Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures.

An interdisciplinary HIV-adherence program combining motivational interviewing and electronic antiretroviral drug monitoring.

To ensure successful treatment, HIV patients must maintain a high degree of medication adherence over time. Since August 2004, patients who are (or are at risk of) experiencing problems with their HIV antiretroviral therapy (ART) have been referred by their physicians to an interdisciplinary HIV-adherence program. The program consists of a multifactorial intervention along with electronic drug monitoring (MEMS(TM)). The pharmacists organize individualized semi-structured motivational interviews based on cognitive, emotional, behavioral, and social issues. At the end of each session, the patient brings an adherence report to the physician. This enables the physician to use the adherence results to evaluate the treatment plan. The aim of this study was to retrospectively analyze this on-going interdisciplinary HIV-adherence program. All patients who were included between August 2004 and the end of April 2008 were analyzed. One hundred and four patients were included (59% women, median age 39 (31.0, 46.0) years, 42% black ethnicity). Eighty (77%) patients were ART-experienced patients and 59% had a protease inhibitor-based treatment. The retention rate was high (92%) in the program. Patient inclusion in this HIV-adherence program was determined by patient issues for naive patients and by nonadherence or suboptimal clinical outcomes for ART-experienced patients. The median time spent by a subject at the pharmacy was 35 (25.0, 48.0) minutes, half for the medication handling and half for the interview. The adherence results showed a persistence of 87% and an execution of 88%. Proportion of undetectable subjects increased during study. In conclusion, retention and persistence rates were high in this highly selected problematic population.

Using the costs of drug therapy to screen patients for a community pharmacy-based medication review program

Objectives: To measure the positive predictive value (PPV) of the cost of drug therapy (threshold = 2000 Swiss francs [CHF], US$1440, <euro>1360) as a screening criterion for identifying patients who may benefit from medication review (MR). To describe identified drug-related problems (DRPs) and expense problems (EPs), and to estimate potential savings if all recommendations were accepted. Setting Five voluntary Swiss community pharmacies. Methods: Of 12,680 patients, 592 (4.7%) had drug therapy costs exceeding 2000 CHF over a six-month period from July 1 to December 31, 2002. This threshold limit was set to identify high-risk patients for DRPs and EPs. Three pharmacists consecutively conducted a medication review based on the pharmaceutical charts of 125 sampled patients who met the inclusion criterion. Main outcome measure: The PPV of a threshold of 2000 CHF for identifying patients who might benefit from a MR: true positives were patients with at least one DRP, while false positives were patients with no DRP. Results: The selection based on this criterion had a PPV of 86% for detecting patients with at least one DRP and 95% if EPs were also considered. There was a mean of 2.64 (SD = 2.20) DRPs per patient and a mean of 2.14 (SD = 1.39) EPs per patient. Of these patients, 90% were over 65 years old or were treated with at least five chronic medications, two common criteria for identifying patients at risk of DRPs. The main types of DRPs were drug-drug interactions, compliance problems and duplicate drugs. Mean daily drug cost per patient was CHF 14.87 (US$10.70, <euro>10.10). A potential savings of CHF 1.67 (US$1.20, <euro>1.14) per day (11%) was estimated if all recommendations to solve DRPs and EPs suggested herein were implemented. Conclusion: Further studies should investigate whether the potential benefit of medication reviews in preventing DRPs and containing costs in this patient group can be confirmed in a real practice environment. [Authors]

Indicateurs de résultats du Promedro III, situation en 2008 : rapport final

[Table des matières] 1. Introduction. 1.1. Rappel du mandat. 1.2. Méthode. 2. Résultats. 2.1. Indicateurs du nombre de consommateurs. 2.2. Indicateurs des problèmes en relation (ou non) avec les drogues chez les jeunes. 2.3. Indicateurs en relation avec la consommation problématique de drogues dures en général. 2.4. Indicateurs des conséquences négatives pour les usagers de drogues illégales. 2.5. Indicateurs des conséquences négatives pour la société. 3. Annexe.

A fast-track program reduces complications and length of hospital stay after open colonic surgery.

BACKGROUND & AIMS: A fast-track program is a multimodal approach for patients undergoing colonic surgery that combines stringent regimens of perioperative care (fluid restriction, optimized analgesia, forced mobilization, and early oral feeding) to reduce perioperative morbidity, hospital stay, and cost. We investigated the impact of a fast-track protocol on postoperative morbidity in patients after open colonic surgery. METHODS: A randomized trial of patients in 4 teaching hospitals in Switzerland included 156 patients undergoing elective open colonic surgery who were assigned to either a fast-track program or standard care. The primary end point was the 30-day complication rate. Secondary end points were severity of complications, hospital stay, and compliance with the fast-track protocol. RESULTS: The fast-track protocol significantly decreased the number of complications (16 of 76 in the fast-track group vs 37 of 75 in the standard care group; P = .0014), resulting in shorter hospital stays (median, 5 days; range, 2-30 vs 9 days, respectively; range, 6-30; P < .0001). There was a trend toward less severe complications in the fast-track group. A multiple logistic regression analysis revealed fluid administration greater than the restriction limits (odds ratio, 4.198; 95% confidence interval, 1.7-10.366; P = .002) and a nonfunctioning epidural analgesia (odds ratio, 3.365; 95% confidence interval, 1.367-8.283; P = .008) as independent predictors of postoperative complications. CONCLUSIONS: The fast-track program reduces the rate of postoperative complications and length of hospital stay and should be considered as standard care. Fluid restriction and an effective epidural analgesia are the key factors that determine outcome of the fast-track program.

Development and evaluation of a shaken baby syndrome prevention program.

OBJECTIVE: To evaluate parents' and nurses' opinions regarding the adequacy of an educational program on shaken baby syndrome: the Perinatal Shaken Baby Syndrome Prevention Program (PSBSPP). DESIGN: Qualitative and quantitative assessments in the form of interviews and questionnaires administered in French. SETTING: Two birthing institutions in Montréal, QC, Canada: a university hospital and a regional center. PARTICIPANTS: Two hundred and sixty-three parents (73.8% mothers, 26.2% fathers) received the intervention after the birth of their child, and 69 nurses administered it. METHODS: Parents' and nurses' assessments of the adequacy and relevance of the program and nurses' assessments of the training they received to administer the program were evaluated. RESULTS: Both parents and nurses supported this initiative. Most parents appreciated the usefulness of the information. Nurses believed the program was adequate, and their training to deliver the program was satisfactory. All participants reported that the program was highly relevant, especially for new parents. CONCLUSION: The Perinatal Shaken Baby Syndrome Prevention Program achieves the goals of (a) increasing parents' knowledge about infant crying, anger, and shaken baby syndrome and (b) helping parents identify coping strategies. The relevance of introducing the PSBSPP in all birthing institutions is supported. Future studies should focus on vulnerable and culturally diverse populations, and longitudinal follow-up could help determine if the PSBSPP reduces the incidence of shaken baby syndrome.

Differential Gene Expression between Fall- and Spring-Run Chinook Salmon Assessed by Long Serial Analysis of Gene Expression

Of all Pacific salmonids, Chinook salmon Oncorhynchus tshawytscha display the greatest variability in return times to freshwater. The molecular mechanisms of these differential return times have not been well described. Current methods, such as long serial analysis of gene expression (LongSAGE) and microarrays, allow gene expression to be analyzed for thousands of genes simultaneously. To investigate whether differential gene expression is observed between fall- and spring-run Chinook salmon from California's Central Valley, LongSAGE libraries were constructed. Three libraries containing between 25,512 and 29,372 sequenced tags (21 base pairs/tag) were generated using messenger RNA from the brains of adult Chinook salmon returning in fall and spring and from one ocean-caught Chinook salmon. Tags were annotated to genes using complementary DNA libraries from Atlantic salmon Salmo salar and rainbow trout O. mykiss. Differentially expressed genes, as estimated by differences in the number of sequence tags, were found in all pairwise comparisons of libraries (freshwater versus saltwater = 40 genes; fall versus spring = 11 genes: and spawning versus nonspawning = 51 genes). The gene for ependymin, an extracellular glycoprotein involved in behavioral plasticity in fish, exhibited the most differential expression among the three groupings. Reverse transcription polymerase chain reaction analysis verified the differential expression of ependymin between the fall- and spring-run samples. These LongSAGE libraries, the first reported for Chinook salmon, provide a window of the transcriptional changes during Chinook salmon return migration to freshwater and spawning and increase the amount of expressed sequence data.

Integrated Analysis of High-Resolution Gene Expression and Copy Number Profiling Identified Biallelic Deletion of CDKN2A/2B Tumor Suppressor Locus As the Most Frequent and Unique Genomic Abnormality in Diffuse Large B-Cell Lymphoma (DLBCL) with Strong Prognostic Value in Both GCB and ABC Subtypes and Not Overcome by a Dose-Intensive Immunochemotherapy Regimen Plus Rituximab. Results of a Prospective GELA Clinical Trial Program

Background and aim of the study: Genomic gains and losses play a crucial role in the development and progression of DLBCL and are closely related to gene expression profiles (GEP), including the germinal center B-cell like (GCB) and activated B-cell like (ABC) cell of origin (COO) molecular signatures. To identify new oncogenes or tumor suppressor genes (TSG) involved in DLBCL pathogenesis and to determine their prognostic values, an integrated analysis of high-resolution gene expression and copy number profiling was performed. Patients and methods: Two hundred and eight adult patients with de novo CD20+ DLBCL enrolled in the prospective multicentric randomized LNH-03 GELA trials (LNH03-1B, -2B, -3B, 39B, -5B, -6B, -7B) with available frozen tumour samples, centralized reviewing and adequate DNA/RNA quality were selected. 116 patients were treated by Rituximab(R)-CHOP/R-miniCHOP and 92 patients were treated by the high dose (R)-ACVBP regimen dedicated to patients younger than 60 years (y) in frontline. Tumour samples were simultaneously analysed by high resolution comparative genomic hybridization (CGH, Agilent, 144K) and gene expression arrays (Affymetrix, U133+2). Minimal common regions (MCR), as defined by segments that affect the same chromosomal region in different cases, were delineated. Gene expression and MCR data sets were merged using Gene expression and dosage integrator algorithm (GEDI, Lenz et al. PNAS 2008) to identify new potential driver genes. Results: A total of 1363 recurrent (defined by a penetrance > 5%) MCRs within the DLBCL data set, ranging in size from 386 bp, affecting a single gene, to more than 24 Mb were identified by CGH. Of these MCRs, 756 (55%) showed a significant association with gene expression: 396 (59%) gains, 354 (52%) single-copy deletions, and 6 (67%) homozygous deletions. By this integrated approach, in addition to previously reported genes (CDKN2A/2B, PTEN, DLEU2, TNFAIP3, B2M, CD58, TNFRSF14, FOXP1, REL...), several genes targeted by gene copy abnormalities with a dosage effect and potential physiopathological impact were identified, including genes with TSG activity involved in cell cycle (HACE1, CDKN2C) immune response (CD68, CD177, CD70, TNFSF9, IRAK2), DNA integrity (XRCC2, BRCA1, NCOR1, NF1, FHIT) or oncogenic functions (CD79b, PTPRT, MALT1, AUTS2, MCL1, PTTG1...) with distinct distribution according to COO signature. The CDKN2A/2B tumor suppressor locus (9p21) was deleted homozygously in 27% of cases and hemizygously in 9% of cases. Biallelic loss was observed in 49% of ABC DLBCL and in 10% of GCB DLBCL. This deletion was strongly correlated to age and associated to a limited number of additional genetic abnormalities including trisomy 3, 18 and short gains/losses of Chr. 1, 2, 19 regions (FDR < 0.01), allowing to identify genes that may have synergistic effects with CDKN2A/2B inactivation. With a median follow-up of 42.9 months, only CDKN2A/2B biallelic deletion strongly correlates (FDR p.value < 0.01) to a poor outcome in the entire cohort (4y PFS = 44% [32-61] respectively vs. 74% [66-82] for patients in germline configuration; 4y OS = 53% [39-72] vs 83% [76-90]). In a Cox proportional hazard prediction of the PFS, CDKN2A/2B deletion remains predictive (HR = 1.9 [1.1-3.2], p = 0.02) when combined with IPI (HR = 2.4 [1.4-4.1], p = 0.001) and GCB status (HR = 1.3 [0.8-2.3], p = 0.31). This difference remains predictive in the subgroup of patients treated by R-CHOP (4y PFS = 43% [29-63] vs. 66% [55-78], p=0.02), in patients treated by R-ACVBP (4y PFS = 49% [28-84] vs. 83% [74-92], p=0.003), and in GCB (4y PFS = 50% [27-93] vs. 81% [73-90], p=0.02), or ABC/unclassified (5y PFS = 42% [28-61] vs. 67% [55-82] p = 0.009) molecular subtypes (Figure 1). Conclusion: We report for the first time an integrated genetic analysis of a large cohort of DLBCL patients included in a prospective multicentric clinical trial program allowing identifying new potential driver genes with pathogenic impact. However CDKN2A/2B deletion constitutes the strongest and unique prognostic factor of chemoresistance to R-CHOP, regardless the COO signature, which is not overcome by a more intensified immunochemotherapy. Patients displaying this frequent genomic abnormality warrant new and dedicated therapeutic approaches.

Evaluation des effets de la campagne de prévention "Mission : possible" de l'Aide suisse contre le sida (2008)

L'Office fédéral de la santé publique (OFSP) a donné pour mandat à l'IUMSP d'évaluer la campagne " Mission : Possible " de l'Aide suisse contre le sida (ASS), réalisée en 2008. Il s'agit d' une campagne de prévention du VIH/sida s'adressant exclusivement aux hommes qui ont des relations sexuelles avec des hommes (HSH). Elle a été mise en oeuvre par l'Aide suisse contre le sida, sur mandat de l'Office fédéral de la santé publique. L'objectif stratégique de " Mission: Possible " consiste à freiner la propagation du VIH parmi les HSH. Actuellement, une partie importante des infections à VIH sont le fait de rapports sexuels non protégés avec des partenaires sexuels en phase de primo-infection, c'est-à-dire la phase suivant directement le contage et durant laquelle la quantité de virus dans le sang est particulièrement élevée. L'ambition de la campagne Mission Possible était de briser les chaînes d'infection ainsi créées en incitant tous les HSH à observer strictement les règles du safer sex, trois mois durant, soit le temps nécessaire pour que les personnes récemment infectées sortent de la phase de primo-infection. Ainsi, le risque de nouvelles transmissions diminuerait de façon globale et l'épidémie serait ralentie. Au terme des trois mois, les HSH étaient incités à faire un test VIH gratuit (sur présentation d'un bon à présenter dans les centres de dépistage et conseils anonymes : policliniques universitaires et certaines antennes de l'ASS). La campagne reposait sur une importante mobilisation communautaire, c'est-à-dire l'implication de tous les acteurs de la scène gaie en Suisse (journaux et sites internet, associations et établissements gais). [Introd. du résumé p. 9] Site internet de la campagne "Mission : possible": http://www.missionp.ch/fr/home/

Programme latin de don d'organes: les intensivistes se mettent en réseau [Latin program for organ donation: the intensivists are networking]

The new Swiss federal law on organ and transplantation strengthens the responsibilities of the intensive care units. In Italian and French speaking parts of Switzerland, the Programme Latin pour le Don d'Organe (PLDO) has been launched to foster a wider collaboration between intensivists and donation coordinators. The PLDO aims at optimising knowledge and expertise in organ donation through improvements in identification, notification and management of organ donors and their next of kin. The PLDO dispenses education to all professionals involved. Such organisation should allow increasing the number of organs available, while improving healthcare professionals experience and next of kin emotion throughout the donation process.

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

Expectation to improve cardiovascular risk factors control in participants to a health promotion program.

BACKGROUND: We assessed expectations to improve cardiovascular disease risk factors (CVD-RF) in participants to a health promotion program. PARTICIPANTS AND METHODS: Blood pressure (BP), blood glucose (BG), blood total cholesterol (TC), body mass index (BMI), and self-reported smoking were assessed in 1,598 volunteers from the general public (men: 40%; mean age: 56.7 +/- 12.7 years) participating in a mobile health promotion program in the Vaud canton, Switzerland. Participants were asked about their expectation to have their CVD-RF improved at a next visit scheduled 2-3 years later. RESULTS: Expectation for improved control was found in 90% of participants with elevated BP, 91% with elevated BG, 45% with elevated TC, 44% who were overweight, and 35% who were smoking. Expectation for TC improvement was reported more often by men, persons with high level of TC, and persons who had consulted a doctor in the past 12 months. Expectations to lose weight and to quit smoking were found more often in younger persons than the older ones. CONCLUSION: Volunteers from the general population participating in a health promotion program expected improved control more often for hypertension and dysglycemia than for dyslipidemia, overweight and smoking.

quantiNemo: an individual-based program to simulate quantitative traits with explicit genetic architecture in a dynamic metapopulation.

quantiNemo is an individual-based, genetically explicit stochastic simulation program. It was developed to investigate the effects of selection, mutation, recombination and drift on quantitative traits with varying architectures in structured populations connected by migration and located in a heterogeneous habitat. quantiNemo is highly flexible at various levels: population, selection, trait(s) architecture, genetic map for QTL and/or markers, environment, demography, mating system, etc. quantiNemo is coded in C++ using an object-oriented approach and runs on any computer platform. Availability: Executables for several platforms, user's manual, and source code are freely available under the GNU General Public License at http://www2.unil.ch/popgen/softwares/quantinemo.

Improving breast cancer education: the case of an evolving multidisciplinary module for undergraduate medical students (lausanne medical school, 1993-2008).

Breast cancer is a public health issue in numerous countries. Multidisciplinary collaboration is required for patient care, research, and also education of future physicians. This paper uses Kern's framework for curriculum design to demonstrate how a breast diseases module for undergraduate medical students created in 1993 evolved over 15 years. The main outcomes of program refinements were better integrated course content, the development of electronic course documents, and implementation of computer-aided small group learning. A main future challenge is to further develop efficient instructional strategies in line with well-defined learning needs for undergraduate students.