Ethanol lock and risk of hemodialysis catheter infection in critically ill patients. A randomized controlled trial.

RATIONALE: Ethanol rapidly eradicated experimental biofilm. Clinical studies of ethanol lock to prevent catheter-related infections (CRIs) suggest preventive efficacy. No such studies have been done in intensive care units (ICU). OBJECTIVES: To determine whether ethanol lock decreases the risk of major CRI in patients with short-term dialysis catheters (DCs). METHODS: A randomized, double-blind, placebo-controlled trial was performed in 16 ICUs in seven university hospitals and one general hospital in France between June 2009 and December 2011. Adults with insertion of a nontunneled, nonantimicrobial-impregnated double-lumen DC for an expected duration greater than 48 hours, to perform renal-replacement therapy or plasma exchange, were randomly allocated (1:1) to receive a 2-minute catheter lock with either 60% wt/wt ethanol solution (ethanol group) or 0.9% saline solution (control group) at the end of DC insertion and after each renal-replacement therapy or plasma exchange session. The main outcome was major CRI defined as either catheter-related clinical sepsis without bloodstream infection or catheter-related bloodstream infection during the ICU stay. MEASUREMENTS AND MAIN RESULTS: The intent-to-treat analysis included 1,460 patients (2,172 catheters, 12,944 catheter-days, and 8,442 study locks). Median DC duration was 4 days (interquartile range, 2-8) and was similar in both groups. Major CRI incidence did not differ between the ethanol and control groups (3.83 vs. 2.64 per 1,000 catheter-days, respectively; hazard ratio, 1.55; 95% confidence interval, 0.83-2.87; P = 0.17). No significant differences occurred for catheter colonization (P = 0.57) or catheter-related bloodstream infection (P = 0.99). CONCLUSIONS: A 2-minute ethanol lock does not decrease the frequency of infection of DCs in ICU patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00875069).

ICU physician-based determinants of life-sustaining therapy during nights and weekends: French multicenter study from the Outcomerea Research Group.

OBJECTIVE: Patient- and organization-related factors are the most common influences affecting the ICU decision-making process. Few studies have investigated ICU physician-related factors and life-sustaining treatment use during nights and weekends, when staffing ratios are low. Here, we described patients admitted during nights/weekends and looked for physician-related determinants of life-sustaining treatment use in these patients after adjustment for patient- and center-related factors. DESIGN: Multicenter observational cohort study of admission procedures during nights/weekends shifts. SUBJECTS: ICU physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were extracted from the prospective Outcomerea database. Physician characteristics were age, gender, religion and religiosity, ICU experience, specialty, being a permanent ICU staff member, degree in ethics, and degree in intensive care. We used hierarchical mixed models to adjust on center, physician random effects, and admission patient characteristics. Of 156 physicians contacted, 119 (77%) participated. Patients admitted during nights/weekends were younger and had fewer comorbidities and lower treatment intensity during the shift. ICU physicians who are younger than 35 years used more renal replacement therapy (odds ratio, 1.04; 95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95% CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p < 0.0001). Internal or emergency medicine as the primary specialty was associated with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p = 0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01). Noninvasive ventilation was used less often by physicians with more than 10 years of night/weekend shifts and more often by those with religious beliefs (odds ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU experience, and religious beliefs of the physicians were significantly associated life-sustaining treatments used.

Evaluation of RECIST in chemotherapy-treated lung cancer: the Pharmacogenoscan Study.

BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST) are widely used to assess the effect of chemotherapy in patients with cancer. We hypothesised that the change in unidimensional tumour size handled as a continuous variable was more reliable than RECIST in predicting overall survival (OS). METHODS: The prospective Pharmacogenoscan study enrolled consecutive patients with non-small-cell lung cancer (NSCLC) at any stage seen between 2005 and 2010 at six hospitals in France, given chemotherapy. After exclusion of patients without RECIST or continuous-scale tumour size data and of those with early death, 464 patients were left for the survival analyses. Cox models were built to assess relationships between RECIST 1.1 categories or change in continuous-scale tumour size and OS. The best model was defined as the model minimising the Akaike Information Criterion (AIC). RESULTS: OS was 14.2 months (IQR, 7.3-28.9 months). According to RECIST 1.1, 146 (31%) patients had a partial or complete response, 245 (53%) stable disease, and 73 (16%) disease progression. RECIST 1.1 predicted better OS than continuous-scale tumour in early (<6 months) predicted survival analyses (p = 0.03) but the accuracy of the two response evaluation methods was similar in late (≥6 months) predicted survival analyses (p = 0.15). CONCLUSION: In this large observational study, change in continuous-scale tumour size did not perform better than RECIST 1.1 in predicting survival of patients given chemotherapy to treat NSCLC. TRIAL REGISTRATION: NCT00222404.

Long-term adherence with non-invasive ventilation improves prognosis in obese COPD patients.

BACKGROUND AND OBJECTIVE: Long-term non-invasive ventilation (NIV) has become a widespread modality of treatment in chronic obstructive pulmonary disease (COPD) patients with chronic respiratory failure. However, benefits in terms of patient-related outcomes are still under debate. Both NIV adherence and heterogeneous responses in different COPD phenotypes may contribute to the difficulty of demonstrating NIV benefits. Our aim was to assess the impact of NIV adherence on the rate of hospitalization for acute exacerbation and death. METHODS: This is a prospective multi-centre cohort study of COPD patients treated by long-term NIV. Comorbidities, anthropometrics, respiratory parameters were collected at inclusion in the study. Follow-up data included vital status, NIV adherence and hospitalizations. The influence of NIV adherence on prognosis was tested using an adjusted Cox model. Sensitivity analyses for obese and non-obese COPD subtypes were also conducted. RESULTS: Two hundred thirteen patients (48% obese) were included with 45.5% died during 47.7 [interquartile range = 27.8; 73] months' follow-up. Survival was better in obese COPD than non-obese COPD. The use of NIV > 9 h/day was associated with an increased risk of death or hospitalization for acute exacerbation [HR = 1.6; 95CI: 1.1-2.4]. In obese COPD, this risk described a U-shaped curve from >1 to >9 h/day NIV usage with an improvement in prognosis when NIV adherence was > 5 h/day [HR = 0.5; 95CI: 0.2-0.9]. CONCLUSIONS: Adherence to NIV was associated with better prognosis only in obese COPD. NIV use > 9 h/day predicted poor outcomes.

Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure.

RATIONALE: The predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain. OBJECTIVES: To describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP. METHODS: From the multicenter OUTCOMEREA database (1997-2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence. MEASUREMENTS AND MAIN RESULTS: A total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3-0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4-1.0]; P = 0.048). CONCLUSIONS: Neither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Insulin Requirements According to Sex and Weight in a Population of 9036 Adult Persons With Type 1 Diabetes Using Closed-Loop Insulin Delivery.

BACKGROUND: The prediction of the individual insulin needs may facilitate the initiation of insulin therapy. Our aim was to explore the relationships between body weight, sex, and daily amounts of insulin delivered by a hybrid closed-loop system. METHODS: We performed a retrospective data collection of all consenting adult patients with type 1 diabetes who were equipped in Europe with the Diabeloop Generation 1 (DBLG1) hybrid closed-loop insulin delivery device between March 1, 2021 and February 28, 2023. RESULTS: A total of 9036 users (59% females, age 45.6 ± 14.3 years) were included, reaching a mean follow-up of 320 ± 143 days, an overall 2 887 188 days of data. We observed a mean insulin-weight ratio of 0.617 ± 0.207 U/kg (0.665 ± 0.217 for males and 0.584 ± 0.193 for females, P < .001). Exploratory analysis of a subset of 4066 patients reaching >70% Time in Range (70-180 mg/dL) showed a mean insulin-weight ratio of 0.55 ± 0.17 U/kg (P < .001) (0.59 ± 0.18 for the 1438 males and 0.53 ± 0.16 for the 2628 females). CONCLUSION: This large real-world analysis provides a quantitative estimation of the daily insulin requirements in adult patients with type 1 diabetes and shows significant differences between sex. These findings have relevant implications in the practical management of insulin therapy.

Diagnosis and management of temperature abnormality in ICUs: a EUROBACT investigators' survey.

INTRODUCTION: Although fever and hypothermia are common abnormal physical signs observed in patients admitted to intensive care units (ICU), little data exist on their optimal management. The objective of this study was to describe contemporary practices and determinants of management of temperature abnormalities among patients admitted to ICUs. METHODS: Site leaders of the multi-national EUROBACT study were surveyed regarding diagnosis and management of temperature abnormalities among patients admitted to their ICUs. RESULTS: Of the 162 ICUs originally included in EUROBACT, responses were received from 139 (86%) centers in 23 countries in Europe (117), South America (8), Asia (5), North America (4), Australia (3) and Africa (2). A total of 117 (84%) respondents reported use of a specific temperature threshold in their ICU to define fever. A total of 14 different discrete levels were reported with a median of 38.2°C (inter-quartile range, IQR, 38.0°C to 38.5°C). The use of thermometers was protocolized in 91 (65%) ICUs and a wide range of methods were reportedly used, with axillary, tympanic and urinary bladder sites as the most common as primary modalities. Only 31 (22%) of respondents indicated that there was a formal written protocol for temperature control among febrile patients in their ICUs. In most or all cases practice was to control temperature, to use acetaminophen, and to perform a full septic workup in febrile patients and that this was usually directed by physician order. While reported practice was to treat nearly all patients with neurological impairment and most patients with acute coronary syndromes and infections, severe sepsis and septic shock, this was not the case for most patients with liver failure and fever. CONCLUSIONS: A wide range of definitions and management practices were reported regarding temperature abnormalities in the critically ill. Documenting temperature abnormality management practices, including variability in clinical care, is important to inform planning of future studies designed to optimize infection and temperature management strategies in the critically ill.

Randomized controlled trial of chlorhexidine dressing and highly adhesive dressing for preventing catheter-related infections in critically ill adults.

RATIONALE: Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. OBJECTIVES: To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. METHODS: In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. MEASUREMENTS AND MAIN RESULTS: A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. CONCLUSIONS: A large randomized trial demonstrated that chlorhexidine-gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials.gov (NCT 01189682).

Severe hypothermia increases the risk for intensive care unit-acquired infection.

BACKGROUND: Although hypothermia is widely accepted as a risk factor for subsequent infection in surgical patients, it has not been well defined in medical patients. We sought to assess the risk of acquiring intensive care unit (ICU)--acquired infection after hypothermia among medical ICU patients. METHODS: Adults (≥18 years) admitted to French ICUs for at least 2 days between April 2000 and November 2010 were included. Surgical patients were excluded. Patient were classified as having had mild hypothermia (35.0°C-35.9°C), moderate hypothermia (32°C-34.9°C), or severe hypothermia (<32°C), and were followed for the development of pneumonia or bloodstream infection until ICU discharge. RESULTS: A total of 6237 patients were included. Within the first day of admission, 648 (10%) patients had mild hypothermia, 288 (5%) patients had moderate hypothermia, and 45 (1%) patients had severe hypothermia. Among the 5256 patients who did not have any hypothermia at day 1, subsequent hypothermia developed in 868 (17%), of which 673 (13%), 176 (3%), and 19 (<1%) patients had lowest temperatures of 35.0°C-35.9°C, 32.0°C-34.9°C, and <32°C, respectively. During the course of ICU admission, 320 (5%) patients developed ICU-acquired bloodstream infection and 724 (12%) patients developed ICU-acquired pneumonia. After controlling for confounding variables in multivariable analyses, severe hypothermia was found to increase the risk for subsequent ICU-acquired infection, particularly in patients who did not present with severe sepsis or septic shock. CONCLUSIONS: The presence of severe hypothermia is a risk factor for development of ICU-acquired infection in medical patients.

Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: the EUELC cohort.

Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in the TP53, KRAS and EGFR genes. The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs), 133 adenocarcinomas (ADCs) and seven large cell carcinomas or mixed histologies. Expression of p53 was analysed by immunohistochemistry. DNA was extracted from frozen tumour tissues. TP53 mutations were detected in 48.8% of cases and were more frequent among SCCs than ADCs (p<0.0001). TP53 mutation status was not associated with prognosis. G to T transversions, known to be associated with smoking, were marginally more common among patients who developed a second primary lung cancer or recurrence/metastasis (progressive disease). EGFR mutations were almost exclusively found in never-smoking females (p=0.0067). KRAS mutations were detected in 18.5% of cases, mainly ADC (p<0.0001), and showed a tendency toward association with progressive disease status. These results suggest that mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception of KRAS mutation, which may have a prognostic value in ADC.

A multifaceted program for improving quality of care in intensive care units: IATROREF study.

OBJECTIVE: To test the effects of three multifaceted safety programs designed to decrease insulin administration errors, anticoagulant prescription and administration errors, and errors leading to accidental removal of endotracheal tubes and central venous catheters, respectively. Medical errors and adverse events are associated with increased mortality in intensive care patients, indicating an urgent need for prevention programs. DESIGN: Multicenter cluster-randomized study. SETTING: One medical intensive care unit in a university hospital and two medical-surgical intensive care units in community hospitals belonging to the Outcomerea Study Group. PATIENTS: Consecutive patients >18 yrs admitted from January 2007 to January 2008 to the intensive care units. INTERVENTIONS: We tested three multifaceted safety programs vs. standard care in random order, each over 2.5 months, after a 1.5-month observation period. MEASUREMENTS AND MAIN RESULTS: Incidence rates of medical errors/1000 patient-days in the multifaceted safety program and standard-care groups were compared using adjusted hierarchical models. In 2117 patients with 15,014 patient-days, 8520 medical errors (567.5/1000 patient-days) were reported, including 1438 adverse events (16.9%, 95.8/1000 patient-days). The insulin multifaceted safety program significantly decreased errors during implementation (risk ratio 0.65; 95% confidence interval [CI] 0.52-0.82; p = .0003) and after implementation (risk ratio 0.51; 95% CI 0.35-0.73; p = .0004). A significant Hawthorne effect was found. The accidental tube/catheter removal multifaceted safety program decreased errors significantly during implementation (odds ratio [OR] 0.34; 95% CI 0.15-0.81; p = .01]) and nonsignificantly after implementation (OR 1.65; 95% CI 0.78-3.48). The anticoagulation multifaceted safety program was not significantly effective (OR 0.64; 95% CI 0.26-1.59) but produced a significant Hawthorne effect. CONCLUSIONS: A multifaceted program was effective in preventing insulin errors and accidental tube/catheter removal. Significant Hawthorne effects occurred, emphasizing the need for appropriately designed studies before definitively implementing strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00461461.

Economic evaluation of chlorhexidine-impregnated sponges for preventing catheter-related infections in critically ill adults in the Dressing Study.

BACKGROUND: The randomized two-way factorial Dressing Study (1,636 patients, 28,931 catheter days) showed that a chlorhexidine-impregnated sponge decreased the incidence of major catheter-related infections from 1.4‰ to 0.6‰ catheter days, and that scheduled dressing changes every 7 days was not inferior to scheduled changes every 3 days. Here, we assessed the cost benefits of chlorhexidine-impregnated sponge use. METHODS: Costs directly related to major catheter-related infections and the costs of chlorhexidine-impregnated sponge and contact dermatitis were calculated prospectively using microcosting methods during the original study. The added length of stay in the intensive care unit due to major catheter-related infection was estimated using the disability model and assuming a cost of $2,118/intensive care unit day. The cost of each strategy was estimated based on all costs and on the probability of major catheter-related infection according to the Dressing Study results. INTERVENTIONS: None. RESULTS: Median direct cost of major catheter-related infection was $792. Estimated added length of stay due to major catheter-related infection was 11 days (95% confidence interval [-2 days; 26 days]). Overall cost of major catheter-related infection was $24,090/episode. Each dressing cost $9.08 (146 observations) and each chlorhexidine-impregnated sponge cost $9.73. Assuming a baseline major catheter-related infection incidence of 1.4‰ catheter days, chlorhexidine-impregnated sponge use saved $197 per patient with the 3-day chlorhexidine-impregnated sponge dressing change strategy, and $83 with the 7-day standard dressing change strategy. Chlorhexidine-impregnated sponge use remained cost saving assuming a baseline major catheter-related infection incidence as low as 0.35‰ catheter days, or an overall cost per major catheter-related infections of up to $4,400. CONCLUSION: Chlorhexidine-impregnated sponge for arterial and central venous catheters saves money by preventing major catheter-related infections, even in intensive care units with low baseline major catheter-related infection levels. TRIAL REGISTRATION: Clinicaltrials.gov number, NCT00417235.

Impact of an intensive care unit diary on psychological distress in patients and relatives*.

OBJECTIVE: To assess the impact of an intensive care unit diary on the psychological well-being of patients and relatives 3 and 12 months after intensive care unit discharge. DESIGN: Prospective single-center study with an intervention period between two control periods. SETTING: Medical-surgical intensive care unit in a 460-bed tertiary hospital. PATIENTS: Consecutive patients from May 2008 to November 2009 and their relatives. Study inclusion occurred after the fourth day in the intensive care unit. INTERVENTIONS: A diary written by both the patient's relatives and the intensive care unit staff. MEASUREMENTS AND MAIN RESULTS: Patients and relatives completed the Hospital Anxiety and Depression Scale and Peritraumatic Dissociative Experiences Questionnaire 3 months after intensive care unit discharge, and completed the Impact of Events Scale assessing posttraumatic stress-related symptoms 12 months after intensive care unit discharge. Of the 378 patients admitted during the study period, 143 were included (48 in the prediary period, 49 in the diary period, and 46 in the postdiary period). In relatives, severe posttraumatic stress-related symptoms after 12 months varied significantly across periods (prediary 80%, diary 31.7%, postdiary 67.6%; p<.0001). Similar results were obtained in the posttraumatic stress-related symptom score after 12 months in the surviving patients (prediary 34.6 ± 15.9, diary 21 ± 12.2, and postdiary 29.8 ± 15.9; p = .02). CONCLUSIONS: The intensive care unit diary significantly affected posttraumatic stress-related symptoms in relatives and surviving patients 12 months after intensive care unit discharge.

Outcome of ICU patients with Clostridium difficile infection.

INTRODUCTION: As data from Clostridium difficile infection (CDI) in intensive care unit (ICU) are still scarce, our objectives were to assess the morbidity and mortality of ICU-acquired CDI. METHODS: We compared patients with ICU-acquired CDI (watery or unformed stools occurring ≥ 72 hours after ICU admission with a stool sample positive for C. difficile toxin A or B) with two groups of controls hospitalized at the same time in the same unit. The first control group comprised patients with ICU-acquired diarrhea occurring ≥ 72 hours after ICU admission with a stool sample negative for C. difficile and for toxin A or B. The second group comprised patients without any diarrhea. RESULTS: Among 5,260 patients, 512 patients developed one episode of diarrhea. Among them, 69 (13.5%) had a CDI; 10 (14.5%) of them were community-acquired, contrasting with 12 (17.4%) that were hospital-acquired and 47 (68%) that were ICU-acquired. A pseudomembranous colitis was associated in 24/47 (51%) ICU patients. The median delay between diagnosis and metronidazole administration was one day (25th Quartile; 75th Quartile (0; 2) days). The case-fatality rate for patients with ICU-acquired CDI was 10/47 (21.5%), as compared to 112/443 (25.3%) for patients with negative tests. Neither the crude mortality (cause specific hazard ratio; CSHR = 0.70, 95% confidence interval; CI 0.36 to 1.35, P = 0.3) nor the adjusted mortality to confounding variables (CSHR = 0.81, 95% CI 0.4 to 1.64, P = 0.6) were significantly different between CDI patients and diarrheic patients without CDI. Compared to the general ICU population, neither the crude mortality (SHR = 0.64, 95% CI 0.34 to 1.21, P = 0.17), nor the mortality adjusted to confounding variables (CSHR = 0.71, 95% confidence interval (CI) 0.38 to 1.35, P = 0.3), were significantly different between the two groups. The estimated increase in the duration of stay due to CDI was 8.0 days ± 9.3 days, (P = 0.4) in comparison to the diarrheic population, and 6.3 days ± 4.3 (P = 0.14) in comparison to the general ICU population. CONCLUSIONS: If treated early, ICU-acquired CDI is not independently associated with an increased mortality and impacts marginally the ICU length of stay.

Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.

RATIONALE: Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. OBJECTIVES: We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. METHODS: Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. MEASUREMENTS AND MAIN RESULTS: Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. CONCLUSIONS: Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.

Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality.

OBJECTIVES: We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections. DESIGN: We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy. SETTING: Twelve intensive care units. PATIENTS: We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups. CONCLUSION: The infectious process may not exert as strong a prognostic effect when severity, organ dysfunction and, above all, appropriateness of early antimicrobials are taken into account. Our findings emphasize the importance of developing valid recommendations for early antimicrobial therapy.

Antifungal use influences Candida species distribution and susceptibility in the intensive care unit.

OBJECTIVES: Antifungal prescription practices have changed over the last decade, and the impact of these changes is unclear. Our objective here was to evaluate the effect of antifungal drug use on the distribution and drug susceptibility of Candida spp. in a French intensive care unit (ICU). METHODS: Antifungal drug use was measured as the number of defined daily doses per 1000 hospital days (DDDs/1000HD). The distribution of Candida spp. over a 6 year period (2004-09) and the MICs of antifungal drugs over 2007-09 were determined. Statistical analyses were performed to assess relationships between antifungal drug use, Candida spp. distribution and MIC changes over time. RESULTS: Of 26,450 samples from 3391 patients, 1511 were positive for Candida spp. Candida albicans predominated (52.5%), followed by Candida glabrata (16.6%) and Candida parapsilosis (7.5%). C. parapsilosis increased significantly, from 5.7% in 2004 to 12.5% in 2009 (P = 0.0005). Caspofungin use increased significantly between 2004 (17.9 DDDs/1000HD) and 2009 (69.9 DDDs/1000HD) (P < 0.0001). Between 2007 and 2009, the increase in caspofungin use correlated significantly with the increase in caspofungin MICs displayed by C. parapsilosis (P < 0.0001) and C. glabrata (P = 0.03). Amphotericin B consumption changed over time and correlated with an increase in amphotericin B MICs for C. albicans (P = 0.0002) and C. glabrata (P = 0.0005). Significant declines occurred in both fluconazole use (P < 0.0001) and fluconazole MICs of C. albicans (P < 0.001) CONCLUSIONS: Antifungal drug use in the ICU is associated with major changes in the distribution and drug susceptibility of Candida spp.

Impact of ureido/carboxypenicillin resistance on the prognosis of ventilator-associated pneumonia due to Pseudomonas aeruginosa.

INTRODUCTION: Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated. METHODS: A total of 223 episodes of PA-VAP recorded into the Outcomerea database were evaluated. Patients with ureido/carboxy-resistant P. aeruginosa (PRPA) were compared with those with ureido/carboxy-sensitive P. aeruginosa (PSPA) after matching on duration of ICU stay at VAP onset and adjustment for confounders. RESULTS: Factors associated with onset of PRPA-VAP were as follows: admission to the ICU with septic shock, broad-spectrum antimicrobials at admission, prior use of ureido/carboxypenicillin, and colonization with PRPA before infection. Adequate antimicrobial therapy was more often delayed in the PRPA group. The crude ICU mortality rate and the hospital mortality rate were not different between the PRPA and the PSPA groups. In multivariate analysis, after controlling for time in the ICU before VAP diagnosis, neither ICU death (odds ratio (OR) = 0.73; 95% confidence interval (CI): 0.32 to 1.69; P = 0.46) nor hospital death (OR = 0.87; 95% CI: 0.38 to 1.99; P = 0.74) were increased in the presence of PRPA infection. This result remained unchanged in the subgroup of 87 patients who received adequate antimicrobial treatment on the day of VAP diagnosis. CONCLUSIONS: After adjustment, and despite the more frequent delay in the initiation of an adequate antimicrobial therapy in these patients, resistance to ureido/carboxypenicillin was not associated with ICU or hospital death in patients with PA-VAP.

Selected medical errors in the intensive care unit: results of the IATROREF study: parts I and II.

RATIONALE: Although intensive care units (ICUs) were created for patients with life-threatening illnesses, the ICU environment generates a high risk of iatrogenic events. Identifying medical errors (MEs) that serve as indicators for iatrogenic risk is crucial for purposes of reporting and prevention. OBJECTIVES: We describe the selection of indicator MEs, the incidence of such MEs, and their relationship with mortality. METHODS: We selected indicator MEs using Delphi techniques. An observational prospective multicenter cohort study of these MEs was conducted from March 27 to April 3, 2006, in 70 ICUs; 16 (23%) centers were audited. Harm from MEs was collected using specific scales. MEASUREMENTS AND MAIN RESULTS: Fourteen types of MEs were selected as indicators; 1,192 MEs were reported for 1,369 patients, and 367 (26.8%) patients experienced at least 1 ME (2.1/1,000 patient-days). The most common MEs were insulin administration errors (185.9/1,000 d of insulin treatment). Of the 1,192 medical errors, 183 (15.4%) in 128 (9.3%) patients were adverse events that were followed by one or more clinical consequences (n = 163) or that required one or more procedures or treatments (n = 58). By multivariable analysis, having two or more adverse events was an independent risk factor for ICU mortality (odds ratio, 3.09; 95% confidence interval, 1.30-7.36; P = 0.039). CONCLUSIONS: The impact of medical errors on mortality indicates an urgent need to develop prevention programs. We have planned a study to assess a program based on our results.

Mortality associated with timing of admission to and discharge from ICU: a retrospective cohort study.

BACKGROUND: Although the association between mortality and admission to intensive care units (ICU) in the "after hours" (weekends and nights) has been the topic of extensive investigation, the timing of discharge from ICU and outcome has been less well investigated. The objective of this study was to assess effect of timing of admission to and discharge from ICUs and subsequent risk for death. METHODS: Adults (≥ 18 years) admitted to French ICUs participating in Outcomerea between January 2006 and November 2010 were included. RESULTS: Among the 7,380 patients included, 61% (4,481) were male, the median age was 62 (IQR, 49-75) years, and the median SAPS II score was 40 (IQR, 28-56). Admissions to ICU occurred during weekends (Saturday and Sunday) in 1,708 (23%) cases, during the night (18:00-07:59) in 3,855 (52%), and on nights and/or weekends in 4,659 (63%) cases. Among 5,992 survivors to ICU discharge, 903 (15%) were discharged on weekends, 659 (11%) at night, and 1,434 (24%) on nights and/or weekends. After controlling for a number of co-variates using logistic regression analysis, admission during the after hours was not associated with an increased risk for death. However, patients discharged from ICU on nights were at higher adjusted risk (odds ratio, 1.54; 95% confidence interval, 1.12-2.11) for death. CONCLUSIONS: In this study, ICU discharge at night but not admission was associated with a significant increased risk for death. Further studies are needed to examine whether minimizing night time discharges from ICU may improve outcome.