CCS was related to the clinical severity of SS/S, therefore timely and appropriate care could be delayed when SSRT is not timely activated. Despite this, systematic approach to early recognition and management of SS/S patients with SSRT improved the compliance with standard care measures and overall mortality.
CLINICAL IMPLICATIONS: Implementation of automated electronic alerts followed by systematic assessment and early intervention will improve compliance with the standard of care measures and outcomes of patients with severe sepsis and septic shock.
DISCLOSURE: The following authors have nothing to disclose: Pablo Moreno Franco, Vikas Bansal, Muhammad Asif Mangi, Emir Festic
No Product/Research Disclosure Information
Animal studies demonstrate sleep disturbance can negatively affect host immunologic defenses and lead to bacteremia and death. However, whether obstructive sleep apnea (OSA) could impact the incidence and outcomes of sepsis in humans is unknown. We planned a pilot prospective observational study to explore whether OSA might affect sepsis severity and sepsis related outcomes.
Methods:
We identified 74 subjects with sepsis admitted to a tertiary academic center (September 2013 to March 2014).Subjects were excluded if patients had an otherwise terminal illness or received palliative care. We analyzed for whether clinically documented OSA would influence sepsis severity and related outcomes, including the need for mechanical ventilation (MV), development of acute respiratory distress syndrome (ARDS), and hospital mortality. Both univariate as well as multivariate analyses were performed.
Results:
The mean age and standard deviation (+/SD) was 68 years +/17;and 59% were male. In all, 47% met criteria for severe sepsis (evidence of organ dysfunction or lactic acidosis) and 47% for septic shock (volume refractory requiring pressors) ;with a mean APACHE IV of 28 +/5.9. OSA was present in 12%.In univariate analyses, OSA was significantly associated with body mass index (BMI), but not with sex, age, APACHEIV, sepsis severity, need for MV,ICU admission, ARDS, length of stay, or hospital mortality. In multivariate analyses, OSA was not independently predictive of sepsis severity or related outcomes, even after adjusting for age, sex, race/ethnicity, BMI, APACHE IV score. Further exploratory analysis of subjects with "untreated" OSA was limited by the unexpectedly high adherence (78%) of OSA patients to nocturnal noninvasive positive pressure ventilation prehospital.
Conclusions:
In this pilot observational study, we found no significant effect of OSA on sepsis severity or sepsis related outcomes, including ARDS and death. This may be confounded by a high treatment adherence rate and limited sample size. Future investigations exploring any potential link between OSA and sepsis should consider OSA severity and treatment adherence
Scoring systems in ICU were introduced almost 30 years ago with the goal of using physiologic data available at ICU admission to predict individual patient outcomes. Later, the Emergency Medicine developed scoring systems for triage ED patient. However, there is limited experience with scoring systems in the ED. Therefore, we plan to perform a systematic review on this. We hypothesized that the scoring systems used in ED would have a low ability to assess severity in critically ill patient at admission.
Methods:
We conducted an extensive literature search using PubMed, Medline, EMBASE and the Cochrane Library, according to the PRISMA guidelines, on scoring systems used to assess severity in patients at admission. The primary endpoints were hospital mortality. The ability to identify patients at risk (discriminatory power) and agreement between observed and predicted outcome (calibration) along with the method of derivation and validation (application on a new cohort) were extracted.
Results:
We identified 1,871 articles. Out of them 16 were included. Studies derived for only a single or few diagnoses were excluded.11 systems used vital signs as variables,2 used vital signs and blood test and 2 relied on blood tests.15 systems derived using regression analysis.7 included patients admitted to MAU,7 in ED,1 included patient transported to hospital by helicopter and 1 included patient who activated EMS. Discriminatory power was specified for 14 of the scoring systems and was acceptable or better in 10 of these. The calibration was only specified for 6 scoring systems. In none of these studies impact analysis or interobserver reliability were analyzed.
Conclusions:
None of the 16 scoring systems are perfect, all have some flaws.Both the HOTEL and the SCS score were good in both discriminatory power and calibration but not externally validated. The REMS showed an acceptable discriminatory power but poor calibration. More research is needed especially external validation and impact analyses before the use of scoring systems can be fully implemented to the risk assessment of critically ill patients in ED admission.
Methods: We retrospectively identified consecutive patients who were referred for evaluation of a chronic cough at our specialist Chronic Cough Clinic, Mayo Clinic, Florida, and who had undergone ambulatory 24-h impedance/pH recording and completed the validated Cough-Specific Quality of Life Questionnaire (CSQLQ) (5).
Results: 79 patients had undergone 24-h impedance/pH (aged 63 ± 12 years (mean ± SD); 56 (71%) female) and completed the CSQLQ, of whom 25 (32%) were on acid suppressants. The mean total number of reflux events was 53 ± 25, with 13 (29%) patients having evidence of pathological reflux. The mean numbers of acid and nonacid reflux events were 28 ± 25 and 25 ± 19, respectively. A weak correlation was found between cough specific QoL and the number of reflux events (r = 0.20,p = 0.073), which appeared to be driven by a relationship between cough-specific QoL and the number of non-acid reflux (r = 0.29, p = 0.009) rather than acid reflux (r = 0.016, p = 0.892) events. There was no correlation between cough-specific QoL and the percentage of time pH <4 (r = 0.107, p = 0.352). In a multivariate analysis including age, sex, use of acid suppressants during the test, percentage of time pH <4 in the proximal/distal esophagus, together with the total number of acid and non-acid events; only sex and the number of non-acid reflux events were significantly predictive of the subject’s cough-specific QoL. On average, an increase in non-acid reflux events of 10 per 24-h worsened the cough-specific QoL 2.1 points.
Conclusion: Cough-specific quality of life worsens with increasing numbers of reflux events, particularly nonacid reflux events but not the percentage of time pH <4. Further studies are required using acoustic cough recording to determine whether this association between the number of reflux events and cough-specific QoL, is related to a worsening in the actual cough frequency.
Refs: (1) Arch Intern Med 1998; 581657, (2) Thorax 2006; 6111, (3) Thorax 2007; 62:329, (4) Gastroenterology 2010;139:754, (5) Chest 2002;121:1123.
Inhaled Corticosteroids (ICS) are currently recommended for use in patients with severe COPD and those with frequent exacerbations. The
TORCH study and several other trials have shown increased incidence of pneumonia among patients using ICS. These trials have relied on
unadjusted adverse event-reports of pneumonia frequently without any radiologic confirmation. Despite increased incidence of
pneumonia, they have not demonstrated increased pneumonia-associated or overall mortality. This meta-analysis was done to affirm the
increased risk of pneumonia and then better define whether ICS use affected unadjusted pneumonia-associated and overall mortality.
METHODS
Study designs consisting of randomized controlled trials or observational studies (cohort or case control) involving COPD patients, using
ICS and a comparison arm lacking ICS and reporting the outcome of interest were considered for enrollment. We searched for potentially
relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994
to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic
review and meta-analyses of included RCTs and observational studies on the topic.
RESULTS
We identified 38 studies, 29 randomized controlled and 9 observational. The estimated unadjusted risk of pneumonia was increased in
randomized trials: RR 1.61; 95% CI 1.35-1.93, I =37%, p<0.001; as well as in observational studies: OR 1.89; 95% CI 1.39-2.59, I =99%, 2 2
p<0.001. Six estimable randomized trials showed no difference in pneumonia-associated mortality, RR 0.91; 95% CI 0.52-1.59, p=0.74, I2
=0% whereas 7 estimable observational studies showed a decrease in pneumonia associated mortality, OR 0.72; 95% CI 0.59-0.88, I =74%, 2
p=0.001, Similarly, 29 estimable randomized trials estimated no difference in unadjusted risk of overall mortality, RR 0.95; 95% CI 0.85-1.05,
I = 0%, p=0.31, whereas 6 estimable observational studies found a decrease in overall mortality in the ICS group, OR 0.79; 95% CI 2
0.65-0.97, I =83%, p=0.02. 2
DISCUSSION
Despite significantly increased unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia-associated and
overall mortality was found not to be different in randomized controlled trials. However, observational studies showed significantly
decreased unadjusted risk of pneumonia-associated and overall mortality, although there was high heterogeneity among these studies.
Previous observations have indicated a combined immunosuppressive effect and potent anti-inflammatory effect of ICS. ICS predisposes
COPD patients to an increased risk of incident pneumonia but conversely appears to have a counterbalancing beneficial effect on
mortality resulting in no net change, or possibly a slight improvement in mortality.
Methods: We performed a comprehensive literature search from January 1, 1993, through March 31, 2014, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries (GlaxoSmithKline and AstraZeneca) with the clinical trial filters using multiple search terms with no language restrictions. We included all studies that compared patients 14 years of age and older on ICS and not on ICS relative to the risk of incident pneumonia (community
acquired, lower respiratory tract infection, non-tuberculous mycobacterial pneumonia). We then summarized individual study estimates into two random-effect meta-analyses, one including randomized controlled trials (RCTs) and another one including observational studies (OBS).
Results: There were total of 12 studies, 7 RCTs including total of 10,585 and 5 OBS including total of 44,127 participants. There was no heterogeneity in RCTs and summarized estimated effect of ICS was protective of pneumonia; OR 0.75 (0.57-0.99. p=0.05). On the contrary, OBS showed moderate heterogeneity (I2 =48%) with resulting summed OR of 1.94 (1.42-2.65, p<0.0001), suggesting increased risk of pneumonia with
use of ICS in asthma patients. However, OBS had lower grade of confidence compared to RCTs. Conclusions: ICS may carry protective effect or at the very least do not have increased risk of incident pneumonia in patients with asthma, based on our meta-analysis of available RCTs. While observational studies suggested higher risk of pneumonia in similar patients, the observed heterogeneity and inherent methodological limitations conferred lower grade of confidence in these studies.
Methods: MEDLINE, EMBASE, SCOPUS and web of science databases were searched for the articles published from July 1983 to June 2013 by using following terms or their combination - Sepsis Grading, Sepsis Severity score, APACHE, SAPS, OSF, MODS, SOFA, MEDS, MPM, REM score and PIRO staging system. This yielded 1999 articles. Retrospective, prospective, comparative studies and RCTs involving adult patients in ED or ICU with diagnosis of severe sepsis/septic shock were included for further review, there by excluding 1003 articles. Of the remaining 996 articles, those using only non-sepsis specific severity scores like APACHE, SOFA and SAPS were further excluded. Remaining 226 articles were then reviewed. Those using single mortality predictors in sepsis like procalcitonin, lactic acid, cardiac index, gene polymorphisms, lipid levels, vitamin D and other biomarkers (interleukins, cardiac markers) were excluded. All the articles with scores using invasive monitoring techniques and evaluating sepsis severity in specific population were also excluded, leaving 6 articles for final review.
Results: All 6 articles used PIRO, MEDS, NEWS, mottling score, MSOF or MEWS as the primary score for determining sepsis severity with primary end-point being long-term mortality. Four (67%) articles described retrospectively conducted studies. Range of total number of included patients was 60–2628. Median (IQR) age of included subjects was 65.5 (61–72). One study (17%) used only physical examination, 2 studies (33%) used only vitals and 3 studies (50%) used a combination of both with laboratory data and imaging to determine sepsis severity. All studies were found to be focusing on mortality, rather than predicting sepsis severity.
Conclusions: There is a lack of a sepsis-specific severity score which could predict sepsis severity using combination of vitals, physical examination and basic laboratory data collected during first 6 hours of presentation.
of the population and significantly impairs quality of life; with physical, psychological and
social consequences (1, 2). Moreover, the frequency of coughing episodes directly correlates
with quality of life (3). Episodes of coughing have been shown to temporally associate with
gastro-esophageal reflux events, irrespective of the presence of other concomitant conditions
contributing to cough, such as nasal disease and/or asthma (4). How reflux in cough relates
to cough-specific quality of life remains unclear. Methods: We retrospectively identified
consecutive patients who were referred for evaluation of a chronic cough at our specialist
Chronic Cough Clinic, Mayo Clinic, Jacksonville, and who had undergone ambulatory 24-
hr impedance/pH recording and completed the validated Cough-Specific Quality of Life
Questionnaire (CSQLQ) (5). Results: Seventy nine patients had undergone 24-hr impedance/
pH [aged 63 +12 yrs (mean + SD); 56 (71%) female] and completed the CSQLQ, of whom
25 (32%) were on acid-suppressant medications. The mean total number of reflux events
was 53 + 25, with 13 (29%) patients having evidence of pathologic reflux. The mean number
of acid and non-acid reflux events were 28 + 25 and 25 + 19, respectively. A weak correlation
was found between cough-specific quality of life (QoL) and the number of reflux events (r=
0.20, p=0.073, Pearson's correlation), which appeared to be driven by a relationship between
cough-specific QoL and the number of non-acid reflux (r=0.29, p=0.009) rather than acid
reflux (r=-0.016, p=0.892) events. There was no correlation between cough-specific QoL
and the percentage of time pH<4 (r=0.107, p=0.352). In a multivariate analysis including
age, sex, use of acid suppressants during the test, percentage of time pH<4 in the proximal/
distal esophagus, together with the total number of acid and non-acid events; only sex and
the number of non-acid reflux events were significantly predictive of the subject's coughspecific
QoL. On average, an increase in non-acid reflux events of 10 per 24-hrs worsened
the cough-specific QoL 2.1 points. Conclusion: Cough-specific quality of life worsens with
increased numbers of reflux events, particularly non-acid reflux events but not the percentage
of time pH<4. Further studies are required using acoustic cough recording to determine
whether this association between the number of reflux events and cough-specific QOL, is
related to a worsening in the actual cough frequency. Refs: (1)French et al. Arch Intern Med
1998; 158: 1657-61; (2) Morice et al. Thorax 2006; 61(suppl 1): 11-24; (3) Decalmer et
al. Thorax 2007; 62: 329-334; (4) Smith et al. Gastroenterology 2010; 139: 754-762; (5)
French et al. Chest 2002; 121: 1123-1131.
Mo1101 Cough-Specific Quality of Life: Relationship to Gastroesophageal Reflux in Patients With Chronic Cough. Available from: https://www.researchgate.net/publication/275960426_Mo1101_Cough-Specific_Quality_of_Life_Relationship_to_Gastroesophageal_Reflux_in_Patients_With_Chronic_Cough [accessed May 7, 2015].