Enteral omega-3 fatty acid supplementation in adult patients with acute respiratory distress syndrome: a systematic review of randomized controlled trials with meta-analysis and trial sequential analysis

Purpose

Controversy remains as to whether enteral supplementation of ω-3 fatty acids (FA) could improve outcomes in patients with acute respiratory distress syndrome (ARDS). Thus, we did a meta-analysis and aimed to investigate the benefit and harm of enteral ω-3 FA supplementation in adult patients with ARDS.

Methods

Databases including PubMed, Embase, the Cochrane Register of Controlled Trials, and Google Scholar were searched to find relevant articles. Randomized controlled trials (RCTs) comparing enteral ω-3 FA supplementation with a control or placebo intervention in adult patients with ARDS were included. The primary outcome was all-cause 28-day mortality. We used the Cochrane Collaboration methodology.

Results

Seven RCTs with 955 adult patients qualified for inclusion, and all the selected trials were considered as at high risk of bias. The use of enteral ω-3 FA did not significantly reduce all-cause 28-day mortality [relative risk (RR), 0.90; 95 % confidence intervals (CI), 0.68–1.18; p = 0.44; I ² = 31 %; random effects]. Trial sequential analysis indicated lack of firm evidence for a 20 % RR reduction in all-cause 28-day mortality. PaO₂/FiO₂ ratio was significantly increased in the ω-3 FA group on day 4 [weighted mean difference (WMD), 45.14; 95 % CI, 16.77–73.51; p = 0.002; I ² = 86 %; random effects] and day 7 (WMD, 33.10; 95 % CI, 1.67–64.52; p = 0.04; I ² = 88 %; random effects). Meta-analysis using a random effects model showed no significant differences in ventilator-free days (VFD) (WMD, 2.47 days; 95 % CI, ?2.85 to 7.79; p = 0.36; I ² = 91 %) or intensive care unit-free days (ICU) (WMD, 2.31 days; 95 % CI, ?2.34 to 6.97; p = 0.33; I ² = 89 %) between the two groups.

Conclusions

Among patients with ARDS, enteral supplementation of ω-3 FA seemed ineffective regarding all-cause 28-day mortality, VFD, and ICU-free days. Routine use of enteral ω-3 FA cannot be recommended based on the available evidence.     

Quality of dying in the ICU: is it worse for patients admitted from the hospital ward compared to those admitted from the emergency department?

Objective

Although most intensive care unit (ICU) admissions originate in the emergency department (ED), a substantial number of admissions arrive from hospital wards. Patients transferred from the hospital ward often share clinical characteristics with those admitted from the ED, but family expectations may differ. An understanding of the impact of ICU admission source on family perceptions of end-of-life care may help improve patient and family outcomes by identifying those at risk for poor outcomes.

Design and setting

This was a cohort study of patients with chronic illness and acute respiratory failure requiring mechanical ventilation who died after admission to an ICU in any of the 14 participating hospitals in the Seattle-Tacoma area between 2003 and 2008 (n = 1,500).

Measurements

Using regression models adjusted for hospital site and patient-, nurse- and family-level characteristics, we examined associations between ICU admission source (hospital ward vs. ED) and (1) family ratings of satisfaction with ICU care; (2) family and nurse ratings of quality of dying; (3) chart-based indicators of palliative care.

Main results

Admission from the hospital ward was associated with lower family ratings of quality of dying [β ?0.90, 95 % confidence interval (CI) ?1.54, ?0.26, p = 0.006] and satisfaction (total score β ?3.97, 95 % CI ?7.89, ?0.05, p = 0.047; satisfaction with care domain score β ?5.40, 95 % CI ?9.44, ?1.36, p = 0.009). Nurses did not report differences in quality of dying. Patients from hospital wards were less likely to have family conferences [odds ratio (OR) 0.68, 95 % CI 0.52, 0.88, p = 0.004] or discussion of prognosis in the first 72 h after ICU admission (OR 0.72, 95 % CI 0.56, 0.91, p = 0.007) but were more likely to receive spiritual care (OR 1.48, 95 % CI 1.14, 1.93, p = 0.003) or have life support withdrawn (OR 1.38, 95 % CI 1.04, 1.82, p = 0.025).

Conclusion

Admission from the hospital ward is associated with family perceptions of a lower quality of dying and less satisfaction with ICU care. Differences in receipt of palliative care suggest that family of patients from the hospital ward receive less communication. Nurse ratings of quality of dying did not significantly differ by ICU admission source, suggesting dissimilarities between family and nurse perspectives. This study identifies a patient population at risk for poor quality palliative and end-of-life care. Future studies are needed to identify interventions to improve care for patients who deteriorate on the wards following hospital admission.     

Efficacy and Safety of Certolizumab Pegol for Crohn’s Disease: A Systematic Review and Meta-Analysis

Introduction

The authors performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to evaluate the efficacy and safety of certolizumab pegol.

Methods

The authors searched PubMed, MEDLINE via Medscape, BioMed Central, Google Scholar, China National Knowledge Infrastructure (CNKI), the Cochrane library, and the Directory of Open Access Journals. The outcomes of interest were response and remission rates and the treatment-related toxicity rate.

Results

A total of five RCTs, involving 1,891 participants, were included. The meta-analysis revealed that certolizumab significantly increased the overall (induction + maintenance therapy) response [odds ratio (OR) 1.565, 95% CI 1.056–2.321, P = 0.026] and remission rates (OR 1.626, 95% CI 1.297–2.038, P < 0.001) compared with placebo. Certolizumab significantly increased the response and remission rates when given as maintenance therapy (OR 2.171, 95% CI 1.644–2.866, P < 0.001 and OR 1.888, 95% CI 1.390–2.565, P < 0.001), but not as induction therapy (OR 1.234, 95% CI 0.912–1.671, P = 0.173 and OR 1.361, 95% CI 0.974–1.901, P = 0.071). Certolizumab (induction + maintenance therapy) did not significantly increase the treatment-related toxicity rate compared with placebo (OR 0.985, 95% CI 0.799–1.214, P = 0.887).

Conclusion

Certolizumab may be an efficacious treatment for Crohn’s disease as maintenance therapy and appears to have a favorable safety profile.     

Heart rate before ICU discharge: a simple and readily available predictor of short- and long-term mortality from critical illness

Purpose

A heart rate >90 bpm serves as one of four characteristics defining the systemic inflammatory response syndrome and is used in scoring systems to predict in-hospital mortality of intensive care unit (ICU) patients. Despite its central role in critical illness, specific data regarding the relationship between heart rate and outcome are rare.

Methods

In this post hoc analysis of a prospectively collected database, we analyzed the value of heart rate averaged from four predefined time points during the last 24 h before ICU discharge as a predictor of post-ICU in-hospital and post-hospital mortality in medical ICU patients. Furthermore, the relationship between heart rate and inflammation, as well as the influence of rate control medications on the association between heart rate and outcome were identified.

Results

Among the 702 ICU patients discharged from the ICU, 7.1 % died before hospital discharge. At 4 years of follow-up, post-hospital mortality was 14.4 %. Multivariate Cox proportional hazards models revealed heart rate before ICU discharge (HR 5.95; 95 % CI 1.24–28.63; p = 0.03) as an independent predictor of post-ICU in-hospital mortality. Both heart rate (HR 2.56; 95 % CI, 1.05?6.34; p = 0.04) and the C-reactive protein serum concentration before ICU discharge (HR, 1.26; 95 % CI, 1.09–1.46; p = 0.002) were independently associated with post-hospital mortality. Heart rate control therapy reduced the risk of post-ICU in-hospital (HR 0.38; 95 % CI, 0.18–0.81; p = 0.01) and post-hospital (HR, 0.47; 95 % CI, 0.22–1.00; p = 0.05) mortality.

Conclusion

Heart rate evaluated 24 h before ICU discharge was independently associated with post-ICU in-hospital and post-hospital mortality. Pharmacological interventions to control heart rate may beneficially influence post-ICU mortality.     

Critical care management of patients with hemophagocytic lymphohistiocytosis

Objective

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition associated with multiple organ dysfunction. We sought to describe ICU management and outcomes in HLH patients meeting HLH-2004 criteria and to identify determinants of mortality.

Design

Retrospective study between January 1998 and January 2009.

Setting

Medical ICU of a teaching hospital.

Patients

Among the 72 patients fulfilling the HLH-2004 criteria, we report the 56 patients with complete follow-up and no missing data.

Interventions

None.

Measurements and main results

Clinical and laboratory data were abstracted from the medical records. Median SOFA score at admission was 6.5 (IQR, 4–8). At ICU admission, the number of HLH-2004 criteria was 6 (5–7). Sixty-six precipitating factors were found in 52 patients and consisted of 43 tumoral causes (8 Castleman’s diseases, 18 B cell lymphoma and 17 various malignancies), 13 non-viral infections and 10 viral infections. Underlying immune deficiency was present in 38 (67.8%) patients. Etoposide was used in 45 patients, corticosteroids in 31 and intravenous immunoglobulins in 3. Mechanical ventilation was required in 32 patients, vasoactive agents in 30 and renal replacement therapy in 19. Hospital mortality was 29/56 patients. By multivariate analysis, factors associated with increased hospital death were shock at ICU admission [OR, 4.33; 95% confidence interval (95% CI), 1.11–16.90; P = 0.03] and platelet count <30 g/l (OR, 4.75; 95% CI, 1.20–18.81; P = 0.02). B cell lymphoma [odds ratio (OR), 0.17; 95% CI, 0.04–0.80; P = 0.02] and Castleman’s disease (OR, 0.11; 95% CI, 0.02–0.90; P = 0.04) were associated with increased hospital survival.

Conclusions

Aggressive supportive care combined with specific treatment of the precipitating factor can produce meaningful survival in patients with HLH responsible for multiple organ failures. Survival is highest in patients with HLH related to Castleman’s disease or B cell lymphoma.     

Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial

Purpose

We aimed to characterize the degree and clinical importance of bleeding in patients treated with hydroxyethyl starch (HES).

Methods

In post hoc analyses, we examined the associations between fluid assignment, hemostatic variables, bleeding events, transfusions, and death among 798 patients with severe sepsis randomized to fluid resuscitation with HES 130/0.42 versus Ringer’s acetate. We used Cox regression analysis adjusted for fluid assignment and baseline characteristics.

Results

Overall, 93 (23 %) patients assigned to HES versus 60 (15 %) patients assigned to Ringer’s acetate bled in the ICU (relative risk (RR) 1.55; 95 % CI 1.16–2.08; P = 0.003). Of these, 38 and 25 (RR 1.52; 95 % CI 0.94–2.48; P = 0.09), respectively, had severe bleeding (intracranial or concomitant transfusion with three units of red blood cells). Most patients bled in the first days after randomization when most trial fluid was given. The hazards ratios for occurrence of any bleeding and severe bleeding in patients treated with HES versus Ringer’s acetate were 1.70 (95 % CI 1.23–2.36; P = 0.001) and 1.55 (95 % CI 0.93–2.56; P = 0.09), respectively. The adjusted hazard ratios for death among patients with any bleeding and severe bleeding compared to those without bleeding were 1.36 (95 % CI 1.04–1.79; P = 0.03) and 1.74 (95 % CI 1.20–2.53; P = 0.004), respectively.

Conclusions

In post hoc analyses of patient with severe sepsis, treatment with HES increased the risk of bleeding which was associated with increased risk of death. HES-induced bleeding complications may negatively affect outcome in patients with severe sepsis.     

Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients

Purpose

To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU).

Methods

We performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95 % confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia.

Results

Twenty trials (n = 1,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95 % CI 0.84–1.20; P = 0.87; I ² = 0 %) or hospital-acquired pneumonia (random effects: RR 1.23, 95 % CI 0.86–1.78; P = 0.28; I ² = 19 %) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95 % CI 0.28–0.68; P = 0.01; I ² = 48 %); however, TSA (TSA adjusted 95 % CI 0.18–1.11) and subgroup analyses could not confirm this finding.

Conclusions

This systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted.     

Comparison of two repositioning schedules for the prevention of pressure ulcers in patients on mechanical ventilation with alternating pressure air mattresses

Purpose

The objective was to compare the effectiveness of repositioning every 2 or 4 h for preventing pressure ulcer development in patients in intensive care unit under mechanical ventilation (MV).

Methods

This was a pragmatic, open-label randomized clinical trial in consecutive patients on an alternating pressure air mattress (APAM) requiring invasive MV for at least 24 h in a university hospital in Spain. Eligible participants were randomly assigned to groups for repositioning every 2 (n = 165) or 4 (n = 164) h. The primary outcome was the incidence of a pressure ulcer of at least grade II during ICU stay.

Results

A pressure ulcer of at least grade II developed in 10.3 % (17/165) of patients turned every 2 h versus 13.4 % (22/164) of those turned every 4 h (hazard ratio [HR] 0.89, 95 % confidence interval [CI] 0.46–1.71, P = 0.73). The composite end point of device-related adverse events was recorded in 47.9 versus 36.6 % (HR 1.50, CI 95 % 1.06–2.11, P = 0.02), unplanned extubation in 11.5 versus 6.7 % (HR 1.77, 95 % CI 0.84–3.75, P = 0. 13), and endotracheal tube obstruction in 36.4 versus 30.5 %, respectively (HR 1.44, 95 % CI 0.98–2.12, P = 0.065). The median (interquartile range) daily nursing workload for manual repositioning was 21 (14–27) versus 11 min/patient (8–15) (P < 0.001).

Conclusions

A strategy aimed at increasing repositioning frequency (2 versus 4 h) in patients under MV and on an APAM did not reduce the incidence of pressure ulcers. However, it did increase device-related adverse events and daily nursing workload.     

Prevalence and impact of frailty on mortality in elderly ICU patients: a prospective,multicenter, observational study

Purpose

Frailty is a recent concept used for evaluating elderly individuals. Our study determined the prevalence of frailty in intensive care unit (ICU) patients and its impact on the rate of mortality.

Methods

A multicenter, prospective, observational study performed in four ICUs in France included 196 patients aged ≥65 years hospitalized for >24 h during a 6-month study period. Frailty was determined using the frailty phenotype (FP) and the clinical frailty score (CFS). The patients were separated as follows: FP score <3 or ≥3 and CFS <5 or ≥5.

Results

Frailty was observed in 41 and 23 % of patients on the basis of an FP score ≥3 and a CFS ≥5, respectively. At admission to the ICU, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores did not differ between the frail and nonfrail patients. In the multivariate analysis, the risk factors for ICU mortality were FP score ≥3 [hazard ratio (HR), 3.3; 95 % confidence interval (CI), 1.6–6.6; p < 0.001], male gender (HR, 2.4; 95 % CI, 1.1–5.3; p = 0.026), cardiac arrest before admission (HR, 2.8; 95 % CI, 1.1–7.4; p = 0.036), SAPS II score ≥46 (HR, 2.6; 95 % CI, 1.2–5.3; p = 0.011), and brain injury before admission (HR, 3.5; 95 % CI, 1.6–7.7; p = 0.002). The risk factors for 6-month mortality were a CFS ≥5 (HR, 2.4; 95 % CI, 1.49–3.87; p < 0.001) and a SOFA score ≥7 (HR, 2.2; 95 % CI, 1.35–3.64; p = 0.002). An increased CFS was associated with significant incremental hospital and 6-month mortalities.

Conclusions

Frailty is a frequent occurrence and is independently associated with increased ICU and 6-month mortalities. Notably, the CFS predicts outcomes more effectively than the commonly used ICU illness scores.     

De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial

Background

In patients with severe sepsis, no randomized clinical trial has tested the concept of de-escalation of empirical antimicrobial therapy. This study aimed to compare the de-escalation strategy with the continuation of an appropriate empirical treatment in those patients.

Methods

This was a multicenter non-blinded randomized noninferiority trial of patients with severe sepsis who were randomly assigned to de-escalation or continuation of empirical antimicrobial treatment. Recruitment began in February 2012 and ended in April 2013 in nine intensive care units (ICUs) in France. Patients with severe sepsis were assigned to de-escalation (n = 59) or continuation of empirical antimicrobial treatment (n = 57). The primary outcome was to measure the duration of ICU stay. We defined a noninferiority margin of 2 days. If the lower boundary of the 95 % confidence interval (CI) for the difference in patients assigned to the de-escalation group was less than 2 days, as compared with that of patients assigned to the continuation group, de-escalation was considered to be noninferior to the continuation strategy. Secondary outcomes included mortality at 90 days, occurrence of organ failure, number of superinfections, and number of days with antibiotics during the ICU stay.

Results

The median duration of ICU stay was 9 [interquartile range (IQR) 5–22] days in the de-escalation group and 8 [IQR 4–15] days in the continuation group, respectively (P = 0.71). The mean difference was 3.4 (95 % CI ?1.7 to 8.5). A superinfection occurred in 16 (27 %) patients in the de-escalation group and six (11 %) patients in the continuation group (P = 0.03). The numbers of antibiotic days were 9 [7–15] and 7.5 [6–13] in the de-escalation group and continuation group, respectively (P = 0.03). Mortality was similar in both groups.

Conclusion

As compared to the continuation of the empirical antimicrobial treatment, a strategy based on de-escalation of antibiotics resulted in prolonged duration of ICU stay. However, it did not affect the mortality rate.     

Risk factors for carbapenem-resistant Gram-negative bacteremia in intensive care unit patients

Purpose

Carbapenem-resistant (CR) Gram-negative pathogens have increased substantially. This study was performed to identify the risk factors for development of CR Gram-negative bacteremia (GNB) in intensive care unit (ICU) patients.

Methods

Prospective study; risk factors for development of CR-GNB were investigated using two groups of case patients: the first group consisted of patients who acquired carbapenem susceptible (CS) GNB and the second group included patients with CR-GNB. Both case groups were compared to a shared control group defined as patients without bacteremia, hospitalized in the ICU during the same period.

Results

Eighty-five patients with CR- and 84 patients with CS-GNB were compared to 630 control patients, without bacteremia. Presence of VAP (OR 7.59, 95 % CI 4.54–12.69, p < 0.001) and additional intravascular devices (OR 3.69, 95 % CI 2.20–6.20, p < 0.001) were independently associated with CR-GNB. Presence of VAP (OR 2.93, 95 % CI 1.74–4.93, p < 0.001), presence of additional intravascular devices (OR 2.10, 95 % CI 1.23–3.60, p = 0.007) and SOFA score on ICU admission (OR 1.11, 95 % CI 1.03–1.20, p = 0.006) were independently associated with CS-GNB. The duration of exposure to carbapenems (OR 1.079, 95 % CI 1.022–1.139, p = 0.006) and colistin (OR 1.113, 95 % CI 1.046–1.184, p = 0.001) were independent risk factors for acquisition of CR-GNB. When the source of bacteremia was other than VAP, previous administration of carbapenems was the only factor related with the development of CR-GNB (OR 1.086, 95 % CI 1.003–1.177, p = 0.042).

Conclusions

Among ICU patients, VAP development and the presence of additional intravascular devices were the major risk factors for CR-GNB. In the absence of VAP, prior use of carbapenems was the only factor independently related to carbapenem resistance.     

Six-month prognosis of patients with lung cancer admitted to the intensive care unit

Background

Intensive care unit (ICU) admission of patients with lung cancer remains debated because of the poor short-term prognosis. However, ICU admission of such patients should also be assessed on the possibility to administer specific anticancer treatment and the long-term outcome thereafter.

Objectives

To identify predictive factors of hospital and 6-month mortality in critically ill lung-cancer patients.

Design and setting

Retrospective study conducted in the ICU of a university hospital.

Patients

One hundred five consecutive lung-cancer patients included between 1 January 1997 and 31 December 2006.

Interventions

None.

Results

Of the 105 patients (mean age 64.8 years), 87 (83%) had a non-small cell lung cancer (NSCLC). Extensive disease was diagnosed in 85 patients (83%) (NSCLC stages IIIB and IV or disseminated small cell lung cancer). The main reasons for ICU admission were acute respiratory failure (59%) and/or hemoptysis (45%). Forty-three patients (41%) needed mechanical ventilation (MV). The ICU, hospital and 6-month mortality rates were 43, 54 and 73%, respectively. A performance status (PS) ≥2 [odds ratio OR = 3.6 (95% confidence interval CI (1.5–8.7)] and acute respiratory failure [OR = 3.5 (95% CI (1.5–8.4)] predicted hospital mortality. In a multivariate Cox model, the cancer progression [hazard ratio HR = 6.1 (95% CI 2.2–17)] and the need for MV [HR = 3.6 (95% CI 1.35–9.4)] were independently associated with 6-month mortality. Two-thirds of the ICU survivors were able to receive anticancer treatment.

Conclusions

ICU admission should be considered in selected patients with lung cancer (PS <2, no cancer disease progression).     

Drug-coated balloons in treatment of in-stent restenosis: a meta-analysis of randomised controlled trials

Background

Drug-coated balloons (DCBs) have been developed for the percutaneous treatment of coronary artery disease. An initial focus has been the management of in-stent restenosis (ISR) but randomised controlled trials (RCTs) have been small and powered only for angiographic endpoints.

Objective

The aim of the work was to assess the clinical and angiographic outcomes of patients treated for ISR with DCB versus control (balloon angioplasty or drug-eluting stents) by a meta-analysis of RCTs.

Methods

A comprehensive search was performed of RCTs where patients with ISR were randomly assigned to either DCB or alternative coronary intervention. Outcome measurements were death, myocardial infarction (MI), target lesion revascularisation (TLR), binary definition of restenosis and in-lesion late luminal loss (LLL).

Results

Four studies were identified that fulfilled the inclusion criteria. Pooled odds ratios (ORs) were calculated for patients treated for ISR (n = 399). Mean follow-up duration was 14.5 months. DCBs were associated with lower rates of TLR [8.8 vs. 29.7 % OR (95 % confidence interval, CI) 0.20 (0.11–0.36), p < 0.0001], binary restenosis [10.3 vs. 41.3 % OR (95 % CI) 0.13 (0.07–0.24), p < 0.00001] and MI [0.5 vs. 3.8 %, OR (95 % CI) 0.21 (0.04–1.00), p = 0.05]. No significant heterogeneity was identified.

Conclusion

Drug-coated balloons appear to be effective versus control in reducing TLR and possibly MI versus balloon angioplasty or drug-eluting stents in the management of ISR.     

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia

Purpose

To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia.

Methods

Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain.

Results

Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4–20) vs. 10 (IQR 5–20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55–1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58–1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44–1.35, p = 0.4).

Conclusion

Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.     

CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

Purpose

Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population.

Methods

In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas.

Results

In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ≥10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88–96) vs. 96% (95% CI: 93–99) for colonoscopy (P = 0.26). For adenomas and carcinomas ≥10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89–97) vs. 97% (95% CI: 94–99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ≥10 mm was 95% (95% CI: 91–99) for CTC vs. 99% (95% CI: 98–100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86–95) and 96% (95% CI: 94–99), respectively (P < 0.001).

Conclusion

CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.     

Implementation of a multifaceted sepsis education program in an emerging country setting: clinical outcomes and cost-effectiveness in a long-term follow-up study

Purpose

To evaluate whether a multifaceted, centrally coordinated quality improvement program in a network of hospitals can increase compliance with the resuscitation bundle and improve clinical and economic outcomes in an emerging country setting.

Methods

This was a pre- and post-intervention study in ten private hospitals (1,650 beds) in Brazil (from May 2010 to January 2012), enrolling 2,120 patients with severe sepsis or septic shock. The program used a multifaceted approach: screening strategies, multidisciplinary educational sessions, case management, and continuous performance assessment. The network administration and an external consultant provided performance feedback and benchmarking within the network. The primary outcome was compliance with the resuscitation bundle. The secondary outcomes were hospital mortality, hospital and ICU length of stay, quality-adjusted life year (QALY) gain, and cost-effectiveness.

Results

The proportion of patients who received all the required items for the resuscitation bundle improved from 13 % [95 % confidence interval (CI) 8–18 %] at baseline to 62 % (95 % CI 54–69 %) in the last trimester (p < 0.001). Hospital mortality decreased from 55 % (95 % CI 48–62 %) to 26 % (95 % CI 19–32 %, p < 0.001). Full compliance with the resuscitation bundle was associated with lower risk of hospital mortality (propensity weighted corrected risk ratio 0.74; 95 % CI 0.56–0.94, p = 0.02). There was a reduction in the total cost per patient from 29.3 (95 % CI 23.9–35.4) to 17.5 (95 % CI 14.3–21.1) thousand US dollars from baseline to the last 3 months (mean difference ?11,815; 95 % CI ?18,604 to ?5,338). The mean QALY increased from 2.63 (95 % CI 2.15–3.14) to 4.06 (95 % CI 3.58–4.57). For each QALY, the full compliance saves US$5,383.

Conclusions

A multifaceted approach to severe sepsis and septic shock patients in an emerging country setting led to high compliance with the resuscitation bundle. The intervention was cost-effective and associated with a reduction in mortality.     

Abnormal findings on multiparametric prostate magnetic resonance imaging predict subsequent biopsy upgrade in patients with low risk prostate cancer managed with active surveillance

Purpose

To determine the ability of multiparametric MR imaging to predict disease progression in patients with prostate cancer managed by active surveillance.

Methods

Sixty-four men with biopsy-proven prostate cancer managed by active surveillance were included in this HIPPA compliant, IRB approved study. We reviewed baseline MR imaging scans for the presence of a suspicious findings on T2-weighted imaging, MR spectroscopic imaging (MRSI), and diffusion-weighted MR imaging (DWI). The Gleason grades at subsequent biopsy were recorded. A Cox proportional hazard model was used to determine the predictive value of MR imaging for Gleason grades, and the model performance was described using Harrell’s C concordance statistic and 95% confidence intervals (CIs).

Results

The Cox model that incorporated T2-weighted MR imaging, DWI, and MRSI showed that only T2-weighted MR imaging and DWI are independent predictors of biopsy upgrade (T2; HR = 2.46; 95% CI 1.36–4.46; P = 0.003—diffusion; HR = 2.76; 95% CI 1.13–6.71; P = 0.03; c statistic = 67.7%; 95% CI 61.1–74.3). There was an increasing rate of Gleason score upgrade with a greater number of concordant findings on multiple MR sequences (HR = 2.49; 95% CI 1.72–3.62; P < 0.001).

Conclusions

Abnormal results on multiparametric prostate MRI confer an increased risk for Gleason score upgrade at subsequent biopsy in men with localized prostate cancer managed by active surveillance. These results may be of help in appropriately selecting candidates for active surveillance.     

Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study

Purpose

To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis.

Methods

Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively.

Results

Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48–3.39, P = 1.24 × 10^?4 (derivation); HR = 2.16, 95% CI 1.33–3.51, P = 1.95 × 10^?3 (validation); and HR = 2.00, 95% CI 1.47–2.72, P = 1.10 × 10^?5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16–2.48, P = 6.62 × 10^?3 (derivation); HR = 1.78, 95% CI 1.15–2.75, P = 9.80 × 10^?3 (validation); and HR = 1.59, 95% CI 1.20–2.10, P = 1.22 × 10^?3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04–2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03–2.02, P = 0.0313).

Conclusions

Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.

     

Trends in admission prevalence,illness severity and survival of haematological patients treated in Dutch intensive care units

Purpose

To explore trends over time in admission prevalence and (risk-adjusted) mortality of critically ill haematological patients and compare these trends to those of several subgroups of patients admitted to the medical intensive care unit (medical ICU patients).

Methods

A total of 1,741 haematological and 60,954 non-haematological patients admitted to the medical ICU were analysed. Trends over time and differences between two subgroups of haematological medical ICU patients and four subgroups of non-haematological medical ICU patients were assessed, as well as the influence of leukocytopenia.

Results

The proportion of haematological patients among all medical ICU patients increased over time [odds ratio (OR) 1.06; 95 % confidence interval (CI) 1.03–1.10 per year; p < 0.001]. Risk-adjusted mortality was significantly higher for haematological patients admitted to the ICU with white blood cell (WBC) counts of <1.0 × 10⁹/L (47 %; 95 % CI 41–54 %) and ≥1.0 × 10⁹/L (45 %; 95 % CI 42–49 %), respectively, than for patients admitted with chronic heart failure (27 %; 95 % CI 26–28 %) and with chronic liver cirrhosis (38 %; 95 % CI 35–42 %), but was not significantly different from patients admitted with solid tumours (40 %; 95 % CI 36–45 %). Over the years, the risk-adjusted hospital mortality rate significantly decreased in both the haematological and non-haematological group with an OR of 0.93 (95 % CI 0.92–0.95) per year. After correction for case-mix using the APACHE-II score (with WBC omitted), a WBC <1.0 × 10⁹/L was not a predictor of mortality in haematological patients (OR 0.86; 95 % CI 0.46–1.64; p = 0.65). We found no case–volume effect on mortality for haematological ICU patients.

Conclusions

An increasing number of haematological patients are being admitted to Dutch ICUs. While mortality is significantly higher in this group of medical ICU patients than in subgroups of non-haematological ones, the former show a similar decrease in raw and risk-adjusted mortality rate over time, while leukocytopenia is not a predictor of mortality. These results suggest that haematological ICU patients have benefitted from improved intensive care support during the last decade.