The neuroanatomical model of post-stroke depression: towards a change of focus?

One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adversely affect rehabilitation and significantly increase risk of death in the post-stroke period. One of the theoretical views on the determinants of PSD focuses on psychosocial factors like disability and social support. Others emphasize biologic mechanisms such as disruption of biogenic amine neurotransmission and release of proinflammatory cytokines. The "lesion location" perspective attempts to establish a relationship between localization of stroke and occurrence of depression, but empirical results remain contradictory. These divergences are partly related to the fact that neuroimaging methods, unlike neuropathology, are not able to assess precisely the full extent of stroke-affected areas and do not specify the different types of vascular lesions. We provide here an overview of the known phenomenological profile and current pathogenic hypotheses of PSD and present neuropathological data challenging the classic "single-stroke"-based neuroanatomical model of PSD. We suggest that vascular burden due to the chronic accumulation of small macrovascular and microvascular lesions may be a crucial determinant of the development and evolution of PSD.

Debris flows as a factor of hillslope evolution controlled by a continuous or a pulse process?

Flood effectiveness observations imply that two families of processes describe the formation of debris flow volume. One is related to the rainfall?erosion relationship, and can be seen as a gradual process, and one is related to additional geological/geotechnical events, those named hereafter extraordinary events. In order to discuss the hypothesis of coexistence of two modes of volume formation, some methodologies are applied. Firstly, classical approaches consisting in relating volume to catchments characteristics are considered. These approaches raise questions about the quality of the data rather than providing answers concerning the controlling processes. Secondly, we consider statistical approaches (cumulative number of events distribution and cluster analysis) and these suggest the possibility of having two distinct families of processes. However the quantitative evaluation of the threshold differs from the one that could be obtained from the first approach, but they all agree in the sense of the coexistence of two families of events. Thirdly, a conceptual model is built exploring how and why debris flow volume in alpine catchments changes with time. Depending on the initial condition (sediment production), the model shows that large debris flows (i.e. with important volume) are observed in the beginning period, before a steady-state is reached. During this second period debris flow volume such as is observed in the beginning period is not observed again. Integrating the results of the three approaches, two case studies are presented showing: (1) the possibility to observe in a catchment large volumes that will never happen again due to a drastic decrease in the sediment availability, supporting its difference from gradual erosion processes; (2) that following a rejuvenation of the sediment storage (by a rock avalanche) the magnitude?frequency relationship of a torrent can be differentiated into two phases, the beginning one with large and frequent debris flow and a later one with debris flow less intense and frequent, supporting the results of the conceptual model. Although the results obtained cannot identify a clear threshold between the two families of processes, they show that some debris flows can be seen as pulse of sediment differing from that expected from gradual erosion.

Expérience de dix ans de réanimation chirurgicale d'un centre hospitalier universitaire. Détermination d'un critère d'identification des patients à risque de décéder de coagulopathie irréversible [10 years experience in surgical resuscitation at a university hospital center. Determination of a criterion for identifying patients at risk for fatal irreversible coagulopathy]

The authors evaluated ten years of surgical reanimation in the University Centre of Lausanne (CHUV). Irreversible coagulopathy (IC) is the predominant cause of death for the polytraumatized patient. Acidosis, hypothermy, and coagulation troubles are crucial elements of this coagulopathy. The authors looked for a criterion allowing the identification of dying of IC. In a retrospective study, laboratory results of pH, TP, PTT, thrombocyte count and the need for blood transfusion units were checked for each major step of the primary evaluation and treatment of the polytraumatized patients. These results were considered as critical according to criteria of the literature (30). The authors conclude that the apparation of a third critical value may be useful to identify the polytraumatized patient at risk of dying of IC status. This criterion may also guide the trauma team in selecting a damage control surgical approach (DCS). This criterion was then introduced into an algorithm involving the Emergency Department, the operating room and the Intensive Care Unit. This criterion is a new tool to address the patient at the crucial moment to the appropriate hospital structure.

Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials.

The purpose of this study was to assess the outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (EGPA) enrolled in 2 prospective, randomized, open-label clinical trials (1994-2005), with or without Five-Factor Score (FFS)-defined poor-prognosis factors, focusing on survival, disease-free survival, relapses, clinical and laboratory findings, therapeutic responses, and factors predictive of relapse. Forty-four patients with FFS ≥ 1 were assigned to receive 6 or 12 cyclophosphamide pulses plus corticosteroids and the seventy-four with FFS = 0 received corticosteroids alone, with immunosuppressant adjunction when corticosteroids failed. Patients were followed (2005-2011) under routine clinical care in an extended study and data were recorded prospectively. Mean ± SD follow-up was 81.3 ± 39.6 months. Among the 118 patients studied, 29% achieved long-term remission and 10% died. Among the 115 patients achieving a first remission, 41% experienced ≥1 relapses, 26.1 ± 26.8 months after treatment onset, with 57% of relapses occurring when corticosteroid-tapering reached <10 mg/day. Treatment achieved new remissions in >90%, but relapses recurred in 38%. Overall survival was good, reaching 90% at 7 years, regardless of baseline severity. Age ≥65 years was the only factor associated with a higher risk of death during follow-up. The risk of relapse was higher for patients with anti-myeloperoxidase antibodies and lower for those with >3000 eosinophils/mm(3). Sequelae remained frequent, usually chronic asthma and peripheral neuropathy. In conclusion, EGPA patients' survival rate is very good when treatment is stratified according to the baseline FFS. Relapses are frequent, especially in patients with anti-myeloperoxidase antibodies and baseline eosinophilia <3000/mm(3).

Fondaparinux for the treatment of superficial-vein thrombosis in the legs.

BACKGROUND: The efficacy and safety of anticoagulant treatment for patients with acute, symptomatic superficial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been established. METHODS: In a randomized, double-blind trial, we assigned 3002 patients to receive either fondaparinux, administered subcutaneously at a dose of 2.5 mg once daily, or placebo for 45 days. The primary efficacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis at day 47. The main safety outcome was major bleeding. The patients were followed until day 77. RESULTS: The primary efficacy outcome occurred in 13 of 1502 patients (0.9%) in the fondaparinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% confidence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-vein thrombosis was 85% lower in the fondaparinux group than in the placebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo. CONCLUSIONS: Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treatment of patients with acute, symptomatic superficial-vein thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00443053.)

Assessing the epidemiology and pattern of care of colorectal cancer in Valais, Switzerland

Background: The Valais's cancer registry (RVsT) of the Observatoire valaisan de le santé (OVS) and the department of oncology of Valais's Hospital conducted a study on the epidemiology and pattern of care of colorectal cancer in Valais. Colorectal cancer is the third cause of death by cancer in Switzerland with about 1600 deaths per year. It is the third most frequent cancer for males and the second most frequent for females in Valais. The number of new colorectal cancer cases (average per year) increased between 1989 and 2009 for males as well as for females in Valais. The number of colorectal cancer death cases (average per year) slightly increased between 1989 and 2009 for males as well as for females in Valais. Age-standardized rates of incidence were stable for males and females in Valais and in Switzerland between 1989 and 2009, while age-standardized rates of mortality decreased for males and females in Valais and Switzerland. Results: 774 cases were recorded (59% males). Median age at diagnosis was 70 years old. Most of cancers were invasive (79%) and the main localization was the colon (71%). The most frequent mode of detection was a consultation for non emergency symptoms (75%), but almost 10% of patients consulted in emergency. 82% of patients were treated within 30 days from diagnosis. 90% of the patients were treated by surgery alone or with combined treatment. The first treatment was surgery, including endoscopic resection in 86% of the cases. The treatment was different according to the localization and the stage of the cancer. Survival rate was 95% at 30 days and 79% at one year. The survival was dependent on the stage and the age at diagnosis. Cox model shows an association between mortality and age (better survival for young people) and between mortality and stage (better survival for the lower stages). Methods: RVsT collects information on all cancer cases since 1989 for people registered in the communes of Valais. RVsT has an authorization to collect non anonymized data. All new incident cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. We studied all cases of in situ and invasive colorectal cancers diagnosed between 2006 and 2009 and registered routinely at the RVsT. We checked for data completeness and if necessary sent questionnaires to avoid missing data. A distance of 15 cm has been chosen to delimitate the colon (sigmoid) and the rectal cancers. We made an active follow-up for vital status to have a valid survival analysis. We analyzed the characteristics of the tumors according to age, sex, localization and stage with stata 9 software. Kaplan-Meier curves were generated and Cox model were fitted to analyze survival. Conclusion: The characteristics of patients and tumors and the one year survival were similar to those observed in Switzerland and some European countries. Patterns of care were close to those recommended in guidelines. Routine data recorded in a cancer registry can be used, not only to provide general statistics, but also to help clinicians assess local practices.

Death following acute poisoning by moclobemide

A fatality due to ingestion of a reversible inhibitor of monoamine-oxidase A (MAO-A) is reported. Moclobemide is generally considered as a safe drug far less toxic than tricyclic anti-depressants. However, severe intoxications may result from interactions with other drugs and food such as selective serotonin reuptake inhibitors (SSRIs), anti-Parkinsonians of the MAOI-type (e.g. selegiline) or tyramine from ripe cheese or other sources. In the present case, high levels of moclobemide were measured in peripheral blood exceeding toxic values reported so far in the scientific literature. The body fluid concentrations of moclobemide were of 498 mg/l in peripheral whole blood, 96.3 mg/l in urine while an amount of approximately 33 g could be recovered from gastric contents. The other xenobiotics were considered of little toxicological relevance. The victim (male, 48-year-old) had a past history of depression and committed one suicide attempt 2 years before death. Autopsy revealed no evidence of significant natural disease or injury. It was concluded that the manner of death was suicide and that the unique cause of death was massive ingestion of moclobemide.

Use of the Cognitive Performance Scale (CPS) to detect cognitive impairment in the acute care setting: concurrent and predictive validity.

The Cognitive Performance Scale (CPS) was initially designed to assess cognition in long term care residents. Subsequently, the CPS has also been used among in-home, post-acute, and acute care populations even though CPS' clinimetric performance has not been studied in these settings. This study aimed to determine CPS agreement with the Mini Mental Status Exam (MMSE) and its predictive validity for institutionalization and death in a cohort (N=401) of elderly medical inpatients aged 75 years and over. Medical, physical and mental status were assessed upon admission. The same day, the patient's nurse completed the CPS by interview. Follow-up data were gathered from the central billing system (nursing home stay) and proxies (death). Cognitive impairment was present in 92 (23%) patients according to CPS (score >or= 2). Agreement with MMSE was moderate (kappa 0.52, P<.001). Analysis of discordant results suggested that cognitive impairment was overestimated by the CPS in dependent patients with comorbidities and depressive symptoms, and underestimated in older ones. During follow-up, subjects with abnormal CPS had increased risks of death (adjusted hazard ratio (adjHR) 1.7, 95% CI 1.0-2.8, P=.035) and institutionalization (adjHR 2.7, 95% CI 1.3-5.3, P=.006), independent of demographic, health and functional status. Interestingly, subjects with abnormal CPS were at increased risk of death only if they also had abnormal MMSE. The CPS predicted death and institutionalization during follow-up, but correlated moderately well with the MMSE. Combining CPS and MMSE provided additional predictive information, suggesting that domains other than cognition are assessed by professionals when using the CPS in elderly medical inpatients.

Accuracy profile validation of a new analytical method for propane measurement using headspace-gas chromatography-mass spectrometry

Propane can be responsible for several types of lethal intoxication and explosions. Quantifying it would be very helpful to determine in some cases the cause of death. Some gas chromatography-mass spectrometry (GC-MS) methods of propane measurements do already exist. The main drawback of these GC-MS methods described in the literature is the absence of a specific propane internal standard necessary for accurate quantitative analysis. The main outcome of the following study was to provide an innovative Headspace-GC-MS method (HS-GC-MS) applicable to the routine determination of propane concentration in forensic toxicology laboratories. To date, no stable isotope of propane is commercially available. The development of an in situ generation of standards is thus presented. An internal-labeled standard gas (C3DH7) is generated in situ by the stoichiometric formation of propane by the reaction of deuterated water (D2O) with Grignard reagent propylmagnesium chloride (C3H7MgCl). The method aims to use this internal standard to quantify propane concentrations and, therefore, to obtain precise measurements. Consequently, a complete validation with an accuracy profile according to two different guidelines, the French Society of Pharmaceutical Sciences and Techniques (SFSTP) and the Gesellschaft für toxikologische und Forensische Chemie (GTFCh), is presented.

Efficacy of in-hospital multidimensional interventions of secondary prevention after acute coronary syndrome: a systematic review and meta-analysis

BACKGROUND: Secondary prevention programs for patients experiencing an acute coronary syndrome have been shown to be effective in the outpatient setting. The efficacy of in-hospital prevention interventions administered soon after acute cardiac events is unclear. We performed a systematic review and meta-analysis to determine whether in-hospital, patient-level interventions targeting multiple cardiovascular risk factors reduce all-cause mortality after an acute coronary syndrome. METHODS AND RESULTS: Using a prespecified search strategy, we included controlled clinical trials and before-after studies of secondary prevention interventions with at least a patient-level component (ie, education, counseling, or patient-specific order sets) initiated in hospital with outcomes of mortality, readmission, or reinfarction rates in acute coronary syndrome patients. We classified the interventions as patient-level interventions with or without associated healthcare provider-level interventions and/or system-level interventions. Twenty-six studies met our inclusion criteria. The summary estimate of 14 studies revealed a relative risk of all-cause mortality of 0.79 (95% CI, 0.69 to 0.92; n=37,585) at 1 year. However, the apparent benefit depended on study design and level of intervention. The before-after studies suggested reduced mortality (relative risk [RR], 0.77; 95% CI, 0.66 to 0.90; n=3680 deaths), whereas the RR was 0.96 (95% CI, 0.64 to 1.44; n=99 deaths) among the controlled clinical trials. Only interventions including a provider- or system-level intervention suggested reduced mortality compared with patient-level-only interventions. CONCLUSIONS: The evidence for in-hospital, patient-level interventions for secondary prevention is promising but not definitive because only before-after studies suggest a significant reduction in mortality. Future research should formally test which components of interventions provide the greatest benefit.

Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: signs of blood-brain barrier healing?

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17 day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, cav-1, cav-2 and cav-3. While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of eNOS (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes.

Derivation and validation of a prognostic model for pulmonary embolism.

RATIONALE: An objective and simple prognostic model for patients with pulmonary embolism could be helpful in guiding initial intensity of treatment. OBJECTIVES: To develop a clinical prediction rule that accurately classifies patients with pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes. METHODS: We randomly allocated 15,531 inpatient discharges with pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our prediction rule using logistic regression with 30-day mortality as the primary outcome, and patient demographic and clinical data routinely available at presentation as potential predictor variables. We externally validated the rule in 221 inpatients with pulmonary embolism from Switzerland and France. MEASUREMENTS: We compared mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. MAIN RESULTS: The prediction rule is based on 11 simple patient characteristics that were independently associated with mortality and stratifies patients with pulmonary embolism into five severity classes, with 30-day mortality rates of 0-1.6% in class I, 1.7-3.5% in class II, 3.2-7.1% in class III, 4.0-11.4% in class IV, and 10.0-24.5% in class V across the derivation and validation samples. Inpatient death and nonfatal complications were <or= 1.1% among patients in class I and <or= 1.9% among patients in class II. CONCLUSIONS: Our rule accurately classifies patients with pulmonary embolism into classes of increasing risk of mortality and other adverse medical outcomes. Further validation of the rule is important before its implementation as a decision aid to guide the initial management of patients with pulmonary embolism.

Haemophilia registry of the medical committee of the Swiss Haemophilia Society. Update and annual survey 2009.

The Swiss Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society started in 1996 but was set as an internet-based, double password-protected facility in the year 2000. With the inclusion of patients' data from two new centres in 2009, we assume a coverage rate of about 90% of all patients with inherited bleeding disorders in our country. Data concerning the phenotype and genotype of the disorder, its severity, its therapy, the prevalence of inhibitors are readily available to the registered users, allowing quality control of haemophilia therapy at a national level, but also rapid care of the patient visiting the emergency room of another treatment centre. Basing on the available data, about two thirds of the WFH global survey can be answered; the mortality statistics shows that bleeding remains a cause of death in haemophiliacs, also in the 21th century. The Registry allows for comparisons with international datasets, especially with respect to treatment (prophylaxis vs. on-demand therapy), factor consumption and costs.

An unusual case of accidental poisoning: fatal methadone inhalation.

In this report, the authors present a case of unusual, accidental methadone intoxication in a 40-year-old man, who had inhaled methadone powder. The drug dealer was a pharmacy technician; methadone had been stolen from a pharmacy and sold as cocaine. After having inhaled methadone powder, he suffered cardiopulmonary arrest. He was admitted to hospital where he died after 24 h of intensive care. The autopsy revealed congestion of internal organs and cerebral and pulmonary edema. Microscopically, the heart showed no changes. The toxicological analyses performed on blood and urine taken at the hospital revealed methadone, cannabinoids, and ethanol. The blood methadone concentration was 290 μg/L. The urine methadone concentration was 160 μg/L. Midazolam and lidocaine, which were administered to the patient at the hospital, were also detected in the blood. The cause of death was determined to be methadone intoxication. The literature has been reviewed and discussed. To date, and to our knowledge, only very few cases of accidental death resulting from methadone inhalation have been described up to the case presented herein.

Reconstruction of the recent history of a large deep prealpine lake (Lake Bourget, France) using subfossil chironomids, diatoms, and organic matter analysis: towards the definition of a lake-specific reference state

This paper presents the recent history of a large prealpine lake (Lake Bourget) using chironomids, diatoms and organic matter analysis, and deals with the ability of paleolimnological approach to define an ecological reference state for the lake in the sense of the European Framework Directive. The study at low resolution of subfossil chironomids in a 4-m-long core shows the remarkable stability over the last 2.5 kyrs of the profundal community dominated by a Micropsectra-association until the beginning of the twentieth century, when oxyphilous taxa disappeared. Focusing on this key recent period, a high resolution and multiproxy study of two short cores reveals a progressive evolution of the lake's ecological state. Until AD 1880, Lake Bourget showed low organic matter content in the deep sediments (TOC less than 1%) and a well-oxygenated hypolimnion that allowed the development of a profundal oxyphilous chironomid fauna (Micropsectra-association). Diatom communities were characteristic of oligotrophic conditions. Around AD 1880, a slight increase in the TOC was the first sign of changes in lake conditions. This was followed by a first limited decline in oligotrophic diatom taxa and the disappearance of two oxyphilous chironomid taxa at the beginning of the twentieth century. The 1940s were a major turning point in recent lake history. Diatom assemblages and accumulation of well preserved planktonic organic matter in the sediment provide evidence of strong eutrophication. The absence of profundal chironomid communities reveals permanent hypolimnetic anoxia. From AD 1995 to 2006, the diatom assemblages suggest a reduction in nutrients, and a return to mesotrophic conditions, a result of improved wastewater management. However, no change in hypolimnion benthic conditions has been shown by either the organic matter or the subfossil chironomid profundal community. Our results emphasize the relevance of the paleolimnological approach for the assessment of reference conditions for modern lakes. Before AD 1900, the profundal Micropsectra-association and the Cyclotella dominated diatom community can be considered as the Lake Bourget reference community, which reflects the reference ecological state of the lake.