Werner Vach

System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention

CONTEXT Timely reperfusion therapy is recommended for patients with ST-segment elevation myocardial infarction (STEMI), and door-to-balloon delay has been proposed as a performance measure in triaging patients for primary percutaneous coronary intervention (PCI). However, focusing on the time from first contact with the health care system to the initiation of reperfusion therapy (system delay) may be more relevant, because it constitutes the total time to reperfusion modifiable by the health care system. No previous studies have focused on the association between system delay and outcome in patients with STEMI treated with primary PCI. OBJECTIVE To evaluate the associations between system, treatment, patient, and door-to-balloon delays and mortality in patients with STEMI. DESIGN, SETTING, AND PATIENTS Historical follow-up study based on population-based Danish medical registries of patients with STEMI transported by the emergency medical service and treated with primary PCI from January 1, 2002, to December 31, 2008, at 3 high-volume PCI centers in Western Denmark. Patients (N = 6209) underwent primary PCI within 12 hours of symptom onset. The median follow-up time was 3.4 (interquartile range, 1.8-5.2) years. MAIN OUTCOME MEASURES Crude and adjusted hazard ratios of mortality obtained by Cox proportional regression analysis. RESULTS A system delay of 0 through 60 minutes (n = 347) corresponded to a long-term mortality rate of 15.4% (n = 43); a delay of 61 through 120 minutes (n = 2643) to a rate of 23.3% (n = 380); a delay of 121 through 180 minutes (n = 2092) to a rate of 28.1% (n = 378); and a delay of 181 through 360 minutes (n = 1127) to a rate of 30.8% (n = 275) (P < .001). In multivariable analysis adjusted for other predictors of mortality, system delay was independently associated with mortality (adjusted hazard ratio, 1.10 [95% confidence interval, 1.04-1.16] per 1-hour delay), as was its components, prehospital system delay and door-to-balloon delay. CONCLUSION System delay was associated with mortality in patients with STEMI treated with primary PCI.

Vascular Risk Factors and Arteriosclerotic Disease in Idiopathic Normal-Pressure Hydrocephalus of the Elderly

BACKGROUND AND PURPOSE There is some evidence from previous studies that idiopathic normal-pressure hydrocephalus (NPH) of the elderly might be linked to vascular leukoencephalopathy. The purpose of this study was to examine the prevalence and impact of vascular risk factors and vascular diseases in idiopathic NPH compared with a control cohort. METHODS The prevalence of arterial hypertension; diabetes mellitus; hypercholesterolemia; hyperlipidemia; smoking; obesity; and cardiac, cerebrovascular, and other arteriosclerotic diseases was assessed in 65 patients with idiopathic NPH. The findings were compared with those of 70 patients with comparable age distribution. To describe the differences of the prevalences of vascular risk factors, odds ratios were obtained by univariate and multivariate analyses. RESULTS The univariate analysis revealed significant associations between idiopathic NPH and arterial hypertension (prevalence, 54 of 65 [83%]; control group, 25 of 70 [36%]; P < .001) and diabetes mellitus (prevalence, 31 of 63 [49%]; control group, 20 of 70 [29%]; P < .015) but not with other vascular risk factors. After multivariate regression analysis, only hypertension remained significantly associated with NPH (P < .0001). There was also a significant association between NPH and cardiac (P < .001), cerebral arteriosclerotic (P = .007), and other arteriosclerotic diseases (P = .001). A positive association was found between the severity of clinical symptoms of NPH and the presence of hypertension, especially for gait disturbance. The presence of hypertension was not related to the duration of NPH. CONCLUSIONS Our data show a highly significant association between idiopathic NPH and arterial hypertension. Arterial hypertension might be involved in the pathophysiological mechanisms promoting idiopathic NPH.

Cerebrospinal fluid shunting in idiopathic normal-pressure hydrocephalus of the elderly: effect of periventricular and deep white matter lesions.

OBJECTIVE We investigated the effect of periventricular and deep white matter lesions (DWMLs) on outcome after cerebrospinal fluid shunting in a prospective series of elderly patients with idiopathic normal-pressure hydrocephalus. METHODS White matter lesions were assessed with T2-weighted magnetic resonance scans according to a standard protocol in 41 patients with idiopathic normal-pressure hydrocephalus of the elderly who underwent subsequent shunting. In all patients, the diagnosis of idiopathic normal-pressure hydrocephalus had been established preoperatively by clinical and diagnostic investigations. RESULTS At a mean follow-up of 16 months, clinical improvement was observed in 37 of 41 patients (90%). There was no persistent morbidity related to surgery. The degree of overall clinical improvement was negatively correlated with the extension of periventricular lesions (correlation coefficient r = -0.324 [P = 0.04]) and DWMLs (correlation coefficient r = -0.373 [P = 0.02]). This negative correlation was also noted when the analysis was conducted separately for each of the cardinal symptoms (gait disturbance, cognitive impairment, and urinary incontinence). There was no consistent pattern of periventricular and DWMLs in the four patients who failed to respond to shunting. CONCLUSION Periventricular and DWMLs of varying degrees are common findings on magnetic resonance scans of patients with idiopathic normal-pressure hydrocephalus of the elderly. After careful preoperative selection of patients with idiopathic normal-pressure hydrocephalus, individuals with DWMLs suggestive of concomitant vascular encephalopathy may also benefit from cerebrospinal fluid diversion. Although, in general, the degree of improvement depends on the severity of periventricular and DWMLs, patients with more extensive WMLs still may derive clinical benefit from the operation.

Neural networks and logistic regression: Part II

Feed-forward neural networks have recently been applied in situations where an analysis based on the logistic regression model would have been a standard statistical approach; direct comparisons of results, however, are seldomly attempted. We therefore present a comparative investigation of both logistic regression models and feed-forward neural networks including some extensions. The theoretical features and properties are reviewed and illustrated in two examples, also discussing practical problems with their application. In Part II of the paper some further important aspects of approximation, overfitting and model selection are investigated in more detail both analytically and by means of simulation studies.

Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice

BACKGROUND Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards. METHODS We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013. RESULTS In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined. CONCLUSIONS The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).

Flow Void of Cerebrospinal Fluid in Idiopathic Normal Pressure Hydrocephalus of the Elderly: Can It Predict Outcome after Shunting?

OBJECTIVE We investigate the predictive value of cerebrospinal fluid (CSF) flow void on outcome after shunting in a prospective series of patients with idiopathic normal pressure hydrocephalus (NPH). METHODS The degree and extension of CSF flow void were examined on T2-weighted magnetic resonance imaging scans of 37 elderly patients with idiopathic NPH who underwent subsequent shunting. The degree of flow void was assessed in comparison with the signal of large cerebral arteries. The extension was evaluated via the calculation of sum scores for the occurrence of flow void in different locations of the ventricular system. Those parameters were not considered in the decision to perform shunting. CSF flow void in the aqueduct and the adjacent third and fourth ventricles of the 37 patients with idiopathic NPH was compared with that of 37 age-matched control patients. CSF flow void scores in patients with idiopathic NPH were investigated for correlations between postoperative outcome scores and ventricular width indices. RESULTS No difference was found between the occurrence of aqueductal CSF flow void in patients with idiopathic NPH and the control group. A significant difference, however, was noted for the extension of the CSF flow void, which was greater in the NPH group. Postoperative improvement was found in 33 of 37 patients with idiopathic NPH at a mean follow-up of 15.6 months. Only small, statistically not significant correlations were found between CSF flow void and postoperative outcome. Flow void sum scores, however, correlated significantly with ventricular width indices. CONCLUSION The degree and extension of CSF flow void on T2-weighted magnetic resonance imaging scans have little predictive value for outcome after shunting in patients with idiopathic NPH. The greater extension of the CSF flow void in patients with NPH is most likely related to increased ventricular width. It is not useful to consider CSF flow void findings on conventional magnetic resonance imaging scans in making the decision to offer shunting in patients with idiopathic NPH.

[18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients

Study Type – Diagnostic (exploratory cohort)

White matter lesions in patients with idiopathic normal pressure hydrocephalus and in an age-matched control group : A comparative study

OBJECTIVE To compare the occurrence of periventricular lesions (PVLs) and deep white matter lesions (DWMLs) in elderly patients with idiopathic normal pressure hydrocephalus (NPH) and in an age-matched control group. METHODS PVLs and DWMLs were evaluated using T2-weighted magnetic resonance scans of 37 patients with idiopathic NPH and 35 participants from an age-matched control group. All patients with idiopathic NPH included in this study improved after shunting. The control group consisted of 16 healthy elderly persons and 19 patients with depression. To allow quantitative assessment and comparison, scores for PVLs and DWMLs were calculated. Furthermore, possible correlations between white matter lesion scores, ventricular width, and age were investigated. RESULTS There was a significantly higher incidence of PVLs and DWMLs in patients with idiopathic NPH. The mean total PVL was 12.1 (range, 2-24) in the NPH group and 3.9 (range, 0-10) in the control group (P < 0.001). The mean total DWML score was 12.9 (range, 3-24) in the NPH group and 4.5 (range, 0-16) in the control group (P < 0.001). There were significant correlations between the severity of PVL and DWML scores in both groups. Only a weak positive correlation between the severity of DWMLs and age was found in the NPH group, whereas this correlation was significant in the control group. There was a significant negative correlation between the width of the anterior horns and the severity of both PVLs and DWMLs in patients with NPH; however, positive correlations were found in the control group. CONCLUSION Elderly patients with idiopathic NPH have more frequent and more severe PVLs and DWMLs than people in age-matched control groups. Our data suggest a frequent co-occurrence of idiopathic NPH and vascular subcortical encephalopathy; however, they do not support a direct causal relationship.

[18F]FDG-PET is superior to [123I]IBZM-SPECT for the differential diagnosis of parkinsonism

Objective: Imaging of regional cerebral glucose metabolism with PET and striatal dopamine D2/D3 receptors (D2R) with SPECT improves the differential diagnosis of parkinsonism. We prospectively investigated 1) the diagnostic merits of these approaches in differentiating between Lewy body diseases (LBD; majority Parkinson disease [PD]) and atypical parkinsonian syndromes (APS); 2) the diagnostic value of [18F]fluorodeoxyglucose (FDG)-PET to differentiate among APS subgroups. Methods: Ninety-five of 107 consecutive patients with clinically suspected APS referred for imaging were recruited. [18F]FDG-PET scans were analyzed by visual assessment (including individual voxel-based statistical maps). Based on a priori defined disease-specific patterns, patients with putative APS were differentiated from LBD (first level) and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) (second level). [123I] iodobenzamide (IBZM)-SPECT datasets were subjected to an observer-independent regions-of-interest analysis to assess striatal D2R availability. Movement disorder specialists made final clinical diagnoses after a median follow-up time of 12 months. Results: Seventy-eight patients with clinically verified APS (n = 44) or LBD (n = 34) were included in the statistical analysis. The area under the receiver operating characteristic curve for discrimination between APS and LBD was significantly larger for [18F]FDG-PET (0.94) than for [123I]IBZM-SPECT (0.74; p = 0.0006). Sensitivity/specificity of [18F]FDG-PET for diagnosing APS was 86%/91%, respectively. Sensitivity/specificity of [18F]FDG-PET in identifying APS subgroups was 77%/97% for MSA, 74%/95% for PSP, and 75%/92% for CBD. Conclusions: The diagnostic accuracy of [18F]FDG-PET for discriminating LBD from APS is considerably higher than for [123I]IBZM-SPECT. [18F]FDG-PET reliably differentiates APS subgroups.

Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer

The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h–1 (range 176–726 l h–1). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P=0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P=0.04) and ABCC1 g.7356253C>G (P=0.04).