e-Health-based management of patients receiving oral anticoagulation therapy: results from the observational thrombEVAL study.

Essentials e-Health based health care by an expert centre may advance management of oral anticoagulation. Outcome of patients was compared between an e-health based coagulation service and regular care. Patients in the coagulation service cohort experienced a significantly better clinical outcome. Lower risk for adverse events was related to anticoagulation-specific and non-specific outcome. SUMMARY: Background Management of oral anticoagulation (OAC) therapy is essential to minimize adverse events in patients receiving vitamin K-antagonists (VKAs). Data on the effect of e-health-based anticoagulation management systems on the clinical outcome of OAC patients are limited. Objectives To compare the clinical outcome of OAC patients managed by an e-health-based coagulation service (CS) with that of patients receiving regular medical care (RMC). Methods The prospective multicenter cohort study thrombEVAL (NCT01809015) comprised 1558 individuals receiving RMC and 760 individuals managed by a CS. Independent study monitoring and adjudication of endpoints by an independent review panel were implemented. Results The primary study endpoint (composite of thromboembolism, clinically relevant bleeding and death) occurred in 15.7 per 100 patient-years (py) with RMC and in 7.0 per 100 py with the CS (rate ratio [RR], 2.3; 95% confidence interval [CI], 1.7-3.1). Rates for major and clinically relevant bleeding were higher with RMC than with the CS: 6.8 vs. 2.6 and 10.1 vs. 3.6 per 100 py, respectively. Thromboembolic events showed an RR of 1.5 (95% CI, 0.8-2.6) comparing RMC with the CS. Hospitalization (RR, 2.6; 95% CI, 2.3-3.0) and all-cause mortality (RR, 4.6; 95% CI, 2.8-7.7) were markedly more frequent with RMC. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, treatment characteristics and sociodemographic status, hazard ratios (HR) for the primary endpoint (HR, 2.2; 95% CI, 1.5-3.4), clinically relevant bleeding (HR, 3.1; 95% CI, 1.7-5.5), hospitalization (HR, 2.2; 95% CI, 1.8-2.8) and all-cause mortality (HR, 5.6; 95% CI, 2.9-11.0) favored CS treatment. Conclusions In this study, e-health-based management of OAC therapy was associated with a lower frequency of OAC-specific and non-specific adverse events.

Area at risk and viability after myocardial ischemia and reperfusion can be determined by contrast-enhanced cardiac magnetic resonance imaging.

BACKGROUND/AIMS: Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. METHODS: Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethylenetriamine pentaacetic acid. The area at risk was determined by intravenous injection of Evans blue and myocardial viability by triphenyltetrazolium-chloride staining. RESULTS: The signal-intense areas at 2 and 15 min after contrast administration matched the area at risk in groups A and B. Nonviable myocardium in group A was overestimated (14-15%) while good agreement was present in group B. CONCLUSION: The area at risk of reperfused ischemic myocardium can be determined by ceCMRI 24 h after coronary recanalization. This type of information might have relevant clinical implications in the treatment and stratification of patients with acute coronary syndrome in particular after surgical interventions.

Training for cervical cancer prevention programs in low-resource settings: focus on visual inspection with acetic acid and cryotherapy.

The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

Experiences of a poison center network with renal insufficiency in acetaminophen overdose: an analysis of 17 cases.

OBJECTIVE: Renal insufficiency is less common than liver failure in acetaminophen overdose but renal tubular damage occurs even in the absence of hepatotoxicity. Data published on this topic are rare consisting mostly of case reports or reports in a small number of patients. Presently, a larger number of patients with renal insufficiency associated with acetaminophen overdose should be analyzed using a multicenter approach. STUDY DESIGN: Retrospective analysis of patients with acetaminophen-related nephrotoxicity reported to a poison center network from 1995 to 2003. Renal insufficiency was defined as elevated serum creatinine of more than double of the normal range (>2.4 mg/dL [212 micromol/L]). Patients were classified into 4 groups (A: creatinine 2.4-5.0 mg/dL, B: creatinine>5.0 mg/dL requiring no dialysis, C: creatinine>5.0 mg/dL requiring dialysis, D: creatinine>5.0 mg/dL with fatal outcome). RESULTS: Seventeen patients were included (8 female, 9 male, average age 31.7 +/- 21.1 yrs) with 6 patients in group A (B: 7, C: 2, D: 2). In 5 patients renal insufficiency occurred without elevation of liver enzymes. Regarding possible risk factors 5 patients concomitantly ingested nephrotoxic substances, 4 presented with dehydration due to vomiting, 4 with chronic excessive dosing (overdose) of acetaminophen, 3 showed pre-existing renal insufficiency, 2 pre-existing liver disease and 2 died with multiple organ failure. CONCLUSIONS: Renal insufficiency in acetaminophen overdose mostly resolved without dialysis and occurred isolated without hepatotoxicity in less than one-third of the investigated patients. Conditions which might play a role as influencing factors for renal complications included concomitant ingestion of nephrotoxic drugs, dehydration, chronic excessive dosing (overdose) of acetaminophen, pre-existing renal or liver disease and multiple organ failure. Renal function should be monitored in acetaminophen overdose particularly in patients showing the latter comorbidity.

Quantifying the effect of intrafraction motion during breast IMRT planning and dose delivery.

Respiratory motion during intensity modulated radiation therapy (IMRT) causes two types of problems. First, the clinical target volume (CTV) to planning target volume (PTV) margin needed to account for respiratory motion means that the lung and heart dose is higher than would occur in the absence of such motion. Second, because respiratory motion is not synchronized with multileaf collimator (MLC) motion, the delivered dose is not the same as the planned dose. The aims of this work were to evaluate these problems to determine (a) the effects of respiratory motion and setup error during breast IMRT treatment planning, (b) the effects of the interplay between respiratory motion and multileaf collimator (MLC) motion during breast IMRT delivery, and (c) the potential benefits of breast IMRT using breath-hold, respiratory gated, and 4D techniques. Seven early stage breast cancer patient data sets were planned for IMRT delivered with a dynamic MLC (DMLC). For each patient case, eight IMRT plans with varying respiratory motion magnitudes and setup errors (and hence CTV to PTV margins) were created. The effects of respiratory motion and setup error on the treatment plan were determined by comparing the eight dose distributions. For each fraction of these plans, the effect of the interplay between respiratory motion and MLC motion during IMRT delivery was simulated by superimposing the respiratory trace on the planned DMLC leaf motion, facilitating comparisons between the planned and expected dose distributions. When considering respiratory motion in the CTV-PTV expansion during breast IMRT planning, our results show that PTV dose heterogeneity increases with respiratory motion. Lung and heart doses also increase with respiratory motion. Due to the interplay between respiratory motion and MLC motion during IMRT delivery, the planned and expected dose distributions differ. This difference increases with respiratory motion. The expected dose varies from fraction to fraction. However, for the seven patients studied and respiratory trace used, for no breathing, shallow breathing, and normal breathing, there were no statistically significant differences between the planned and expected dose distributions. Thus, for breast IMRT, intrafraction motion degrades treatment plans predominantly by the necessary addition of a larger CTV to PTV margin than would be required in the absence of such motion. This motion can be limited by breath-hold, respiratory gated, or 4D techniques.

[Deliberate self-poisoning with paracetamol (acetaminophen): an analysis from 1995 to 2002]. / Suizidale und parasuizidale Intoxikationen mit Paracetamol - Eine Analyse von 1995 bis 2002.

BACKGROUND AND OBJECTIVE: Paracetamol is frequently used in deliberate self-poisoning resulting in a major risk for the patients due to its dose-dependent hepatotoxicity. In the present study the cases of intoxications consulting our Poison Center should be analysed illustrating recent results and trends. PATIENTS AND METHODS: From 38 065 patients (25 098 female, 12447 male, 520 sex unknown, average age 36.8 years) registered during the study period from 1.1.1995 until 31.5.2002 4021 with paracetamol intoxication were analysed with respect to the ingested dose, concomitant substances, the degree of observed symptoms and the length of hospital stay. RESULTS: The use of paracetamol in deliberate self-poisoning continuously increased during the study period from 8.9 % in the year 1995 to 12.4 % in 2002. Paracetamol was mainly used from female patients and patients in the age group between 10 and 29 years. 88.6 % of cases were reported to the poison center within the first twelve hours after ingestion. Concomitantly non-steroidal antirheumatics (38.0 %), ethanol (20.6 %) and antibiotics (15.0 %) were ingested. Monointoxications as well as mixed intoxications with paracetamol caused severe intoxications and deaths less frequently as compared to the group of the remainder substances with the degree of symptoms tended to be dose-dependent. In 73.7 % of cases the length of hospital stay did not exceed 3 days. CONCLUSIONS: In recent years, an increasing importance of paracetamol in deliberate self-poisoning was determined particularly concerning female and younger patients. The dose of paracetamol and the duration of exposition are crucial for prognosis. With an early antidote therapy hospitalization is usually observed for a few days only. A risk for complications are frequently used concomitant substances requiring a detailed registration.

Neonatal hypoxic risk in preterm birth infants: the influence of sex and severity of respiratory distress on cognitive recovery.

The authors examined the differential effects of neonatal respiratory distress syndrome (RDS)--a condition associated with elevated risk for neonatal hypoxia-ischemia--on the cognitive development of the two sexes. The authors also attempted to establish whether the severity of respiratory distress is linked to cognitive outcome. Findings revealed an appreciable female advantage in cognitive recovery from RDS, yet the association between severity of RDS and outcome did not reach conventional statistical significance level. The sex effect on intelligence test performance was significantly greater for nonverbal subtests than for verbal ones. These results augment earlier findings of sex differences in cognitive recovery from perinatal intracranial hemorrhage. The current investigation also extends these results to a population of children at neonatal hypoxic risk for whom early brain injury was excluded on the basis of neonatal cranial ultrasound findings.

Plasma protein loss during surgery: beneficial effects of albumin substitution.

Plasma protein loss during abdominal surgery is a known phenomenon, but its possible pathophysiological relevance has remained unknown. The present study evaluates the effects of albumin substitution on systemic and local hemodynamics and cellular interactions in the mesenteric microcirculation. Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Plasma protein concentrations, systemic and local hemodynamics were recorded during the follow up period, with or without albumin substitution. Depending on the time course of plasma protein loss in control experiments, 80% of the calculated protein loss was infused during the first 2 h of surgery, and the other 20% over the following 5 h of intravital microscopy. The control group received a continuous infusion of normal saline. Plasma protein loss was mainly due to loss of albumin. A significant increase in adherent and rolling leukocytes was observed during the course of mesenteric exteriorization, which was almost entirely reversed by albumin replacement. Albumin substitution led to stabilisation of mean arterial pressure and abdominal blood flow and also attenuated reductions in arterial base excess. Albumin infusions to replace plasma protein loss may be a simple and effective measure to attenuate microcirculatory disturbances and may be of benefit in patients undergoing abdominal surgery.

Acceleration of dose calculations for intensity-modulated radiotherapy.

The requirements and trade-offs between accuracy and speed for radiotherapy dose computations have been discussed for decades. Inverse planning used for intensity-modulated radiotherapy (IMRT) optimization imposes additional demands on dose calculation since it is an iterative process in which dose calculations might be repeated many (10's to 1000's) of times. This work discusses the accuracy and speed issues as related to IMRT dose calculations. A hybrid dose calculation method which accelerates the optimization process is proposed and applied in which a fast-pencil beam (PB) model is used for initial optimization iterations, followed by superposition/convolution (SC) calculations. Optimization dose results are compared for pure PB optimization, pure SC optimization, and PB optimization followed by SC optimization. Plans were evaluated in terms of isodose coverage, dose-volume histograms, and total dose calculation time for five head and neck cases with diverse locations, sizes, and shapes for tumors and critical structures. Patient plans were designed for nine equispaced beams. For one patient, an additional five-beam configuration was tested. We found that gross features of intensity distributions resulting from all schemes were similar, however there were differences in the fine detail. Differences were small between composite dose distributions optimized with PB and SC methods, yet differences in individual beam dose distributions were quite significant. When the SC method was used to compute dose following optimization with PB method, dose differences were reduced significantly both for composite plans and for individual beams. Substantial overall timesavings were observed, allowing IMRT dose planning to become a more interactive activity.

C1-esterase-inhibitor treatment at early reperfusion of hemorrhagic shock reduces mesentry leukocyte adhesion and rolling.

OBJECTIVE: Complement activation probably plays a pathogenic role in multiple organ failure in shock. This study evaluates the effects of C1-esterase-inhibitor treatment on leukocyte-endothelial interaction in the mesenteric microcirculation in hemorrhagic shock. METHODS: Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body wt. for 60 minutes) followed by a 4-hour reperfusion period. C1-INH (100 IU/kg body wt. i.v.) or 0.9% NaCl i.v. were administered as a bolus at the beginning of reperfusion. Reperfusion time mimicked a "pre-hospital" phase of 30 minutes followed by a quasi "in-hospital" phase of 3.5 hours. The "in-hospital" phase was initiated by substitution of blood followed by fluid resuscitation with normal saline. RESULTS: Application of C1-INH markedly reduced rolling and adherent leukocytes to numbers approaching baseline values. Vmax and shear rate of the mesenteric microcirculation improved in both groups after reperfusion with a trend to higher values in the C1-INH group (n.s. p = 0.08). CONCLUSION: C1-INH applied in a bolus dose of 100 IU/kg body wt. i.v. abrogated enhanced leukocyte adhesion and rolling in the mesenteric microcirculation after hemorrhagic shock. Single bolus treatment with a complement inhibitor may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.

Plastic foil technique attenuates inflammation in mesenteric intravital microscopy.

BACKGROUND: Interpretation of intravital microscopic observations is complicated by the "inflammatory"-type response to the trauma inflicted on the tissue by the surgical preparation. The present study evaluates different experimental conditions for prolonged observations of the mesenteric microcirculation in the rat. METHODS: The mesentery was exteriorized through a median laparotomy and subjected to an organ bath or a modified plastic foil technique. Hemodynamic, metabolic, respiratory, and microcirculatory data were analyzed. RESULTS: In contrast to the plastic foil technique, which yielded stable baseline values over a 5-h observation period, venular velocity and wall shear rates decreased significantly in the organ bath technique, and leukocyte adhesion to the endothelium was significantly increased. Likewise, abdominal blood flow decreased significantly by 35% and base excess declined (-10.0+/-0.4 mmol/L) in the organ bath, with reduced pco(2) (26.4+/-2.5 mm Hg vs. 33.7+/-1.1 mm Hg in plastic foil technique) due to respiratory pH compensation. CONCLUSIONS: The plastic foil technique was found clearly superior to the organ bath technique for maintenance of stable baseline metabolic, hemodynamic, and microcirculatory conditions in mesenteric intravital microscopy.

XINPUT: a program to edit "DOSRZ" input files.

The DOSRZ user code, which is part of the EGS4 standard distribution, is widely used in medical physics for the calculation of dose deposition in cylindrical geometries. The code provides the use of advanced Monte-Carlo techniques (PRESTA) and variance reduction methods. In the case of complex cylinder geometries the input of coordinates and radii is not only tedious but also prone to a high error rate. Coordinates are to be stated in absolute numbers. A change of one number, e.g., the slab thickness, requires the change of all subsequent numbers. Furthermore, parameters are only stated as numbers with no indication of their meaning. Obviously, there is a need for a user interface to facilitate the input for DOSRZ and to largely reduce the possibility for errors. We, therefore, wrote a graphical user interface (GUI) consisting of an input mask, a coordinate input interpreter, and a two-dimensional and/or pseudo-three-dimensional display section. The GUI is based on the scripting language Tcl/Tk, which runs under various platforms such as UNIX (LINUX), w95, and WIN NT. It consists of a main window which provides common-style menus and buttons to navigate through the edit dialog boxes. The most important tools are the region input, which enables the user to create the simulation geometry, and the graphics section where the scaled output can be displayed. Different media are shown in different colors which are user defined. Furthermore, the program contains some tools to reduce the probability of an erroneous input in the EGS4 input file. Since Tcl/Tk is a modern scripting language, it offers advanced tools to create the GUI and to "glue" different applications to it. XINPUT may also be considered as a model program for the development of a more general interface to other input areas of the EGS4 simulation code.

The effects of perinatal hypoxic risk on developmental outcome in early and middle childhood: a twin study.

The goal of this study of 66 twins was to determine whether motor and cognitive functions assessed in early and middle childhood are vulnerable to perinatal hypoxic risk. In an earlier study of 76 infant and toddler twins (S. Raz, F. Shah, & C. Sander, 1996), the authors found that intrapair discrepancy on the Mental Developmental Index, but not on the Psychomotor Developmental Index, of the Bayley Scales of Infant Development was associated with discordance for perinatal hypoxic risk. The twins at lower risk outperformed their higher risk co-twins. In the present study the authors sought to establish in a new sample of preschool and school-age twins whether gaps in performance persist into early and middle childhood. Although the disparity in hypoxic risk between the co-twins was typically moderate, significant intrapair differences were observed on the measure of motor performance. Among the motor abilities examined, skills involving visually guided ballistic arm movements appeared to be the most vulnerable to perinatal risk.

DNA damage induced by N-nitrosodibenzylamine and N-nitroso-alpha-acetoxybenzyl-benzylamine in mammalian cell systems and in vivo.

N-nitrosodibenzylamine (NDBzA) and N-nitroso-alpha-acetoxybenzyl-benzylamine (alpha-acetoxy-NDBzA) were tested for induction of DNA single-strand breaks (SSBs) in V 79 Chinese hamster cells (V 79 cells) and isolated rat hepatocytes. The alkaline elution assay was used for the detection of DNA strand breaks. Treatment of V 79 cells with alpha-acetoxy-NDBzA effectively increased the rate of DNA SSBs, while with NDBzA, no DNA-damaging activity was detectable. Both substances produced significant DNA damage in rat hepatocytes. Interestingly, NDBzA was able to induce SSBs at significantly lower concentrations than alpha-acetoxy-NDBzA. The possible reasons for these findings are discussed. In contrast to these in vitro results, NDBzA exhibited very weak in vivo activity.

[CEA determination in the follow-up of colorectal cancers]. / Die CEA-Bestimmung zur Verlaufsbeobachtung kolorektaler Karzinome.

CEA follow-up checks of 135 patients with colorectal carcinoma are described in a retrospective analysis. Unambiguous correlations were found to exist between clinical tumour staging and CEA findings in the context of both primary findings and recurrences and metastasation. Typical courses are described of 107 patients who received curative treatment. An assessment is made of the value of CEA determination in postoperative follow-up.

[Criteria for the hygienic appraisal of intensive care units (author's transl)]. / Kriterien zur hygienischen Beurteilung von Intensivpflegestationen.

7 intensiv-care-units (I.U.C.) were compared by analysing the charts of 100 patients from each station. They showed remarkable differences concerning the diagnosis of admittance, age and other factors related to the risk of infection. Consequently, kind and number of intensive care related medical procedures, the use of antibiotics, the duration of the patients stay on the station and the death rate differed widely. Some criteria concerning the layout, personnel, organisation and therapy on I.C.U. are named, which are mainly related to the patients condition and to the thereby given risk of infection.