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.

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.

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.

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.

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.

Dose-response relationship of propranolol in the treatment of essential tremor.

The effect of doses of propranolol hydrochloride, 80 to 800 mg/day, was investigated in 15 patients with essential tremor. The dose was increased by 80 mg weekly. Tremor was recorded by an accelerometer and its amplitude and frequency was determined by spectral analysis. Serum propranolol level was measured by radioreceptor assay. Tremor control varied greatly from complete suppression at 80 mg/day to no reduction at 800 mg/day. Mean serum propranolol levels increased with increasing dosage, but they did not correlate with tremor suppression. Five patients did not tolerate doses higher than 640 mg/day. Maximum tremor suppression occurred within a dose range between 160 and 320 mg/day. Higher doses did not cause additional tremor reduction.

Pharmacologic treatment of parkinsonian tremor.

The relative efficacy of trihexiphenidyl hydrochloride, amantadine hydrochloride, and low-dose carbidopa-levodopa in reducing parkinsonian tremor was investigated using objective techniques. Trihexiphenidyl and carbidopa-levodopa decreased tremor by greater than 50%. Some patients responded to one drug but not to the other. Amantadine decreased tremor less than 25%. Monotherapy with trihexiphenidyl or carbidopa-levodopa should be the initial treatment for the tremor of Parkinson's disease.

Dysfluency (stuttering) in extrapyramidal disease.

Acquired stuttering in the adult is rare and is usually associated with trauma or vascular disease. A recent patient had adult-onset dysfluency, and, subsequently, signs of progressive supranuclear palsy developed. A review of cases of extrapyramidal disease identified five parkinsonian patients with stutteringlike behavior. Dysfluencies were of slow onset and were an early symptom. Speech was characterized by repetitions/prolongations on initial syllables, which occurred on both small grammatical and substantive words. Dysfluency was found mostly in self-formulated speech. There was a positive adaptation effect. No secondary motor symptoms occurred and behavioral response to dysfluency was minimal. Speech characteristics of dysfluency associated with extrapyramidal disease differ from both developmental dysfluency and acquired dysfluency secondary to vascular or traumatic insults. In patients with adult-onset stutteringlike dysfluencies it is important to consider extrapyramidal disease.

Pharmacologic trials in the treatment of cerebellar tremor.

We studied the effect of long-term administration of propranolol hydrochloride and isoniazid and the acute action of ethyl alcohol on cerebellar tremor in patients with multiple sclerosis and primary cerebellar degeneration in a placebo-controlled double-blind crossover test. None of the drugs decreased the severity of either static or kinetic cerebellar tremors.

Handedness and essential tremor.

In patients with essential tremor, a direct relationship was found between hand dominance and severity of hand tremor. A higher incidence of left-handedness was found in patients with essential tremor than in controls.

Adjuvant therapy of parkinsonian tremor.

The effect of long-acting propranolol hydrochloride (160 mg/d), primidone (250 mg at night), and clonazepam (4 mg/d) on the resting, postural, and kinetic component of tremor was investigated in ten parkinsonian patients in a double-blind crossover design. Tremor was assessed by patient opinion, clinical scoring, and accelerometer recordings. The amplitude and frequency of tremorgrams were determined by spectral analysis. Most patients preferred long-acting propranolol and chose to continue taking the drug. The mean clinical score for resting and postural tremor was significantly decreased by long-acting propranolol but not by primidone or clonazepam. Long-acting propranolol reduced the mean amplitude of resting tremor by 70% and the mean amplitude of postural tremor by 50%. Mean tremor amplitudes were not changed by primidone or clonazepam. Tremor frequency was unaltered by the drugs. No side effects occurred with long-acting propranolol but adverse reactions were common with primidone and clonazepam. Long-acting propranolol is a useful adjuvant therapy for the tremors associated with Parkinson's disease.

Combined resting-postural tremors.

We studied eight patients with combined resting-postural tremors, which are classified as a subtype of essential tremor. Trihexyphenidyl hydrochloride, levodopa, and propranolol hydrochloride therapy were not effective in reducing these tremors.

Metoprolol compared with propranolol in the treatment of essential tremor.

We analyzed effects of metoprolol tartrate and propranolol hydrochloride on 23 patients with essential tremor. Tremor was assessed by patient self-evaluation, clinical scoring, and tremorgrams. Ten of 20 patients had tremor reduction with propranolol. Metoprolol decreased tremor in 13 of 23 patients, including three patients with asthma in whom propranolol had caused respiratory distress. Adverse reactions were infrequent. Individual patients either responded to both propranolol and metoprolol or to neither drug. Patient age, duration of tremor, tremor frequency, family history, or response to intravenous ethyl alcohol did not distinguish responders from nonresponders.

Pharmacologic probe with progabide of GABA mechanisms in essential tremor.

Progabide, a gamma-aminobutyric acid agonist, was given to ten patients with essential tremor in a double-blind, placebo-controlled crossover study. The effect of progabide did not differ from that of placebo. Alterations in gamma-aminobutyric acid neurotransmission do not appear to be involved in the pathogenesis of essential tremor.

Psychogenic parkinsonism.

BACKGROUND: Parkinsonism resulting from a primary psychiatric disorder has not been well characterized previously. We had been impressed that this was a rare but definite cause of parkinsonism in patients presenting to our subspecialty movement disorders clinics. OBJECTIVE: To define the clinical characteristics of "psychogenic parkinsonism" to assist in the differentiation of these patients from those with "organic" parkinsonian disorders. DESIGN: Retrospective chart reviews of patients seen at three large movement disorders centers. PATIENTS: Seven men and seven women were diagnosed as having "documented" or "clinically established" psychogenic parkinsonism after repeated assessments. RESULTS: Tremor (12 patients) was present at rest but continued without the usual transient dampening on taking up a posture and persisted with action. Tremor frequency and rhythmicity varied markedly. Tremor could often be entrained to the frequency of other movements or subsided with distraction. Rigidity (six patients) had features of voluntary resistance, often decreasing with distraction and/or activating synkinetic movements in opposite limbs. Arm swing was usually diminished or absent on the affected side; however, the arm could be held tightly to the side or cradled in front of the patient. Slowness of movement (all 14 patients) usually lacked the typical decrementing amplitude feature of bradykinesia. The slowness, ambulatory abnormalities, and postural instability (12 patients) often had bizarre, inconsistent, or incongruous features. Functional "give-way" weakness and nonorganic sensory disturbances were common (10 patients). Spontaneous remissions and remissions with placebo treatment or psychotherapy and response fluctuations related to unusual interventions were occasionally seen (five patients). Underlying psychological factors varied considerably. Most patients had been seen by several physicians and had undergone multiple unrevealing investigations. Fluorodopa F 18 (F-dopa) positron emission tomographic scanning yielded normal findings in three patients. Abnormal positron emission tomographic scanning results in a fourth patient, whose signs and symptoms had improved with psychotherapy and haloperidol therapy, emphasizes the possibility that prominent psychogenic features may be superimposed on organic parkinsonism in some patients. CONCLUSION: Psychogenic parkinsonism occurs rarely. It is a diagnosis of exclusion that should be made only by physicians with considerable experience in the care and treatment of patients with parkinsonism.

Posttraumatic torticollis.

We report six cases of torticollis precipitated by neck trauma. The dystonia began 1 to 4 days after the trauma and differed clinically from idiopathic torticollis by marked limitation of range of motion, lack of improvement after sleep ("honeymoon period"), and absence of geste antagonistique. Worsening with action was not present; nor was there improvement with support as seen with idiopathic torticollis. Onset of pain immediately after the trauma and marked spasms of the paracervical muscles were other predominant features. Anticholinergic therapy was without benefit; however, some improvement occurred with botulinum toxin injection. It is concluded that torticollis can be caused by peripheral trauma and that it has unique clinical characteristics.

Environmental risk factors in siblings with Parkinson's disease.

To investigate possible risk factors in Parkinson's disease, we conducted a case-controlled study of 19 families having two or more siblings with Parkinson's disease. Demographic data were collected, including lifetime histories of places of residence; sources of drinking water; occupations, such as farming; and exposure to herbicides and pesticides. Rural living and drinking well water, but not farming and herbicide exposure, were significantly increased in 38 parkinsonians compared with 38 normal control subjects. A comparison of parkinsonian siblings with siblings with essential tremor revealed no differences in any risk factors for the years of shared environment. These data suggest that living in a rural environment and drinking well water are risk factors for Parkinson's disease and that the total life exposure to an environmental toxin may be more important than exposure in early life.

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.

Neuropsychological impairment in Parkinson's disease with and without depression.

OBJECTIVES: To compare quantitative and qualitative aspects of neuropsychological test performance in patients with Parkinson's disease who currently had depression (PDD) and those without depression (PDN) so as to evaluate the influence of depression on cognition in Parkinson's disease. DESIGN: Cross-sectional comparisons among PDN, PDD, and normal control (NC) groups. The setting was a neurodegenerative disease research center in a teaching hospital. Groups consisted of 44 patients with PDN and 44 patients with PDD matched for age, education, gender, age at onset of disease, disease duration, and disease severity; a group of 44 NC subjects matched for age, education, and gender; and a second set of comparisons between 15 patients with PDN and 15 patients with PDD also matched for overall severity of cognitive impairment. MEASURES: The neuropsychological measures used were the Mattis Dementia Rating Scale, Beck Depression Inventory, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Logical Memory subtest of the Wechsler Memory Scale-Revised, Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised, and the Boston Diagnostic Aphasia Examination's Animal Naming test and Boston Naming Test. RESULTS: Relative to the NC group, both PDN and PDD groups demonstrated impairments in immediate and delayed verbal recall, semantic fluency, and problem solving. When PDN and PDD groups were matched for demographic and disease variables, only the PDD group evidenced impairment relative to NC in visual confrontation naming, and in lexical and semantic fluency. In addition, impairments on immediate recall and semantic fluency in the PDD group were more pronounced than those in the PDN group. However, when PDN and PDD groups were also matched for overall severity of cognitive impairment, no significant differences emerged among the two groups' neuropsychological test performances. CONCLUSIONS: Depression exacerbates some memory and language impairments associated with PD, even when the PDN and PDD groups are matched for demographic and disease variables. However, the extent and pattern of cognitive impairment is similar in PDN and PDD when the groups are also matched also for overall severity of cognitive impairment. Depression influences the quantity rather than the quality of cognitive impairment associated with Parkinson's disease.

Factors predictive of the need for levodopa therapy in early, untreated Parkinson's disease. The Parkinson Study Group.

OBJECTIVE: To identify characteristics of patients with early, untreated Parkinson's disease that are the most important predictors of rapid functional decline. DESIGN: Prospective observational study of a cohort of 800 patients with early, untreated Parkinson's disease who were involved in a multicenter, randomized, double-blind, controlled clinical trial of selegiline hydrochloride (L-deprenyl) and vitamin E (alpha-tocopherol). PRIMARY OUTCOME VARIABLE: Time from randomization to the onset of disability that necessitated levodopa therapy (end point), as judged by the enrolling investigator. METHODS: Stepwise Cox regression was used in combination with clinical judgment to identify the most important independent baseline predictors of the primary end point among a host of variables, including treatment with selegiline and vitamin E, global and specific clinical measures of disease severity, demographic variables, and neuropsychological test results. RESULTS: In addition to selegiline treatment and global disease severity measures, such as the stage according to the criteria of Hoehn and Yahr, impaired domestic capacity, and the activities of daily living score, the complex of postural instability/gait difficulty and bradykinesia were found to be the factors that were most highly associated with the risk of reaching the end point. CONCLUSIONS: The findings suggest that patients with Parkinson's disease whose early clinical presentation includes either postural instability/gait difficulty or bradykinesia are at high risk for rapid functional decline.