A new individualized prognostic approach to the management of women at risk of extreme preterm birth in France: Effect on neonatal outcome.

INTRODUCTION: After discussion with the parents, periviable infants can receive either active treatment or palliative care. The rate of active treatment in France is lower than in other developed countries, as is the survival rate of infants in this gestational age range. This study's main objective was to assess the effect of a standardized perinatal management protocol (EXPRIM) on the neonatal outcome of children born before 27 weeks of gestation. METHODS: A before-and-after study was conducted in the two level-3 hospitals of the Risks and Pregnancy DHU to compare two 16-month periods. The EXPRIM protocol was based on routine administration of prenatal corticosteroid therapy and a scheduled combined obstetric-pediatric group prenatal prognostic evaluation, not based solely on gestational age. The study included all births between 22 weeks and 26 weeks+6 days of gestation, except in utero deaths diagnosed at admission and medical terminations of pregnancy for fetal malformation, both excluded. The principal endpoint was survival without severe neonatal morbidity. RESULTS: The study included 267 women: 116 (128 newborns) in period 1 and 151 (172 newborns) in period 2. The median gestational age at admission to the maternity unit was 2.5 days younger in period 2, and the number of women admitted at 22-23 weeks doubled in period 2 (59 vs 29, respectively). Overall, the rates of live births, NICU transfer, and survival without severe morbidity were similar during the two periods. More infants were liveborn between 22 and 24 weeks in period 2 (66 vs 43). Of all newborns transferred to the NICU, 26 (29%) survived without severe morbidity in period 1 and 46 (39%) in period 2. After multivariate analysis, survival without severe morbidity did not differ significantly. CONCLUSION: Implementation of the EXPRIM protocol led to active treatment of more mothers and their children at the border of viability, and increased the number of children who survived without severe morbidity even if, overall, there was no statistically significant difference in percentage.

Impact of intensive care unit relocation and role of tap water on an outbreak of Pseudomonas aeruginosa expressing OprD-mediated resistance to imipenem.

BACKGROUND: To assess the impact of the incidental relocation of an intensive care unit (ICU) on the risk of colonizations/infections with Pseudomonas aeruginosa exhibiting OprD-mediated resistance to imipenem (PA-OprD). AIM: The primary aim was to compare the proportion of PA-OprD among P. aeruginosa samples before and after an incidental relocation of the ICU. The role of tap water as a route of contamination for colonization/infection of patients with PA-OprD was assessed as a secondary aim. METHODS: A single-centre, observational, before/after comparison study was conducted from October 2013 to October 2015. The ICU was relocated at the end of October 2014. All P. aeruginosa-positive samples isolated from patients hospitalized ≥48 h in the ICU were included. Tap water specimens were collected every three months in the ICU. PA-OprD strains isolated from patients and tap water were genotyped using pulse-field gel electrophoresis. FINDINGS: A total of 139 clinical specimens of P. aeruginosa and 19 tap water samples were analysed. The proportion of PA-OprD strains decreased significantly from 31% to 7.7% after the relocation of the ICU (P = 0.004). All PA-OprD clinical specimens had a distinct genotype. Surprisingly, tap water was colonized with a single PA-OprD strain during both periods, but this single clone has never been isolated from clinical specimens. CONCLUSION: Relocation of the ICU was associated with a marked decrease in P. aeruginosa strains resistant to imipenem. The polyclonal character of PA-OprD strains isolated from patients and the absence of tap-water-to-patient contamination highlight the complexity of the environmental impact on the endogenous colonization/infection with P. aeruginosa.

Delta Opioid Receptors: Learning and Motivation.

Delta opioid receptor (DOR) displays a unique, highly conserved, structure and an original pattern of distribution in the central nervous system, pointing to a distinct and specific functional role among opioid peptide receptors. Over the last 15 years, in vivo pharmacology and genetic models have allowed significant advances in the understanding of this role. In this review, we will focus on the involvement of DOR in modulating different types of hippocampal- and striatal-dependent learning processes as well as motor function, motivation, and reward. Remarkably, DOR seems to play a key role in balancing hippocampal and striatal functions, with major implications for the control of cognitive performance and motor function under healthy and pathological conditions.

Risk factors for acquisition of OXA-48-producing Klebsiella pneumonia among contact patients: a multicentre study.

BACKGROUND: Cohorting carbapenemase-producing Enterobacteriaceae (CPE) carriers during hospitalization limits in-hospital spreading. AIM: To identify risk factors for CPE acquisition among contacts of an index patient in non-cohorted populations. METHODS: A multicentre retrospective matched case-control study was conducted in five hospitals. Each contact patient (case) who acquired Klebsiella pneumoniae (KP)-OXA-48 from an index patient was compared to three contact (controls) with the same index patients matched with hospitalization in the same unit and similar exposure times. FINDINGS: Fifty-one secondary cases and 131 controls were included. By univariate analysis, exposure time (odds ratio: 1.06; 95% confidence interval: 1.02-1.1; P = 0.006), concomitant infection at admission (3.23; 1.42-7.35; P = 0.005), antimicrobial therapy within the last month before hospitalization (2.88; 1.34-6.2; P = 0.007), antimicrobial therapy during the exposure time (5.36; 2.28-12.6; P < 0.001), use of at least one invasive procedure (2.99; 1.25-7.15; P = 0.014), number of invasive procedures (1.52; 1.05-2.19; P = 0.025), and geographical proximity (2.84; 1.15-7.00; P = 0.023) were associated with CPE acquisition. By multivariate analysis, antimicrobial therapy during the exposure time (odds ratio: 6.36; 95% confidence interval: 2.46-16.44; P < 0.001), at least one invasive procedure (2.92; 1.04-8.17; P = 0.041), and geographical proximity (3.69; 1.15-11.86; P = 0.028) were associated with acquisition. CONCLUSION: In this study, geographical proximity, invasive procedure, and antimicrobial therapy during exposure time were significantly associated with KP-OXA-48 acquisition.

Unplanned return to theater: A quality of care and risk management index?

INTRODUCTION: Surgical quality and risk management is a major public health issue. The consequences of unplanned return to theater are social, occupational, financial and even legal. Unscheduled revision surgery is a major adverse event, resulting from serious complications - some of which are thought to be avoidable. The present study sought to assess and analyze the incidence of unplanned return to theater in an orthopedic surgery department. The study hypothesis was that some of the complications involved could be avoided. PATIENTS AND METHOD: A mixed retrospective-prospective study examined a consecutive series of 10,158 patients operated on in an orthopedic and traumatologic surgery department between January 2011 and December 2013. Patients undergoing revision surgery for reasons directly related to the primary procedure were analyzed. Patients were distributed among the following subgroups: infection, implant dislocation; hemorrhagic complication, mechanical complication, problem of primary technique, stiffness, wound healing disorder. Specific indicators of dysfunction liable to have contributed to onset of the complication were applied in each subgroup, to determine the avoidable or unavoidable nature of the event. RESULTS: Two hundred and twenty-four patients (2.2%) underwent revision surgery for reasons directly related to the primary procedure. One hundred and eight cases (48.2%) were considered to have been avoidable: 48 infections (21.4%), 27 implant dislocations (12%), 15 hemorrhagic complications (6.7%), 66 mechanical complications (29.5%), 35 technical problems at primary surgery (15.6%), 21 cases of stiffness (9.3%), and 12 cases of delayed wound healing (5.3%). Mean time to revision surgery was 2.7 ± 2.6 months. Extending the time-window to 1 year recruited extra cases: in 31.7% of cases, onset was after the 90th postoperative day, which is the usual deadline. The rate of unplanned return to theater was higher after unscheduled (traumatic: 3.2%) than scheduled surgery (1.7%, P < 0.001). CONCLUSION: Return to surgery in orthopedic and traumatologic surgery is underestimated. Annual incidence was 2.2%, and twice as high (3.2%) following traumatologic compared to scheduled surgery (1.7%). Analysis found that almost half the cases were avoidable. They represent a relevant and easily assessed indicator of treatment quality and associated risk management. A national or even international database in the form of an anonymous registry of revision surgeries would be useful.

Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice.

Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian brain. This peptide regulates many physiological functions and behaviors, such as cardio-respiratory control, thermoregulation, nociception, feeding, memory processes and motivational responses, and plays a prominent role in emotional responses including anxiety and depression. CCK-expressing brain regions involved in these functions remain unclear and their identification represents an important step towards understanding CCK function in the brain. The basolateral amygdala (BLA) is strongly involved in emotional processing and expresses high levels of CCK. In this study we examined the contribution of CCK expressed in this brain region to emotional responses in mice. To knockdown CCK specifically in the BLA, we used stereotaxic delivery of recombinant adeno-associated viral vectors expressing a CCK-targeted shRNA. This procedure efficiently reduced CCK levels locally. shCCK-treated animals showed reduced levels of anxiety in the elevated plus-maze, and lower despair-like behavior in the forced swim test. Our data demonstrate that CCK expressed in the BLA represents a key brain substrate for anxiogenic and depressant effects of the peptide. The study also suggests that elevated amygdalar CCK could contribute to panic and major depressive disorders that have been associated with CCK dysfunction in humans.

[Sorafenib-induced multiple eruptive keratoacanthomas]. / Kératoacanthomes multiples éruptifs induits par le sorafénib.

BACKGROUND: Sorafenib has been approved for use in the treatment of metastatic renal cell carcinoma. Cutaneous side-effects are common, including rash, hand-foot syndrome, alopecia, pruritus, dry skin and erythema. We report an original unexpected cutaneous effect: multiple keratoacanthomas. In the light of a literature review of drug-induced keratoacanthomas, we discuss the potential underlying physiopathological mechanism. CASE REPORT: Three weeks after starting treatment with sorafenib for metastatic renal cell carcinoma, a 64-year-old man developed skin lesions on the face, ears, forearms and thighs having the appearance of dome-shaped nodules with central keratotic cores. Eruptive keratoacanthomas were suspected and were in fact confirmed by histology. Thanks to effective antiangiogenic treatment and the mild discomfort of the keratoacanthomas, sorafenib could be continued. Three weeks after the end of treatment, all lesions had regressed and the patient's skin returned to normal. DISCUSSION: Although the precise aetiology is unknown, the development of eruptive keratoacanthomas is associated with impaired immunity, sun exposure, viral infection, genetic predisposition, radiation therapy and exposure to chemical carcinogens. A few cases of drug-induced keratoacanthomas have been described in the literature and certain immunosuppressant drugs have been implicated. This case suggests that the novel antineoplastic agent sorafenib has a complex activity that, in addition to tyrosine kinases inhibition, includes an immunosuppressant mechanism that can occasionally cause skin lesions.

Mu-opioid receptor activation induces transcriptional plasticity in the central extended amygdala.

Addiction develops from the gradual adaptation of the brain to chronic drug exposure, and involves genetic reprogramming of neuronal function. The central extended amygdala (EAc) is a network formed by the central amygdala and the bed nucleus of the stria terminalis. This key site controls drug craving and seeking behaviors, and has not been investigated at the gene regulation level. We used Affymetrix microarrays to analyze transcriptional activity in the murine EAc, with a focus on mu-opioid receptor-associated events because these receptors mediate drug reward and dependence. We identified 132 genes whose expression is regulated by a chronic escalating morphine regimen in the EAc from wild-type but not mu-opioid receptor knockout mice. These modifications are mostly EAc-specific. Gene ontology analysis reveals an overrepresentation of neurogenesis, cell growth and signaling protein categories. A separate quantitative PCR analysis of genes in the last of these groups confirms the dysregulation of both orphan (Gpr88) and known (DrD1A, Adora2A, Cnr1, Grm5, Gpr6) G protein-coupled receptors, scaffolding (PSD95, Homer1) and signaling (Sgk, Cap1) proteins, and neuropeptides (CCK, galanin). These transcriptional modifications do not occur following a single morphine injection, and hence result from long-term adaptation to excessive mu receptor activation. Proteins encoded by these genes are classically associated with spine modules function in other brain areas, and therefore our data suggest a remodeling of EAc circuits at sites where glutamatergic and monoaminergic afferences interact. Together, mu receptor-dependent genes identified in this study potentially contribute to drug-induced neural plasticity, and provide a unique molecular repertoire towards understanding drug craving and relapse.

Impact of a five-year surveillance of central venous catheter infections in the REACAT intensive care unit network in France.

Central venous catheter (CVC)-related infections (CRIs) are a key target for infection control in intensive care units (ICUs). The aim of this study was to describe temporal trends of CRI incidence in a network of volunteer ICUs in Northern France. During a 4 month surveillance period each year, all CVCs in place for more than 48h were prospectively followed until removal or patient discharge. Standard clinical and microbiological criteria were used to define colonization and CRI. The standardized incidence ratio (SIR) was estimated by dividing the number of observed CRIs by the number of expected CRIs, which was computed using a logistic regression model including risk factors for CRI. CRI incidence and SIR were fed back to ICUs as a benchmark at the end of each period. From 2001 to 2005, 135 ICUs participated for at least one surveillance period. Overall, 11 703 CVC in 9182 patients (122 495 CVC-days) were included. CRI incidence was 2.8 per 1000 CVC-days. Among 35 ICUs that participated for three or more consecutive periods, CRI incidence decreased significantly by 58.6%. SIR also decreased significantly from the first to the third surveillance period in these ICUs. These results suggest that surveillance programmes have a significant impact on CRI risk in ICUs and remain an important strategy for combating nosocomial infections in these settings.

[How to improve central venous catheter use in intensive care unit?]. / Comment optimiser l'utilisation des cathéters veineux centraux en réanimation?

OBJECTIVE: Central venous catheter (CVC) insertion is routinely performed in critically ill patients but causes mechanical, thrombotic, or infectious adverse events in 15% of cases. It should be possible to improve the benefit/risk ratio of central venous catheterization in intensive care unit. DATA SOURCE: We searched Pubmed using the terms: "catheterization, central venous, peripheral, adverse effects"; then "thrombosis, phlebitis, thrombophlebitis, jugular vein, femoral vein, subclavian vein, pneumothorax, haemothorax, extravasation of diagnostic and therapeutic materials". We then discuss this with a panel of intensivists in a workshop. DATA SYNTHESIS: Few data are available on the risk/benefit ratio of central vs. peripheral venous catheterization. In some cases (cardiac arrest, rapid fluid loading, parenteral nutrition) the choice is based on clear recommendations. In others (irritating drugs, pressure monitoring, peripheral access failure), the choice depends on medical and nurses daily evaluation. When CVC insertion is mandatory, it is important to implement the recommendations of the consensus conferences to prevent infectious and thrombotic complications. Mechanical complications should be improved by selecting the most appropriate insertion site, and, if unsuccessful, switching to another operator before the complications occurs. Doppler-ultrasound guidance is recommended, but is limited by the cost and training of the technique. CONCLUSION: Studies evaluating the risk/benefit ratio of CVCs versus peripheral catheters are needed to develop a venous-access strategy for ICU patients. When a CVC is mandatory, recent data are available to improve the risk/benefit ratio and can be used to build a decision algorithm.

[Epidemiology of catheter-related infections in intensive care unit]. / Epidémiologie des infections liées aux cathéters en réanimation.

Catheter-related infections remain an important cause of nosocomial infection in the ICU. They include colonization of the device, exit-site infection and catheter-related bloodstream infection with or without bacteraemia. Data from clinical studies and surveillance networks should be compared cautiously due to important methodological differences and wide variations of device-utilization ratio between units or countries. In France, two regional networks (C-CLIN Paris-Nord and C-CLIN Sud-Est) produced comparable and reproducible results. Colonization represents five-six cases per 1000 catheter-days and bacteraemia represents one case per 1000 catheter-days. Incidence rates from North American studies are usually four to five times higher. Numerous risk factors have been identified. Some of them could be used to stratify patients according to risk of catheter-related infection and to allow more valid comparison between ICU's performances. Participation of French ICUs to the recent national surveillance networks (REA RAISIN and REACAT RAISIN) should be encouraged.

Nosocomial infections and hospital mortality: a multicentre epidemiology study.

The aim of this study was to evaluate the number of deaths associated with nosocomial infections (NI) and the contribution of these NI to death. A multicentre descriptive study was conducted in 16 tertiary-care hospitals (14 222 beds) in Northern France. Medical records of consecutive patients who died at least 48 h after admission were reviewed for cause of death, NI and disease severity, before admission and before NI onset. The contribution of NI to death was assessed by agreement between two physicians according to a three-category scale of probability. Among the 1945 patients who died during the study, 26.6% had an NI. According to the agreed diagnosis, NI contributed to the deaths of 284 (14.6%) patients(certainly for 6.6% and possibly for 8%), thereby ranking NI as the fourth most frequent cause of death. Considering the deaths that had not been anticipated independently of NI two weeks before they occurred, NI definitely contributed to 2.8% of them. Lower respiratory tract, bloodstream and surgical wound infections were responsible for 39, 20 and 14%, respectively,of all NI in these patients. The impact of NI on in-hospital mortality seems to be lower than had previously been estimated in France based on US data from the 1970s and 1980s. To improve healthcare quality, further studies are needed to elucidate the processes that may contribute to fatal severe NI.

[Hantavirus infections in Ile-de-France]. / Infections à Hantavirus en Ile-de-France.

Hantavirus infections, Puumala serotype, is a well-known disease in the northeast of France, but not in the Paris area, despite regularly diagnosed cases. A retrospective study was performed from January 1999 to December 2000 to assess the clinical and epidemiological characteristics of this disease in the "Région Ile-de-France". Fourteen cases were diagnosed. All required hospitalisation. Patients presented usually with high fever, pain, renal failure, moderate thrombocytopenia and, sometimes, transitional acute myopia witch is pathognomonic of the disease. In each case, a contact with a forest was found. Twelve patients recovered completely. One patient with pre-existing chronic renal and hepatic failure died and another developed a persistent arterial hypertension. Invasive procedures were often used before the diagnosis. Hantavirus infections does exist in the "Région Ile-de-France". Failure to recognise this disease in this area lead to unnecessary invasive procedures and hospitalizations.

[Enterococcal meningitis revealing endocarditis]. / Méningite à entérocoque révélant une endocardite.

INTRODUCTION: Enterococci are frequently responsible for endocarditis, but a rare cause of meningitis. OBSERVATION: A 55 years-old man presented with Enterococcus faecium meningitis. Systematic transoesophageal echocardiography (TOE), despite the absence of organic murmur and the negativity of the hemocultures, revealed a concomitant aortic endocarditis. CONCLUSION: Review of the literature suggests that the association of endocarditis with enterococcal meningitis is far from accidental. We suggest that a TOS be conducted systematically when faced with this disease. The therapeutic implications are important, notably regarding the duration of antibiotherapy.

Mechanical ventilation in patients with acute ischemic stroke: survival and outcome at one year.

OBJECTIVE: To assess the prognosis of patients with acute ischemic stroke who require mechanical ventilation and to determine early factors influencing mortality. DESIGN: Prospective observational study. SETTING: Medical intensive care unit with a cerebrovascular emergency unit in a university-affiliated hospital. PATIENTS: Fifty-eight consecutive patients (mean age 65+/-13 years) requiring mechanical ventilation in the early course of an acute ischemic stroke. MEASUREMENTS AND RESULTS: Clinical data were recorded before intubation according to a standardized procedure. Mortality and functional outcome were assessed after a 1-year follow-up. Mechanical ventilation was started within 48 h after admission in 53 patients (91.4%). The mean duration of ventilation was similar in survivors (9.7+/-9.0 days) and non-survivors (8.6+/-8.7 days). Mortality was 72.4% at 1 year. Among the 16 survivors, none were in a persistent vegetative state and 11 had a Barthel index of 60, reflecting good functional status. Bilateral absence of corneal reflex and bilateral absence of pupillary light reflex had a positive predictive value of death of 1 (95% CI 0.78-1.00 and 0.74-1.00, respectively). After Cox regression analysis, presence of stupor or coma (OR 2.6, 95% CI 1.5-5.0), bilateral absence of corneal reflex before intubation (OR 3.4, 95% CI 1.4-8.7) and presence of ischemic cardiopathy (OR 2.8, 95% CI 1.4-5.5) were independent predictors of mortality. CONCLUSIONS: Systematic withholding of endotracheal intubation in patients with AIS is not recommended. Careful and rigorous neurologic examination, including assessment of brain stem reflexes, might help to identify patients with a very high probability of death despite mechanical ventilation.

Candida albicans prosthetic arthritis treated with fluconazole alone.

Conventional treatment of Candida prosthetic joint infection usually includes surgery followed by a long period of antifungal medication. We report a case of Candida albicans prosthetic arthritis successfully treated with fluconazole alone.

Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial.

CONTEXT: Whether venous catheterization at the femoral site is associated with an increased risk of complications compared with that at the subclavian site is debated. OBJECTIVE: To compare mechanical, infectious, and thrombotic complications of femoral and subclavian venous catheterization. DESIGN AND SETTING: Concealed, randomized controlled clinical trial conducted between December 1997 and July 2000 at 8 intensive care units (ICUs) in France. PATIENTS: Two hundred eighty-nine adult patients receiving a first central venous catheter. INTERVENTIONS: Patients were randomly assigned to undergo central venous catheterization at the femoral site (n = 145) or subclavian site (n = 144). MAIN OUTCOME MEASURES: Rate and severity of mechanical, infectious, and thrombotic complications, compared by catheterization site in 289, 270, and 223 patients, respectively. RESULTS: Femoral catheterization was associated with a higher incidence rate of overall infectious complications (19.8% vs 4.5%; P<.001; incidence density of 20 vs 3.7 per 1000 catheter-days) and of major infectious complications (clinical sepsis with or without bloodstream infection, 4.4% vs 1.5%; P =.07; incidence density of 4.5 vs 1.2 per 1000 catheter-days), as well as of overall thrombotic complications (21.5% vs 1.9%; P<.001) and complete thrombosis of the vessel (6% vs 0%; P =.01); rates of overall and major mechanical complications were similar between the 2 groups (17.3% vs 18.8 %; P =.74 and 1.4% vs 2.8%; P =.44, respectively). Risk factors for mechanical complications were duration of insertion (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.08 per additional minute; P<.001); insertion in 2 of the centers (OR, 4.52; 95% CI, 1.81-11.23; P =.001); and insertion during the night (OR, 2.06; 95% CI, 1.04-4.08; P =.03). The only factor associated with infectious complications was femoral catheterization (hazard ratio [HR], 4.83; 95% CI, 1.96-11.93; P<.001); antibiotic administration via the catheter decreased risk of infectious complications (HR, 0.41; 95% CI, 0.18-0.93; P =.03). Femoral catheterization was the only risk factor for thrombotic complications (OR, 14.42; 95% CI, 3.33-62.57; P<.001). CONCLUSION: Femoral venous catheterization is associated with a greater risk of infectious and thrombotic complications than subclavian catheterization in ICU patients.

A prospective survey of nutritional support practices in intensive care unit patients: what is prescribed? What is delivered?

OBJECTIVES: To assess the amount of nutrients delivered, prescribed, and required for critically ill patients and to identify the reasons for discrepancies between prescriptions and requirements and between prescriptions and actual delivery of nutrition. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university-affiliated general hospital. PATIENTS: Fifty-one consecutive patients, receiving nutritional support either enterally or intravenously for > or = 2 days. We followed patients for the first 14 days of nutritional delivery. MEASUREMENTS AND MAIN RESULTS: The amount of calories prescribed and the amount actually delivered were recorded daily and compared with the theoretical energy requirements. A combined regimen of enteral and parenteral nutrition was administered on 58% of the 484 nutrition days analyzed, and 63.5% of total caloric intake was delivered enterally. Seventy-eight percent of the mean caloric amount required was prescribed, and 71% was effectively delivered. The amount of calories actually delivered compared with the amount prescribed was significantly lower in enteral than in parenteral administration (86.8% vs. 112.4%, p < .001). Discrepancies between prescription and delivery of enterally administered nutrients were attributable to interruptions caused by digestive intolerance (27.7%, mean daily wasted volume 641 mL), airway management (30.8%, wasted volume 745 mL), and diagnostic procedures (26.6%, wasted volume 567 mL). Factors significantly associated with a low prescription rate of nutritional support were the administration of vasoactive drugs, central venous catheterization, and the need for extrarenal replacement. CONCLUSIONS: An inadequate delivery of enteral nutrition and a low rate of nutrition prescription resulted in low caloric intake in our intensive care unit patients. A large volume of enterally administered nutrients was wasted because of inadequate timing in stopping and restarting enteral feeding. The inverse correlation between the prescription rate of nutrition and the intensity of care required suggests that physicians need to pay more attention to providing appropriate nutritional support for the most severely ill patients.

First evidence of a delay-dependent working memory-enhancing effect of modafinil in mice.

This study investigated the effects of pretest injection of modafinil on delayed spontaneous alternation rates (SA) used to evaluate working memory in C57 Bl/6 mice. In a first experiment, systemic modafinil at 64 mg/kg, but not at 8 mg/kg or 32 mg/kg doses produced a significant increase of alternation scores (intertrial interval (ITI) 60s) when compared with controls. In a second experiment, modafinil (64 mg/kg) enhanced the alternation rates mainly at long (60 s and 180 s) but not at short (5 s) ITIs. Exploratory latencies and activity in a four hole-board apparatus were not modified by modafinil administration. These experiments are the first to demonstrate a delay-dependent working memory-enhancing effect of modafinil.

"Colonization pressure" and risk of acquisition of methicillin-resistant Staphylococcus aureus in a medical intensive care unit.

OBJECTIVE: To determine the roles of "colonization pressure," work load or patient severity in patient acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs). DESIGN: Prospectively collected data from October 1996 through December 1998. SETTING: A 12-bed medical ICU in a university-affiliated general hospital. PATIENTS: Patients with risk factors for MRSA admitted to the ICU were screened within 72 hours of admission and weekly thereafter. MRSA was considered imported if detected during the first 72 hours of admission and nosocomial if detected only thereafter. Three screening strategies were used on admission during three consecutive periods. INTERVENTIONS: The unit of time chosen for measurements was the week. Weekly colonization pressure (WCP) was defined as the number of MRSA-carrier patient-days/total number of patient-days. Patient severity (number of deaths, Simplified Acute Physiologic Score [SAPS] II), work load (number of admis sions, Omega score), and colonization pressure (number of MRSA carriers at the time of admission, WCP) were compared with the number of MRSA-nosocomial cases during the following week. RESULTS: Of the 1,016 patients admitted over 116 weeks, 691 (68%) were screened. MRSA was imported in 91 (8.9%) admitted patients (13.1% of screened patients) and nosocomial in 46 (4.5%). The number of MRSA-nosocomial cases was correlated to the SAPS II (P=.007), the Omega 3 score (P=.007), the number of MRSA-imported cases (P=.01), WCP (P<.0001), and the screening period (P<.0001). In multivariate analysis, WCP was the only independent predictive factor for MRSA acquisition (P=.0002). Above 30% of WCP, the risk of acquisition of MRSA was approximately fivefold times higher (relative risk, 4.9; 95% confidence interval, 1.2-19.9; P<.0001). CONCLUSION: Acquisition of MRSA in ICU patients is strongly and independently influenced by colonization pressure.