Cerebrovascular accidents in adult patients with congenital heart disease

To investigate the prevalence and characteristics of cerebrovascular accidents (CVA) in a large population of adults with congenital heart disease (CHD).

Non-fatal cardiovascular outcome in patients with posttraumatic stress symptoms caused by myocardial infarction

Objectives Posttraumatic stress disorder (PTSD) prospectively increases the risk of incident cardiovascular disease (CVD) independent of other risk factors in otherwise healthy individuals. Between 10% and 20% of patients develop PTSD related to the traumatic experience of myocardial infarction (MI). We investigated the hypothesis that PTSD symptoms caused by MI predict adverse cardiovascular outcome. Methods We studied 297 patients (61 ± 10 years, 83% men) who self-rated PTSD symptoms attributable to a previous index MI. Non-fatal CVD-related hospital readmissions (i.e. recurrent MI, elective and non-elective intracoronary stenting, bypass surgery, pacemaker implantation, cardiac arrhythmia, cerebrovascular event) were assessed at follow-up. Cox proportional hazard models controlled for demographic factors, coronary heart disease severity, major CVD risk factors, cardiac medication, and mental health treatment. Results Forty-three patients (14.5%) experienced an adverse event during a mean follow-up of 2.8 years (range 1.3–3.8). A 10 point higher level in the PTSD symptom score (mean 8.8 ± 9.0, range 0–47) revealed a hazard ratio (HR) of 1.42 (95% CI 1.07–1.88) for a CVD-related hospital readmission in the fully adjusted model. A similarly increased risk (HR 1.45, 95% CI 1.07–1.97) emerged for patients with a major or unscheduled CVD-related readmission (i.e. when excluding patients with elective stenting). Conclusions Elevated levels of PTSD symptoms caused by MI may adversely impact non-fatal cardiovascular outcome in post-MI patients independent of other important prognostic factors. The possible importance of PTSD symptoms as a novel prognostic psychosocial risk factor in post-MI patients warrants further study.

Importance of 3D-CT imaging in single-bullet cranioencephalic gunshot wounds

PURPOSE: The aim of this paper is to demonstrate that computed tomography (CT) and three-dimensional (3D) CT imaging techniques can be useful tools for evaluating gunshot wounds of the skull in forensic medicine. Three purposes can be achieved: (1) identifying and recognising the bullet entrance wound - and exit wound, if present; (2) recognising the bullet's intracranial course by studying damage to bone and brain tissue; (3) suggesting hypotheses as to the dynamics of the event. MATERIALS AND METHODS: Ten cadavers of people who died of a fatal head injury caused by a single gunshot were imaged with total-body CT prior to conventional autoptic examination. Three-dimensional-CT reconstructions were obtained with the volume-rendering technique, and data were analysed by two independent observers and compared with autopsy results. RESULTS: In our experience, CT analysis and volumetric reconstruction techniques allowed the identification of the bullet entrance and exit wounds and intracranial trajectory, as well as helping to formulate a hypothesis on the extracranial trajectory to corroborate circumstantial evidence. CONCLUSIONS: CT imaging techniques are excellent tools for addressing the most important questions of forensic medicine in the case of gunshot wounds of the skull, with results as good as (or sometimes better than) traditional autoptic methods.

Electroencephalographic topography measures of experienced utility

Economic theory distinguishes two concepts of utility: decision utility, objectively quantifiable by choices, and experienced utility, referring to the satisfaction by an obtainment. To date, experienced utility is typically measured with subjective ratings. This study intended to quantify experienced utility by global levels of neuronal activity. Neuronal activity was measured by means of electroencephalographic (EEG) responses to gain and omission of graded monetary rewards at the level of the EEG topography in human subjects. A novel analysis approach allowed approximating psychophysiological value functions for the experienced utility of monetary rewards. In addition, we identified the time windows of the event-related potentials (ERP) and the respective intracortical sources, in which variations in neuronal activity were significantly related to the value or valence of outcomes. Results indicate that value functions of experienced utility and regret disproportionally increase with monetary value, and thus contradict the compressing value functions of decision utility. The temporal pattern of outcome evaluation suggests an initial (∼250 ms) coarse evaluation regarding the valence, concurrent with a finer-grained evaluation of the value of gained rewards, whereas the evaluation of the value of omitted rewards emerges later. We hypothesize that this temporal double dissociation is explained by reward prediction errors. Finally, a late, yet unreported, reward-sensitive ERP topography (∼500 ms) was identified. The sources of these topographical covariations are estimated in the ventromedial prefrontal cortex, the medial frontal gyrus, the anterior and posterior cingulate cortex and the hippocampus/amygdala. The results provide important new evidence regarding “how,” “when,” and “where” the brain evaluates outcomes with different hedonic impact.

Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: The CoRisk Study

RATIONALE: Copeptin independently predicts functional outcome and mortality at 90 days and one-year after ischemic stroke. In patients with transient ischemic attack, elevated copeptin values indicate an increased risk of further cerebrovascular events. AIMS: The Copeptin Risk Stratification (CoRisk) study aims to validate the predictive value of copeptin in patients with ischemic stroke and transient ischemic attack. In patients with ischemic stroke, the CoRisk study aims to further explore the effect of treatment (i.e. thrombolysis) on the predictive value of copeptin. DESIGN: Prospective observational multicenter study analyzing three groups of patients, i.e. patients with ischemic stroke treated with and without thrombolysis and patients with transient ischemic attack. OUTCOMES: Primary end-point: In patients with ischemic stroke, the primary end-point includes disability (modified Rankin scale from 3 to 5) and mortality (modified Rankin scale 6) at three-months after stroke. In patients with transient ischemic attack, the primary end-point is a recurrent ischemic cerebrovascular event (i.e. ischemic stroke or recurrent transient ischemic attack). Secondary end-point: In patients with ischemic stroke, the secondary end-points include in-house complications (i.e. symptomatic intracerebral hemorrhage, malignant edema, aspiration pneumonia or seizures during hospitalization, and in-house mortality).

Phase contrast and time-of-flight magnetic resonance angiography of the intracerebral arteries at 1.5, 3 and 7 T

Time-of-flight (ToF) and phase contrast (PC) magnetic resonance angiographies (MRAs) are noninvasive applications to depict the cerebral arteries. Both approaches can image the cerebral vasculature without the administration of intravenous contrast. Therefore, it is used in routine clinical evaluation of cerebrovascular diseases, e.g., aneurysm and arteriovenous malformations. However, subtle microvascular disease usually cannot be resolved with standard, clinical-field-strength MRA. The purpose of this study was to compare the ability of ToF and PC MRA to visualize the cerebral arteries at increasing field strengths.

Time to admission in acute ischemic stroke and transient ischemic attack

BACKGROUND AND PURPOSE: The effect of thrombolysis depends on the time from stroke onset to treatment and therefore also on the time when patients come to the hospital. This study was designed to analyze the variables that influence the time from symptom onset to admission (TTA) to the stroke unit. METHODS: We evaluated the medical records of 615 consecutive stroke or transient ischemic attack (TIA) patients admitted to our neurological department within 48 hours after symptom onset. RESULTS: The median TTA was 180 minutes. Referral by emergency medical services (EMS; P<0.001), high National Institutes of Health Stroke Scale (NIHSS) scores (P<0.001), strokes in the carotid territory (P<0.001), and strokes not attributable to small vessel disease (P<0.001) were associated with shorter prehospital delays. The TTA was adjusted for travel times (adjTTA), and all these variables remained significantly associated with time to admission. In addition, patients with previous experience with stroke or TIA had longer adjTTA (P=0.028). Regression analysis confirmed the independent association between referral by EMS (P=0.010), high NIHSS scores (P<0.001), carotid territory stroke (P<0.001), and first-ever cerebrovascular event (P=0.022) with shorter adjTTA. CONCLUSIONS: Factors such as NIHSS scores and stroke location influence the time to admission but, unlike referral pathways, cannot be modified. Educational programs and stroke campaigns should therefore not only teach typical and less common stroke symptoms and signs but also that EMS provides the fastest means of transportation to a stroke unit and the best chances to get treatment early.

Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG)

BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

A multivariate approach for processing magnetization effects in triggered event-related functional magnetic resonance imaging time series

Triggered event-related functional magnetic resonance imaging requires sparse intervals of temporally resolved functional data acquisitions, whose initiation corresponds to the occurrence of an event, typically an epileptic spike in the electroencephalographic trace. However, conventional fMRI time series are greatly affected by non-steady-state magnetization effects, which obscure initial blood oxygen level-dependent (BOLD) signals. Here, conventional echo-planar imaging and a post-processing solution based on principal component analysis were employed to remove the dominant eigenimages of the time series, to filter out the global signal changes induced by magnetization decay and to recover BOLD signals starting with the first functional volume. This approach was compared with a physical solution using radiofrequency preparation, which nullifies magnetization effects. As an application of the method, the detectability of the initial transient BOLD response in the auditory cortex, which is elicited by the onset of acoustic scanner noise, was used to demonstrate that post-processing-based removal of magnetization effects allows to detect brain activity patterns identical with those obtained using the radiofrequency preparation. Using the auditory responses as an ideal experimental model of triggered brain activity, our results suggest that reducing the initial magnetization effects by removing a few principal components from fMRI data may be potentially useful in the analysis of triggered event-related echo-planar time series. The implications of this study are discussed with special caution to remaining technical limitations and the additional neurophysiological issues of the triggered acquisition.

Effects of non-ionic iodinated contrast media on patient heart rate and pressures during intra-cardiac or intra-arterial injection

PURPOSE: To compare the effects on heart rate (HR), on left ventricular (LV) or arterial pressures, and the general safety of a non-ionic low-osmolar contrast medium (CM) and a non-ionic iso-osmolar CM in patients undergoing cardiac angiography (CA) or peripheral intra-arterial digital subtraction angiography (IA-DSA). MATERIALS AND METHODS: Two double-blind, randomized studies were conducted in 216 patients who underwent CA (n=120) or peripheral IA-DSA (n=96). Patients referred for CA received a low-osmolar monomeric CM (iomeprol-350, n=60) or an iso-osmolar dimeric CM (iodixanol-320; n=60). HR and LV peak systolic and end-diastolic pressures were determined before and after the first injection during left and right coronary arteriography and left ventriculography. Monitoring for all types of adverse event (AE) was performed for 24 h following the procedure. t-tests were performed to compare CM for effects on HR. Patients referred for IA-DSA received iomeprol-300 (n=49) or iodixanol-320 (n=47). HR and arterial blood pressure (BP) were evaluated before and after the first 4 injections. Monitoring for AE was performed for 4 h following the procedure. Repeated-measures ANOVA was used to compare mean HR changes across the first 4 injections, whereas changes after the first injection were compared using t-tests. RESULTS: No significant differences were noted between iomeprol and iodixanol in terms of mean changes in HR during left coronary arteriography (p=0.8), right coronary arteriography (p=0.9), and left ventriculography (p=0.8). In patients undergoing IA-DSA, no differences between CM were noted for effects on mean HR after the first injection (p=0.6) or across the first 4 injections (p=0.2). No significant differences (p>0.05) were noted in terms of effects on arterial BP in either study or on LV pressures in patients undergoing CA. Non-serious AE considered possibly CM-related (primarily headache and events affecting the cardiovascular and digestive systems) were reported more frequently by patients undergoing CA and more frequently after iodixanol (14/60 [23.3%] and 2/47 [4.3%]; CA and IA-DSA, respectively) than iomeprol (10/60 [16.7%] and 1/49 [2%], respectively). CONCLUSIONS: Iomeprol and iodixanol are safe and have equally negligible effects on HR and LV pressures or arterial BP during and after selective intra-cardiac injection and peripheral IA-DSA. CLINICAL APPLICATION: Iomeprol and iodixanol are safe and equally well tolerated with regard to cardiac rhythm and clinical preference should be based on diagnostic image quality alone.

Methodical study of nitrous oxide eddy covariance measurements using quantum cascade laser spectrometery over a Swiss forest

Nitrous oxide fluxes were measured at the Lägeren CarboEurope IP flux site over the multi-species mixed forest dominated by European beech and Norway spruce. Measurements were carried out during a four-week period in October–November 2005 during leaf senescence. Fluxes were measured with a standard ultrasonic anemometer in combination with a quantum cascade laser absorption spectrometer that measured N2O, CO2, and H2O mixing ratios simultaneously at 5 Hz time resolution. To distinguish insignificant fluxes from significant ones it is proposed to use a new approach based on the significance of the correlation coefficient between vertical wind speed and mixing ratio fluctuations. This procedure eliminated roughly 56% of our half-hourly fluxes. Based on the remaining, quality checked N2O fluxes we quantified the mean efflux at 0.8±0.4 μmol m−2 h−1 (mean ± standard error). Most of the contribution to the N2O flux occurred during a 6.5-h period starting 4.5 h before each precipitation event. No relation with precipitation amount could be found. Visibility data representing fog density and duration at the site indicate that wetting of the canopy may have as strong an effect on N2O effluxes as does below-ground microbial activity. It is speculated that above-ground N2O production from the senescing leaves at high moisture (fog, drizzle, onset of precipitation event) may be responsible for part of the measured flux.

Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis

The effects of hydration status on cerebral blood flow (CBF) and development of cerebrospinal fluid (CSF) lactic acidosis were evaluated in rabbits with experimental pneumococcal meningitis. As loss of cerebrovascular autoregulation has been previously demonstrated in this model, we reasoned that compromise of intravascular volume might severely affect cerebral perfusion. Furthermore, as acute exacerbation of the inflammatory response in the subarachnoid space has been observed after antibiotic therapy, animals were studied not only while meningitis evolved, but also 4-6 h after treatment with antibiotics to determine whether there would also be an effect on CBF. To produce different levels of hydration, animals were given either 50 ml/kg per 24 h of normal saline ("low fluid") or 150 ml/kg 24 h ("high fluid"). After 16 h of infection, rabbits that were given the lower fluid regimen had lower mean arterial blood pressure (MABP), lower CBF, and higher CSF lactate compared with animals that received the higher fluid regimen. In the first 4-6 h after antibiotic administration, low fluid rabbits had a significant decrease in MABP and CBF compared with, and a significantly greater increase in CSF lactate concentration than, high fluid rabbits. This study suggests that intravascular volume status may be a critical variable in determining CBF and therefore the degree of cerebral ischemia in meningitis.

Clinical diagnosis of posttraumatic stress disorder after myocardial infarction

BACKGROUND: Clinician-rated large-scale studies estimating the prevalence of posttraumatic stress disorder (PTSD) related to myocardial infarction (MI) and identifying predictors of clinical PTSD are currently lacking. HYPOTHESES: We hypothesized that PTSD is prevalent in post-MI patients and that the subjective experience of the MI determines PTSD status. METHODS: We approached 951 post-MI patients with a questionnaire screening for PTSD symptoms related to their MI. Those responding and meeting a cutoff of PTSD symptom levels were invited to participate in a structured clinical interview to diagnose PTSD following Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Fear of dying, feelings of helplessness, and severity of pain perceived during the MI were also assessed by visual analog scales. RESULTS: The screening questionnaire was completed by 394 patients, whereby 77 met the cutoff for the interview (8 patients declined the interview). Forty of 394 patients (10.2%) had clinical PTSD (subsyndromal and syndromal forms combined). Younger age (OR 0.95, 95% CI 0.91-0.99), greater fear of dying (OR 2.77, 95% CI 1.28-5.97), and more intense feelings of helplessness (OR 2.97, 95% CI 1.42-6.21) were independent predictors of PTSD status. Perceived pain intensity during MI, sex, type of index MI, left ventricular ejection fraction, number of coronary occlusions, and highest level of total creatinine kinase were not significant predictors. CONCLUSIONS: Clinical PTSD is prevalent in post-MI patients. Demographic and particularly psychological variables related to the subjective experience of the event were stronger predictors of PTSD status than were objective measures of MI severity.

[Second victim : Critical incident stress management in clinical medicine]

BACKGROUND Critical incidents in clinical medicine can have far-reaching consequences on patient health. In cases of severe medical errors they can seriously harm the patient or even lead to death. The involvement in such an event can result in a stress reaction, a so-called acute posttraumatic stress disorder in the healthcare provider, the so-called second victim of an adverse event. Psychological distress may not only have a long lasting impact on quality of life of the physician or caregiver involved but it may also affect the ability to provide safe patient care in the aftermath of adverse events. METHODS A literature review was performed to obtain information on care giver responses to medical errors and to determine possible supportive strategies to mitigate negative consequences of an adverse event on the second victim. An internet search and a search in Medline/Pubmed for scientific studies were conducted using the key words "second victim, "medical error", "critical incident stress management" (CISM) and "critical incident stress reporting system" (CIRS). Sources from academic medical societies and public institutions which offer crisis management programs where analyzed. The data were sorted by main categories and relevance for hospitals. Analysis was carried out using descriptive measures. RESULTS In disaster medicine and aviation navigation services the implementation of a CISM program is an efficient intervention to help staff to recover after a traumatic event and to return to normal functioning and behavior. Several other concepts for a clinical crisis management plan were identified. CONCLUSIONS The integration of CISM and CISM-related programs in a clinical setting may provide efficient support in an acute crisis and may help the caregiver to deal effectively with future error events and employee safety.

Climate and chemistry effects of a regional scale nuclear conflict

Previous studies have highlighted the severity of detrimental effects for life on earth after an assumed regionally limited nuclear war. These effects are caused by climatic, chemical and radiative changes persisting for up to one decade. However, so far only a very limited number of climate model simulations have been performed, giving rise to the question how realistic previous computations have been. This study uses the coupled chemistry climate model (CCM) SOCOL, which belongs to a different family of CCMs than previously used, to investigate the consequences of such a hypothetical nuclear conflict. In accordance with previous studies, the present work assumes a scenario of a nuclear conflict between India and Pakistan, each applying 50 warheads with an individual blasting power of 15 kt ("Hiroshima size") against the major population centers, resulting in the emission of tiny soot particles, which are generated in the firestorms expected in the aftermath of the detonations. Substantial uncertainties related to the calculation of likely soot emissions, particularly concerning assumptions of target fuel loading and targeting of weapons, have been addressed by simulating several scenarios, with soot emissions ranging from 1 to 12 Tg. Their high absorptivity with respect to solar radiation leads to a rapid self-lofting of the soot particles into the strato- and mesosphere within a few days after emission, where they remain for several years. Consequently, the model suggests earth's surface temperatures to drop by several degrees Celsius due to the shielding of solar irradiance by the soot, indicating a major global cooling. In addition, there is a substantial reduction of precipitation lasting 5 to 10 yr after the conflict, depending on the magnitude of the initial soot release. Extreme cold spells associated with an increase in sea ice formation are found during Northern Hemisphere winter, which expose the continental land masses of North America and Eurasia to a cooling of several degrees. In the stratosphere, the strong heating leads to an acceleration of catalytic ozone loss and, consequently, to enhancements of UV radiation at the ground. In contrast to surface temperature and precipitation changes, which show a linear dependence to the soot burden, there is a saturation effect with respect to stratospheric ozone chemistry. Soot emissions of 5 Tg lead to an ozone column reduction of almost 50% in northern high latitudes, while emitting 12 Tg only increases ozone loss by a further 10%. In summary, this study, though using a different chemistry climate model, corroborates the previous investigations with respect to the atmospheric impacts. In addition to these persistent effects, the present study draws attention to episodically cold phases, which would likely add to the severity of human harm worldwide. The best insurance against such a catastrophic development would be the delegitimization of nuclear weapons.