Enteral nutrition as primary therapy in Crohn's disease

The developments in enteral feeding for Crohn's disease in the past decade are critically reviewed. The advent of amino acid based chemically defined elemental diets signalled the end of 'total bowel rest' in the management of these patients. Subsequently, controlled clinical trials showed that elemental diets were as effective as corticosteroids in inducing clinical remission in patients with acute exacerbations of Crohn's disease. The later use of peptide based elemental diets, in Crohn's disease produced somewhat conflicting results. The initial uncontrolled studies suggest that polymeric whole protein diets might also be effective in the management of acute exacerbations of the disease, casting in turn doubts concerning the role of dietary antigens in the pathogenesis of Crohn's disease. Results of controlled studies comparing the use of elemental and polymeric diets as primary therapy in Crohn's disease have, however, also produced conflicting results. The results of one recent controlled trial in which

Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

BACKGROUND AND PURPOSE: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy. METHODS: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2. RESULTS: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33). CONCLUSIONS: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.

Improving the chance of cure of follicular lymphoma by combining immunotherapy and radioimmunotherapy based on anti-CD20 antibodies?

Right ventricular and left ventricular systolic time intervals (RVSTIs and LVSTIs) were measured in normal term and preterm infants from 1 hour to 90 days of life. LVSTIs in both term and preterm infants were similar in the first five days of life. The ratio of left pre-ejection period (LPEP) to left ventricular ejection time (LVET) was lower in preterm infants older than age 5 days. Estimated gestational age had no influence on LVSTI. The ratio of right pre-ejection period (RPEP) to right ventricular ejection time (RVET) was lower in preterm infants (0.32) than in term newborns (0.37). The preterm RPEP/RVET ratio decreased with age, but at a slower rate than in term babies. This was consistent with the lower pulmonary vascular resistance present in preterm infants.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS: A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS: Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION: The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

PURPOSE: In the radiopharmaceutical therapy approach to the fight against cancer, in particular when it comes to translating laboratory results to the clinical setting, modeling has served as an invaluable tool for guidance and for understanding the processes operating at the cellular level and how these relate to macroscopic observables. Tumor control probability (TCP) is the dosimetric end point quantity of choice which relates to experimental and clinical data: it requires knowledge of individual cellular absorbed doses since it depends on the assessment of the treatment's ability to kill each and every cell. Macroscopic tumors, seen in both clinical and experimental studies, contain too many cells to be modeled individually in Monte Carlo simulation; yet, in particular for low ratios of decays to cells, a cell-based model that does not smooth away statistical considerations associated with low activity is a necessity. The authors present here an adaptation of the simple sphere-based model from which cellular level dosimetry for macroscopic tumors and their end point quantities, such as TCP, may be extrapolated more reliably. METHODS: Ten homogenous spheres representing tumors of different sizes were constructed in GEANT4. The radionuclide 131I was randomly allowed to decay for each model size and for seven different ratios of number of decays to number of cells, N(r): 1000, 500, 200, 100, 50, 20, and 10 decays per cell. The deposited energy was collected in radial bins and divided by the bin mass to obtain the average bin absorbed dose. To simulate a cellular model, the number of cells present in each bin was calculated and an absorbed dose attributed to each cell equal to the bin average absorbed dose with a randomly determined adjustment based on a Gaussian probability distribution with a width equal to the statistical uncertainty consistent with the ratio of decays to cells, i.e., equal to Nr-1/2. From dose volume histograms the surviving fraction of cells, equivalent uniform dose (EUD), and TCP for the different scenarios were calculated. Comparably sized spherical models containing individual spherical cells (15 microm diameter) in hexagonal lattices were constructed, and Monte Carlo simulations were executed for all the same previous scenarios. The dosimetric quantities were calculated and compared to the adjusted simple sphere model results. The model was then applied to the Bortezomib-induced enzyme-targeted radiotherapy (BETR) strategy of targeting Epstein-Barr virus (EBV)-expressing cancers. RESULTS: The TCP values were comparable to within 2% between the adjusted simple sphere and full cellular models. Additionally, models were generated for a nonuniform distribution of activity, and results were compared between the adjusted spherical and cellular models with similar comparability. The TCP values from the experimental macroscopic tumor results were consistent with the experimental observations for BETR-treated 1 g EBV-expressing lymphoma tumors in mice. CONCLUSIONS: The adjusted spherical model presented here provides more accurate TCP values than simple spheres, on par with full cellular Monte Carlo simulations while maintaining the simplicity of the simple sphere model. This model provides a basis for complementing and understanding laboratory and clinical results pertaining to radiopharmaceutical therapy.

Drug targeting strategies for photodynamic therapy.

In human pathologies, therapeutic treatments are often limited by the lack of selectivity of drugs and their elevated effective concentrations. Targeting these agents to a defined tissue could enhance their selectivity and then diminish their side effects when compared to drugs that accumulate in the entire body. Targeting could also improve treatment efficiency by allowing a localized high concentration of the agents. Based on the different behaviors and patterns of expression between diseased and normal cells, strategies for targeting can be explored. For example, receptors, proteases or trans-membrane carriers could be different or differently expressed. Many therapeutic procedures rely on this fact, including photodynamic therapy (PDT). PDT is already used in the treatment of some cancers, of inflammatory diseases and others diseases such as age-related macular degeneration or acne. PDT relies on the activation of a photosensitizer (PS) by visible light which results in the production of cytotoxic reactive oxygen species. In PDT, the general distribution of PS to the whole body leads to generalized photosensitization and poor acceptance of treatments by patients. One way to avoid these effects is to improve the targeting of PSs to diseased tissues using modification of PS with peptides or proteins that will target specific receptors or enzymes. PSs could also be functionalized with non-proteic ligands such as organometalics to achieve targeted and/or combined therapies. Alternatively, PSs could be encapsulated in nanoparticles bearing targeting agents which will decrease concentration of free circulating PS and improve photodynamic efficiency. These different approaches will be discussed in the present review with an emphasis on the use of peptides and proteins.

Statistical Modeling of the Eye for Multimodal Treatment Planning for External Beam Radiation Therapy of Intraocular Tumors.

PURPOSE: Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors. METHODS AND MATERIALS: Manual and automatic segmentations were compared for 17 patients, based on head computed tomography (CT) volume scans. A 3D statistical shape model of the cornea, lens, and sclera as well as of the optic disc position was developed. Furthermore, an active shape model was built to enable automatic fitting of the eye model to CT slice stacks. Cross-validation was performed based on leave-one-out tests for all training shapes by measuring dice coefficients and mean segmentation errors between automatic segmentation and manual segmentation by an expert. RESULTS: Cross-validation revealed a dice similarity of 95% ± 2% for the sclera and cornea and 91% ± 2% for the lens. Overall, mean segmentation error was found to be 0.3 ± 0.1 mm. Average segmentation time was 14 ± 2 s on a standard personal computer. CONCLUSIONS: Our results show that the solution presented outperforms state-of-the-art methods in terms of accuracy, reliability, and robustness. Moreover, the eye model shape as well as its variability is learned from a training set rather than by making shape assumptions (eg, as with the spherical or elliptical model). Therefore, the model appears to be capable of modeling nonspherically and nonelliptically shaped eyes.

MRI-based prostate brachytherapy seed localization.

A magnetic resonance imaging (MRI) pulse sequence and a corresponding image processing algorithm to localize prostate brachytherapy seeds during or after therapy are presented. Inversion-Recovery with ON-resonant water suppression (IRON) is an MRI methodology that generates positive contrast in regions of magnetic field susceptibility, as created by prostate brachytherapy seeds. Phantoms comprising of several materials found in brachytherapy seeds were created to assess the usability of the IRON pulse sequence for imaging seeds. Resulting images show that seed materials are clearly visible with high contrast using IRON, agreeing with theoretical predictions. A seed localization algorithm to process IRON images demonstrates the potential of this imaging technique for seed localization and dosimetry.

First explicit criteria to decide on the appropriateness of therapy of ulcerative colitis: the European EPATUC panel

Background: Ulcerative colitis (UC) is a chronic disease with a wide variety of treatment options many of which are not evidence based. Supplementing available guidelines, which are often broadly defined, consensus-based and generally not tailored to specifically reflect the individual patient situation, we developed explicit appropriateness criteria to assist, and improve treatment decisions. Methods: We used the RAND appropriateness method which does not force consensus. An extensive literature review was compiled based on and supplementing, where necessary, the ECCO UC 2011 guidelines. EPATUC (endorsed by ECCO) was formed by 7 gastroenterologists, 2 surgeons and 2 general practitioners from throughout Europe. Clinical scenarios reflecting practice were rated on a 9-point scale from 1 (extremely inappropriate) to 9 (extremely appropriate), based on the expert's experience and the available literature. After extensive discussion, all scenarios were re-rated at a two-day panel meeting. Median and disagreement (D) were used to categorize ratings into 3 categories: appropriate (A), uncertain (U) and inappropriate (I). Results: 718 clinical scenarios were rated, structured in 13 main clinical presentations: not refractory (n = 64) or refractory (n = 33) proctitis, mild to moderate left-sided (n = 72) or extensive (n = 48) colitis, severe colitis (n = 36), steroid- dependant colitis (n = 36), steroid-refractory colitis (n = 55), acute pouchitis (n = 96), maintenance of remission (n = 248), colorectal cancer prevention (n = 9) and fulminant colitis (n = 9). Overall, 100 indications were judged appropriate (14%), 129 uncertain (18%) and 489 inappropriate (68%). Disagreement between experts was very low (6%). Conclusions: For the very first time, explicit appropriateness criteria for therapy of UC were developed that allow both specific and rapid therapeutic decision making and prospective assessment of treatment appropriateness. Comparison of these detailed scenarios with patient profiles encountered in the Swiss IBD cohort study indicates good concordance. EPATUC criteria will be freely accessible on the internet (epatuc.ch)

A Monte Carlo-based procedure for independent monitor unit calculation in IMRT treatment plans.

Intensity-modulated radiotherapy (IMRT) treatment plan verification by comparison with measured data requires having access to the linear accelerator and is time consuming. In this paper, we propose a method for monitor unit (MU) calculation and plan comparison for step and shoot IMRT based on the Monte Carlo code EGSnrc/BEAMnrc. The beamlets of an IMRT treatment plan are individually simulated using Monte Carlo and converted into absorbed dose to water per MU. The dose of the whole treatment can be expressed through a linear matrix equation of the MU and dose per MU of every beamlet. Due to the positivity of the absorbed dose and MU values, this equation is solved for the MU values using a non-negative least-squares fit optimization algorithm (NNLS). The Monte Carlo plan is formed by multiplying the Monte Carlo absorbed dose to water per MU with the Monte Carlo/NNLS MU. Several treatment plan localizations calculated with a commercial treatment planning system (TPS) are compared with the proposed method for validation. The Monte Carlo/NNLS MUs are close to the ones calculated by the TPS and lead to a treatment dose distribution which is clinically equivalent to the one calculated by the TPS. This procedure can be used as an IMRT QA and further development could allow this technique to be used for other radiotherapy techniques like tomotherapy or volumetric modulated arc therapy.

Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial.

BACKGROUND: Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. METHODS/DESIGN: Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. DISCUSSION: Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345669.

Busulphan-melphalan is the superior myeloablative therapy (mat) for high risk neuroblastoma: results from the hr-nbl1/siopen trial

Purpose: The HR-NBL1 trial of the European SIOP Neuroblastoma Group randomised 2 MAT regimens to demonstrate superiority based on event free survival (EFS).Method: Response eligibility criteria prior to randomisation after Rapid COJEC Induction (J Clin Oncol, 2010) 3 4 2 courses of TVD (Cancer, 2003) included complete bone marrow remission andA ^ 3, but improved, mIBG positive spots. The MAT regimens were BuMel (oral busulfan till 2006, 4_150 mg/m2 in 4 equal doses, or after 2006 intravenous use according to body weight and melphalan 140 mg/m__/day) and CEM (carboplatin ctn. infusion (4xAUC 4.1 mg/ml.min/day), etoposide ctn. infusion (4_338 mg/m__day or 4_200 mg/m__/ day*), melphalan (3_70 mg/m__/day or 3_60 mg/m__/day*. *reduced if GFR<100 ml/ min/1.73m__)). A minimum of 3_10E6 CD34/kgBW PBSC were requested. VOD prophylaxis included ursadiol, but not prophylactic defibrotide. Local control included surgery and radiotherapy of 21 Gy. A total of 598 high risk neuroblastoma patients were randomised (296 BuMel, 302 CEM). The median age at randomisation was 3 years (1-17.2).Results: A significant difference in EFS in favour of BuMel (3-years EFS 49% vs. 33%) was observed as well as for overall survival (3-years OS 60% vs. 48%, p¼0.004) with a median follow up of 3 years. This difference was mainly related to the relapse and progression incidence, which was significantly (p<0.001) lower with BuMel (48% vs. 60%). The severe toxicity rate up to day 100 (ICU and toxic deaths) was below 10%, but was significantly higher for CEM (p¼0.014). The acute toxic death rate was 3% for BuMel and 5% for CEM (NS). The acute MAT toxicity profile favours the BuMel regimen in spite of a total VOD incidence of 18% (grade 3:5%). Based on these results and following advice from the DMC, the randomisation was closed early.

Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial.

BACKGROUND: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adults infected with HIV-1. METHODS: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 10(6) cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, the UK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo. Group allocation was masked from participants and investigators. Four primary immunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were given intradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption. Analyses were by modified intention to treat: all participants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed. The 52 week follow-up period was completed in June, 2011. For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate. This study is registered with ClinicalTrials.gov, number NCT00659789. FINDINGS: 174 individuals were screened; because of slow recruitment, enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28. Of the participants who resumed cART, 30 (34%) were in the Vacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4 counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to 1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23 100 copies per mL Vacc-4x vs 71 800 copies per mL placebo; p=0·025) and week 52 (median 19 550 copies per mL vs 51 000 copies per mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic, inducing proliferative responses in both CD4 and CD8 T-cell populations. INTERPRETATION: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worth consideration in future HIV-cure investigative strategies. FUNDING: Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA.

Stepwise evaluation of syncope: a prospective population-based controlled study.

BACKGROUND: Evaluation of syncope remains often unstructured. The aim of the study was to assess the effectiveness of a standardized protocol designed to improve the diagnosis of syncope. METHODS: Consecutive patients with syncope presenting to the emergency departments of two primary and tertiary care hospitals over a period of 18 months underwent a two-phase evaluation including: 1) noninvasive assessment (phase I); and 2) specialized tests (phase II), if syncope remained unexplained after phase I. During phase II, the evaluation strategy was alternately left to physicians in charge of patients (control), or guided by a standardized protocol relying on cardiac status and frequency of events (intervention). The primary outcomes were the diagnostic yield of each phase, and the impact of the intervention (phase II) measured by multivariable analysis. RESULTS: Among 1725 patients with syncope, 1579 (92%) entered phase I which permitted to establish a diagnosis in 1061 (67%) of them, including mainly reflex causes and orthostatic hypotension. Five-hundred-eighteen patients (33%) were considered as having unexplained syncope and 363 (70%) entered phase II. A cause for syncope was found in 67 (38%) of 174 patients during intervention periods, compared to 18 (9%) of 189 during control (p<0.001). Compared to control periods, intervention permitted diagnosing more cardiac (8%, vs 3%, p=0.04) and reflex syncope (25% vs 6%, p<0.001), and increased the odds of identifying a cause for syncope by a factor of 4.5 (95% CI: 2.6-8.7, p<0.001). Overall, adding the diagnostic yield obtained during phase I and phase II (intervention periods) permitted establishing the cause of syncope in 76% of patients. CONCLUSION: Application of a standardized diagnostic protocol in patients with syncope improved the likelihood of identifying a cause for this symptom. Future trials should assess the efficacy of diagnosis-specific therapy.

Dépistage et intervention brève par internet pour la consommation d'alcool a risque: www.alcooquizz.ch [Web-based screening and brief intervention for unhealthy alcohol use: www.alcooquizz.ch].

Many individuals with unhealthy alcohol use have few or no contact with the health care system and are therefore unlikely to receive information or a brief intervention from a health care professional. Consequently, many Internet-based interventions have been developed. These interventions can reach a large population. We present in this report www.alcooquizz.ch, a website providing tailored feedback and information on alcohol use and its consequences. In six months and a half, more than 15000 individuals visited the website. It appropriately targets individuals with unhealthy alcohol use and users' satisfaction was high. Internet is a valuable option to provide health related information and secondary prevention interventions for unhealthy alcohol use.