Determinants of Regional Variation in Health Expenditures in Germany

Health care expenditure in Germany shows clear regional differences. Such geographic variations are often seen as an indicator for inefficiency. With its homogeneous health care system, low co‐payments and uniform prices, Germany is a particularly suited example to analyse regional variations. We use data for the year 2011 on expenditure, utilization of health services and state of health in Germany's statutory health insurance system. This data, which originate from a variety of administrative sources and cover about 90% of the population, are enriched with a wealth of socio‐economic variables, data on pollutants, prices and individual preferences. State of health and demography explains 55% of the differences as measured by the standard deviation while all control variables account for a total of 72% of the differences at county level. With other measures of variation, we can account for an even greater proportion. A higher proportion of variation than usually supposed can thus be explained. Whilst this study cannot quantify inefficiencies, our results contradict the thesis that regional variations reflect inefficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells

Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs was detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones—a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity.     

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia

Background: Hypotension due to vasodilatation after spinal anesthesia (SA) may be harmful. Heart rate variability, an indirect measure of autonomic control, may predict hypotension.

Methods: One hundred patients were studied. Retrospectively, heart rate variability was analyzed in 30 patients, classified depending on the lowest systolic blood pressure (SBP) after SA. Seventy patients were studied prospectively, assigned to one of two groups by their low to high frequency ratio (LF/HF) before SA. Sensitivity and specificity of LF/HF for prediction of decrease of SBP greater 20% of baseline were tested.

Results: Retrospective analysis showed differences of LF/HF depending on the degree of hypotension after SA. Prospective analysis demonstrated significant differences of SBP after SA depending on baseline LF/HF (mean +/- SD): low LF/HF (1.3 +/- 0.7) = > SBP: 91 +/- 8% of baseline versus high LF/HF (5.5 +/- 2.4) = > SBP: 66 +/- 10% of baseline (P < 0.05). Baseline LF/HF as well as high frequency and proportional decrease of SBP after SA correlated significantly, in contrast to baseline hemodynamic parameters heart rate and SBP. A receiver operator curve characteristic analysis showed a sensitivity and specificity of LF/HF > 2.5 of 85% to predict SBP decrease of greater than 20% of baseline after SA.     

Surgical management of bile duct injuries following laparoscopic cholecystectomy: analysis and follow-up of 28 cases

BACKGROUND: Biliary tract lesions pose a dreaded complication of laparoscopic cholecystectomy. In a retrospective study we analyzed the clinical presentation, diagnostic and therapeutic management and outcome of 28 patients presenting with iatrogenic bile duct injuries. PATIENTS AND METHODS: Between 1994 and 2001 we treated 28 patients with bile duct lesions following laparoscopic cholecystectomy at our center. Operation notes and charts of all patients were reviewed systematically. A follow-up examination of each patient was performed after a median of 12 months (range 1-90). RESULTS: Twenty-two patients presented with major circumferential bile duct defect lesions. Less severe injuries (n=6) were two minor bile leaks, one bile duct stricture and three tangential lesions. Twenty-six patients were referred to our institution within 16 days (range 0-226 days). Six patients were treated by nonsurgical procedures: endoscopic stenting in four and percutaneous intervention in two. In one of the remaining patients a cystic duct leak was closed via laparotomy, and in 21 a hepaticojejunostomy was performed. Reconstruction of a hepaticojenunostomy was performed in two of these patients. Patients were dismissed from the hospital after a median of 13 days (range 4-156). Four patients presenting with generalized biliary peritonitis required prolonged intensive care. One or more episodes of cholangitis were seen in five patients during follow-up examinations. CONCLUSIONS: Major iatrogenic bile duct injuries are associated with high morbidity and prolonged hospitalization. Interdisciplinary cooperation and early referral to an experienced center is crucial in the management of patients suffering from this affliction. Cholangitis is a marked problem in the follow-up.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

The added value of simultaneous EEG and amplitude-integrated EEG recordings in three newborn infants

Amplitude-integrated electroencephalograms (aEEGs) recorded by cerebral function monitors (CFMs) are used increasingly to monitor the cerebral activity of newborn infants with encephalopathy. Recently, new CFM devices became available which also reveal the original EEG signals from the same leads. To date it was unclear whether this single-lead EEG provides additional information towards interpreting the aEEG traces more accurately. Our report deals with three cases in which the single-lead EEG from the CFM device did indeed reveal important additional information not provided by the aEEG alone. In cases 1 and 3, the aEEGs showed drifting of the baseline to higher amplitudes. The single-lead EEG revealed that this was due to muscle artefacts, high-frequency oscillation ventilation and the electrocardiogram rather than to cerebral activity. Hence, without knowledge of the EEG, the aEEG trace might have been misinterpreted as being fairly normal. Case 2 showed paroxysmal elevation of the lower margin of the amplitude on the aEEG which looked like epileptic activity. However, additional information from the single-lead EEG revealed that it was due to muscle artefacts. Thus, simultaneously recorded EEG can help to interpret seizure-like episodes on the aEEG. CONCLUSION: Simultaneously recorded single-lead EEGs can help to interpret aEEG traces more accurately.     

Simultaneous assessment of cardiac perfusion and function using 5-dimensional imaging with Tc-99m teboroxime

BACKGROUND: Dynamic single photon emission computed tomography (SPECT) acquisition and reconstruction of early poststress technetium 99m teboroxime washout images has been shown to be useful in the detection of coronary disease. Assessment of poststress regional wall motion may offer additional use in assessing coronary disease. Our goal was to investigate the feasibility of simultaneously imaging myocardial ischemia and transient poststress akinesis using gated-dynamic SPECT. METHODS AND RESULTS: A gated-dynamic mathematical cardiac torso (MCAT) phantom was developed to model both teboroxime kinetics and cardiac regional wall motion. A lesion was simulated as having delayed poststress teboroxime washout together with a transient poststress wall motion abnormality. Gated projection data were created to represent a 3-headed SPECT system undergoing a total rotation of 480 degrees . The dynamic expectation-maximization reconstruction algorithm with postsmoothing across gating intervals by Wiener filtering, and the ordered-subset expectation maximization reconstruction algorithm with 3-point smoothing across gating intervals were compared. Compared with the ordered-subset expectation maximization with 3-point smoothing, the dynamic expectation-maximization algorithm with Wiener filtering was able to produce visually higher-quality images and more accurate left ventricular ejection fraction estimates. CONCLUSION: From simulations, we conclude that changing cardiac function and tracer localization possibly can be assessed by using a gated-dynamic acquisition protocol combined with a 5-dimensional reconstruction strategy.