Long-Term Outcomes in Critically Ill Septic Patients Who Survived Cardiopulmonary Resuscitation.

OBJECTIVE: To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale. DESIGN: Retrospective and observational cohort study. SETTING: Data were extracted from Taiwan's National Health Insurance Research Database. PATIENTS: A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay. CONCLUSION: The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge.

Association of postdischarge rehabilitation with mortality in intensive care unit survivors of sepsis.

RATIONALE: Intensive care unit (ICU)-acquired weakness is a common issue for sepsis survivors that is characterized by impaired muscle strength and causes functional disability. Although inpatient rehabilitation has not been found to reduce in-hospital mortality, the impact of postdischarge rehabilitation on sepsis survivors is uncertain. OBJECTIVES: To investigate the benefit of postdischarge rehabilitation to long-term mortality in sepsis survivors. METHODS: We conducted a nationwide, population-based, high-dimensional propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. The rehabilitation cohort comprised 15,535 ICU patients who survived sepsis and received rehabilitation within 3 months after discharge between 2000 and 2010. The control cohort consisted of 15,535 high-dimensional propensity score-matched subjects who did not receive rehabilitation within 3 months after discharge. The endpoint was mortality during the 10-year follow-up period. MEASUREMENTS AND MAIN RESULTS: Compared with the control cohort, the rehabilitation cohort had a significantly lower risk of 10-year mortality (adjusted hazard ratio, 0.94; 95% confidence interval, 0.92-0.97; P < 0.001), with an absolute risk reduction of 1.4 per 100 person-years. The frequency of rehabilitation was inversely associated with 10-year mortality (≥3 vs. 1 course: adjusted hazard ratio, 0.82; P < 0.001). Compared with the control cohort, improved survival was observed in the rehabilitation cohort among ill patients who had more comorbidities, required more prolonged mechanical ventilation, and had longer ICU or hospital stays, but not among those with the opposite conditions (i.e., less ill patients). CONCLUSIONS: Postdischarge rehabilitation may be associated with a reduced risk of 10-year mortality in the subset of patients with particularly long ICU courses.

Serum tumor markers as predictors for survival in advanced non-small cell lung cancer patients treated with gefitinib.

BACKGROUND: Though the imaging-based response (IBR) is the most frequently used index of the therapeutic effect in cancer patients, an index based on serum tumor markers might prove to be useful, especially in patients without measurable tumors. METHODS: Paired pre- and post-treatment serum tumor markers (CEA, CA-125, and CA-199) were measured in 89 of 100 registered non-small cell lung cancer (NSCLC) patients who received gefitinib. Correlation and agreement analyses between the IBR at the 8th week and the tumor marker response (TMR) at the 4th or the 8th week were performed in patients with measurable lesions (n=68). Analysis of survival in relation to TMR was performed in all patients and in patients with no measurable lesions (n=21). RESULTS: IBR was closely correlated with individual tumor marker responses and the response of all 3 markers combined at 4 weeks (P values ranged from <0.001 to 0.002). The agreements were also significant (P values ranged from 0.001 to 0.004). In the whole group, 4-week TMR was predictive for progression-free survival (P values ranged from <0.0001 to 0.0086). In patients without measurable lesions, differences in progression-free survival and overall survival were closely correlated with the 4-week CA-125 response, CA-199 response, and TMR(overall) (P values ranged from 0.0002 to 0.0399). However, the correlation between the 8-week TMR and either IBR or survival was not significant. CONCLUSIONS: In gefitinib-treated NSCLC patients, correlation was good between 4-week TMR and IBR. Four-week TMR was predictive for survival. TMR may serve as a tool for assessing the gefitinib response in patients without measurable lesions.

Association of weekend effect with early mortality in severe sepsis patients over time.

BACKGROUND: The aim of this study is to investigate the "weekend effect" and early mortality of patients with severe sepsis. METHODS: Using the Taiwanese National Healthcare Insurance Research Database, all patients who were hospitalized for the first time with an episode of severe sepsis between January 2000 and December 2011 were identified and the short-term mortality of patients admitted on weekdays was compared to those admitted on weekends. The primary endpoint was 7-day mortality. The secondary endpoints were 14 and 28-day mortality. RESULTS: A total of 398,043 patients were identified to have had the diagnosis of severe sepsis. Compared with patients admitted on weekends, patients admitted on weekdays had a lower 7-day mortality rate (adjusted odds ratio [OR] 0.89, 95% confidential interval [CI] 0.87-0.91), 14-day mortality rate (adjusted OR 0.92, 95% CI 0.90-0.93), and 28-day mortality rate (adjusted OR 0.97, 95% CI 0.95-0.98). This "weekend effect" was maintained every year throughout the 11-year study period. CONCLUSIONS: Patients with severe sepsis are more likely to die in the hospital if they were admitted on weekends than if they were admitted on weekdays.

Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis.

BACKGROUND: Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis. METHODS: This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups. RESULTS: A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910-0.953), 180-day (HR 0.930, 95% CI 0.914-0.946), 365-day (HR 0.944, 95% CI 0.929-0.960) and overall mortality (HR 0.965, 95% CI 0.952-0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873-0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949-0.997). CONCLUSIONS: Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.

Interstitial pneumonia during gefitinib treatment of non-small-cell lung cancer.

Gefitinib, an orally active, selective inhibitor of epidermal growth factor-receptor tyrosine kinase, is an effective treatment for patients with advanced non-small-cell lung cancer (NSCLC). Most drug-related adverse events are mild to moderate; however, some patients may develop acute interstitial pneumonia that is sometimes fatal. In a prospective study of gefitinib in 76 patients with advanced NSCLC, 69 patients were evaluable for toxicity, and 4 cases (5.8%) of gefitinib-related interstitial pneumonia were diagnosed: 1 occurred in the second week; 2 in the second month; and 1 during the fourth month of treatment. When interstitial pneumonia occurred, the patients had stable disease (n = 2), a partial response (n = 1), or progressive disease (n = 1). All 4 patients recovered when gefitinib treatment was stopped and glucocorticosteroid therapy was started; no deaths related to gefitinib therapy were noted in this series. While treating NSCLC patients with gefitinib, it is important to carefully evaluate any new-onset respiratory symptoms and promptly arrange radiographic examinations, and to stop gefitinib treatment and begin glucocorticosteroid therapy whenever pulmonary toxicity is highly suspected.

Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study.

BACKGROUND: Antiplatelet agents are widely used for cardiovascular disea ses, but their pleiotropic effects in sepsis are controversial. OBJECTIVE: To investigate the association between antiplatelet agents and the survival benefit for sepsis patients. DESIGN: A nationwide population-based cohort and nested case-control study. SETTING: Taiwan National Health Insurance database. PARTICIPANTS: All patients (age ≥18 years) who were hospitalized for sepsis between January 2000 and December 2010. MEASUREMENTS: Conditional logistic regression was used to adjust for confounding. Adjusted odd ratios (ORs) were used to compare the mortality rate due to sepsis in antiplatelet drug users and nonusers. RESULTS: Of 683,421 included patients, 229,792 (33.6 %) patients died during hospitalization for sepsis, and the rest (64.4 %) survived to discharge. Use of antiplatelet agents before admission was associated with a lower risk of mortality in sepsis patients (aOR 0.82, 95 % confidence interval [CI] 0.81-0.83, P < 0.001). By using another case-control study design, the beneficial effect was more significant in current users (aOR 0.78, 95 % CI 0.76-0.79) than in recent users (aOR 0.88, 95 % CI 0.85-0.91), but was not significant in past users (aOR 1.00, 95 % CI 0.98-1.02). LIMITATIONS: Observational study. CONCLUSIONS: Prior use of antiplatelet agents was associated with a survival benefit in sepsis patients.

Risk of tuberculosis among healthcare workers in an intermediate-burden country: a nationwide population study.

OBJECTIVE: The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. METHODS: A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000-2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. RESULTS: The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs. 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08-2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02-2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37-4.72) compared to the matched cohort. CONCLUSIONS: HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.