Identifying substance misuse in primary care: TAPS Tool compared to the WHO ASSIST.

BACKGROUND: There is a need for screening and brief assessment instruments to identify primary care patients with substance use problems. This study's aim was to examine the performance of a two-step screening and brief assessment instrument, the TAPS Tool, compared to the WHO ASSIST. METHODS: Two thousand adult primary care patients recruited from five primary care clinics in four Eastern US states completed the TAPS Tool followed by the ASSIST. The ability of the TAPS Tool to identify moderate- and high-risk use scores on the ASSIST was examined using sensitivity and specificity analyses. RESULTS: The interviewer and self-administered computer tablet versions of the TAPS Tool generated similar results. The interviewer-administered version (at cut-off of 2), had acceptable sensitivity and specificity for high-risk tobacco (0.90 and 0.77) and alcohol (0.87 and 0.80) use. For illicit drugs, sensitivities were >0.82 and specificities >0.92. The TAPS (at a cut-off of 1) had good sensitivity and specificity for moderate-risk tobacco use (0.83 and 0.97) and alcohol (0.83 and 0.74). Among illicit drugs, sensitivity was acceptable for moderate-risk of marijuana (0.71), while it was low for all other illicit drugs and non-medical use of prescription medications. Specificities were 0.97 or higher for all illicit drugs and prescription medications. CONCLUSIONS: The TAPS Tool identified adult primary care patients with high-risk ASSIST scores for all substances as well moderate-risk users of tobacco, alcohol, and marijuana, although it did not perform well in identifying patients with moderate-risk use of other drugs or non-medical use of prescription medications. The advantages of the TAPS Tool over the ASSIST are its more limited number of items and focus solely on substance use in the past 3months.

Cystatin C Is Associated with the Extent and Characteristics of Coronary Atherosclerosis in Patients with Preserved Renal Function.

Cystatin C (CysC), an endogenous inhibitor of cysteine proteases and a sensitive and accurate marker of renal function, is associated with the severity of coronary atherosclerosis assessed by angiography and future cardiovascular events according to previous studies. We aimed to evaluate the association between CysC levels and coronary plaque volume, composition and phenotype assessed by intravascular ultrasound and intravascular ultrasound-derived virtual histology in patients with preserved renal function. Forty-four patients with angiographically documented coronary artery disease and complete intravascular imaging were included in the study. Patients were categorized into tertiles by CysC levels. Subjects in the high CysC tertile had significantly higher mean plaque burden (48.0 % ± 6.9 vs. 42.8 % ± 7.4, P = 0.029), lower mean lumen area (8.1 mm2 ± 1.7 vs. 9.9 mm2 ± 3.1, P = 0.044) and a higher number of 5-mm vessel segments with minimum lumen area < 4 mm2 (17.9 ± 18.9 vs. 6.8 ± 11.7, P = 0.021) compared to patients in the lower tertiles. In addition, CysC levels demonstrated significant positive correlation with the mean plaque burden (r = 0.35, P = 0.021). Neither relative, nor absolute plaque components differed significantly according to CysC tertiles. The Liverpool Active Plaque Score was significantly higher in the high CysC tertile patients (0.91 ± 1.0 vs. 0.18 ± 0.92, P = 0.02). In conclusion, our study demonstrated a significant association of increased CysC levels with more advanced coronary artery disease and higher risk plaque phenotype in patients with preserved renal function.

Clinical characterization of epilepsy of unknown cause in cats.

BACKGROUND: The diagnosis of feline epilepsy of unknown cause (EUC) requires a thorough diagnostic evaluation, otherwise the prevalence of EUC could be overestimated. HYPOTHESIS: Feline EUC is a clinically defined disease entity, which differs from feline hippocampal necrosis by the absence of magnetic resonance imaging (MRI) signal alteration of the hippocampus. The objectives of this study were (1) to evaluate the prevalence of EUC in a hospital population of cats by applying well-defined inclusion criteria, and (2) to describe the clinical course of EUC. ANIMALS: Eighty-one cats with recurrent seizures. METHODS: Retrospective study--medical records were reviewed for cats presented for evaluation of recurrent seizures (2005-2010). Inclusion criteria were a defined diagnosis based on laboratory data, and either MRI or histopathology. Final outcome was confirmed by telephone interview with the owner. Magnetic resonance images were reviewed to evaluate hippocampal morphology and signal alterations. RESULTS: Epilepsy of unknown cause was diagnosed in 22% of cats with epilepsy. Physical, neurologic, and laboratory examinations, and either 1.5 T MRI and cerebrospinal fluid analysis or postmortem examination failed to identify an underlying cause. Cats with EUC had a higher survival rate (P < .05) and seizure remission occurred frequently (44.4%). CONCLUSION AND CLINICAL IMPORTANCE: A detailed clinical evaluation and diagnostic imaging with MRI is recommended in any cat with recurrent seizures. The prognosis of cats with normal MRI findings and a clinical diagnosis of EUC are good. Standardized imaging guidelines should be established to assess the hippocampus in cats.

Prediction of coronary vessel involvement on the basis of atherosclerosis risk factor analysis.

The prediction of coronary vessel involvement by means of noninvasive tests is one of the fundamental objectives of preventive cardiology. This review describes the current possibilities of coronary vessel involvement prediction by means of ultrasonographic examination of carotid arteries, analysis of polymorphisms in the genes encoding enzymes responsible for production of nitric oxide and carbon monoxide and assessment of levels of certain proinflammatory cytokines. In the presented work these noninvasive markers are correlated with the extent of coronary vessel involvement as assessed by coronary angiography, intravascular ultrasound and virtual histology (Fig. 5, Ref. 40).

Generation of donor-specific anti-human leukocyte antigen antibodies after the transplantation of a fully matched kidney allograft and its impact on the selection of a subsequent renal regraft: a case report.

Detection of anti-human leukocyte antigen (HLA) antibodies and identification of their specificities represent important tasks for patients awaiting kidney allografts. Regarding patients immunized by pregnancies, transfusions, or previous transplantations of solid organs, the immunization status must be observed carefully because grafting them with HLA phenotypes recognized by their antibodies represents the main cause for hyper-acute or acute rejection episodes, often leading to transplant loss. A 10-year-old patient with end-stage renal insufficiency of HLA type A3, 25; B8, 18, (Bw6); Cw7,12; DR15,17; DR51,52; DQ2,6 received a deceased donor graft showing no HLA mismatch in 1998. It lost function after 8 years, resulting in the patient's re-entry onto the waiting list for kidney transplantation in 2006. Antibody screening detected anti-HLA-A25, A26, A34, and A66 (broad A10) antibodies using various techniques (DynaChip, Single Antigen enzyme-linked immunosorbent assay [ELISA]). Additionally, a kidney offer expressing the HLA-A25 phenotype was not acceptable for the patient due to a positive complement-dependent cytotoxicity assay (CDC)-based cross-match. The question arose whether this reactivity might be due to auto-reactive antibodies directed against the HLA-A25 phenotype. However, no auto-reactive antibodies were detectable using either the CDC-based or the antibody monitoring system-ELISA-based cross-match assays. Consequently the patient was re-examined at high resolution showing the rare HLA-A*25:14 genotype. This case showed that rare alleles may result in allele-specific antibodies directed against the common variants, thus leading to unexpected positive cross-match results against apparently matched allografts.

Genetic variants in haem oxygenase-1 and endothelial nitric oxide synthase influence the extent and evolution of coronary artery atherosclerosis.

The genetic basis for atherosclerosis development and progression is poorly characterized. We aimed to assess the relationship between endothelial nitric oxide synthase (ENOS) 894 G/T, haem oxygenase-1 (HO1) dinucleotide-length promoter polymorphisms and coronary artery atherosclerotic invol vement and its changes during statin therapy. Coronary angiography, intravascular ultrasound (IVUS), IVUS-derived virtual histology (VH) and genetic polymorphism analysis were performed at study entry. Patients were randomized 1:1 to standard or aggressive hypolipidaemic treatment, and a follow-up evaluation was performed after twelve months. Plaque magnitude was significantly higher in carriers of HO1 risk variants when compared with carriers of the protective variants (< 25 GT repeats). Similarly, the total coronary atherosclerotic burden was significantly greater in HO1 risk variant carriers than in HO1 protective variant carriers. Both parameters did not differ with respect to the ENOS genotype. A higher prevalence of thin-cap fibroatheroma (TCFA) in HO1 risk variant carriers was observed, compared with the HO1 protective variant carriers. The prevalence of TCFA was not influenced by the ENOS genotype. Baseline plaque composition did not differ significantly with respect to both polymorphisms. Significant interactions between plaque composition changes and ENOS and HO1 genotypes were observed during statin treatment. In conclusion, the protective HO1 promoter polymorphism correlates with a lower coronary artery plaque burden, whereas the protective ENOS 894 G/T polymorphism seems to favourably influence changes of coronary artery plaque composition during statin therapy, but has no significant correlation to the magnitude of coronary atherosclerosis.

Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation.

BACKGROUND: Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation. AIM: To assess the efficacy and safety of three lubiprostone doses for irritable bowel syndrome with constipation. METHODS: 195 irritable bowel syndrome with constipation patients received daily doses of 16 [8 microg twice daily (b.d.)], 32 (16 microg b.d.) or 48 microg (24 microg b.d.) lubiprostone or placebo b.d. for 3 months. Gastrointestinal parameters were recorded in diaries daily by patients. RESULTS: After 1 month, lubiprostone showed significantly greater improvements in mean abdominal discomfort/pain scores vs. placebo (P = 0.023). After 2 months, all lubiprostone groups showed significantly greater improvements in mean abdominal discomfort/pain scores (P < or = 0.039). After 3 months of treatment, the improvement in each lubiprostone arm was greater than placebo, but the test for trend was no longer significant. Treatment with lubiprostone showed significantly higher rates of gastrointestinal adverse events (P = 0.020), especially diarrhoea and nausea. CONCLUSION: Lubiprostone significantly improved gastrointestinal symptoms of irritable bowel syndrome with constipation at all doses. Higher doses of lubiprostone, especially the 48 microg/day group, were associated with more gastrointestinal adverse events. From these data, the 16 microg/day dose demonstrated the optimal combination of efficacy and safety. These results warrant further study of lubiprostone for treatment of irritable bowel syndrome with constipation patients.

A novel HLA-A*0119 allele of a Caucasian family containing a mutation in a highly conserved region.

A novel human leucocyte antigen (HLA)-A (HLA-A*0119) allele has been identified in two individuals of a Caucasian family from Middle Europe using a single-allele-specific sequencing strategy. This allele is identical to the HLA-A*0101 allele except for one point mutation in the highly conserved codon 92 (TCT --> GCT) resulting in an amino acid change from serine to alanine.

Comparison of left anterior descending coronary artery hemodynamics before and after angioplasty.

Coronary artery disease (CAD) is characterized by the progression of atherosclerosis, a complex pathological process involving the initiation, deposition, development, and breakdown of the plaque. The blood flow mechanics in arteries play a critical role in the targeted locations and progression of atherosclerotic plaque. In coronary arteries with motion during the cardiac contraction and relaxation, the hemodynamic flow field is substantially different from the other arterial sites with predilection of atherosclerosis. In this study, our efforts focused on the effects of arterial motion and local geometry on the hemodynamics of a left anterior descending (LAD) coronary artery before and after clinical intervention to treat the disease. Three-dimensional (3D) arterial segments were reconstructed at 10 phases of the cardiac cycle for both pre- and postintervention based on the fusion of intravascular ultrasound (IVUS) and biplane angiographic images. An arbitrary Lagrangian-Eulerian formulation was used for the computational fluid dynamic analysis. The measured arterial translation was observed to be larger during systole after intervention and more out-of-plane motion was observed before intervention, indicating substantial alterations in the cardiac contraction after angioplasty. The time averaged axial wall shear stress ranged from -0.2 to 9.5 Pa before intervention compared to -0.02 to 3.53 Pa after intervention. Substantial oscillatory shear stress was present in the preintervention flow dynamics compared to that in the postintervention case.

Fluid dynamic analysis in a human left anterior descending coronary artery with arterial motion.

A computational fluid dynamic (CFD) analysis is pre sented to describe local flow dynamics in both 3-D spatial and 4-D spatial and temporal domains from reconstructions of intravascular ultrasound (IVUS) and bi-plane angiographic fusion images. A left anterior descending (LAD) coronary artery segment geometry was accurately reconstructed and subsequently its motion was incorporated into the CFD model. The results indicate that the incorporation of motion had appreciable effects on blood flow patterns. The velocity profiles in the region of a stenosis and the circumferential distribution of the axial wall shear stress (WSS) patterns in the vessel are altered with the wall motion introduced in the simulation. The time-averaged axial WSS between simulations of steady flow and unsteady flow without arterial motion were comparable (-0.3 to 13.7 Pa in unsteady flow versus -0.2 to 10.1 Pa in steady flow) while the magnitudes decreased when motion was introduced (0.3-4.5 Pa). The arterial wall motion affects the time-mean WSS and the oscillatory shear index in the coronary vessel fluid dynamics and may provide more realistic predictions on the progression of atherosclerotic disease.

Validation of an accurate method for three-dimensional reconstruction and quantitative assessment of volumes, lengths and diameters of coronary vascular branches and segments from biplane angiographic projections.

UNLABELLED: The goal of the study was the validation of an accurate method for three-dimensional reconstruction and quantitative assessment of volumes, lengths and diameters of coronary vascular branches and segments from biplane angiographic projections. METHODS: The accuracy was tested in a complex phantom. In vivo, inter- and intraobserver agreement were assessed by analysis of routine angiograms. The sensitivity was evaluated using angiograms of patients having diagnostic vasoactive pharmacological intervention. Two-dimensional quantitative coronary angiography (2-D QCA) and 3-D QCA were compared concerning the accuracy of diameter evaluation. RESULTS: 3-D QCA yields accurate results (< 3% error) even based on nonorthogonal views, provided that projections parallel to the object are avoided. The inter- and intraobserver variability is < or = 5%. Significant (p < 0.01) changes of the volume (36-39%) and the diameter (19-21%) are detected following pharmacological intervention. 2-D QCA and 3-D QCA agree in short matched segments without foreshortening. 2-D QCA is rather sensitive to foreshortening and not suitable for evaluation of diameters of longer branches or total coronaries. CONCLUSION: 3-D QCA permits an accurate, reproducible and sensitive comprehensive three-dimensional geometric analysis of the coronaries and is superior to 2-D QCA with respect to extended diameter evaluation.

Fusion of angiography and intravascular ultrasound in vivo: establishing the absolute 3-D frame orientation.

Data fusion of biplane angiography and intravascular ultrasound (IVUS) facilitates geometrically correct reconstruction of coronary vessels. The locations of IVUS frames along the catheter pullback trajectory can be identified, however the IVUS image orientations remain ambiguous. An automated approach to determination of correct IVUS image orientation in three-dimensional space is reported. Analytical calculation of the catheter twist is followed by statistical optimization determining the absolute IVUS image orientation. The fusion method was applied to data acquired in patients undergoing routine coronary intervention, demonstrating the feasibility and good performance of our approach.

Geometrically correct 3-D reconstruction of intravascular ultrasound images by fusion with biplane angiography--methods and validation.

In the rapidly evolving field of intravascular ultrasound (IVUS), the assessment of vessel morphology still lacks a geometrically correct three-dimensional (3-D) reconstruction. The IVUS frames are usually stacked up to form a straight vessel, neglecting curvature and the axial twisting of the catheter during the pullback. Our method combines the information about vessel cross-sections obtained from IVUS with the information about the vessel geometry derived from biplane angiography. First, the catheter path is reconstructed from its biplane projections, resulting in a spatial model. The locations of the IVUS frames are determined and their orientations relative to each other are calculated using a discrete approximation of the Frenet-Serret formulas known from differential geometry. The absolute orientation of the frame set is established, utilizing the imaging catheter itself as an artificial landmark. The IVUS images are segmented, using our previously developed algorithm. The fusion approach has been extensively validated in computer simulations, phantoms, and cadaveric pig hearts.

Biplane X-ray angiograms, intravascular ultrasound, and 3D visualization of coronary vessels.

The technology for determination of the 3D vascular tree and quantitative characterization of the vessel lumen and vessel wall has become available. With this technology, cardiologists will no longer rely primarily on visual inspection of coronary angiograms but use sophisticated modeling techniques combining images from various modalities for the evaluation of coronary artery disease and the effects of treatment. Techniques have been developed which allow the calculation of the imaging geometry and the 3D position of the vessel centerlines of the vascular tree from biplane views without a calibration object, i.e., from the images themselves, removing the awkwardness of moving the patient to obtain 3D information. With the geometry and positional information, techniques for reconstructing the vessel lumen can now be applied that provide more accurate estimates of the area and shape of the vessel lumen. In conjunction with these developments, techniques have been developed for combining information from intravascular ultrasound images with the information obtained from angiography. The combination of these technologies will yield a more comprehensive characterization and understanding of coronary artery disease and should lead to improved and perhaps less invasive patient care.

Assessment of diffuse coronary artery disease by quantitative analysis of coronary morphology based upon 3-D reconstruction from biplane angiograms.

Quantitative evaluations on coronary vessel systems are of increasing importance in cardiovascular diagnosis, therapy planning, and surgical verification. Whereas local evaluations, such as stenosis analysis, are already available with sufficient accuracy, global evaluations of vessel segments or vessel subsystems are not yet common. Especially for the diagnosis of diffuse coronary artery diseases, the authors combined a 3D reconstruction system operating on biplane angiograms with a length/volume calculation. The 3D reconstruction results in a 3D model of the coronary vessel system, consisting of the vessel skeleton and a discrete number of contours. To obtain an utmost accurate model, the authors focussed on exact geometry determination. Several algorithms for calculating missing geometric parameters and correcting remaining geometry errors were implemented and verified. The length/volume evaluation can be performed either on single vessel segments, on a set of segments, or on subtrees. A volume model based on generalized elliptical conic sections is created for the selected segments. Volumes and lengths (measured along the vessel course) of those elements are summed up. In this way, the morphological parameters of a vessel subsystem can be set in relation to the parameters of the proximal segment supplying it. These relations allow objective assessments of diffuse coronary artery diseases.

Pressure-controlled reperfusion improves postischemic recovery of LV-hypertrophied rat hearts.

The influence of pressure-controlled postischemic reperfusion (Rp) on functional and metabolic parameters in hearts of sham-operated rats and hypertrophied hearts of rats with aortic constriction were studied. Hypertrophied hearts are considered to be more susceptible to ischemia. The hearts were perfused in the Langendorff-technique for thirty minutes at 35 degrees C with Krebs-Henseleit bicarbonate buffer at a perfusion pressure (PP) of 75 mmHg and for five minutes at 15 degrees C with St. Thomas' Hospital cardioplegic solution at a PP of 60 mmHg. After a period of global ischemia of forty minutes' duration at 15 degrees C, reperfusion was started either abruptly (aRp: PP 75 mmHg immediately) or gently (gRp: PP 75 mmHg within thirty minutes); it lasted for forty-five minutes. Intraventricular peak systolic pressure (ISP) was monitored and energy-rich compounds (ATP, ADP, AMP, CrP, free Cr) were analyzed. In normal hearts, metabolic recovery was not affected by the mode of reperfusion, but functional recovery (ISP) averaged 88% of the preischemic control value after gRp as compared with 73% after aRp. In hypertrophied hearts, gentle reperfusion ameliorated both metabolic and functional recovery. At forty-five minute recovery, CrP averaged 5.1 mumol/g ww after aRp and 6.6 mumol/g ww after gRp (p less than 0.01), and ISP amounted to 73% of the preischemic control after aRp and to 85% after gRp.