Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins.

OBJECTIVES: This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. METHODS: A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. RESULTS: Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. CONCLUSIONS: Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.

Fully Automated Surveillance of Healthcare-Associated Infections with MONI-ICU: A Breakthrough in Clinical Infection Surveillance.

OBJECTIVE: Expert surveillance of healthcare-associated infections (HCAIs) is a key parameter for good clinical practice, especially in intensive care medicine. Assessment of clinical entities such as HCAIs is a time-consuming task for highly trained experts. Such are neither available nor affordable in sufficient numbers for continuous surveillance services. Intelligent information technology (IT) tools are in urgent demand. METHODS: MONI-ICU (monitoring of nosocomial infections in intensive care units (ICUs)) has been developed methodologically and practically in a stepwise manner and is a reliable surveillance IT tool for clinical experts. It uses information from the patient data management systems in the ICUs, the laboratory information system, and the administrative hospital information system of the Vienna General Hospital as well as medical expert knowledge on infection criteria applied in a multilevel approach which includes fuzzy logic rules. RESULTS: We describe the use of this system in clinical routine and compare the results generated automatically by MONI-ICU with those generated in parallel by trained surveillance staff using patient chart reviews and other available information ("gold standard"). A total of 99 ICU patient admissions representing 1007 patient days were analyzed. MONI-ICU identified correctly the presence of an HCAI condition in 28/31 cases (sensitivity, 90.3%) and their absence in 68/68 of the non-HCAI cases (specificity, 100%), the latter meaning that MONI-ICU produced no "false alarms". The 3 missed cases were due to correctable technical errors. The time taken for conventional surveillance at the 52 ward visits was 82.5 hours. MONI-ICU analysis of the same patient cases, including careful review of the generated results, required only 12.5 hours (15.2%). CONCLUSION: Provided structured and sufficient information on clinical findings is online available, MONI-ICU provides an almost real-time view of clinical indicators for HCAI - at the cost of almost no additional time on the part of surveillance staff or clinicians.

Re-evaluation of current A0 value recommendations for thermal disinfection of reusable human waste containers based on new experimental data.

Issues over the correct cleaning and disinfection of reusable medical devices are of great concern for local infection control teams. We investigated the heat resistance of two important micro-organisms implicated in nosocomial infections, Enterococcus spp. and spores of Bacillus subtilis (a surrogate for Clostridium difficile). Disinfection with moist heat, based on the A(0) concept (EN ISO 15883-1), is the most common method for disinfection of human waste containers in the hospital setting. The aim of this study was to scrutinise the A(0) concept regarding the inactivation of the above-mentioned micro-organisms and to look for possible interferences. Experiments were carried out in phosphate-buffered saline, artificial soil in suspension (ASS) and dried artificial soil (AS). Artificial soil was used to simulate insufficient cleaning of bedpans. Micro-organisms were treated at different temperatures and time periods. It was shown that soil protected the micro-organisms against heat and that dried soil enhanced this effect, probably as a result of thermal insulation. The results of the current study do not support the general recommendation to use an A(0) of 60 for the disinfection of bedpans but warrant differential strategies depending on the expected microbial load. We generally recommend for disinfection processes aimed at vegetative bacteria an A(0) of >or=180. Furthermore we want to emphasise the utmost importance of not allowing freshly contaminated bedpans to dry for longer time periods, as the significance of thorough cleaning of contaminated human waste containers before being exposed to heat treatment for their disinfection was clearly demonstrated.

Subthalamic deep brain stimulation and impulse control in Parkinson's disease.

BACKGROUND AND PURPOSE: Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson's disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy. METHODS: In a cross-sectional evaluation, 53 consecutively eligible patients were assessed for impulsivity with the Barratt Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota Impulsive Disorders Interview, and for obsessive-compulsive symptoms using the Maudsley Obsessional-Compulsive Inventory. RESULTS: Independent samples t-tests revealed that compulsivity scores were not different between DBS patients and patients without DBS. However, impulsivity scores were significantly higher in DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and in 3 of 37 (8%) medically treated patients. No association was found between the use of dopamine agonists and impulsivity in DBS patients. CONCLUSIONS: Our data suggest that screening for impulsivity and ICDs should be performed prior to DBS, and that patients should be monitored for these problems during follow-up. Prospective trials are needed to confirm the findings of this exploratory study and to elucidate the reasons of a possible induction of impulsivity by STN DBS.

Topiramate in essential tremor: a double-blind, placebo-controlled trial.

BACKGROUND: Essential tremor is most prevalent and most disabling in older patients. Additional therapies are required for patients with an inadequate response or intolerable side effects. In small trials, topiramate appeared to be beneficial in essential tremor. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-design trial, patients with moderate to severe essential tremor of the upper limbs were randomized to 24 weeks of treatment with placebo or topiramate (target dose, 400 mg/day) as monotherapy or as an adjunct to one antitremor medication. The primary efficacy variable was the final visit tremor score based on the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS: The intent-to-treat population was 208 patients (topiramate, 108; placebo, 100). The final visit score (last observation carried forward) was lower in the topiramate group than with placebo (p < 0.001). Mean percentage improvement in overall TRS scores was 29% with topiramate at a mean final dose of 292 mg/day and 16% with placebo (p < 0.001). Topiramate was associated with greater improvement in function and disability (p = 0.001). A between-group difference (p < 0.001) was observed at the first on-treatment visit at 4 weeks when the target topiramate dose was 100 mg/day (mean achieved dose, 62 +/- 9 mg/day). The most common treatment-limiting adverse events in topiramate-treated patients were paresthesia (5%), nausea (3%), concentration/attention difficulty (3%), and somnolence (3%). Adverse events were treatment limiting in 31.9% of topiramate patients and 9.5% of placebo patients. CONCLUSIONS: Topiramate was effective in the treatment of moderate to severe essential tremor. Tremor reduction was accompanied by functional improvements, such as in motor tasks, writing, and speaking.

Economic burden associated with multi-resistant Gram-negative organisms compared with that for methicillin-resistant Staphylococcus aureus in a university teaching hospital.

The aim of this study was to investigate the hospital costs of patients with multi-drug-resistant Gram-negative bacilli (MR-GNB) compared with those for patients with methicillin-resistant Staphylococcus aureus (MRSA), using the Austrian performance-related hospital financing system (LKF). The study was performed retrospectively at Vienna General Hospital, a 2,160-bed university teaching hospital, from January to June 2002. There were 99 patients in the MR-GNB group (median age 58 years) and 74 patients in the MRSA group (median age 60 years). More patients in the MR-GNB group (59 patients, 60%) were treated in the intensive care unit compared with patients in the MRSA group (25 patients, 34%) (P<0.01). The median hospital stay (42 and 37 days, respectively) and mortality (18 and nine deaths, respectively) of the two groups were similar. The total hospital cost for patients in the MR-GNB group was higher [4 915 712 LKF credit points (median: 34,180) equivalent to 2,605,327 pounds (median: 18,115 pounds )] than that for patients in the MRSA group [2,088,904 LKF credit points (median: 12,650) equivalent to 1, 093, 906 pounds (median: 6,624 pounds)] (P<0.01). This study is limited by being retrospective and having charge-based costings. However, it suggests that the hospital costs of patients with MR-GNB are substantial and may be greater than those of patients with MRSA.

Polaronic quasiparticles in a strongly correlated electron band.

We show that a strongly renormalized band of polaronic quasiparticle excitations is induced at the Fermi level of an interacting many-electron system on increasing the coupling of the electrons to local phonons. We give results for the local density of states at zero temperature both for the electrons and phonons. The polaronic quasiparticles satisfy Luttinger's theorem for all regimes considered, and their dispersion shows a kink similar to that observed experimentally in copper oxides. Our calculations are based on the dynamical mean field theory and the numerical renormalization group for the hole-doped Holstein-Hubbard model and large on-site repulsion.

The training curriculum in hospital infection control.

Standardised training curricula for infection control nurses (ICNs) and recognition of the specialty exist in many European countries, but infection control physician (ICP) is not a specialty recognised by the UEMS. To gather information on curricula for ICPs, members of the ESCMID Study Group on Nosocomial Infections received a questionnaire. There is discussion about which 'professions' should be included in an infection control team. Within the 12 countries included, the average full-time equivalents (FTEs) for ICPs and ICNs per 1000 beds were 1.2 and 3.4, respectively. In addition to ICNs and ICPs, an infection control team should also include a data manager, an epidemiologist, secretarial/administrative support, and possibly, surveillance technicians. Overall, the composition of an ideal infection control team was estimated to be 9.3 FTE per 1000 beds. The background of ICPs can be clinical microbiology or infectious diseases. Among the participants, it was predominantly clinical microbiology. The ideal training curriculum for the ICP should include 6 years of postgraduate training. Of these, at least 2 years should be 'clinical training' (e.g., internal medicine) to acquire experience in the management of high-risk patients. Furthermore, training with regard to infection control and hospital epidemiology should be offered as a 'common trunk' for those being trained in clinical microbiology or infectious diseases. Important issues that remain are: implementation/standardisation of training curricula for doctors, recognition of ICP as a separate specialty or sub-specialty of clinical microbiology and/or infectious diseases, validation of on-the-job training facilities in terms of the number of doctors and nurses who can give training and the category of patients/problems present, and mandatory postgraduate education/continuing medical education specific for infection control for doctors and nurses in the field.

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months (staged surgery). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day (simultaneous surgery). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the off and on drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5 percent) and on (35.5 percent) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the off and on medication states preoperatively and at 2 years postoperatively also revealed a significant improvement...(AU)

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response.

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.

An open-label evaluation of the tolerability and safety of Stalevo (carbidopa, levodopa and entacapone) in Parkinson's disease patients experiencing wearing-off.

OBJECTIVES: To evaluate the tolerability, safety and efficacy of Stalevo (carbidopa, levodopa and entacapone) in Parkinson's disease (PD). BACKGROUND: Levodopa provides the most effective symptom control for the treatment of Parkinson's disease (PD). However, its long-term use is limited by the development of motor complications such as wearing-off. Catechol-O-methyltransferase (COMT) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce 'off' time. Stalevo is a new levodopa product that combines carbidopa, levodopa and entacapone in one tablet. Clinical studies have not been reported with this compound. DESIGN METHODS: An open-label, multi-center US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing-off, with (n = 39) and without (n = 130) mild dyskinesia. Patients were switched from immediate-release carbidopa/levodopa to Stalevo and were treated for four weeks. Assessments included tolerability measures, adverse events profile, the disease-specific quality of life instrument PDQ-39, UPDRS parts II, III, and question 39 and investigator and patient global clinical assessments. RESULTS: 14 subjects (8%) discontinued treatment with Stalevo, of which 12 (7%) were due to adverse events. 11/130 (8.5%) subjects developed new onset dyskinesia and 17/39 (43.6%) of patients with existing dyskinesia reported a worsening in their dyskinesia. However, this was managed by a change in dose in 21.4% of patients and in another 10.7% dyskinesias resolved without any need for dose adjustment. Other side effects were infrequent and mild, the most common being nausea (12.4%) dizziness (6.5%) and somnolence (6.5%). Stalevo treatment resulted in significant improvements in PDQ-39 and UPDRS (II + III) scores (p < 0.001). Assessment of 'off' time demonstrated a reduction in off time in 32% of patients, compared with an increase in 7% of patients. Improvements were noted by both investigator (68.1%) and patient (68.6%) assessments. CONCLUSIONS: Switching PD patients experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe, well tolerated and resulted in clinical improvement.

Apolipoprotein E controls the risk and age at onset of Parkinson disease.

BACKGROUND: Similarities between Alzheimer disease (AD) and Parkinson disease (PD) suggest a possible role for apolipoprotein E (APOE) in PD. Most previous studies seeking to establish such a link used case-control datasets and results have been inconsistent. OBJECTIVE: To investigate APOE's role in PD using family-based association analyses. METHODS: APOE functional polymorphisms were genotyped for 658 PD affected families, including 282 multiplex and 376 singleton families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the effect of APOE on age at onset of PD. RESULTS: APOE was significantly associated with risk of developing PD. Stratified analysis revealed that APOE was most strongly associated with families with a positive PD family history (global p = 0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a negative association of APOE-4 (p = 0.015) with age at onset in PD. CONCLUSIONS: The APOE-4 allele increases risk and decreases age at onset of PD, an association that may not be dependent upon cognitive impairment.

Chorea and contraceptives: case report with pet study and review of the literature.

Chorea is a well-recognized but rare complication of oral contraceptive use. A 27-year-old woman developed right hemichorea while taking an oral contraceptive (OC). No other causes of chorea were found. A positron emission tomography (PET) study with (18)F-fluorodeoxyglucose demonstrated a dense focus of increased glucose metabolism involving the body of the left caudate nucleus. To our knowledge, this is the first report of a PET study in a patient with OC-induced chorea in the absence of systemic lupus erythematosus or antiphospholipid antibodies.

National surveillance of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in Austrian hospitals: 1994-1998.

In 1994, the Austrian Federal Ministry for Labour, Health and Social Affairs initiated a nationwide survey of the prevalence of methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) in Austrian hospitals. A questionnaire had to be filled out by the medical directors of participating hospitals. During the five years of surveillance (1994-1998), a total of 9385 MRSA and 71510 MSSA episodes of infection/colonization were reported. The rate of MRSA decreased from 15.8% in 1994 to 8.2% in 1998. However, the frequency per 1000 hospital admissions increased from 0.85 to 1.29 with a maximum of 2.42 MRSA episodes per 1000 admissions in 1997. Overall, in 53.6% of 5020 S. aureus episodes, signs and symptoms of an infection were reported, of these 9.3% (251/2692) were due to MRSA. For large hospitals with more than 1000 beds, 20.9% of reported MRSA episodes were associated with infection, 54.9% of MRSA episodes from hospitals with 301-1000 beds, 60.1% from hospitals with 101-300 beds, and 80.0% from small hospitals with less than 100 beds. Our data do not support the hypothesis of higher virulence of MRSA compared with MSSA. Indeed, in this survey, MSSA episodes were more frequently associated with signs and symptoms of infection (OR=1.35, 95% CI: 1.12-1.62, P<0.001).

[Biomechanical properties of cartilage repair tissue after different cartilage repair procedures in sheep]. / Biomechanische Eigenschaften von Knorpelersatzgewebe nach verschiedenen Methoden der Knorpeldefektbehandlung beim Schaf.

AIM: The purpose of this study was to evaluate the biomechanical quality of cartilage and repair tissue in a sheep's knee. 4 standardized 7 mm defects were created on the medial femoral condyle and on the patellar groove (n = 22). These were treated with 4 different cartilage repair procedures and examined 1 year later. MATERIAL AND METHODS: The different groups were: (1) a cell-seeded collagen type-I/III-membrane (Chondro Gide(R)) glued into the defect; (2) a collagen type-I/III-membrane, sutured and cells injected underneath; (3) an engineered, cell-seeded collagen type-II-membrane, glued; (4) periosteum sutured and cells injected underneath; (5) CONTROLS: healthy contra-lateral knees. Indentation tests were performed to reveal the biomechanical capacity. From creep indentation over 35 s a "25-s creep index" was calculated. A high creep index means that the cartilage can undergo greater and faster compression. RESULTS: The repair tissue was significantly thinner than the normal cartilage. The mean creep index of all repair tissues was measured at 111 and 125, respectively (p < 0.05). There were no significant differences among the treated groups. CONCLUSION: In this animal study, none of the induced repair tissues was biomechanically comparable to genuine articular cartilage.

Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's disease.

Recently, the authors demonstrated linkage in idiopathic PD to a region on chromosome 8p that contains the N-acetyltransferase genes, NAT1 and NAT2. The authors examined NAT1 and NAT2 for association with PD using family-based association methods and single nucleotide polymorphisms (SNPs). The authors did not find evidence for association with increased risk for PD between any individual NAT1 or NAT2 SNP or acetylation haplotype (N = 397 families, 1,580 individuals).

Neuropsychological and quality of life outcomes 12 months after unilateral thalamic stimulation for essential tremor.

OBJECTIVES: To evaluate the one year cognitive, mood state, and quality of life (QoL) outcomes of unilateral thalamic deep brain stimulation (DBS) for essential tremor (ET). METHODS: 40 patients diagnosed with ET completed comprehensive neuropsychological assessments about one month before and three and 12 months after DBS electrode implantation. Data were subjected to multivariate analyses, and significant results were further analysed using univariate techniques. RESULTS: Analyses revealed statistically significant improvements on a cognitive screening measure and in aspects of fine visuomotor and visuoperceptual functions, verbal memory, mood state, and QoL. No group-wise declines in cognition were observed, but more patients showed declines than improvements on language and visual memory tests. Semantic verbal fluency declined significantly in four (10%) of the patients. In these four patients, diminished lexical verbal fluency was present at baseline. CONCLUSION: Cognitive, mood, and QoL outcomes after one year of DBS for ET are favourable; there were no overall deleterious effects on cognition, and DBS was accompanied by a significant reduction in anxiety and improvements in quality of life. However, preoperative verbal fluency diminution may predispose to further fluency declines after DBS.

Antimicrobial susceptibility profiles of clinically relevant blood culture isolates from nine surgical intensive care units, 1996-2000.

In order to elucidate trends in the incidence and susceptibility profiles of causative agents of bacteremia/fungemia in nine surgical intensive care units, a total of 744 isolates obtained during a 5-year period (1996-2000) were studied. The isolates included 698 bacteria and 46 fungi obtained from 523 positive blood cultures, representing 317 episodes of bacteremia/fungemia. Methicillin-resistant Staphylococcus aureus accounted for 2.3 episodes per 1000 surgical ICU admissions in 1996, 1.6 in 1997, 0.3 in 1998, 0.6 in 1999, and 1.7 in 2000. One Enterococcus faecalis (VanA) isolate resistant to both vancomycin and teicoplanin was recovered in 1996. Ciprofloxacin resistance in Pseudomonas aeruginosa decreased from 36% in 1996 to 20% in 2000, and resistance to third-generation cephalosporins decreased from 40% in 1996 to 9% in 2000. In light of differences between these results and those found elsewhere, these findings might prove useful for making infection control policy decisions in intensive care units.