Statins and outcomes in patients with pneumonia: not only healthy user bias.
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Bias↗
Biomedical subjects
Eric M Mortensen
Publications and source records attributed to Eric M Mortensen.
Reply to Bodi et al.
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Anti-Bacterial Agents↗
Impact of guideline-concordant empiric antibiotic therapy in community-acquired pneumonia.
PURPOSE: We evaluated the impact of guideline-concordant empiric antibiotic therapy on time to clinical stability, time to switch therapy, length of hospital stay, and mortality among patients with community-acquired pneumonia. METHODS: This is a retrospective cohort study of all adult community-acquired pneumonia patients managed at 5 community hospitals from November 1, 1999 to April 30, 2000. Patients were stratified into guideline-concordant and discordant groups as defined by the 2001 American Thoracic Society and the 2003 Infectious Diseases Society of America guidelines. Time to clinical stability, time to switch therapy, length of hospital stay, and in-hospital mortality were evaluated in per-protocol and intention-to-treat stepwise regression models that included the outcome as the dependent variable, guideline-concordant antibiotic therapy as the independent variable, and Pneumonia Severity Index score as a covariate. RESULTS: Of the 631 evaluable patients, 357 (57%) received guideline-concordant empiric antibiotic therapy. Groups were similar with respect to age, sex, comorbidities, severity of illness, and processes of care. Guideline-concordant antibiotic therapy was associated with a significant decrease in time to switch therapy (P < or =.01), length of hospital stay (P < or =.01), and in-hospital mortality (P=.04) for both per-protocol and intention-to-treat analyses. In addition, guideline-concordant antibiotic therapy was associated with a significant decrease in time to clinical stability for intention-to-treat analysis only (P=.03). CONCLUSIONS: Among hospitalized community-acquired patients, guideline-concordant antibiotic therapy is associated with improved in-hospital survival and shorter time to clinical stability, time to switch therapy, and length of hospital stay.
Aged↗
Antibiotic therapy and 48-hour mortality for patients with pneumonia.
PURPOSE: Although numerous articles have demonstrated that recommended empiric antimicrobial regimens are associated with decreased mortality at 30 days, there is controversy over whether appropriate antibiotic selection has a beneficial impact on mortality within the first 48 to 96 hours after admission. Our aim was to determine whether the use of guideline-concordant antibiotic therapy is associated with decreased mortality within the first 48 hours after admission for patients with pneumonia. METHODS: A retrospective cohort study was conducted at two tertiary teaching hospitals in San Antonio, Texas. A propensity score was used to balance the covariates associated with the use of guideline-concordant antimicrobial therapy. A multivariable logistic regression model was used to assess the association between mortality within 48 hours and the use of guideline-concordant antibiotic therapy, after adjusting for potential confounders including the propensity score. RESULTS: Information was obtained on 787 patients with community-acquired pneumonia. The median age was 60 years, 79% were male, and 20% were initially admitted to the intensive care unit. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. Within the first 48 hours, 20 patients died. After adjustment for potential confounders, the use of guideline-concordant antimicrobial therapy (odds ratio 0.37, 95% confidence interval, 0.14-0.95) was significantly associated with decreased mortality at 48 hours after admission. CONCLUSION: Using initial empiric guideline-concordant antimicrobial therapy is associated with decreased mortality at 48 hours. Further research needs to investigate methods to ensure that patients with community-acquired pneumonia are treated with appropriate antimicrobial therapies.
Adult↗
The impact of empiric antimicrobial therapy with a β-lactam and fluoroquinolone on mortality for patients hospitalized with severe pneumonia.
INTRODUCTION: National clinical practice guidelines have recommended specific empiric antimicrobial regimes for patients with severe community-acquired pneumonia. However, evidence confirming improved mortality with many of these regimes is lacking. Our aim was to determine the association between the empiric use of a β-lactam with fluoroquinolone, compared with other recommended antimicrobial therapies, and mortality in patients hospitalized with severe community-acquired pneumonia. METHODS: A retrospective observational study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of community-acquired pneumonia and had a chest X-ray and a discharge ICD-9 diagnosis consistent with this. Subjects were excluded if they received 'comfort measures only' during the admission, had been transferred from another acute care hospital, did not meet criteria for severe pneumonia, or were treated with non-guideline-concordant antibiotics. A multivariable logistic regression model was used to assess the association between 30-day mortality and the use of a β-lactam antibiotic with a fluoroquinolone compared with other guideline-concordant therapies, after adjustment for potential confounders including a propensity score. RESULTS: Data were abstracted on 172 subjects at the two hospitals. The mean age was 63.5 years (SD 15.0). The population was 88% male; 91% were admitted through the emergency department and 62% were admitted to the intensive care unit within the first 24 hours after admission. Mortality was 19.8% at 30 days. After adjustment for potential confounders the use of a β-lactam with a fluoroquinolone (odds ratio 2.71, 95% confidence interval 1.2 to 6.1) was associated with increased mortality. CONCLUSION: The use of initial empiric antimicrobial therapy with a β-lactam and a fluoroquinolone was associated with increased short-term mortality for patients with severe pneumonia in comparison with other guideline-concordant antimicrobial regimes. Further research is needed to determine the range of appropriate empiric antimicrobial therapies for patients with severe community-acquired pneumonia.
Aged↗
Cdc28-dependent regulation of the Cdc5/Polo kinase.
Polo kinase is activated as cells enter mitosis and plays a central role in coordinating diverse mitotic events, yet the mechanisms leading to activation of Polo kinase are poorly understood . Work in Xenopus meiotic cell cycles has suggested that Polo kinase functions in a pathway that helps trigger activation of Cdk1 . However, studies in other organisms have suggested that activation of Polo kinase is dependent upon Cdk1 and therefore occurs downstream of Cdk1 activation . In this study, we have investigated the role of Cdk1 in the activation of budding yeast Polo kinase. The budding yeast homologs of Cdk1 and Polo kinase are referred to as Cdc28 and Cdc5. We show that signaling from Cdc28 is required to maintain Cdc5 activity in vivo. Furthermore, purified Cdc28 associated with the mitotic cyclin Clb2 is sufficient to activate purified Cdc5 in vitro. A single Cdc28 consensus phosphorylation site found at threonine 242 in the activation loop segment of Cdc5 is required for Cdc5 function in vivo and for kinase activity in vitro, whereas four other Cdc28 consensus sites are dispensable. Analysis of Cdc5 phosphorylation by mass spectrometry indicates that threonine 242 is phosphorylated in vivo. These results suggest that Cdc28 activates Cdc5 via phosphorylation of threonine 242.
Amino Acid Sequence↗
Steroid infusion for severe pneumonia: not so fast...
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Community-Acquired Infections↗
The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia.
BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22-0.89) was significantly associated with 30-day mortality. CONCLUSION: Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.
Adult↗
The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia.
BACKGROUND: Recent studies suggest that HMG-CoA reductase inhibitors ("statins") may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of statins on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk based on the pneumonia severity index. In the multivariable regression analysis, after adjusting for potential confounders including a propensity score, the use of statins at presentation (odds ratio 0.36, 95% confidence interval 0.14-0.92) was associated with decreased 30-day mortality. DISCUSSION: Prior outpatient statin use was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.
Cohort Studies↗
Effects of guideline-concordant antimicrobial therapy on mortality among patients with community-acquired pneumonia.
PURPOSE: National practice guidelines have recommended specific initial empiric antimicrobial regimens for patients with community-acquired pneumonia. Our aim was to determine the association between the use of guideline-concordant antimicrobial therapy and 30-day mortality in patients with pneumonia. METHODS: We conducted a retrospective cohort study at two tertiary teaching hospitals. Eligible patients were admitted with a diagnosis of community-acquired pneumonia, had a chest radiograph consistent with pneumonia, and had a discharge diagnosis of pneumonia. All eligible patients were identified and a random sample was abstracted. We determined whether the use of guideline-concordant antibiotics was associated with 30-day mortality in an analysis that adjusted for potential confounders using propensity scores. RESULTS: Information was obtained on 420 patients with pneumonia. The mean (+/- SD) age was 63 +/- 16 years, 355 were men, and 82 patients were initially admitted to the intensive care unit. At 30 days after presentation, 41 patients (9.8%) had died: 21 of 97 (21.7%) in the non-guideline-concordant group and 20 of 323 (6.2%) in the guideline-concordant group. Antibiotics were concordant with national guidelines in 323 patients. In the regression analysis, after adjustment for the propensity score, failure to comply with antimicrobial therapy guidelines was associated with increased 30-day mortality (odds ratio = 5.7; 95% confidence interval: 2.0 to 16.0). CONCLUSION: Receipt of antimicrobial regimens concordant with national published guidelines may reduce 30-day mortality among patients hospitalized with pneumonia.
Aged↗
Racial variations in processes of care for patients with community-acquired pneumonia.
BACKGROUND: Patients hospitalized with community acquired pneumonia (CAP) have a substantial risk of death, but there is evidence that adherence to certain processes of care, including antibiotic administration within 8 hours, can decrease this risk. Although national mortality data shows blacks have a substantially increased odds of death due to pneumonia as compared to whites previous studies of short-term mortality have found decreased mortality for blacks. Therefore we examined pneumonia-related processes of care and short-term mortality in a population of patients hospitalized with CAP. METHODS: We reviewed the records of all identified Medicare beneficiaries hospitalized for pneumonia between 10/1/1998 and 9/30/1999 at one of 101 Pennsylvania hospitals, and randomly selected 60 patients at each hospital for inclusion. We reviewed the medical records to gather process measures of quality, pneumonia severity and demographics. We used Medicare administrative data to identify 30-day mortality. Because only a small proportion of the study population was black, we included all 240 black patients and randomly selected 720 white patients matched on age and gender. We performed a resampling of the white patients 10 times. RESULTS: Males were 43% of the cohort, and the median age was 76 years. After controlling for potential confounders, blacks were less likely to receive antibiotics within 8 hours (odds ratio with 95% confidence interval 0.6, 0.4-0.97), but were as likely as whites to have blood cultures obtained prior to receiving antibiotics (0.7, 0.3-1.5), to have oxygenation assessed within 24 hours of presentation (1.6, 0.9-3.0), and to receive guideline concordant antibiotics (OR 0.9, 0.6-1.7). Black patients had a trend towards decreased 30-day mortality (0.4, 0.2 to 1.0). CONCLUSION: Although blacks were less likely to receive optimal care, our findings are consistent with other studies that suggest better risk-adjusted survival among blacks than among whites. Further study is needed to determine why this is the case.
Black or African American↗
Assessment of mortality after long-term follow-up of patients with community-acquired pneumonia.
Although studies have assessed short-term mortality among patients with community-acquired pneumonia, there is limited data on prognosis and risk factors that affect long-term mortality. The mortality among patients enrolled at 4 sites of the Pneumonia Patient Outcome Research Team cohort study who survived at least 90 days after presentation to the hospital was compared with that among age-matched control subjects. Overall, 1419 of 1555 patients survived for >90 days, with a mean follow-up period of 5.9 years. There was significantly higher long-term mortality among patients with pneumonia than among age-matched controls. Factors significantly associated with long-term mortality were age (stratified by decade), do-not-resuscitate status, poor nutritional status, pleural effusion, glucocorticoid use, nursing home residence, high school graduation level or less, male sex, preexisting comorbid illnesses, and the lack of feverishness. This study demonstrates that there is significantly higher long-term mortality among patients with pneumonia than among age-matched controls and that long-term mortality largely is not affected by acute physiologic derangements.
Adolescent↗
Causes of death for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team cohort study.
BACKGROUND: To our knowledge, no previous study has systematically examined pneumonia-related and pneumonia-unrelated mortality. This study was performed to identify the cause(s) of death and to compare the timing and risk factors associated with pneumonia-related and pneumonia-unrelated mortality. METHODS: For all deaths within 90 days of presentation, a synopsis of all events preceding death was independently reviewed by 2 members of a 5-member review panel (C.M.C., D.E.S., T.J.M., W.N.K., and M.J.F.). The underlying and immediate causes of death and whether pneumonia had a major, a minor, or no apparent role in the death were determined using consensus. Death was defined as pneumonia related if pneumonia was the underlying or immediate cause of death or played a major role in the cause of death. Competing-risk Cox proportional hazards regression models were used to identify baseline characteristics associated with mortality. RESULTS: Patients (944 outpatients and 1343 inpatients) with clinical and radiographic evidence of pneumonia were enrolled, and 208 (9%) died by 90 days. The most frequent immediate causes of death were respiratory failure (38%), cardiac conditions (13%), and infectious conditions (11%); the most frequent underlying causes of death were neurological conditions (29%), malignancies (24%), and cardiac conditions (14%). Mortality was pneumonia related in 110 (53%) of the 208 deaths. Pneumonia-related deaths were 7.7 times more likely to occur within 30 days of presentation compared with pneumonia-unrelated deaths. Factors independently associated with pneumonia-related mortality were hypothermia, altered mental status, elevated serum urea nitrogen level, chronic liver disease, leukopenia, and hypoxemia. Factors independently associated with pneumonia-unrelated mortality were dementia, immunosuppression, active cancer, systolic hypotension, male sex, and multilobar pulmonary infiltrates. Increasing age and evidence of aspiration were independent predictors of both types of mortality. CONCLUSIONS: For patients with community-acquired pneumonia, only half of all deaths are attributable to their acute illness. Differences in the timing of death and risk factors for mortality suggest that future studies of community-acquired pneumonia should differentiate all-cause and pneumonia-related mortality.
Cause of Death↗
Cell cycle-dependent assembly of a Gin4-septin complex.
Gin4, a Nim1-related kinase, is required in budding yeast for localization of the septins and for proper control of daughter cell growth during G2/M. Gin4 becomes hyperphosphorylated when cells enter mitosis, leading to activation of Gin4 kinase activity. In this study, we have used immunoaffinity chromatography to identify proteins that associate with Gin4 during mitosis, with the goal of finding targets of Gin4 kinase activity and proteins that play a role in Gin4 activation. We show that during mitosis Gin4 is assembled into a multiprotein complex that includes Nap1, Bni5, the septins, and at least two molecules of Gin4. The associated Gin4 molecules present in this complex phosphorylate each other, leading to Gin4 hyperphosphorylation. Furthermore, the Shs1 septin present in the complex undergoes Gin4-dependent phosphorylation during mitosis and appears to be a substrate of Gin4 in vitro, suggesting that it is a target of Gin4 kinase activity in vivo. Genetic data support the idea that Shs1 is an important target of Gin4 kinase activity. Association of Gin4 with the septins during mitosis requires Shs1, Nap1, Cla4, Elm1, and the kinase activities of Gin4 and Cdc28. Self-association of Gin4 molecules requires Shs1 but not Cla4 or Nap1. Previous work has suggested that the septins function together as a tight complex, and we found that the majority of the Shs1 in the cell is tightly bound to the other septins Cdc3, Cdc10, Cdc11, and Cdc12. Interestingly, however, Shs1 can bind to Gin4 and induce Gin4 oligomerization under conditions in which the Cdc11 septin does not bind to Gin4, suggesting that Shs1 can function independently of the other septins. Taken together, these findings suggest that highly regulated protein-binding events ensure that the Gin4 kinase is activated only during mitosis and only in association with Shs1, a likely in vivo substrate of Gin4. In addition, these results provide clues to how Gin4 may regulate the localization or function of the septins.
Cell Cycle↗