Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.

BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.

Format of medical order sheet improves security of antibiotics prescription: The experience of an intensive care unit.

OBJECTIVE: To assess whether formatting the medical order sheet has an effect on the accuracy and security of antibiotics prescription. DESIGN: Prospective assessment of antibiotics prescription over time, before and after the intervention, in comparison with a control ward. SETTING: The medical and surgical intensive care unit (ICU) of a university hospital. PATIENTS: All patients hospitalized in the medical or surgical ICU between February 1 and April 30, 1997, and July 1 and August 31, 2000, for whom antibiotics were prescribed. INTERVENTION: Formatting of the medical order sheet in the surgical ICU in 1998. MEASUREMENTS AND MAIN RESULTS: Compliance with the American Society of Hospital Pharmacists' criteria for prescription safety was measured. The proportion of safe orders increased in both units, but the increase was 4.6 times greater in the surgical ICU (66% vs. 74% in the medical ICU and 48% vs. 74% in the surgical ICU). For unsafe orders, the proportion of ambiguous orders decreased by half in the medical ICU (9% vs. 17%) and nearly disappeared in the surgical ICU (1% vs. 30%). The only missing criterion remaining in the surgical ICU was the drug dose unit, which could not be preformatted. The aim of antibiotics prescription (either prophylactic or therapeutic) was indicated only in 51% of the order sheets. CONCLUSIONS: Formatting of the order sheet markedly increased security of antibiotics prescription. These findings must be confirmed in other settings and with different drug classes. Formatting the medical order sheet decreases the potential for prescribing errors before full computerized prescription is available.

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

BACKGROUND: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7), 0.8 (0.4-1.6), 1.6 (0.8-3.2), 3.3 (1.7-6.6) respectively, and 2.3 (1.1-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5), 2.8 (1.7-4.5) and 7.8 (4.5-13.5), respectively, and 2.8 (1.6-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

The effect of COX-2 inhibitors on the formation of heterotopic bone in a rat model : O1323

Aims: 1) to create a new and reproducible animal model to produce heterotopic ossification (HO) 2) to be able to exactly quantify the amount of HO using a microCT scan and 3) to prove the hypothesis that COX-2 inhibitors are efficacious in the prevention of HO. Methods: We developed a IACUC-approved Lewis rat model, in which the ventral side of the right femur was scraped to mechanically disrupt the periosteum. By clamping the vastus intermedius ischemic injury to the muscle was produced to enhance HO. Finally homologous bone marrow from a donor rat was placed on the anterior surface of the femur. Half of the study group (8 rats) received chow mixed with a COX-2 inhibitor, while the other half received normal chow. After 6 weeks the animals were sacrificed, the femurs removed and imaged by microCT. Grading of HO was based on the thickness of ectopic bone as evaluated in a blinded fashion by 3 independent observers. Results: All animals developed bilateral HO. Rats treated with COX-2 inhibitors developed significantly less ectopic bone than the control group rats. Conclusions: The results suggest that we have created a very reliable, reproducible model to form ectopic bone in rats. Using the microCT we can precisely quantify the amount of HO. We have been able to show that COX-2 inhibitors significantly decrease the amount of HO formation and are thus a good alternative to non-specific NSAIDs with their potential serious side effects on the gastrointestinal tract and on hemo-stastis.

The Effect Of Induced Intraocular Straylight (cataract Simulation) On Sensitivity Measures Of Standard Automated Perimetry, Pulsar Perimetry And Moorfields Motion Displacement Test

Purpose: To investigate the effect of incremental increases in intraocular straylight on threshold measurements made by three modern forms of perimetry: Standard Automated Perimetry (SAP) using Octopus (Dynamic, G-Pattern), Pulsar Perimetry (PP) (TOP, 66 points) and the Moorfields Motion Displacement Test (MDT) (WEBS, 32 points).Methods: Four healthy young observers were recruited (mean age 26yrs [25yrs, 28yrs]), refractive correction [+2 D, -4.25D]). Five white opacity filters (WOF), each scattering light by different amounts were used to create incremental increases in intraocular straylight (IS). Resultant IS values were measured with each WOF and at baseline (no WOF) for each subject using a C-Quant Straylight Meter (Oculus, Wetzlar, Germany). A 25 yr old has an IS value of ~0.85 log(s). An increase of 40% in IS to 1.2log(s) corresponds to the physiological value of a 70yr old. Each WOFs created an increase in IS between 10-150% from baseline, ranging from effects similar to normal aging to those found with considerable cataract. Each subject underwent 6 test sessions over a 2-week period; each session consisted of the 3 perimetric tests using one of the five WOFs and baseline (both instrument and filter were randomised).Results: The reduction in sensitivity from baseline was calculated. A two-way ANOVA on mean change in threshold (where subjects were treated as rows in the block and each increment in fog filters was treated as column) was used to examine the effect of incremental increases in straylight. Both SAP (p<0.001) and Pulsar (p<0.001) were significantly affected by increases in straylight. The MDT (p=0.35) remained comparatively robust to increases in straylight.Conclusions: The Moorfields MDT measurement of threshold is robust to effects of additional straylight as compared to SAP and PP.

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation.

BACKGROUND: Polymorphisms in IFNL3 and IFNL4, the genes encoding interferon λ3 and interferon λ4, respectively, have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of cytomegalovirus (CMV) infection in solid-organ transplant recipients. METHODS: White patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. RESULTS: A total of 840 solid-organ transplant recipients at risk for CMV infection were included, among whom 373 (44%) received antiviral prophylaxis. The 12-month cumulative incidence of CMV replication and disease were 0.44 and 0.08 cases, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (subdistribution hazard ratio [SHR], 1.30 [95% confidence interval {CI}, .97-1.74]; P = .07), compared with other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR, 1.46 [95% CI, 1.01-2.12]; P = .047), especially in patients receiving an organ from a seropositive donor (SHR, 1.92 [95% CI, 1.30-2.85]; P = .001), but not among those who received antiviral prophylaxis (SHR, 1.13 [95% CI, .70-1.83]; P = .6). These associations remained significant in multivariate competing risk regression models. CONCLUSIONS: Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in solid-organ transplant recipients, particularly in patients not receiving antiviral prophylaxis.

On the origin of the MR image phase contrast: an in vivo MR microscopy study of the rat brain at 14.1 T.

Recent studies at high magnetic fields using the phase of gradient-echo MR images have shown the ability to unveil cortical substructure in the human brain. To investigate the contrast mechanisms in phase imaging, this study extends, for the first time, phase imaging to the rodent brain. Using a 14.1 T horizontal bore animal MRI scanner for in vivo micro-imaging, images with an in-plane resolution of 33 microm were acquired. Phase images revealed, often more clearly than the corresponding magnitude images, hippocampal fields, cortical layers (e.g. layer 4), cerebellar layers (molecular and granule cell layers) and small white matter structures present in the striatum and septal nucleus. The contrast of the phase images depended in part on the orientation of anatomical structures relative to the magnetic field, consistent with bulk susceptibility variations between tissues. This was found not only for vessels, but also for white matter structures, such as the anterior commissure, and cortical layers in the cerebellum. Such susceptibility changes could result from variable blood volume. However, when the deoxyhemoglobin content was reduced by increasing cerebral blood flow (CBF) with a carbogen breathing challenge, contrast between white and gray matter and cortical layers was not affected, suggesting that tissue cerebral blood volume (and therefore deoxyhemoglobin) is not a major source of the tissue phase contrast. We conclude that phase variations in gradient-echo images are likely due to susceptibility shifts of non-vascular origin.

Impact de la consommation de sel sur la santé: les croyances de la population suisse [Impact of salt intake on health: beliefs of the Swiss population].

Excessive salt intake increases the risk of developing hypertension and cardiovascular disease. Sodium intake remains high both in developed and emerging countries. The Swiss Federal Office of Public Health has ordered a national survey on the salt intake in Switzerland, realized in different centers. This article presents the results of the awareness of the Swiss population concerning the relationship between excessive salt intake and health. This survey reveals a lack of knowledge regarding the association between high salt intake and cardiovascular disease, the sodium content of usual food, and the recommended daily value of sodium intake. Strategies to reduce salt consumption need to be reinforced by collaborations between health authorities and health care professionals.