Expression of MYC, IgM, As Well As Non-Germinal Centre B-Cell Like Immunophenotype and Positive Immunofish Index Predict a Worse Progression Free Survival and Overall Survival in a Series of 670 De Novo Diffuse Large B-Cell Lymphomas Included in Clinical Trials: A GELA Study of the 2003 Program

Introduction: Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous disease with variable clinical outcome. Identifying phenotypic biomarkers of tumor cells on paraffin sections that predict different clinical outcome remain an important goal that may also help to better understand the biology of this lymphoma. Differentiating non-germinal centre B-cell-like (non-GCB) from Germinal Centre B-cell-like (GCB) DLBCL according to Hans algorithm has been considered as an important immunohistochemical biomarker with prognostic value among patients treated with R-CHOP although not reproducibly found by all groups. Gene expression studies have also shown that IgM expression might be used as a surrogate for the GCB and ABC subtypes with a strong preferential expression of IgM in ABC DLBCL subtype. ImmunoFISH index based on the differential expression of MUM-1, FOXP1 by immunohistochemistry and on the BCL6 rearrangement by FISH has been previously reported (C Copie-Bergman, J Clin Oncol. 2009;27:5573-9) as prognostic in an homogeneous series of DLBCL treated with R-CHOP. In addition, oncogenic MYC protein overexpression by immunohistochemistry may represent an easy tool to identify the consequences of MYC deregulation in DLBCL. Our aim was to analyse by immunohistochemistry the prognostic relevance of MYC, IgM, GCB/nonGCB subtype and ImmunoFISH index in a large series of de novo DLBCL treated with Rituximab (R)-chemotherapy (anthracyclin based) included in the 2003 program of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. Methods: The 2003 program included patients with de novo CD20+ DLBCL enrolled in 6 different LNH-03 GELA trials (LNH-03-1B, -B, -3B, 39B, -6B, 7B) stratifying patients according to age and age-adjusted IPI. Tumor samples were analyzed by immunohistochemistry using CD10, BCL6, MUM1, FOXP1 (according to Barrans threshold), MYC, IgM antibodies on tissue microarrays and by FISH using BCL6 split signal DNA probes. Considering evaluable Hans score, 670 patients were included in the study with 237 (35.4%) receiving intensive R-ACVBP regimen and 433 (64.6%) R-CHOP/R-mini-CHOP. Results: 304 (45.4%) DLBCL were classified as GCB and 366 (54.6%) as non-GCB according to Hans algorithm. 337/567 cases (59.4%) were positive for the ImmunoFISH index (i.e. two out of the three markers positive: MUM1 protein positive, FOXP1 protein Variable or Strong, BCL6 rearrangement). Immunofish index was preferentially positive in the non-GCB subtype (81.3%) compared to the GCB subtype (31.2%), (p<0.001). IgM was recorded as positive in tumor cells in 351/637 (52.4%) DLBCL cases with a preferential expression in non-GCB 195 (53.3%) vs GCB subtype 100(32.9%), p<0.001). MYC was positive in 170/577 (29.5%) cases with a 40% cut-off and in 44/577 (14.2%) cases with a cut-off of 70%. There was no preferential expression of MYC among GCB or non-GCB subtype (p>0.4) for both cut-offs. Progression-free Survival (PFS) was significantly worse among patients with high IPI score (p<0.0001), IgM positive tumor (p<0.0001), MYC positive tumor with a 40% threshold (p<0.001), ImmunoFISH positive index (p<0.002), non-GCB DLBCL subtype (p<0.0001). Overall Survival (OS) was also significantly worse among patients with high IPI score (p<0.0001), IgM positive tumor (p=0.02), MYC positive tumor with a 40% threshold (p<0.01), ImmunoFISH positive index (p=0.02), non-GCB DLBCL subtype (p<0.0001). All significant parameters were included in a multivariate analysis using Cox Model and in addition to IPI, only the GCB/non-GCB subtype according to Hans algorithm predicted significantly a worse PFS among non-GCB subgroup (HR 1.9 [1.3-2.8] p=0.002) as well as a worse OS (HR 2.0 [1.3-3.2], p=0.003). This strong prognostic value of non-GCB subtyping was confirmed considering only patients treated with R- CHOP for PFS (HR 2.1 [1.4-3.3], p=0.001) and for OS (HR 2.3 [1.3-3.8], p=0.002). Conclusion: Our study on a large series of patients included in trials confirmed the relevance of immunohistochemistry as a useful tool to identify significant prognostic biomarkers for clinical use. We show here that IgM and MYC might be useful prognostic biomarkers. In addition, we confirmed in this series the prognostic value of the ImmunoFISH index. Above all, we fully validated the strong and independent prognostic value of the Hans algorithm, daily used by the pathologists to subtype DLBCL.

Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses.

B-cell-activating factor of the TNF family (BAFF)/BLyS contributes to B-cell homeostasis and function in the periphery. BAFF is expressed as a membrane-bound protein or released by proteolytic cleavage, but the functional importance of this processing event is poorly understood. Mice expressing BAFF with a mutated furin consensus cleavage site, i.e. furin-mutant BAFF (fmBAFF), were not different from BAFF-deficient mice with regard to their B-cell populations and responses to immunization. It is however noteworthy that an alternative processing event releases some soluble BAFF in fmBAFF mice. Mild overexpression (∼ 5-fold) of fmBAFF alone generated intermediate levels of B cells without improving humoral responses to immunization. Processed BAFF was however important for B-cell homeostasis, as peripheral B-cell populations and antibody responses were readily restored by administration of soluble BAFF trimers in BAFF-deficient mice. However, the rescue of CD23 expression in B cells of BAFF-deficient mice required both soluble BAFF trimers and fmBAFF, or a polymeric form of soluble BAFF (BAFF 60-mer). These results point to a predominant role of processed BAFF for B-cell homeostasis and function, and indicate possible accessory roles for membrane-bound BAFF.

Looking for Validity or Testing It? The Perils of Stepwise Regression, Extreme-Scores Analysis, Heteroscedasticity, and Measurement Error

When researchers introduce a new test they have to demonstrate that it is valid, using unbiased designs and suitable statistical procedures. In this article we use Monte Carlo analyses to highlight how incorrect statistical procedures (i.e., stepwise regression, extreme scores analyses) or ignoring regression assumptions (e.g., heteroscedasticity) contribute to wrong validity estimates. Beyond these demonstrations, and as an example, we re-examined the results reported by Warwick, Nettelbeck, and Ward (2010) concerning the validity of the Ability Emotional Intelligence Measure (AEIM). Warwick et al. used the wrong statistical procedures to conclude that the AEIM was incrementally valid beyond intelligence and personality traits in predicting various outcomes. In our re-analysis, we found that the reliability-corrected multiple correlation of their measures with personality and intelligence was up to .69. Using robust statistical procedures and appropriate controls, we also found that the AEIM did not predict incremental variance in GPA, stress, loneliness, or well-being, demonstrating the importance for testing validity instead of looking for it.

Evaluating effects of spectral training data distribution on continuous field mapping performance

Continuous field mapping has to address two conflicting remote sensing requirements when collecting training data. On one hand, continuous field mapping trains fractional land cover and thus favours mixed training pixels. On the other hand, the spectral signature has to be preferably distinct and thus favours pure training pixels. The aim of this study was to evaluate the sensitivity of training data distribution along fractional and spectral gradients on the resulting mapping performance. We derived four continuous fields (tree, shrubherb, bare, water) from aerial photographs as response variables and processed corresponding spectral signatures from multitemporal Landsat 5 TM data as explanatory variables. Subsequent controlled experiments along fractional cover gradients were then based on generalised linear models. Resulting fractional and spectral distribution differed between single continuous fields, but could be satisfactorily trained and mapped. Pixels with fractional or without respective cover were much more critical than pure full cover pixels. Error distribution of continuous field models was non-uniform with respect to horizontal and vertical spatial distribution of target fields. We conclude that a sampling for continuous field training data should be based on extent and densities in the fractional and spectral, rather than the real spatial space. Consequently, adequate training plots are most probably not systematically distributed in the real spatial space, but cover the gradient and covariate structure of the fractional and spectral space well. (C) 2009 International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS). Published by Elsevier B.V. All rights reserved.

An Evaluation of the Troxler 3241-B Nuclear Asphalt Gauge, MLR-85-11, 1986

The Troxler 3241-B Asphalt Content Gauge is intended for rapidly determining the bitumen content of bituminous paving mixtures. A 300 Millicurie Americuium 241: Beryllium source emitts neutrons which are affected by the hydrogen in the mix. The affected neutrons are detected by Helium 3 detectors, counted and computed into a percentage bitumen of the asphalt mix. The current methods of determining the bitumen content of bituminous paving mixtures requires the use of potentially hazardous chemicals and several hours of testing time. When extracted aggregates are not needed, determination of the bitumen content of a paving mixture by the nuclear method may be easier, quicker and potentially safer. The objective of the project is to study the accuracy of the Troxler 3241-B Nuclear Asphalt Content Gauge in measuring the asphalt cement (AC) content of asphalt concrete mixtures produced with different asphalt cements and different aggregates.

Clinical proteomics : a focus on transformed human T and B lymphocytes

Résumé large public La protéomique clinique est une discipline qui vise l'étude des protéines dans un but diagnostique ou thérapeutique. Nous avons utilisé cette approche pour étudier les lymphocytes T «tueurs » ou cytotoxiques qui font partie des globules blancs du système sanguin et agissent dans la lutte contre les infections et les tumeurs. Ces cellules sont impliquées dans l'immunothérapie cellulaire qui se fonde sur la capacité naturelle des ces lymphocytes à repérer les cellules tumorales et à les détruire. L'introduction du gène de la télomérase dans les lymphocytes T résulte en une prolongation de leur longévité, ce qui en ferait des candidats intéressants pour l'immunothérapie cellulaire. Il subsiste cependant des doutes quant aux conséquences de l'utilisation de ces lymphocytes «immortalisés ». Pour répondre à cette question, nous avons comparé le profile protéique de lymphocytes T cytotoxiques «jeunes » et vieux » avec celui des lymphocytes «immortalisés ». Nous avons trouvé que ces derniers présentent une double face et partagent à la fois les caractéristiques de la jeunesse et de la vieillesse. Dans une seconde étude de protéomique clinique, nous nous sommes penchés sur les lymphocytes B «immortalisés » cette fois-ci non pas avec la télomérase, mais avec le virus d'Epstein-Barr. Ces derniers sont utilisés comme modèle dans l'étude de la leucodystrophie, une maladie génétique rare qui affecte le cerveau. Notre but est d'identifier des marqueurs biologiques potentiels qui pourraient aider le diagnostic et le traitement de cette maladie neurodégénérative. Nous avons pour ce faire comparé les profiles protéiques des lymphocytes B «immortalisés » provenant d'individus sains et malades. Malheureusement, notre analyse n'a pas révélé de différences notoires entre ces deux classes de lymphocytes. Ceci nous permet toutefois de conclure que la maladie n'affecte pas la synthèse des protéines de manière prépondérante dans ces cellules sanguines. En résumé, le travail présenté dans cette thèse montre à la fois le potentiel et les limites de l'analyse des protéines lymphocytaires, dans différentes situations biologiques. Résumé La protéomique clinique ouvre la porte vers de multiples horizons relatifs au traitement de diverses maladies. Ce domaine particulier alliant la protéomique à la médecine, implique l'intervention de la biologie moléculaire et cellulaire. Dans notre étude, nous nous sommes d'abord intéressés aux lymphocytes T CD8+ cytotoxiques dans le contexte de l'immunothérapie adoptive. Le fondement de cette thérapie repose sur la capacité naturelle de ces lymphocytes à reconnaître les cellules tumorales et à les détruire chez les patients atteints de cancer. L'introduction du gène de la transcriptase réverse de la télomérase (hTERT) dans les lymphocytes T humains permet de rallonger leur durée de vie, sans toutefois induire d'altérations liées à la transformation. Cependant, des incertitudes subsistent quant à la ressemblance physiologique et biochimique entre ces cellules surexprirnant la télomérase et les cellules normales. Afin de répondre à cette question, nous avons comparé l'expression des protéines de lymphocytes humains T CD8+ «jeunes » et «vieux »avec celle de lymphocytes transduits avec hTERT. Nous avons trouvé que les lymphocytes T surexprimant la télomérase ont un profile protéique intermédiaire, avec certaines expressions protéiques similaires aux jeunes cellules T et d'autres se rapprochant des cellules vieilles. Dans la seconde partie de notre étude, nous nous sommes intéressés aux lymphocytes B transformés avec le virus d'Epstein-Barr provenant de patients atteints d'une maladie génétique rare du cerveau, la leucodystrophie. Dans cette maladie, des mutations dans le facteur de transcription eIF2B, impliqué dans la synthèse protéique, ont été trouvées. Afin d'analyser les conséquences de ces mutations et de trouver des biomarqueurs spécifiques à cette maladie, nous avons effectué une analyse protéomique des lymphoblastes provenant de malades et d'individus sains. Nous avons trouvé que les mutations dans le complexe ubiquitaire eIF2B n'affectent pas de manière significative l'expression des protéines des lymphoblastes mutés. En conclusion, notre travail illustre le potentiel et les limitations des technologies protéomiques utilisées pour disséquer l'implication des protéines dans différentes situations biologiques. Summary Clinical proteomics opens the door to multiple applications related to the treatment of diseases. This particular field is at the crossroad of proteomics and medicine and involves tools from cellular and molecular biology. We focused first our investigations on cytotoxic T cells in the context of adoptive immunotherapy, which is an interesting and evolving field. The basis of this therapy relies on the natural capacity of cytotoxic CD8+ T lymphocytes in recognizing tumor cells and destroying them in cancer patients. As their number is reduced, the idea would be to use transformed T lymphocytes with extended life span. Overexpression of telomerase into human T lymphocytes results in the extension of their replicative life span, but it still remains unclear whether these cells are physiologically indistinguishable from normal ones. To address this question, we compared the proteome of young and aged CD8+ T lymphocytes with that of T cells transduced with hTERT and found that the latter cells displayed an intermediate protein pattern, sharing similar protein expression with young, but also with aged T cells. We were then interested in studying Epstein-Barr virus transformed B lymphocytes in the context of a rare human brain genetic disorder called leukodystrophy. In this disease, mutations in the ubiquitous factor eIF2B involved in protein synthesis and its regulation have been reported. In order to analyze the functional consequences of the mutations and to find out specific biomarkers of eIF2B-related disorders, proteomic and peptidomic studies were carried out on lymphoblasts from eIF2Bmutated patients versus healthy patients. Following two-dimensional gel electrophoresis and mass fingerprints, mutations in the eIF2B complex did not appear to significantly affect the proteome of the mutated lymphoblasts extracts. To conclude, our work emphasizes the potentials and the limitations of the proteomic technologies used to analyze the role of lymphocyte proteins in different biological situations.

An SH2 domain-containing 5' inositolphosphatase inhibits insulin-induced GLUT4 translocation and growth factor-induced actin filament rearrangement.

Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) and the subsequent formation of phosphatidylinositides (PtdIns) 3,4-P2 and PtdIns 3,4, 5-P3, which are thought to be involved in signaling for glucose transporter GLUT4 translocation, cytoskeletal rearrangement, and DNA synthesis. However, the specific role of each of these PtdIns in insulin and growth factor signaling is still mainly unknown. Therefore, we assessed, in the current study, the effect of SH2-containing inositol phosphatase (SHIP) expression on these biological effects. SHIP is a 5' phosphatase that decreases the intracellular levels of PtdIns 3,4,5-P3. Expression of SHIP after nuclear microinjection in 3T3-L1 adipocytes inhibited insulin-induced GLUT4 translocation by 100 +/- 21% (mean +/- the standard error) at submaximal (3 ng/ml) and 64 +/- 5% at maximal (10 ng/ml) insulin concentrations (P < 0.05 and P < 0.001, respectively). A catalytically inactive mutant of SHIP had no effect on insulin-induced GLUT4 translocation. Furthermore, SHIP also abolished GLUT4 translocation induced by a membrane-targeted catalytic subunit of PI3 kinase. In addition, insulin-, insulin-like growth factor I (IGF-I)-, and platelet-derived growth factor-induced cytoskeletal rearrangement, i.e., membrane ruffling, was significantly inhibited (78 +/- 10, 64 +/- 3, and 62 +/- 5%, respectively; P < 0.05 for all) in 3T3-L1 adipocytes. In a rat fibroblast cell line overexpressing the human insulin receptor (HIRc-B), SHIP inhibited membrane ruffling induced by insulin and IGF-I by 76 +/- 3% (P < 0.001) and 68 +/- 5% (P < 0.005), respectively. However, growth factor-induced stress fiber breakdown was not affected by SHIP expression. Finally, SHIP decreased significantly growth factor-induced mitogen-activated protein kinase activation and DNA synthesis. Expression of the catalytically inactive mutant had no effect on these cellular responses. In summary, our results show that expression of SHIP inhibits insulin-induced GLUT4 translocation, growth factor-induced membrane ruffling, and DNA synthesis, indicating that PtdIns 3,4,5-P3 is the key phospholipid product mediating these biological actions.

Conduit artery compliance and distensibility are not necessarily reduced in hypertension.

The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.

Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B).

Background The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. Patients and methods Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. Results A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). Conclusion In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.

The Th2 lymphoproliferation developing in LatY136F mutant mice triggers polyclonal B cell activation and systemic autoimmunity.

Lat(Y136F) knock-in mice harbor a point mutation in Tyr(136) of the linker for activation of T cells and show accumulation of Th2 effector cells and IgG1 and IgE hypergammaglobulinemia. B cell activation is not a direct effect of the mutation on B cells since in the absence of T cells, mutant B cells do not show an activated phenotype. After adoptive transfer of linker for activation of T cell mutant T cells into wild-type, T cell-deficient recipients, recipient B cells become activated. We show in vivo and in vitro that the Lat(Y136F) mutation promotes T cell-dependent B cell activation leading to germinal center, memory, and plasma cell formation even in an MHC class II-independent manner. All the plasma and memory B cell populations found in physiological T cell-dependent B cell responses are found. Characterization of the abundant plasmablasts found in secondary lymphoid organs of Lat(Y136F) mice revealed the presence of a previously uncharacterized CD93-expressing subpopulation, whose presence was confirmed in wild-type mice after immunization. In Lat(Y136F) mice, B cell activation was polyclonal and not Ag-driven because the increase in serum IgG1 and IgE concentrations involved Abs and autoantibodies with different specificities equally. Although the noncomplement-fixing IgG1 and IgE are the only isotypes significantly increased in Lat(Y136F) serum, we observed early-onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and severe proteinuria. These results show that Th2 cells developing in Lat(Y136F) mice can trigger polyclonal B cell activation and thereby lead to systemic autoimmune disease.

Benevolent voices are not so kind: the functional significance of auditory hallucinations

BACKGROUND: This study measures the impact of beliefs about auditory hallucinations on social functioning. SAMPLING AND METHODS: Twenty-nine subjects who met the ICD-10 criteria for schizophrenia or a schizo-affective disorder were included. Beliefs about voices and coping responses as measured by the Beliefs about Voices Questionnaire were compared with social functioning as assessed with the Life Skills Profile (LSP). RESULTS: The belief that voices are benevolent was associated with poor communication. Engagement with voices was correlated with the non-turbulence and the compliance factors of the LSP. Patients who held the belief that their voices were benevolent functioned significantly more poorly on the communication factor of the LSP than patients who interpreted their voices as malevolent. DISCUSSION: The results indicate that a positive relationship with voices may affect social functioning. However, the size of the sample is small and patients with benevolent voices are overrepresented. Nonetheless, these results have implications for the use of cognitive therapy for psychotic symptoms

09028-014 Tributary B to Fourmile Creek Final Report

The city of Ankeny is submitting this WIRB application for development of green urban stormwater practices on city and private property in the Fourmile Creek watershed. The stormwater project proposed includes stream restoration of the SE Tributary to Fourmile Creek (Tributary B), including weirs, bank shaping, toe protection, trees, and native plantings. The project also includes the creation of a native buffer along the stream channel in the city’s Summerbrook Park, installing four native planting beds, installing a pervious surface trail, installing a series of rain gardens/biorentention cells, and installing educational signage. Polk County Soil and Water Conservation District has committed $17,000 towards the native buffer and rain garden/biorentention cell. The city of Ankeny was also awarded a $100,000 I-JOBS grant from IDNR to complete the stormwater retrofit practices. The largest component of this project is public education. Our vision for this project is to take the entire 281 acre watershed and address it as a whole. We want to make a collaborative watershed that not only addresses the water entering the stream channel through adjacent properties, but takes each individual parcel within the watershed and strives to reduce contributions to the stormwater system. The stormwater issues of concern for Tributary B include stormwater volume, sediment, and nutrients. The stream restoration, best management practices (BMP) at Summerbrook Park, and BMPs on private property should help decrease the volume of stormwater and reduce the amount of sediment and nutrients that enter Tributary B and ultimately Fourmile Creek.

Brief alcohol intervention and alcohol assessment do not influence alcohol use in injured patients treated in the emergency department: a randomized controlled clinical trial.

AIMS: To evaluate the effectiveness of brief alcohol intervention (BAI) in reducing alcohol use among hazardous drinkers treated in the emergency department (ED) after an injury; in addition it tests whether assessment of alcohol use without BAI is sufficient to reduce hazardous drinking. DESIGN: Randomized controlled clinical trial with 12-month follow-up conducted between January 2003 and June 2005. SETTING: Urban academic emergency department (ED) of the Lausanne University Hospital, Lausanne, Switzerland. PARTICIPANTS: A total of 5136 consecutive patients attending ED after an injury completed a seven-item general and a three-item alcohol screen and 1472 (28.7%) were positive for hazardous drinking according to the National Institute on Alcohol Abuse and Addiction definition; of these 987 (67.1%) were randomized into a BAI group (n = 310) or a control group with screening and assessment (n = 342) or a control group with screening only (n = 335) and then a total of 770 patients (78.0%) completed the 12-month follow-up procedures. INTERVENTION: A single 10-15-minute session of standardized BAI conducted by a trained research assistant. MEASUREMENTS: Percentage of participants who have changed to low-risk drinking at follow-up. FINDINGS: Data obtained at 12 months indicated that similar proportions were low-risk drinkers in BAI versus control groups with and without assessment (35.6%, 34.0%, 37.0%, respectively, P = 0.71). Data also indicated similar reductions in drinking frequency, quantity, binge drinking frequency and Alcohol Use Disorders Identification Test (AUDIT) scores across groups. All groups reported similar numbers of days hospitalized and numbers of medical consults in the last 12 months. A model including age groups, gender, AUDIT and injury severity scores indicated that BAI had no influence on the main alcohol use outcome. CONCLUSIONS: This study provides the evidence that a 10-15-minute BAI does not decrease alcohol use and health resource utilization in hazardous drinkers treated in the ED, and demonstrates that commonly found decreases in hazardous alcohol use in control groups cannot be attributed to the baseline alcohol assessment.

'Do not attempt resuscitation' and 'cardiopulmonary resuscitation' in an inpatient setting: factors influencing physicians' decisions in Switzerland.

OBJECTIVE: To determine the prevalence of cardiopulmonary resuscitation (CPR) and do-not-attempt-resuscitation (DNAR) orders, to define factors associated with CPR/DNAR orders and to explore how physicians make and document these decisions. METHODS: We prospectively reviewed CPR/DNAR forms of 1,446 patients admitted to the General Internal Medicine Department of the Geneva University Hospitals, a tertiary-care teaching hospital in Switzerland. We additionally administered a face-to-face survey to residents in charge of 206 patients including DNAR and CPR orders, with or without patient inclusion. RESULTS: 21.2% of the patients had a DNAR order, 61.7% a CPR order and 17.1% had neither. The two main factors associated with DNAR orders were a worse prognosis and/or a worse quality of life. Others factors were an older age, cancer and psychiatric diagnoses, and the absence of decision-making capacity. Residents gave four major justifications for DNAR orders: important comorbid conditions (34%), the patients' or their family's resuscitation preferences (18%), the patients' age (14.2%), and the absence of decision-making capacity (8%). Residents who wrote DNAR orders were more experienced. In many of the DNAR or CPR forms (19.8 and 16%, respectively), the order was written using a variety of formulations. For 24% of the residents, the distinction between the resuscitation order and the care objective was not clear. 38% of the residents found the resuscitation form useful. CONCLUSION: Patients' prognosis and quality of life were the two main independent factors associated with CPR/DNAR orders. However, in the majority of cases, residents evaluated prognosis only intuitively, and quality of life without involving the patients. The distinction between CPR/DNAR orders and the care objectives was not always clear. Specific training regarding CPR/DNAR orders is necessary to improve the CPR/DNAR decision process used by physicians.