An observational study of adult admissions to a medical ICU due to adverse drug events.

BACKGROUND: The objectives of the study were to estimate the incidence of intensive care unit (ICU) admissions due to adverse drug events (ADEs), to assess preventability, severity and costs of the corresponding ADE and to determine the leading causes of preventable ADEs. METHODS: An observational study was conducted in a medical ICU of a teaching hospital from February 2013 to February 2014. RESULTS: A total of 743 consecutive admissions were included, and they involved 701 different patients. The included admissions were categorized into three groups (admissions due to preventable ADE, admissions due to unpreventable ADE and the control group). Among the 743 ICU admissions included during the study period, 173 (23.3 %) were due to ADE, with 102 (13.7 %) related to preventable ADE and 71 (9.6 %) to unpreventable ADE, yielding a preventability rate of ADE of 0.59 (102/173). Admissions due to unpreventable ADE concerned patients with more comorbidities, a greater number of drugs and higher Simplified Acute Physiology Score II than admissions due to preventable ADE and the control group admissions (n = 570). Hospital mortality rates, corresponding costs and length of stay were all similar in the preventable ADE and control groups, whereas they were always significantly higher in the unpreventable ADE group. ICU mortality, length of stay and the corresponding costs were similar in the three groups. Non-compliance was the principal leading cause of preventable ADE (n = 31/102). The 102 preventable ADE-related admissions accounted for a total of 528 days of hospitalization in the ICU, requiring a mean of 1.4 ICU beds per day over the one-year period, with an associated total cost amounting to 747,651 €. CONCLUSIONS: ADE was a major cause of admission in the studied ICU, and in 59 % of the cases, ADEs were preventable. The reported burden of ICU admissions due to ADE advocates for further investigations to explore how the rate of such admissions could be decreased.

Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells.

Clostridium difficile has become the most common enteropathogen responsible for intestinal nosocomial post-antibiotic infections. This has coincided with the appearance of serious cases related to the emergence of hypervirulent strains. The toxins are the main virulence factors and elicit an inflammatory response during C. difficile infection. However, other bacterial components appear to be involved in the inflammatory process. In some pathogens, flagella play a role in pathogenesis through abnormal stimulation of the TLR5-mediated host immune response. To date, few studies have addressed this role for C. difficile flagella. In the current study, we confirm in two different epithelial cell models that C. difficile thanks to its FliC flagellin interacts with TLR5. In addition, thanks to inhibition and transcriptomic studies we demonstrate that the interaction of flagellin and TLR5 predominantly activates the NF-κB and, in a lesser degree, the MAPK pathways, via TLR5, leading to up-regulation of pro-inflammatory gene expression and synthesis of pro-inflammatory mediators. These results suggest a role for C. difficile flagella in contributing to inflammatory response in host intestinal cells.

A case of melphalan sustained accumulation in an 80-year old patient.

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

A systematic review of adult admissions to ICUs related to adverse drug events.

Adverse drug events (ADE) may lead to hospital admission, and in some cases admission to an ICU is mandatory. We conducted a systematic review dealing with the incidence of ADE requiring ICU admission in adult patients, the reference population being all ICU admissions. Medline, Embase and Web of Science databases were screened from January 1982 to July 2014, using appropriate key words. Only original articles in English reporting the incidence of ADE requiring ICU admission in adult patients among total ICU admissions were included. Article eligibility was assessed by two independent reviewers, a third being involved in cases of disagreement. All reported characteristics (type of ICU, characteristics of patients, incidence of ADE, severity and preventability, drugs involved, causality) in the selected articles were collected for the review. The quality of studies was independently assessed by two reviewers with a specific score that we developed. A meta-analysis was conducted. Inclusion criteria were fulfilled by 11 studies out of the 4,311 identified in the initial literature search. The median (interquartile) quality score was 0.61 (0.44; 0.69). The reported incidences of ADE requiring ICU admission in adult patients ranged from 0.37 to 27.4%, with an associated mortality rate ranging from 2 to 28.1% and a mean length of stay ranging from 2.3 to 6.4 days. Preventable events accounted for 17.5 to 85.7% of the events. Costs and mechanisms at the root of ADE were investigated in only two and five studies, respectively. The forest plot examining the incidence of ADE requiring ICU admission in adult patients was associated with high heterogeneity (I (2) statistic > 98%), and the shape of the corresponding funnel plot was asymmetric. Heterogeneity across studies concerned many features, including studied populations, events considered, causality assessment methods, definitions of preventability and severity. Despite the heterogeneity of the reports, our review indicates that ICU admission due to ADE is a significant issue that should deserve further interest. The review led us to propose a list of items devoted to the reporting of future studies on ADE requiring ICU admissions.

Effectiveness of cleaning of workplace cytotoxic surface.

PURPOSE: To minimize the risk of chronic occupational exposure of antineoplastic drugs, cleaning procedures must be evaluated. This study was conducted to compare the detergent efficiency of cleaning solutions (two hydro-alcoholic solutions, three disinfectants and two detergents) used in different cleaning protocols. METHODS: The central surface of a stainless steel plate (30 × 50 cm) was exposed to a carboplatin solution equivalent to 105,100 ng of platinum. After cleaning according to a standardized protocol, residual platinum contaminations were assayed on 10 × 10 cm sections. RESULTS: After standardized cleaning, the residual quantity of platinum on the surface of the deposit accounted for between 1.0 and >15 % of the initial deposit. Spread of contamination on the plate depended on the cleaning movement and was between 2.1 and 53.9 % of the total quantity on the plate. The two detergents were more efficient (2,793-4,780 ng/plate) than hydro-alcoholic solutions (>20,000 ng/plate). The efficacy of the disinfectant was intermediate (5,891-6,122 ng/plate for solutions and 15,360 ng/plate for pre-soaked gauze). The cleaning protocol was also important with better efficiency of 8 mL of cleaning solution for 1,500 cm(2) (versus 4 mL), sprayed directly on the plate (versus wiping) with no contact time (versus 5 min). CONCLUSION: The efficacy of chemical decontamination of cytotoxic work surfaces depends not only on the cleaning solution used, but also on the cleaning protocol. It is necessary to adapt the protocol to the surface to clean and it must be standardized and validated. This work is an example of an experimental procedure to evaluate the efficacy of cleaning solutions and protocols used at a workstation after exposure to antineoplastic drugs.