The probability of treatment success,failure and duration—what can be learned from empirical data to support decision making in clinical practice?

Empirical methods have been found to be superior to clinical judgment for the purpose of correctly identifying patients at risk for treatment failure and, hence, to enhance psychotherapy outcomes. The development and evaluation of an empirical approach aimed at supporting clinical decisions during the course of psychotherapy is described. The tool provides predictions based on a patient‐specific sampling strategy called the nearest neighbors method and on growth curve approaches to model an expected treatment course for each patient. Using session‐by‐session data from an outpatient center in the US (N = 4365), this new empirically derived decision model was evaluated and compared with a clinically based approach loosely based on an adaptation of clinically significant change concepts. The empirically derived decision system was found to be superior to the rational clinically based one in almost all measures of prediction accuracy, indicating its potential to identify patients at risk for treatment failure. Copyright © 2006 John Wiley & Sons, Ltd.     

18F-FDG PET for detecting myocardial viability: validation of 3D data acquisition.

(18)F-FDG PET is an important diagnostic tool for detecting myocardial viability in patients with coronary artery disease. In combination with perfusion scanning, (18)F-FDG PET allows differentiation between reversibly and irreversibly damaged myocardium and selection of patients likely to benefit from revascularization. Viability PET is usually performed in two-dimensional (2D) mode. Taking into account the rising number of three-dimensional (3D)-only scanners, a validation of 3D acquisition is required. METHODS: Twenty-one patients with coronary artery disease referred for (18)F-FDG PET underwent an imaging protocol of nongated 2D (2D-NG) and gated 2D (2D-G) acquisitions for 15 min each, followed by 3D gated acquisitions for 10 min (3D-10) and 5 min (3D-5), using an ECAT Exact HR+ scanner. Results were analyzed using a 20-segment polar map in terms of activity concentration (Bq/mL), viability (50% uptake threshold), regional activity distribution, visual assessment of viability based on a 3-point rating scale, and left ventricular ejection fraction. RESULTS: Activity concentration measured in each segment with 2D-G, 3D-10, and 3D-5 showed a good linear correlation with 2D-NG. Quantitative viability assessment with 3D-5 gave a sensitivity of 84% and a specificity of 98%, compared with 2D-NG. No differences in regional activity distribution and visual viability assessment were found between the various protocols. Left ventricular ejection fractions obtained with 3D-10 and 3D-5 showed a good linear correlation with those measured with 2D-G. CONCLUSION: An ECG-gated 3D imaging protocol gave results comparable to those of 2D acquisition with regard to absolute and regional myocardial activity distribution, left ventricular function, and visual viability assessment. Sensitivity for viability assessment with a 50% uptake threshold was significantly less with 3D, but specificity was maintained. This protocol delivers a clinical performance nearly equivalent to that of 2D acquisition.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes.

BACKGROUND: Blue dyes used for lymphatic mapping in sentinel lymph node biopsy cause intraoperative anaphylactic reactions in up to 2.7% of patients. With increasing implementation of this technique, the incidence of anaphylaxis to these dyes can be expected to increase. In the literature, the chemically often unrelated and inconsistently designated dyes have been confused, adding to other inconsistencies in the nomenclature. OBJECTIVE: To demonstrate the nomenclature, chemical and physiologic differences, and allergenicity of the various blue dyes used in a medical context. METHODS: We describe a patient with an intraoperative grade IV anaphylactic reaction to isosulfan blue. Immediate-type hypersensitivity was proved by positive skin test reactions and CD63 expression to isosulfan blue and cross-reactivity to patent blue V. RESULTS: A review of the literature clarified the exact nomenclature of the blue dyes and the possible pitfalls of confusing nomenclature in the context of structurally closely related dyes with different allergenic properties. For the detection of type I hypersensitivity, intracutaneous tests are valuable tools. An IgE-mediated mechanism has been shown recently. In most cases, sensitization exists without known previous exposure in a medical context. This may be due to the widespread use of such dyes in objects of everyday life. Preoperative antiallergic medication use does not prevent anaphylactic reactions but apparently reduces their severity. CONCLUSION: For better comparison and precision, the Chemical Abstracts Service number of the respective dye should always be given.     

Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Interdisziplin?re Leitlinien zur Diagnostik und Therapie der extrazerebralen Amyloidosen

Ohne Zusammenfassung     

Cardiac efficiency and oxygen consumption measured with 11C-acetate PET after long-term cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a treatment option in patients with severe heart failure and left bundle-branch block (LBBB). This study evaluated the effects of 4 and 13 mo of CRT on myocardial oxygen consumption (MVO2) and cardiac efficiency as compared with mild heart failure patients without LBBB. METHODS: Sixteen patients with severe heart failure and LBBB due to idiopathic cardiomyopathy were studied at baseline and after 4 and after 13 mo of therapy. Thirteen patients with mild heart failure without LBBB served as a comparison group. The clearance rate (k2) of 11C-acetate was measured with PET to assess MVO2. Stroke volume was derived from the dynamic PET data according to the Stewart-Hamilton principle and, furthermore, cardiac efficiency using the work metabolic index. RESULTS: After 4 mo of CRT, stroke volume index (SVI) increased by 50% (P = 0.012) and cardiac efficiency increased by 41% (P < 0.001). Global k2 remained unchanged but regional k2 demonstrated a more homogeneous distribution pattern. The parameters showed no significant changes during therapy. Under CRT, cardiac efficiency, SVI, and the distribution pattern of regional k2 did not differ from mild heart failure patients without LBBB. CONCLUSION: CRT improves cardiac efficiency for at least 13 mo, as demonstrated by a higher SVI, whereas MVO2 remains unchanged. Cardiac efficiency, SVI, and the MVO2 distribution pattern reach the level of patients with mild heart failure without LBBB. The unfavorable hemodynamic performance in heart failure with LBBB is effectively restored by long-term CRT to the level of an earlier disease state.     

Comparison of three different purification methods for the routine preparation of [11C] Metomidate.

PET with (R)-[O-methyl-11C] metomidate ([11C] MTO) is an attractive method for the characterisation of adrenal masses discriminating lesions of adrenal cortical origin from noncortical lesions. [11C] MTO was prepared by the reaction of [11C] methyliodide with the corresponding free acid. Three purification methods have been compared. The method of choice uses preparative HPLC with a ready-to-use weak acidic solvent.