Influence of transportation distance on mortality in ruptured abdominal aortic aneurysms

Different opinions exist about the influence of transportation distance to vascular surgical emergency service on outcome for ruptured abdominal aortic aneurysms (RAAAs). Therefore, retrospective study based on the Finnvasc registry and the Finnish Cause of Death registry (Statistics Finland) was carried out. A total of 404 RAAAs were registered in the catchment areas of two university hospitals during a four-year period; 203 of them were operated. The operative mortality rate was 50% based on the Finnvasc registry and 55% based on Statistics Finland. The total hospital mortality rate including operated and nonoperated patients was 69% and the overall case fatality including all deaths for RAAA was 77%. There was no association between transportation distance and results of RAAA treatment.     

Patient injury claims involving fractures of the distal radius

Background and purpose — Optimal treatment for distal radius fractures remains controversial, with a significant number of fractures resulting in complications and long-term morbidity. We investigated patient injury claims related to distal radius fractures to detect the critical steps in the treatment leading to avoidable adverse events

Patients and methods — We analyzed all compensated patient injury claims in Finland between 2007 and 2011. Claims were collected from the Patient Insurance Center’s (PIC) nationwide claim register. Patients of all ages were included. Each claim decision, original patient records, and radiographs related to treatment were reviewed.

Results — During the study period, the PIC received 584 claims regarding distal radius fractures, of which 208 (36%) were compensated. Pain and impaired wrist function were the most common subjective reasons to file claims among compensated patients. In 66/208 patients, more than 1 adverse event leading to patient injury was detected. The detected adverse events could be divided into 3 main groups: diagnostic errors (36%, n = 103), decision/planning errors (30%, n = 87), and insufficient technical execution (32%, n = 91). Issues related to malalignment were the main concerns in each group. Diagnostic errors were often related to incorrect assessment of the fracture (re)displacement (75%, n = 78). All of the decision-making errors concerned physicians’ decisions to accept unsatisfactory fracture alignment. The most common technical error was insufficient reduction (29%, n = 26).

Interpretation — We identified avoidable adverse events behind patient injuries related to distal radius fracture treatment. This study will help physicians to recognize the critical steps in the treatment of this common fracture and enhance patient safety.     

Detecting a dexmedetomidine‐evoked reduction of noradrenaline release in the human brain with the alpha2C‐adrenoceptor PET ligand [11C]ORM‐13070

PET imaging can for some neurotransmitters be used to measure synaptic neurotransmitter concentrations. The objective of this study was to test whether the receptor binding of the α_2C‐AR antagonist PET tracer [¹¹C]ORM‐13070 would increase in response to reductions in synaptic noradrenaline, evoked by dexmedetomidine as a sympatholytic drug challenge. Six subjects underwent a control PET scan and two dexmedetomidine PET scans. Dexmedetomidine was infused with target plasma concentrations of 0.6 and 0.2 ng/ml. Tracer binding was measured by voxel‐based analysis of bound per free (B/F) images. ROI‐based analysis was performed in the dorsal striatum and in the thalamus. Vital signs and drug concentrations in plasma were measured and the sedative effect was estimated with the visual analog scale. In the voxel‐based analysis, dexmedetomidine administration was associated with a tendency to increased B/F tracer in the right thalamus (mean, +17%, P = 0.14, and +19%, P = 0.05, with the low and high dose, respectively). Tracer binding in the dorsal striatum was unaffected by dexmedetomidine. A cluster with significantly increased B/F tracer (+42%, P = 0.01) was seen in the right superior temporal gyrus with low‐dose dexmedetomidine, but not after the high dose. Brain uptake of [¹¹C]ORM‐13070 has previously been shown to be reduced in conditions of increased synaptic noradrenaline concentrations. In this study, tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, but statistical significance was not reached. Synapse 70:57–65, 2016. © 2015 Wiley Periodicals, Inc.     

Starch acetate as a tablet matrix for sustained drug release.

The aim of this study was to investigate the effect of a high degree on substitution (DS) on starch acetate (SA) and SA concentration on tablet properties. SAs with a DS of 2.6 and 3.0 were used as matrix formers with propranolol hydrochloride (PH) as a model drug. The SA-3.0 powder had better compactibility than the SA-2.6 powder. A decrease in SA concentration decreased compactibility of PH/SA blended powders when compared to neat SA powders. In general, drug release was considerably slower from SA-3.0 matrices than from SA-2.6 matrices. Also, a decrease in SA concentration increased the drug release rate. Water penetration into 80% (w/w) SA-3.0 matrices was incomplete during 24-h dissolution tests. Diffusion path length increased with time and PH was released by Fickian diffusion. However, all other PH/SA tablets were completely hydrated during dissolution tests. Macroscopic cracks were formed during dissolution, which increased area available for Fickian diffusion and resulted in slow attenuation of the drug release rate. Crack formation, not been reported earlier, must be taken into account in order to understand drug release from SA matrices.     

Molecular heterogeneity has a major impact on the measurement of circulating N-terminal fragments of A- and B-type natriuretic peptides

BACKGROUND: The N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) are powerful markers of cardiac function. The current assays require refinement with regard to standardization with native calibrators and the ability to detect the actual circulating forms. METHODS: The following peptides were prepared with recombinant methods: NT-proANP, NT-proBNP, proBNP1-108, and Tyr0-proBNP77-108. Fifteen peptides of 13-22 amino acids, spanning the sequences of NT-proANP and NT-proBNP, were prepared by solid-phase peptide synthesis. Two immunoassays for NT-proANP and four for NT-proBNP were set up, each with a different epitope specificity. The assays were applied for the measurement of NT-proANP and NT-proBNP in healthy individuals and in patients with acute myocardial infarction. The circulating molecular forms were analyzed by gel-filtration and reversed-phase HPLC. RESULTS: According to the HPLC analyses, circulating NT-proANP consists mainly of the full-length peptide, with some degradation at both ends. In contrast, circulating NT-proBNP is very heterogeneous. Most immunoreactive NT-proBNP is significantly smaller in size than NT-proBNP1-76, with truncation at both termini. The smallest fragments can be detected by assays directed at the central part of NT-proBNP only; assays directed at the ends gave 30-40% lower values. Despite the difference, the various assays correlated reasonably well with each other (r2 = 0.77-0.85). In patients with acute myocardial infarction, NT-proANP and NT-proBNP concentrations were 1.8-2.3 and 4.2-4.5 times higher than in healthy individuals. The development of heart failure further increased the concentrations. CONCLUSIONS: Molecular heterogeneity of the circulating forms causes a serious risk of preanalytical errors in assays for NT-proBNP and, to a lesser extent, NT-proANP. The development of a sandwich assay for NT-proBNP would be especially challenging. The most robust and reliable assays use antibodies directed at the central portions of NT-proANP or NT-proBNP.     

Ultrasound transmission measurements for tensile strength evaluation of tablets

Ultrasound transmission measurements were performed to evaluate the tensile strength of tablets. Tablets consisting of one ingredient were compressed from dibasic calcium phosphate dehydrate, two grades of microcrystalline cellulose and two grades of lactose monohydrate powders. From each powder, tablets with five different tensile strengths were directly compressed. Ultrasound transmission measurements were conducted on every tablet at frequencies of 2.25 MHz, 5 MHz and 10 MHz and the speed of sound was calculated from the acquired waveforms. The tensile strength of the tablets was determined using a diametrical mechanical testing machine and compared to the calculated speed of sound values. It was found that the speed of sound increased with the tensile strength for the tested excipients. There was a good correlation between the speed of sound and tensile strength. Moreover, based on the statistical tests, the groups with different tensile strengths can be differentiated from each other by measuring the speed of sound. Thus, the ultrasound transmission measurement technique is a potentially useful method for non-destructive and fast evaluation of the tensile strength of tablets.     

Lack of effect of central nervous system-active doses of nabilone on capsaicin-induced pain and hyperalgesia

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Predictive value of histopathologic parameters in early squamous cell carcinoma of oral tongue

The clinical course of early squamous cell carcinoma of oral tongue (OTSCC) is unpredictable and various histopathologic parameters of the primary tumour have been suggested as prognostic factors to be used in clinical decision-making. We reviewed clinicopathologic data of 73 patients diagnosed with Stage I–II OTSCC. Predictive value of pathological T-stage, depth of infiltration, grade, and mode of invasion with respect to local recurrences, occult cervical metastases, and disease specific survival (DSS) was analysed. Depth of infiltration and pT-stage significantly predicted occult nodal disease, while only pT-stage predicted local recurrence. Specific cut-off value for depth of infiltration separating high-risk and low-risk patients was not found. Significant correlations between the histopathologic parameters and DSS were not found. We conclude that depth of infiltration predicted occult nodal disease but its value in clinical decision-making is limited because of poor specificity when using a cut-off value that offers reasonable sensitivity for finding the patients with occult nodal disease. The risk for occult metastases and local recurrence was high in patients with pT2 tumours.     

Analyzing consistency of independent components: an fMRI illustration

Independent component analysis (ICA) is a powerful data-driven signal processing technique. It has proved to be helpful in, e.g., biomedicine, telecommunication, finance and machine vision. Yet, some problems persist in its wider use. One concern is the reliability of solutions found with ICA algorithms, resulting from the stochastic changes each time the analysis is performed. The consistency of the solutions can be analyzed by clustering solutions from multiple runs of bootstrapped ICA. Related methods have been recently published either for analyzing algorithmic stability or reducing the variability. The presented approach targets the extraction of additional information related to the independent components, by focusing on the nature of the variability. Practical implications are illustrated through a functional magnetic resonance imaging (fMRI) experiment.