French Swiss physicians' attitude toward palliative sedation: Influence of prognosis and type of suffering.

OBJECTIVE: Palliative sedation is a last resort medical act aimed at relieving intolerable suffering induced by intractable symptoms in patients at the end-of-life. This act is generally accepted as being medically indicated under certain circumstances. A controversy remains in the literature as to its ethical validity. There is a certain vagueness in the literature regarding the legitimacy of palliative sedation in cases of non-physical refractory symptoms, especially "existential suffering." This pilot study aims to measure the influence of two independent variables (short/long prognosis and physical/existential suffering) on the physicians' attitudes toward palliative sedation (dependent variable). METHODS: We used a 2 × 2 experimental design as described by Blondeau et al. Four clinical vignettes were developed (vignette 1: short prognosis/existential suffering; vignette 2: long prognosis/existential suffering; vignette 3: short prognosis/physical suffering; vignette 4: long prognosis/physical suffering). Each vignette presented a terminally ill patient with a summary description of his physical and psychological condition, medication, and family situation. The respondents' attitude towards sedation was assessed with a six-point Likert scale. A total of 240 vignettes were sent to selected Swiss physicians. RESULTS: 74 vignettes were completed (36%). The means scores for attitudes were 2.62 ± 2.06 (v1), 1.88 ± 1.54 (v2), 4.54 ± 1.67 (v3), and 4.75 ± 1.71 (v4). General linear model analyses indicated that only the type of suffering had a significant impact on the attitude towards sedation (F = 33.92, df = 1, p = 0.000). Significance of the results: The French Swiss physicians' attitude toward palliative sedation is more favorable in case of physical suffering than in existential suffering. These results are in line with those found in the study of Blondeau et al. with Canadian physicians and will be discussed in light of the arguments given by physicians to explain their decisions.

Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam.

Purpose:  Phenytoin (PHT), valproic acid (VPA), or levetiracetam (LEV) are commonly used as second-line treatment of status epilepticus (SE), but comparative studies are not available. Methods:  Among 279 adult SE episodes identified prospectively in our tertiary care hospital over 4 years, we retrospectively identified 187 episodes in which PHT, VPA, or LEV were given after benzodiazepines. Patients with postanoxic SE were not included. Demographics, clinical SE features, failure of second-line treatment to control SE, new handicap, and mortality at hospital discharge were assessed. Uni- and multivariable statistical analyses were applied to compare the three agents. Key Findings:  Each compound was used in about one third of SE episodes. VPA failed to control SE in 25.4%, PHT in 41.4%, and LEV in 48.3% of episodes in which these were prescribed. A deadly etiology was more frequent in the VPA group, whereas SE episodes tended to be more severe in the PHT group. After adjustment for these known SE outcome predictors, LEV failed more often than VPA [odds ratio (OR) 2.69; 95% confidence interval (CI) 1.19-6.08]; 16.8% (95% CI: 6.0-31.4%) of second-line treatment failures could be attributed to LEV. PHT was not statistically different from the other two compounds. Second-line treatment did not seem to influence new handicap and mortality, whereas etiology and the SE Severity Score (STESS) were robust independent predictors. Significance:  Even without significant differences on outcome at discharge, LEV seems less efficient than VPA to control SE after benzodiazepines. A prospective comparative trial is needed to address this potentially concerning finding.

Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection.

BACKGROUND: Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. METHODS: We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. RESULTS: A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. CONCLUSIONS: Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.

Social and medical vulnerability factors of frequent users at the emergency department: a case-control study

BACKGROUND: Up to 5% of patients presenting to the emergency department (ED) four or more times within a 12 month period represent 21% of total ED visits. In this study we sought to characterize social and medical vulnerability factors of ED frequent users (FUs) and to explore if these factors hold simultaneously. METHODS: We performed a case-control study at Lausanne University Hospital, Switzerland. Patients over 18 years presenting to the ED at least once within the study period (April 2008 toMarch 2009) were included. FUs were defined as patients with four or more ED visits within the previous 12 months. Outcome data were extracted from medical records of the first ED attendance within the study period. Outcomes included basic demographics and social variables, ED admission diagnosis, somatic and psychiatric days hospitalized over 12 months, and having a primary care physician.We calculated the percentage of FUs and non-FUs having at least one social and one medical vulnerability factor. The four chosen social factors included: unemployed and/or dependence on government welfare, institutionalized and/or without fixed residence, either separated, divorced or widowed, and under guardianship. The fourmedical vulnerability factors were: ≥6 somatic days hospitalized, ≥1 psychiatric days hospitalized, ≥5 clinical departments used (all three factors measured over 12 months), and ED admission diagnosis of alcohol and/or drug abuse. Univariate and multivariate logistical regression analyses allowed comparison of two JGIM ABSTRACTS S391 random samples of 354 FUs and 354 non-FUs (statistical power 0.9, alpha 0.05 for all outcomes except gender, country of birth, and insurance type). RESULTS: FUs accounted for 7.7% of ED patients and 24.9% of ED visits. Univariate logistic regression showed that FUs were older (mean age 49.8 vs. 45.2 yrs, p=0.003),more often separated and/or divorced (17.5%vs. 13.9%, p=0.029) or widowed (13.8% vs. 8.8%, p=0.029), and either unemployed or dependent on government welfare (31.3% vs. 13.3%, p<0.001), compared to non-FUs. FUs cumulated more days hospitalized over 12 months (mean number of somatic days per patient 1.0 vs. 0.3, p<0.001; mean number of psychiatric days per patient 0.12 vs. 0.03, p<0.001). The two groups were similar regarding gender distribution (females 51.7% vs. 48.3%). The multivariate linear regression model was based on the six most significant factors identified by univariate analysis The model showed that FUs had more social problems, as they were more likely to be institutionalized or not have a fixed residence (OR 4.62; 95% CI, 1.65 to 12.93), and to be unemployed or dependent on government welfare (OR 2.03; 95% CI, 1.31 to 3.14) compared to non-FUs. FUs were more likely to need medical care, as indicated by involvement of≥5 clinical departments over 12 months (OR 6.2; 95%CI, 3.74 to 10.15), having an ED admission diagnosis of substance abuse (OR 3.23; 95% CI, 1.23 to 8.46) and having a primary care physician (OR 1.70;95%CI, 1.13 to 2.56); however, they were less likely to present with an admission diagnosis of injury (OR 0.64; 95% CI, 0.40 to 1.00) compared to non-FUs. FUs were more likely to combine at least one social with one medical vulnerability factor (38.4% vs. 12.1%, OR 7.74; 95% CI 5.03 to 11.93). CONCLUSIONS: FUs were more likely than non-FUs to have social and medical vulnerability factors and to have multiple factors in combination.

Population genomics of eusocial insects: the costs of a vertebrate-like effective population size

The evolution of reproductive division of labour and social life in social insects has lead to the emergence of several life-history traits and adaptations typical of larger organisms: social insect colonies can reach masses of several kilograms, they start reproducing only when they are several years old, and can live for decades. These features and the monopolization of reproduction by only one or few individuals in a colony should affect molecular evolution by reducing the effective population size. We tested this prediction by analysing genome-wide patterns of coding sequence polymorphism and divergence in eusocial vs. noneusocial insects based on newly generated RNA-seq data. We report very low amounts of genetic polymorphism and an elevated ratio of nonsynonymous to synonymous changes - a marker of the effective population size - in four distinct species of eusocial insects, which were more similar to vertebrates than to solitary insects regarding molecular evolutionary processes. Moreover, the ratio of nonsynonymous to synonymous substitutions was positively correlated with the level of social complexity across ant species. These results are fully consistent with the hypothesis of a reduced effective population size and an increased genetic load in eusocial insects, indicating that the evolution of social life has important consequences at both the genomic and population levels.

Prévalence et prévention de l'excès de poids chez les écoliers en Valais

[Table des matières] Résumé. Introduction. But du rapport. I. Prévalence du surpoids et de l'obésité chez les écoliers en Valais. II. Programme de prévention et possibilités de prise en charge de l'excès de poids en Valais. III. Propositions pour la surveillance épidémiologique de l'excès de poids et l'évaluation des programmes de prévention. Références. Annexes.

Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters.

Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (T(FH)) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed T(FH) markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.