Justice and Court Administrations, Their Workings and Efficiency in Switzerland : Aspects of Sentencing And Its Outcome In Swiss Cantons

The comparison of the operations of the administration of justice among cantons shows on one side large differences in the three major types of sentencing, in the use of pre-trial detention and the unsuspended prison sanction. When combined, one finds however very weak relationships when considering absolute, percentage or weighted results. On the other side, the outcome of these different policies is much paradoxical as there are no differences when comparing recidivism rates among cantons, despite strong differences in the use of pre-trial detention and the sentencing with prison sanctions. The paradoxical outcome of crime policies in terms of recidivism - e.g. the absence of differences of the outcome based on sanctions in the domain of less severe delinquency - suggests the need for more empirically informed crime policies. The role of justice administrators could be to participate in the dissemination of those findings as well as the dissemination of best practices among cantons with regard to outcomes and the use of resources - especially with consideration to the use of the prison sanction as it is the most costly and the most inefficient of all sanctions. Furthermore, the observance of the principle of equality before the law would be most likely be promoted.

Second-hand tobacco smoke in prison: tackling a public health matter through research.

OBJECTIVES: This action-research study conducted in a Swiss male post-trial detention centre (120 detainees and 120 staff) explored the attitudes of detainees and staff towards tobacco smoking. Tackling public health matters through research involving stakeholders in prisons implies benefits and risks that need exploration. STUDY DESIGN: The observational study involved multiple strands (quantitative and qualitative components, and air quality measurements). This article presents qualitative data on participants' attitudes and expectations about research in a prison setting. METHODS: Semi-structured interviews were used to explore the attitudes of detainees and staff towards smoking before and after a smoke-free regulation change in the prison in 2009. Specific coding and thematic content analysis for research were performed with the support of ATLAS.ti. RESULTS: In total, 77 interviews were conducted (38 before the regulation change and 39 after the regulation change) with 31 detainees (mean age 35 years, range 22-60 years) and 27 prison staff (mean age 46 years, range 29-65 years). Both detainees and staff expressed satisfaction regarding their involvement in the study, and wished to be informed about the results. They expected concrete changes in smoke-free regulation, and that the research would help to find ways to motivate detainees to quit smoking. CONCLUSION: Active involvement of stakeholders promotes public health. Interviewing detainees and prison staff as part of an action-research study aimed at tackling a public health matter is a way of raising awareness and facilitating change in prisons. Research needs to be conducted independently from the prison administrators in order to increase trust and to avoid misunderstandings.

The costs of crossing paths and switching tasks between audition and vision.

Switching from one functional or cognitive operation to another is thought to rely on executive/control processes. The efficacy of these processes may depend on the extent of overlap between neural circuitry mediating the different tasks; more effective task preparation (and by extension smaller switch costs) is achieved when this overlap is small. We investigated the performance costs associated with switching tasks and/or switching sensory modalities. Participants discriminated either the identity or spatial location of objects that were presented either visually or acoustically. Switch costs between tasks were significantly smaller when the sensory modality of the task switched versus when it repeated. This was the case irrespective of whether the pre-trial cue informed participants only of the upcoming task, but not sensory modality (Experiment 1) or whether the pre-trial cue was informative about both the upcoming task and sensory modality (Experiment 2). In addition, in both experiments switch costs between the senses were positively correlated when the sensory modality of the task repeated across trials and not when it switched. The collective evidence supports the independence of control processes mediating task switching and modality switching and also the hypothesis that switch costs reflect competitive interference between neural circuits.

Influence of CYP2D6 activity on pre-emptive analgesia by the N-methyl-D-aspartate antagonist dextromethorphan in a randomized controlled trial of acute pain.

BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent.  DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism in acute post-operative pain. STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute pain. METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS: Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory effect of oral dextromethorphan.

Lapband Versus SAGB for Morbid Obesity. Long-Term Results of a Prospective Randomized Trial

Background: Gastric banding is currently one of the most performed procedures for morbid obesity. Results are related in part to the surgical technique and the quality of follow-up. Several bands are currently on the market, and it may bethat the type of band also plays a role in long-term results. The aim of this prospective randomized study was to compare the long-term results of the Lapband and the SAGB.Patients and methods: In three institutions with a common bariatric surgeon, consecutive patients undergoing laparoscopic gastric banding for morbid obesity were randomized to receive either a Lapband or a SAGB. The Lapband was placed using the perigastric and the SAGB with the pars flaccida technique. All data were collected prospectively. The median duration of follow-up was 131 months (103-147). Patients who lost their band were excluded from analysis as of band removal.Results: 180 patients were included between December 1998 and June 2002, 90 in each group. Except for age, which was lower in SAGB patients, the pre-operative characteristics were similar in the two patient groups. Early band-related morbidity was higher in the SAGB group (6,6 vs 0 %, p=0,03). Patients with a Lapband lost weight quicker than those with SAGB (EBMIL 50,8 vs 39,8 after 12 months, p<0,001), but the two weight loss curves joined after 24 months, and no difference could be observed later on up to 12 years after surgery (EBMIL 53,7 vs 58,1 % after 10 years, P=0,68). Long-term complications developed in 91 patients (50,5 %). Severe complications leading to band removal±conversion to another procedure developed in 30 and 40 patients in the Lapband and SAGB group respectively (33,3 vs 44,4 %, p=0,16).Conclusions: This prospective randomized study shows no significant difference in the long-term results of gastric banding between the Lapband and the SAGB. Both bands were associated with significant long-term complication and band removal/conversion rates. Patients who retain their band have acceptable long-term weight loss. It is likely that the concept of gastric banding rather than the device itself plays the most important role in longterm results.

Pelvic organ prolapse surgery with and without tension-free vaginal tape in women with occult or asymptomatic urodynamic stress incontinence: a randomised controlled trial.

INTRODUCTION: We set out to determine if insertion of a retropubic tension-free vaginal tape (TVT) sling at the time of pelvic organ prolapse surgery improves continence outcomes in women with pre-operative occult stress incontinence (OSI) or asymptomatic urodynamic stress incontinence (USI). METHODS: We conducted a randomised controlled study of prolapse surgery with or without a TVT midurethral sling. The pre- and post-operative assessment at 6 months included history, physical examination and urodynamic testing. Quality of life (QOL) and treatment success was assessed with the UDI-6 SF, IIQ-7 SF and a numerical success score. The primary outcome was symptomatic stress urinary incontinence (SUI) requiring continence surgery (TVT) at 6 months. Long-term follow-up continued to a minimum of 24 months. Secondary outcomes were quality of life parameters. RESULTS: Eighty women received prolapse surgery alone (n = 43) or prolapse surgery with concurrent TVT (n = 37). Six months following prolapse surgery 3 out of 43 (7 %) patients in the no TVT group requested sling surgery compared with 0 out of 37 (0 %) in the TVT group (ARR 7 % [95 %CI: 3 to 19 %], p = 0.11). After 24 months there was one further participant in the no TVT group who received a TVT for treatment of SUI compared with none in the TVT group (4 out of 43, 9.3 % versus 0 out of 37; ARR 9.3 % [95 %CI: -1 to 22 %], p = 0.06). Both groups showed improvement in QOL difference scores for within-group analysis, without difference between groups. CONCLUSION: These results support a policy that routine insertion of a sling in women with OSI at the time of prolapse repair is questionable and should be subject to shared decision-making between clinician and patient.

A prospective, randomized, open label, phase iii clinical trial of novottf-100a vs best standard of care chemotherapy in patients with recurrent glioblastoma

BACKGROUND: Glioblastoma, the most common adult primary malignant brain tumor, confers poor prognosis (median survival of 15 months) notwithstanding aggressive treatment. Combination chemotherapy including carmustine (BCNU) or temozolomide (TMZ) with the MGMT inhibitor O6-benzylguanine (O6BG) has been used, but has been associated with dose-limiting hematopoietic toxicity. OBJECTIVE: To assess safety and efficacy of a retroviral vector encoding the O6BG-resistant MGMTP140K gene for transduction and autologous transplantation of hematopoietic stem cells (HSCs) in MGMT unmethylated, newly diagnosed glioblastoma patients in an attempt to chemoprotect bone marrowduring combination O6BG/TMZ therapy. METHODS: Three patients have been enrolled in the first cohort. Patients underwent standard radiation therapy without TMZ followed by G-CSF mobilization, apheresis, and conditioning with 600 mg/m2 BCNU prior to infusion of gene-modified cells. Posttransplant, patients were treated with 28-day cycles of single doseTMZ (472 mg/m2) with 48-hour intravenous O6BG (120 mg/m2 bolus, then 30 mg/m2/d). RESULTS: The BCNU dose was nonmyeloablative with ANC ,500/mL for ≤3 d and nadir thrombocytopenia of 28,000/mL. Gene marking in pre-infusion colony forming units (CFUs) was 70.6%, 79.0%, and 74.0% in Patients 1, 2, and 3, respectively, by CFU-PCR. Following engraftment, gene marking in white blood cells and sorted granulocytes ranged between 0.37-0.84 and 0.33-0.83 provirus copies, respectively, by real-time PCR. Posttransplant gene marking in CFUs from CD34-selected cells ranged from 28.5% to 47.4%. Patients have received 4, 3, and 2 cycles of O6BG/TMZ, respectively, with evidence for selection of gene-modified cells. One patient has received a single dose-escalated cycle at 590 mg/m2 TMZ. No additional extra-hematopoietic toxicity has been observed thus far and all three patients exhibit stable disease at 7-8 months since diagnosis CONCLUSIONS: We believe that these data demonstrate the feasibility of achieving significant engraftment of MGMTP140K-modified cells with a well-tolerated dose of BCNU. Further follow-up will determine whether this approach will allow for further dose escalation of TMZ and improved survival.

Randomized trial of pacemaker and lead system for safe scanning at 1.5 Tesla.

BACKGROUND: Magnetic resonance imaging (MRI) of pacemakers is a relative contraindication because of the risks to the patient from potentially hazardous interactions between the MRI and the pacemaker system. Chest scans (ie, cardiac magnetic resonance scans) are of particular importance and higher risk. The previously Food and Drug Administration-approved magnetic resonance conditional system includes positioning restrictions, limiting the powerful utility of MRI. OBJECTIVE: To confirm the safety and effectiveness of a pacemaker system designed for safe whole body MRI without MRI scan positioning restrictions. METHODS: Primary eligibility criteria included standard dual-chamber pacing indications. Patients (n = 263) were randomized in a 2:1 ratio to undergo 16 chest and head scans at 1.5 T between 9 and 12 weeks postimplant (n = 177) or to not undergo MRI (n = 86) post-implant. Evaluation of the pacemaker system occurred immediately before, during (monitoring), and after MRI, 1-week post-MRI, and 1-month post-MRI, and similarly for controls. Primary end points measured the MRI-related complication-free rate for safety and compared pacing capture threshold between MRI and control subjects for effectiveness. RESULTS: There were no MRI-related complications during or after MRI in subjects undergoing MRI (n = 148). Differences in pacing capture threshold values from pre-MRI to 1-month post-MRI were minimal and similar between the MRI and control groups. CONCLUSIONS: This randomized trial demonstrates that the Advisa MRI pulse generator and CapSureFix MRI 5086MRI lead system is safe and effective in the 1.5 T MRI environment without positioning restrictions for MRI scans or limitations of body parts scanned.

Long-term follow-up of follicular lymphoma (FL) patients receiving single agent rituximab at two different schedules in trial SAKK 35/98

Background: In FL, Rituximab as a single agent delivered in the standard schedule (4 times weekly) may induce a response rate of 50−70% with an event-free survival (EFS) of 1−3 years according to patients' characteristics. Prolonged Rituximab exposure seems to improve EFS at least in responding patients and to increase the rate of longterm responders. Here we report long-term results of a clinical trial comparing single agent Rituximab delivered in the standard schedule versus prolonged exposure, with focus on the proportion of long-term responders and their characteristics. Material and Methods: Between 1998 and 2002, chemotherapy na¨ıve (n = 64) or pre-treated (n = 138) FL patients received Rituximab in the standard schedule. Those responding or with stable disease were randomized to no further treatment (observation, n = 78) or 4 additional doses of Rituximab given at 2-month intervals (prolonged exposure, n = 73). EFS was calculated from the first dose of standard schedule until progression, relapse, second tumor or death. Results: At a median follow up of 9.4 years and with all living patients having been followed for at least 5 years, the median EFS is 13 months for the observation and 24 months for the prolonged exposure arm (p = 0.0007). In the observation arm 13% had no event at 5-years and only 4% at 8 years, while in the prolonged exposure arm it was 27% at 5 years and remained 21% at 8 years. The only significant prognostic factor for EFS in a multivariate Cox regression was the prolonged Rituximab schedule (hazard ratio 0.58, CI 0.39−0.86, p = 0.007), whereas being chemotherapy na¨ıve, presenting with stage

Impact of Pre-Existing Immunity on the Selection of Rare Adenovirus Vector Candidates: Implications for HIV Vaccine Development

Background: Adenovirus serotype 5 (Ad5) phase IIb vaccine trial (STEP) was prematurely stopped due to a lack of efficacy and two-fold higher incidence of HIV infection among Ad5 seropositive vaccine recipients. We have recently demonstrated that Ad5 immune complexes (Ad5 ICs)-mediated activation of the dendritic cell (DC)-T cell axis was associated with the enhancement of HIV infection in vitro. Although the direct role of Ad5 neutralizing antibodies (NAbs) in the increase of HIV susceptibility during the STEP trial is still under debate, vector-specific NAbs remain a major hurdle for vector-based gene therapies or vaccine strategies. To surmount this obstacle, vectors based on ''rare'' Ad serotypes including Ad6, Ad26, Ad36 and Ad41 were engineered.Methods: The present study aimed to determine whether Ad ICmediated DC maturation could be circumvented using these Advector candidates.Results: We found that all Ad vectors tested forming ICs with plasma containing serotype-specific NAbs had the capacity to 1) mature human DCs as monitored by the up-regulation of costimulatory molecules and the release of pro-inflammatory cytokines (TNF-a), via the stabilization of Ad capsid at endosomal but not lysosomal pH rendering Ad DNA/TLR9 interactions possible and 2) potentiate Ad-specific CD4 and CD8 T cell responses.Conclusion: In conclusion, despite a conserved DC maturation potential, the low prevalence of serotype-specific NAbs renders rare Ad vectors attractive for vaccine strategies.

Existential behavioural therapy for informal caregivers of palliative patients: a randomised controlled trial.

BACKGROUND: Existential behavioural therapy (EBT) was developed to support informal caregivers of palliative patients in the last stage of life and during bereavement as a manualised group psychotherapy comprising six sessions. We tested the effectiveness of EBT on mental stress and quality of life (QOL). METHODS: Informal caregivers were randomly assigned (1:1) to EBT or a treatment-as-usual control group using computer-generated numbers in blocks of 10. Primary outcomes were assessed with the Brief Symptom Inventory (subscales somatisation, anxiety and depression), the Satisfaction with Life Scale (SWLS), the WHOQOL-BREF and a numeric rating scale for QOL (QOL-NRS, range 0-10). Data were collected at baseline, pre-treatment, post-treatment and follow-ups after 3 and 12âeuro0/00months. Treatment effects were assessed with a multivariate analysis of covariance. RESULTS: Out of 160 relatives, 81 were assigned to EBT and 79 to the control group. Participants were 54.5âeuro0/00±âeuro0/0013.2âeuro0/00years old; 69.9% were female. The multivariate model was significant for the pre-/post-comparison (pâeuro0/00=âeuro0/000.005) and the pre-/12-month comparison (pâeuro0/00=âeuro0/000.05) but not for the pre-/3-month comparison. Medium to large effects on anxiety and QOL (SWLS, WHOQOL-BREF, QOL-NRS) were found at post-treatment; medium effects on depression and QOL (QOL-NRS) emerged in the 12-month follow-up. No adverse effects of the intervention were observed. CONCLUSION: Existential behavioural therapy appears to exert beneficial effects on distress and QOL of informal caregivers of palliative patients. Further longitudinal evidence is needed to confirm these findings. Copyright © 2013 John Wiley & Sons, Ltd.

Spontaneous pre-stimulus fluctuations in the activity of right fronto-parietal areas influence inhibitory control performance.

Inhibitory control refers to the ability to suppress planned or ongoing cognitive or motor processes. Electrophysiological indices of inhibitory control failure have been found to manifest even before the presentation of the stimuli triggering the inhibition, suggesting that pre-stimulus brain-states modulate inhibition performance. However, previous electrophysiological investigations on the state-dependency of inhibitory control were based on averaged event-related potentials (ERPs), a method eliminating the variability in the ongoing brain activity not time-locked to the event of interest. These studies thus left unresolved whether spontaneous variations in the brain-state immediately preceding unpredictable inhibition-triggering stimuli also influence inhibitory control performance. To address this question, we applied single-trial EEG topographic analyses on the time interval immediately preceding NoGo stimuli in conditions where the responses to NoGo trials were correctly inhibited [correct rejection (CR)] vs. committed [false alarms (FAs)] during an auditory spatial Go/NoGo task. We found a specific configuration of the EEG voltage field manifesting more frequently before correctly inhibited responses to NoGo stimuli than before FAs. There was no evidence for an EEG topography occurring more frequently before FAs than before CR. The visualization of distributed electrical source estimations of the EEG topography preceding successful response inhibition suggested that it resulted from the activity of a right fronto-parietal brain network. Our results suggest that the fluctuations in the ongoing brain activity immediately preceding stimulus presentation contribute to the behavioral outcomes during an inhibitory control task. Our results further suggest that the state-dependency of sensory-cognitive processing might not only concern perceptual processes, but also high-order, top-down inhibitory control mechanisms.

LAPATAX: A randomized phase II trial of FEC-docetaxel combined with lapatinib and/or trastuzumab as neoadjuvant therapy of HER2- positive breast cancer-EORTC 10054 trial.

Background: Patients with HER2 +ve breast cancer suitable for neoadjuvant chemotherapy (NAC) have been shown in a series of clinical trials to have the best outcome when treated with anthracyclines (A), taxanes (T), and trastuzumab (Tz). Recent evidence confirms that adjuvant Tz is more effective when given concomitantly rather than sequentially with T (Perez SABCS 2009). Whilst there remains uncertainty as to the most efficacious A-T regimen and duration of Tz, there is widespread use in Europe of FEC-D [3 cycles of 5-FU 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 (FEC100) followed by 3 cycles of docetaxel 100 mg/m2 (D) q3w] following the results of PACS-01. The advent of TKI anti-HER2 agents such as L could offer superior outcomes if combined with NAC. However, a phase I study in heavily pre-treated advanced breast cancer reported difficulties in combining lapatinib (L) with D 100 mg/m2 (LoRusso JCO 2008). Methods: EORTC 10054 is designed as a two-part study to compare FEC-D with either Tz, L or their combination as NAC for patients with HER2 +ve large operable or locally advanced breast cancer. Before and on-treatment frozen tumor and blood samples will be taken to better define which tumours are particularly sensitive to either Tz and/or L. Stage 1: (complete) a dose- finding study has confirmed that with primary prophylactic G-CSF, D 100 mg/m2 can be safely and effectively given with L 1,250 mg daily continuously. The dose-limiting toxicity was myelosuppression, and there was no significant diarrhoea or cardiac toxicity (ESMO 2009 abstr P- 5073). Stage 2: (opening Q1 2010) will enroll 150 patients from European centres into a 3-arm randomized trial whose primary endpoint is pathological complete response. All patients will receive FEC-D before primary surgery: 3 cycles of FEC (without anti-HER2 therapy) followed by 3 cycles of D plus either Tz (conventional weekly schedule), monotherapy L, or the combination of Tz and L, using doses based on the EGF100161 dose-finding study in 1st line metastatic therapy of D+L+Tz. After surgery all patients will receive standard 3-weekly Tz, radiotherapy and endocrine therapy as per local guidelines.

Metacognitive training for schizophrenia: a multicentre randomised controlled trial.

A psychotherapeutic approach for schizophrenia is now recommended as an adjuvant for psychopharmacology, since antipsychotic medications only have a partial impact especially as regards positive symptoms and insight. In addition, cognitive distortions and the lack of metacognitive skills might increase positive symptoms leading to poor social functioning. This underlines the need for specific approaches which target cognitive processes relevant for insight, and abilities in metacognition. Metacognitive training (MCT) is a structured group intervention, which enhances a patient's reflection on cognitive biases and improves problem-solving. The aim of our study was to assess MCTs' short term impact on insight, symptoms and quality of life. Fifty patients with schizophrenia or schizoaffective disorders and persistent positive symptoms (delusions or hallucinations) were enrolled in the study. After baseline assessment participants were randomised either to supportive therapy or MCT. Both groups used the same design (1h-session twice a week during 8weeks) although the basic knowledge given to participants was different between interventions. Participants were assessed at eight weeks based on the Scale to Assess Unawareness of Mental Disorder, Positive and Negative Syndrome Scale (PANSS), Psychotic Symptom Rating Scales, the Calgary Depression Scale for Schizophrenia and the Quality of Life Scale. Between-group differences were significant in favour of MCT on the PANSS positive scale. Between-group differences in post- and pre-test values showed a trend in favour of MCT for insight on hallucinations. Results of our study indicate that the MCT has an effect on reducing positive symptomatology, and a trend impact on insight and social functioning.