Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis.

The original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa toward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

Photodynamic therapy induces selective extravasation of macromolecules: Insights using intravital microscopy.

Photodynamic therapy (PDT) with Visudyne acts by direct cellular phototoxicity and/or by an indirect vascular-mediated effect. Here, we demonstrate that the vessel integrity interruption by PDT can promote the extravasation of a macromolecular agent in normal tissue. To obtain extravasation in normal tissue PDT conditions were one order of magnitude more intensive than the ones in tissue containing neovessels reported in the literature. Fluorescein isothiocyanate dextran (FITC-D, 2000 kDa), a macromolecular agent, was intravenously injected 10 min before (LK0 group, n=14) or 2h (LK2 group, n=16) after Visudyne-mediated PDT in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL group, n=8). The extravasation of FITC-D from blood vessels in striated muscle tissue was observed in both groups in real-time for up to 2500 s after injection. We also monitored PDT-induced leukocyte rolling in vivo and assessed, by histology, the corresponding inflammatory reaction score in the dorsal skin fold chambers. In all animals, at the applied PDT conditions, FITC-D extravasation was significantly enhanced in the PDT-treated areas as compared to the surrounding non-treated areas (p<0.0001). There was no FITC-D leakage in the control animals. Animals from the LK0 group had significantly less FITC-D extravasation than those from the LK2 group (p=0.0002). In the LK0 group FITC-D leakage correlated significantly with the inflammation (p<0.001). At the selected conditions, Visudyne-mediated PDT promotes vascular leakage and FITC-D extravasation into the interstitial space of normal tissue. The intensity of vascular leakage depends on the time interval between PDT and FITC-D injection. This concept could be used to locally modulate the delivery of macromolecules in vivo.

Combining bone resorption markers and heel quantitative ultrasound to discriminate between fracture cases and controls.

SUMMARY: This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. INTRODUCTION: Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. METHODS: In a nested case-control analysis, we studied 368 women (mean age 76.2 +/- 3.2 years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. RESULTS: Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. CONCLUSIONS: Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alone.

Preserved decision making ability in early multiple sclerosis.

BACKGROUND: The purpose of this study was to assess decision making in patients with multiple sclerosis (MS) at the earliest clinically detectable time point of the disease. METHODS: Patients with definite MS (n = 109) or with clinically isolated syndrome (CIS, n = 56), a disease duration of 3 months to 5 years, and no or only minor neurological impairment (Expanded Disability Status Scale [EDSS] score 0-2.5) were compared to 50 healthy controls using the Iowa Gambling Task (IGT). RESULTS: The performance of definite MS, CIS patients, and controls was comparable for the two main outcomes of the IGT (learning index: p = 0.7; total score: p = 0.6). The IGT learning index was influenced by the educational level and the co-occurrence of minor depression. CIS and MS patients developing a relapse during an observation period of 15 months dated from IGT testing demonstrated a lower learning index in the IGT than patients who had no exacerbation (p = 0.02). When controlling for age, gender and education, the difference between relapsing and non-relapsing patients was at the limit of significance (p = 0.06). CONCLUSION: Decision making in a task mimicking real life decisions is generally preserved in early MS patients as compared to controls. A possible consequence of MS relapsing activity in the impairment of decision making ability is also suspected in the early phase of MS.

Cognition, mood and fatigue in patients in the early stage of multiple sclerosis.

QUESTION UNDER STUDY: Cognitive impairment occurs during multiple sclerosis (MS) and contributes to the burden of the disease, but its effect in the initial phase of MS still needs to be better understood. METHODS: We prospectively studied 127 early MS patients presenting with a clinically isolated syndrome (CIS) or definite MS, a mean disease duration of 2.6 years, and with minor disability (mean Expanded Disability Status Scale score 1.8). Patients were tested for long-term memory, executive functions, attention, fatigue, mood disorders, functional handicap and quality of life (QoL). Twenty-one CIS patients were excluded from study as the diagnosis of MS could not be confirmed. RESULTS: Over the 106 MS patients analysed, 31 (29.3%) were cognitively impaired (23.6% for memory, 10.4% for attention and 5.7% for executive functions). Cognitive deficits were already present in CIS patients in whom the diagnosis was not yet confirmed (20%). Impaired cognition was associated with anxiety (p = 0.05), depression(p = 0.004), fatigue (p = 0.03), handicap (p <0.001) and a lower QoL (p <0.001). After adjustment for QoL, handicap, depression, anxiety and fatigue were no longer associated with the presence of cognitive deficits. CONCLUSIONS: In this well-defined early MS group one third of the patients already exhibited cognitive deficits, which were usually apparent in an effortful learning situation and were generally mild. Mood disorders, fatigue, handicap and decreased QoL were all associated with the occurrence of cognitive deficits. QoL itself appeared to take all the other factors into account. Our results confirm the existence of an interplay between cognitive, affective and functional changes and fatigue in early MS.

Status epilepticus: an independent outcome predictor after cerebral anoxia.

BACKGROUND: Prognosis of status epilepticus (SE) depends on its cause, but there is uncertainty as to whether SE represents an independent outcome predictor for a given etiology. Cerebral anoxia is a relatively homogenous severe encephalopathy. Postanoxic SE is associated to a nearly 100% mortality in this setting; however, it is still unclear whether this is a severity marker of the underlying encephalopathy, or an independent factor influencing outcome. The goal of this study was to assess if postanoxic SE is independently associated with mortality after cerebral anoxia. METHODS: This was a retrospective observation of consecutive comatose survivors of cardiac arrest, including subjects treated with hypothermia. On the subgroup with EEG recordings in the first hospitalization days, univariate and multivariate analyses were applied to potential determinants of in-hospital mortality, and included the following variables: age, gender, type and length of cardiac arrest, occurrence of circulatory shock, presence of therapeutic hypothermia, and electrographic SE. RESULTS: Out of 166 postanoxic patients, 107 (64%) had an EEG (median latency from admission, 2 days); in this group, therapeutic hypothermia was administered in 59%. Death occurred in 71 (67%) patients. Postanoxic SE was associated with mortality regardless of type of acute cardiac rhythm and administration of hypothermic treatment. CONCLUSION: In this hospital-based cohort, postanoxic status epilepticus (SE) seems to be independently related to death in cardiac arrest survivors, suggesting that SE might determine a bad prognosis for a given etiology. Confirmation of these results in a prospective assessment is needed.

Combining clinical factors and quantitative ultrasound improves the detection of women both at low and high risk for hip fracture.

UNLABELLED: We hypothesized that combining clinical risk factors (CRF) with the heel stiffness index (SI) measured via quantitative ultrasound (QUS) would improve the detection of women both at low and high risk for hip fracture. Categorizing women by risk score improved the specificity of detection to 42.4%, versus 33.8% using CRF alone and 38.4% using the SI alone. This combined CRF-SI score could be used wherever and whenever DXA is not readily accessible. INTRODUCTION AND HYPOTHESIS: Several strategies have been proposed to identify women at high risk for osteoporosis-related fractures; we wanted to investigate whether combining clinical risk factors (CRF) and heel QUS parameters could provide a more accurate tool to identify women at both low and high risk for hip fracture than either CRF or QUS alone. METHODS: We pooled two Caucasian cohorts, EPIDOS and SEMOF, into a large database named "EPISEM", in which 12,064 women, 70 to 100 years old, were analyzed. Amongst all the CRF available in EPISEM, we used only the ones which were statistically significant in a Cox multivariate model. Then, we constructed a risk score, by combining the QUS-derived heel stiffness index (SI) and the following seven CRF: patient age, body mass index (BMI), fracture history, fall history, diabetes history, chair-test results, and past estrogen treatment. RESULTS: Using the composite SI-CRF score, 42% of the women who did not report a hip fracture were found to be at low risk at baseline, and 57% of those who subsequently sustained a fracture were at high risk. Using the SI alone, corresponding percentages were 38% and 52%; using CRF alone, 34% and 53%. The number of subjects in the intermediate group was reduced from 5,400 (including 112 hip fractures) and 5,032 (including 111 hip fractures) to 4,549 (including 100 including fractures) for the CRF and QUS alone versus the combination score. CONCLUSIONS: Combining clinical risk factors to heel bone ultrasound appears to correctly identify more women at low risk for hip fracture than either the stiffness index or the CRF alone; it improves the detection of women both at low and high risk.

Continuous assessment of electrical epileptic activity in acute stroke.

OBJECTIVE: To determine the incidence and risk factors of electrical seizures and other electrical epileptic activity using continuous EEG (cEEG) in patients with acute stroke. METHODS: One hundred consecutive patients with acute stroke admitted to our stroke unit underwent cEEG using 10 electrodes. In addition to electrical seizures, repetitive focal sharp waves (RSHWs), repetitive focal spikes (RSPs), and periodic lateralized epileptic discharges (PLEDs) were recorded. RESULTS: In the 100 patients, cEEG was recorded for a mean duration of 17 hours 34 minutes (range 1 hour 12 minutes to 37 hours 10 minutes). Epileptic activity occurred in 17 patients and consisted of RSHWs in seven, RSPs in seven, and PLEDs in three. Electrical seizures occurred in two patients. On univariate Cox regression analysis, predictors for electrical epileptic activity were stroke severity (high score on the National Institutes of Health Stroke Scale) (hazard ratio [HR] 1.12; p = 0.002), cortical involvement (HR 5.71; p = 0.021), and thrombolysis (HR 3.27; p = 0.040). Age, sex, stroke type, use of EEG-modifying medication, and cardiovascular risk factors were not predictors of electrical epileptic activity. On multivariate analysis, stroke severity was the only independent predictor (HR 1.09; p = 0.016). CONCLUSION: In patients with acute stroke, electrical epileptic activity occurs more frequently than previously suspected.

Comparison of three bone ultrasounds for the discrimination of subjects with and without osteoporotic fractures among 7562 elderly women.

UNLABELLED: Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70-80 years of age. The association between nonvertebral fracture was higher for heel than phalangeal QUS. INTRODUCTION: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross-sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening. MATERIAL AND METHODS: This cross-sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ [GE-Lunar] and Sahara [Hologic]; the phalanges: ultrasound DBM sonic 1200 [IGEA]) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 +/- 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude-dependent SOS (AD-SOS). RESULTS: Eighty-six women had a history of a traumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD-SOS of DBM sonic 1200. CONCLUSION: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.

Irritancy of the skin disinfectant n-propanol.

Hand disinfection with short-chain aliphatic alcohols, so-called "rub-ins" is the method of choice for cross-infection prevention in health care environments, but their irritant potential is not well known. Skin tolerance is a major compliance factor, and a high proportion of health care workers suffer from low-grade irritant contact dermatitis. Therefore, assessment of the irritancy of the skin disinfectant n-propanol 60%, and comparative 100% and 0% solutions, was performed in the setting of experimental low-grade ICD. ICD was induced by overnight patch exposure to H2O, and to 0.3% sodium dodecyl sulfate (SDS), in 12 probands, followed by repeated open exposure to the test substances. Outcome variables were transepidermal water loss (TEWL), and skin surface capacitance. On skin sites pre-irritated by SDS, all n-propanol concentrations (100%, 60%, 0%) increased TEWL. However, a clear divergence appeared between pure n-propanol, and the lower concentrations. In contrast to pure n-propanol, n-propanol 60% and 0% had no significant effect on TEWL on H2O-pre-irritated skin sites. Capacitance of pre-irritated skin sites was increased by exposure to H2O-containing n-propanol solutions (60% and 0%). These results show a clear difference between the irritant potential of n-propanol 100% on one side, and n-propanol 60% and 0% on the other side. The level of pre-existent skin irritation is a pertinent factor in susceptibility to irritation, as the irritant potential of n-propanol 60%, the concentration used in daily practice, and n-propanol 0% (water) became significant only on detergent-irritated skin. Thus, preventive skin care may be a constructive approach in increasing tolerance of modern hand disinfection practices.

Fitting the distributions of length of stay by parametric models.

OBJECTIVES: The purpose of this study was to assess the adequacy of three widely used models--Lognormal, Weibull, and Gamma--for describing the distribution of length of stay. This is a fundamental step in the development of outliers resistant (robust) methods for the statistical analysis of this kind of data, where the main objective is to determine measures of average and total resource consumption of groups of patients. Current practice uses several types of trimming rules, many of which are based on the Lognormal model, although theoretical and experimental bases are still insufficient. METHODS: The three models were adjusted using robust procedures based on M-estimators to approximately 5 million stays grouped by Diagnosis-Related Groups (DRGs). The resulting 3,279 samples were collected in five European countries during 3 years. RESULTS: Most of the distributions observed could be fitted with one of these models. The descriptions provided by the Gamma and the Weibull models were similar, and the Gamma model could be omitted. The casemix description provided by the Log-normal-Weibull family was, for certain countries, significantly better than the one provided by the single Lognormal model. Often, for a given DRG and a given country, length of stay distributions could be described with the same model during several years. A given DRG, however, usually had to be described by means of different models for different countries. CONCLUSIONS: Practical and conceptual consequences of the results are discussed. They can be extended to the analyses of other consumption variables used in health services. Statistical procedures for casemix description, including current rules of trimming, should be improved by means of more flexible families of models.

Rosemary components inhibit benzo[a]pyrene-induced genotoxicity in human bronchial cells.

The commonly used spice and flavouring agent, rosemary, derived from the leaves of the plant Rosmarinus officinalis L., displays antioxidant properties in foods and in biological systems. Moreover, in animal models rosemary components were found to inhibit the initiation and tumour promotion phases of carcinogenesis. In this work, we studied the mechanisms by which rosemary components block initiation of carcinogenesis by the procarcinogen benzo[a]pyrene (B[a]P) in human bronchial epithelial cells (BEAS-2B). Whole rosemary extract (6 micrograms/ml) or an equivalent concentration of its most potent antioxidant constituents, carnosol or carnosic acid, inhibited DNA adduct formation by 80% after 6 h co-incubation with 1.5 muM B[a]P. Under similar conditions, cytochrome P450 (CYP) 1A1 mRNA expression was 50% lower in the presence of rosemary components, and CYP1A1 activity was inhibited 70-90%. The observed reduction of DNA adduct formation by rosemary components may mostly result from the inhibition of the activation of benzo[a]pyrene to its ultimate metabolites. Carnosol also affected expression of the phase II enzyme glutathione-S-transferase which is known to detoxify the proximate carcinogenic metabolite of B[a]P. Treatment of BEAS-2B cells with carnosol (1 microgram/ml) for 24 h resulted in a 3- to 4-fold induction of GST pi mRNA. Moreover, expression of a second important phase II enzyme, NAD(P)H: quinone reductase, was induced by carnosol in parallel with GST pi. Therefore, rosemary components have the potential to decrease activation and increase detoxification of an important human carcinogen, identifying them as promising candidates for chemopreventive programs.

Exploring models for the length of stay distribution.

Diagnosis Related Groups (DRG) are frequently used to standardize the comparison of consumption variables, such as length of stay (LOS). In order to be reliable, this comparison must control for the presence of outliers, i.e. values far removed from the pattern set by the majority of the data. Indeed, outliers can distort the usual statistical summaries, such as means and variances. A common practice is to trim LOS values according to various empirical rules, but there is little theoretical support for choosing between alternative procedures. This pilot study explores the possibility of describing LOS distributions with parametric models which provide the necessary framework for the use of robust methods.

Serum T-kininogen levels increase two to four months before death.

We have reported an accumulation of T-kininogen mRNA in the liver of aging Sprague-Dawley rats. T-kininogen is a cysteine proteinase inhibitor. Since a disruption of the intracellular protein degradation machinery is known to occur during senescence, we wished to further define the role of this protein in the aging process. As a first step, we have measured T-kininogen levels both in serum and within the liver. We have found that serum protein levels are indeed augmented during senescence, although not as dramatically as the mRNA (2.5-fold versus 8.3-fold). Immunocytochemistry, as well as Western blot analysis suggests that this is due to the presence of T-kininogen within hepatic cells in aged rats. Life-long dietary restriction, a known age-prolonging treatment, decreases the overexpression of the protein in 24-month-old rats. Later, diet-restricted animals still show an increased expression from the gene, the effect being delayed but not abolished by dietary manipulation. Interestingly, a longitudinal study indicated the existence of a positive correlation between the time of increase of serum T-kininogen and the time of death of the animal. Serum T-kininogen was found to increase 2.5-4 months before death.

The circadian rhythm of the perinatal mortality rate in Switzerland.

The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight-specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior.

Tufted angioma.

The clinical and histological description of 2 cases of tufted angioma is presented.

[Treatment of condylomata acuminata: efficacy of the carbon dioxide laser]. / Traitement des condylomes acuminés: efficacité du laser CO2.

The treatment of condyloma acuminatum may be long and tiresome owing to frequent recurrences, and the multiple physical or chemical therapies utilized bear witness to the difficulties often encountered in trying to eradicate the lesions. CO2 laser is a therapeutic alternative with some advantages, such as minimal peripheral thermal necrosis with a lower risk of scar or stricture, haemostasis and perhaps sterilizing effect. Between 1985 and 1987, 69 patients (58 men and 11 women; mean age 29 years) treated with CO2 laser and followed up for at least 6 months without recurrence entered our study. All patients had multiple lesions located in the genital region in 32 cases, in the anal region in 22 cases and in both the genital and anal regions in 15 cases. The majority of patients (85%) had been referred to us owing to failure of previous treatments. We used the CO2 laser coupled with a hand-piece, working by continuous emission, with a power of 300 to 800 watts/sq.cm. Superficial vaporization of the area around the condyloma was systematically performed. Seventy-seven percent of the patients were treated under local anaesthesia. In 16 patients with intra-anal or profuse ano-genital lesions the first vaporization was carried out under general anaesthesia. Twenty-two patients (32%) were cured in one session and 19 (28%) in two sessions. Twenty-eight patients had several recurrences requiring repeated treatments (3 to 5 in 17 cases, 6 to 10 in 10 cases, 31 in 1 case) over a 2 to 17 months' period. No major complications, notably scarring, were observed.(ABSTRACT TRUNCATED AT 250 WORDS)