Colorectal polypectomy during insertion and withdrawal or only during withdrawal? A randomized controlled trial.

BACKGROUND AND STUDY AIMS: Removal of colorectal polyps is routinely performed during withdrawal of the endoscope. However, polyps detected during insertion of the colonoscope may be missed at withdrawal. We aimed to evaluate whether polypectomy during both insertion and withdrawal increases polyp detection and removal rates compared with polypectomy at withdrawal only, and to assess the duration of both approaches. PATIENTS AND METHODS: Patients were included into the study when the first polyp was detected, and randomized into two groups; in group A, polyps ≤ 10 mm in diameter were removed during insertion and withdrawal of the colonoscope, while in group B, these polyps were removed at withdrawal only. Main outcome measures were duration of colonoscopy, number of polyps detected during insertion but not recovered during withdrawal, technical ease, patient discomfort, and complications. RESULTS: 150 patients were randomized to group A and 151 to group B. Mean (± standard deviation [SD]) duration of colonoscopy did not differ between the groups (30.8 ± 15.6 min [A] vs. 28.5 ± 13.8 min [B], P = 0.176). In group A 387 polyps (mean 2.58 per colonoscopy) were detected and removed compared with 389 polyps detected (mean 2.58 per colonoscopy) in group B of which 376 were removed (13 polyps were missed, mean size [SD] 3.2 [1.3] mm; 7.3 % of patients). Patient tolerance was similar in the two groups. CONCLUSIONS: Removal of polyps ≤ 10 mm during withdrawal only is associated with a considerable polyp miss rate. We therefore recommend that these polyps are removed during both insertion and withdrawal.

Changes in running mechanics and spring-mass behaviour during a 5-km time trial.

Research into the biomechanical manifestation of fatigue during exhaustive runs is increasingly popular but additional understanding of the adaptation of the spring-mass behaviour during the course of strenuous, self-paced exercises continues to be a challenge in order to develop optimized training and injury prevention programs. This study investigated continuous changes in running mechanics and spring-mass behaviour during a 5-km run. 12 competitive triathletes performed a 5-km running time trial (mean performance: ̴17 min 30 s) on a 200 m indoor track. Vertical and anterior-posterior ground reaction forces were measured every 200 m by a 5-m long force platform system, and used to determine spring-mass model characteristics. After a fast start, running velocity progressively decreased (- 11.6%; P<0.001) in the middle part of the race before an end spurt in the final 400-600 m. Stride length (- 7.4%; P<0.001) and frequency (- 4.1%; P=0.001) decreased over the 25 laps, while contact time (+ 8.9%; P<0.001) and total stride duration (+ 4.1%; P<0.001) progressively lengthened. Peak vertical forces (- 2.0%; P<0.01) and leg compression (- 4.3%; P<0.05), but not centre of mass vertical displacement (+ 3.2%; P>0.05), decreased with time. As a result, vertical stiffness decreased (- 6.0%; P<0.001) during the run, whereas leg stiffness changes were not significant (+ 1.3%; P>0.05). Spring-mass behaviour progressively changes during a 5-km time trial towards deteriorated vertical stiffness, which alters impact and force production characteristics.

Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial.

BACKGROUND: Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt-chromium drug-eluting stent with silicon carbide-coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro; Biotronik, Bülach, Switzerland) with the durable polymer-based Xience Prime/Xpedition everolimus-eluting stent (EES) (Xience Prime/Xpedition stent, Abbott Vascular, IL) in an all-comers patient population. DESIGN: The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer sirolimus-eluting stents (SES) or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least 1 lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary end point target lesion failure (TLF) is a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for noninferiority, inclusion of 2,060 patients would provide more than 80% power to detect noninferiority of the biodegradable polymer SES compared with the durable polymer EES at a 1-sided type I error of 0.05. Clinical follow-up will be continued through 5 years. CONCLUSION: The BIOSCIENCE trial will determine whether the biodegradable polymer SES is noninferior to the durable polymer EES with respect to TLF.

Key cognitive and collaborative aptitudes in ambulance people

The aim of our study was to identify and document some key cognitive aptitudes used by ambulance people in emergency situations. Better knowing such aptitudes is necessary for a school of ambulance people in order to improve the selection and education of students. The idea was to better consider real work activity requirements and characteristics, and to develop and implement genuine educational content and selection tools. We followed the work activity of ambulance professionals involved in real emergency situations. Some interventions were filmed and post-analyzed. We completed and validated our analysis by means of interviews with ambulance personnel. We selected some video sequences and used them as a support for the interviews. We identified and documented many different key aptitudes like orientation and spatial sense, the capacity to perform complex cognitive tasks and delicate manipulations in the context of divided attention, as well as diverse aptitudes relevant in collaborative work.

Temozolomide combined with bevacizumab in metastatic melanoma. A multicenter phase II trial (SAKK 50/07)

Background: Single agent DTIC is the standard therapy for metastatic melanoma (MM) with response rates of 5−20%. Temozolomide (Tem) as an oral drug has shown equal efficacy in phase III trials. Preclinical models have shown an inhibitory effect for bevacizumab (Bev) on the proliferation of melanoma cells as well as on sprouting endothelial cells. Therefore, a therapeutic approach that combines angiogenesis inhibitors with cytotoxic agents may provide clinical benefit in MM. Methods: Design: Multicenter phase II trial. Primary endpoint: Clinical benefit (CR, PR and SD) at 12 weeks; secondary endpoints: best overall response by RECIST, response duration, progression free survival, adverse events, survival after 6 months and overall survival. Sample size was calculated according to Simon's two stage optimal design (5% significance level and 80% power) with an overall sample size of 62 patients (pts) to test H0: 20% versus H1: 35% rate of clinical benefit. Response assessment was done every 6 weeks (3 cycles). Eligibility: Stage IV MM, ECOG PS 0−2, no prior treatment for metastatic disease. Treatment regimen: One cycle consisted of Tem at 150 mg/m2 days 1−7 po and Bev at 10 mg/kg day 1 over 30 min iv and was repeated every 2 weeks until progression or unacceptable toxicity. Results: Between January 2008 and April 2009, 62 pts (40 male/22 female) at a median age of 61 years (range 30−86) with stage IV (M1a:4, M1b:12, M1c:46) melanoma were enrolled in 9 centers. The first 50 pts, who received 415 cycles are included in this interim report. The overall response rate was 26% (CR: 1 pt, PR: 12 pts; PR not confirmed yet in 3 pts), and 44% (22 pts) had stable disease over 1.5−7.5 months (median: 3). Only 30% (15 pts) had disease progression at the first evaluation at week 6. The hematological grade 3/4 toxicities according to NCI CTAE 3.0 were thrombocytopenia 10% (5 pts), neutropenia 8% (4 pts), lymphopenia and leucocytopenia each 2% (1 pt). Cumulative non-hematological toxicities grade 3/4 were nausea and fatigue each 6% (3 pts), hypertension, vomiting and hemorrhage, each 4% (2 pts), thrombosis/embolism, infection, constipation, anorexia, elevation of alkaline phosphatase, bilirubin, GGT, ALT and AST each 2% (1 pt). Conclusion: In metastatic melanoma the combination of Tem/Bev is a safe regimen with a promising efficacy and few grade 3/4 toxicities. Updated results of all 62 pts will be presented.

Personality and personality disorders in urban and rural Africa: results from a field trial in Burkina Faso

When conducting research in different cultural settings, assessing measurement equivalence is of prime importance to determine if constructs and scores can be compared across groups. Structural equivalence implies that constructs have the same meaning across groups, metric equivalence implies that the metric of the scales remains stable across groups, and full scale or scalar equivalence implies that the origin of the scales is the same across groups. Several studies have observed that the structure underlying both normal personality and personality disorders (PDs) is stable across cultures. Most of this cross-cultural research was conducted in Western and Asian cultures. In Africa, the few studies were conducted with well-educated participants using French or English instruments. No research was conducted in Africa with less privileged or preliterate samples. The aim of this research was to study the structure and expression of normal and abnormal personality in an urban and a rural sample in Burkina Faso. The sample included 1,750 participants, with a sub-sample from the urban area of Ouagadougou (n = 1,249) and another sub-sample from a rural village, Soumiaga (n = 501). Most participants answered an interview consisting of a Mooré language adaptation of the Revised NEO Personality Inventory and of the International Personality Disorders Examination. Mooré is the language of the Mossi ethnic group, and the most frequently spoken local language in Burkina Faso. A sub-sample completed the same self-report instruments in French. Demographic variables only had a small impact on normal and abnormal personality traits mean levels. The structure underlying normal personality was unstable across regions and languages, illustrating that translating a complex psychological inventory into a native African language is a very difficult task. The structure underlying abnormal personality and the metric of PDs scales were stable across regions. As scalar equivalence was not reached, mean differences cannot be interpreted. Nevertheless, these differences could be due to an exaggerated expression of abnormal traits valued in the two cultural settings. Our results suggest that studies using a different methodology should be conducted to understand what is considered, in different cultures, as deviating from the expectations of the individual's culture, and as a significant impairment in self and interpersonal functioning, as defined by the DSM-5.

Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: Ten-year Follow-up of a Randomized Phase III Trial (SAKK 10/94)

PURPOSE/OBJECTIVE(S): To analyze the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer compared with hyperfractionated radiotherapy alone. MATERIALS/METHODS: From July 1994 to July 2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiotherapy (median dose 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20mg/m2 for 5 consecutive days of weeks 1 and 5). The primary endpoint was time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to RTOG criteria. The trial was registered at the National Institutes of Health (www.clinicaltrials.gov; identifier number: NCT00002654). RESULTS: Median follow-up was 9.5 years (range, 0.1 - 15.4 years). Median time to any treatment failure was not significantly different between treatment arms (p = 0.19). Locoregional control (p\0.05), distant metastasis-free survival (p = 0.02) and cancer specific survival (p = 0.03) were significantly improved in the combined treatment arm, with no difference in late toxicity between treatment arms. However, overall survival was not significantly different (p = 0.19). CONCLUSIONS: After long-term follow-up combined treatment with cisplatin and hyperfractionated, radiotherapy maintained an improved locoregional control, distant metastasis-free survival, and cancer specific survival as compared to hyperfractionated radiotherapy alone with no difference in late toxicity.

Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07.

The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR + PR + SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints.

Partnership for fragility bone fracture care provision and prevention program (P4Bones): study protocol for a secondary fracture prevention pragmatic controlled trial.

ABSTRACT: BACKGROUND: Fractures associated with bone fragility in older adults signal the potential for secondary fracture. Fragility fractures often precipitate further decline in health and loss of mobility, with high associated costs for patients, families, society and the healthcare system. Promptly initiating a coordinated, comprehensive pharmacological bone health and falls prevention program post-fracture may improve osteoporosis treatment compliance; and reduce rates of falls and secondary fractures, and associated morbidity, mortality and costs.Methods/design: This pragmatic, controlled trial at 11 hospital sites in eight regions in Quebec, Canada, will recruit community-dwelling patients over age 50 who have sustained a fragility fracture to an intervention coordinated program or to standard care, according to the site. Site study coordinators will identify and recruit 1,596 participants for each study arm. Coordinators at intervention sites will facilitate continuity of care for bone health, and arrange fall prevention programs including physical exercise. The intervention teams include medical bone specialists, primary care physicians, pharmacists, nurses, rehabilitation clinicians, and community program organizers.The primary outcome of this study is the incidence of secondary fragility fractures within an 18-month follow-up period. Secondary outcomes include initiation and compliance with bone health medication; time to first fall and number of clinically significant falls; fall-related hospitalization and mortality; physical activity; quality of life; fragility fracture-related costs; admission to a long term care facility; participants' perceptions of care integration, expectations and satisfaction with the program; and participants' compliance with the fall prevention program. Finally, professionals at intervention sites will participate in focus groups to identify barriers and facilitating factors for the integrated fragility fracture prevention program.This integrated program will facilitate knowledge translation and dissemination via the following: involvement of various collaborators during the development and set-up of the integrated program; distribution of pamphlets about osteoporosis and fall prevention strategies to primary care physicians in the intervention group and patients in the control group; participation in evaluation activities; and eventual dissemination of study results.Study/trial registration: Clinical Trial.Gov NCT01745068Study ID number: CIHR grant # 267395.

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial.

PURPOSE: The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class. PATIENTS AND METHODS: Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination. RESULTS: Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054). CONCLUSION: RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.