Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: dummy run and individual case review.

INTRODUCTION: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review.

INTRODUCTION: The phase III EORTC 22033-26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. METHODS: Fifty-eight institutions were asked to submit 1-2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. RESULTS: Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. CONCLUSIONS: Digital RT plan submission and review within the EORTC 22033-26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively.

EORTC Radiation Oncology Group quality assurance platform: establishment of a digital central review facility.

OBJECTIVE: Quality assurance (QA) in clinical trials is essential to ensure treatment is safely and effectively delivered. As QA requirements have increased in complexity in parallel with evolution of radiation therapy (RT) delivery, a need to facilitate digital data exchange emerged. Our objective is to present the platform developed for the integration and standardization of QART activities across all EORTC trials involving RT. METHODS: The following essential requirements were identified: secure and easy access without on-site software installation; integration within the existing EORTC clinical remote data capture system; and the ability to both customize the platform to specific studies and adapt to future needs. After retrospective testing within several clinical trials, the platform was introduced in phases to participating sites and QART study reviewers. RESULTS: The resulting QA platform, integrating RT analysis software installed at EORTC Headquarters, permits timely, secure, and fully digital central DICOM-RT based data review. Participating sites submit data through a standard secure upload webpage. Supplemental information is submitted in parallel through web-based forms. An internal quality check by the QART office verifies data consistency, formatting, and anonymization. QART reviewers have remote access through a terminal server. Reviewers evaluate submissions for protocol compliance through an online evaluation matrix. Comments are collected by the coordinating centre and institutions are informed of the results. CONCLUSIONS: This web-based central review platform facilitates rapid, extensive, and prospective QART review. This reduces the risk that trial outcomes are compromised through inadequate radiotherapy and facilitates correlation of results with clinical outcomes.

Physical activity level and health-related quality of life in the general adult population: a systematic review.

OBJECTIVE: Little is known regarding health-related quality of life and its relation with physical activity level in the general population. Our primary objective was to systematically review data examining this relationship. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL, and PsycINFO for health-related quality of life and physical activity related keywords in titles, abstracts, or indexing fields. RESULTS: From 1426 retrieved references, 55 citations were judged to require further evaluation. Fourteen studies were retained for data extraction and analysis; seven were cross-sectional studies, two were cohort studies, four were randomized controlled trials and one used a combined cross sectional and longitudinal design. Thirteen different methods of physical activity assessment were used. Most health-related quality of life instruments related to the Medical Outcome Study SF-36 questionnaire. Cross-sectional studies showed a consistently positive association between self-reported physical activity and health-related quality of life. The largest cross-sectional study reported an adjusted odds ratio of "having 14 or more unhealthy days" during the previous month to be 0.40 (95% Confidence Interval 0.36-0.45) for those meeting recommended levels of physical activity compared to inactive subjects. Cohort studies and randomized controlled trials tended to show a positive effect of physical activity on health-related quality of life, but similar to the cross-sectional studies, had methodological limitations. CONCLUSION: Cross-sectional data showed a consistently positive association between physical activity level and health-related quality of life. Limited evidence from randomized controlled trials and cohort studies precludes a definitive statement about the nature of this association.

Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011.

BACKGROUND AND PURPOSE: Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. METHODS: A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990-April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I(2), and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. RESULTS: 60 studies with 9845 patients harbouring 10 845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I(2)=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I(2)=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. CONCLUSIONS: In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

Femtosecond-laser assisted cataract surgery: a review.

Introduced in 2008, the femtosecond laser is a promising new technological advance which plays an ever increasing role in cataract surgery where it automates the three main surgical steps: corneal incision, capsulotomy and lens fragmentation. The proven advantages over manual surgery are: a better quality of incision with reduced induced astigmatism; increased reliability and reproducibility of the capsulotomy with increased stability of the implanted lens; a reduction in the use of ultrasound. Regarding refractive results or safety, however, no prospective randomized study to date has shown significant superiority compared with standard manual technique. The significant extra cost generated by this laser, undertaken by the patient, is a limiting factor for both its use and study. This review outlines the potential benefits of femtosecond-laser-assisted cataract surgery due to the automation of key steps and the safety of this new technology.

Alcohol Brief Intervention in Primary Care: A Systematic Review

BACKGROUND: The purpose of the present review was to evaluate the evidence of the effectiveness of brief interventions aimed at reducing chronic alcohol use and harm related to alcohol consumption, conducted among individuals actively attending primary care but who were not seeking help for alcohol problems. METHODS: Randomised trials reporting at-least one outcome related to alcohol consumption and conducted in outpatients who were actively attending primary care centre or provider were selected using Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of the retrieved references and previous reviews. Selection and data abstraction were performed independently and in duplicate. We assessed validity of the studies and performed a meta-analysis for studies reporting alcohol consumption at 6 or 12 months follow up. RESULTS: We included 24 reports, reporting results of 19 trials and including 5,639 individuals. Seventeen trials reported a measure of alcohol consumption, eight reporting a significant effect of intervention. The meta-analysis showed a mean pooled difference of -41 (95% CI: −54; −28) g of pure ethanol per week in favour of brief intervention group. Evidences for other outcomes (laboratory values, health related quality of life, morbidity and mortality, health care utilisation) were inconclusive. CONCLUSION: Our systematic review indicated that brief intervention might be effective for both men and women in reducing alcohol consumption compared to a controlled intervention, in a primary health care population. The meta-analysis confirmed the reduction in alcohol consumption at 6 and 12 month. Further research should precise the components of effectiveness of brief intervention and the evidence of effects on morbidity, mortality, and quality of life related outcomes.

β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3).

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening complications in patients with hemato-oncological malignancies, and early diagnosis is crucial for outcome. The compound 1,3-β-D-glucan (BG), a cell wall component of most fungal species, can be detected in blood during IFI. Four commercial BG antigenemia assays are available (Fungitell, Fungitec-G, Wako, and Maruha). This meta-analysis from the Third European Conference on Infections in Leukemia (ECIL-3) assessed the performance of BG assays for the diagnosis of IFI in hemato-oncological patients. METHODS: Studies reporting the performance of BG antigenemia assays for the diagnosis of IFI (European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria) in hemato-oncological patients were identified. The analysis was focused on high-quality cohort studies with exclusion of case-control studies. Meta-analysis was performed by conventional meta-analytical pooling and bivariate analysis. RESULTS: Six cohort studies were included (1771 adult patients with 414 IFIs of which 215 were proven or probable). Similar performance was observed among the different BG assays. For the cutoff recommended by the manufacturer, the diagnostic performance of the BG assay in proven or probable IFI was better with 2 consecutive positive test results (diagnostic odds ratio for 2 consecutive vs one single positive results, 111.8 [95% confidence interval {CI}, 38.6-324.1] vs 16.3 [95% CI, 6.5-40.8], respectively; heterogeneity index for 2 consecutive vs one single positive results, 0% vs 72.6%, respectively). For 2 consecutive tests, sensitivity and specificity were 49.6% (95% CI, 34.0%-65.3%) and 98.9% (95% CI, 97.4%-99.5%), respectively. Estimated positive and negative predictive values for an IFI prevalence of 10% were 83.5% and 94.6%, respectively. CONCLUSIONS: Different BG assays have similar accuracy for the diagnosis of IFI in hemato-oncological patients. Two consecutive positive antigenemia assays have very high specificity, positive predictive value, and negative predictive value. Because sensitivity is low, the test needs to be combined with clinical, radiological, and microbiological findings.

Clinician characteristics, communication, and patient outcome in oncology: a systematic review.

OBJECTIVE: The aim of this study was to review the literature on clinician characteristics influencing patient-clinician communication or patient outcome in oncology. METHODS: Studies investigating the association of clinician characteristics with quality of communication and with outcome for adult cancer patients were systematically searched in MEDLINE, PSYINFO, PUBMED, EMBASE, CINHAL, Web of Science and The Cochrane Library up to November 2012. We used the preferred reporting items for systematic reviews and meta-analyses statement to guide our review. Articles were extracted independently by two of the authors using predefined criteria. RESULTS: Twenty seven articles met the inclusion criteria. Clinician characteristics included a variety of sociodemographic, relational, and personal characteristics. A positive impact on quality of communication and/or patient outcome was reported for communication skills training, an external locus of control, empathy, a socioemotional approach, shared decision-making style, higher anxiety, and defensiveness. A negative impact was reported for increased level of fatigue and burnout and expression of worry. Professional experience of clinicians was not related to communication and/or to patient outcome, and divergent results were reported for clinician gender, age, stress, posture, and confidence or self-efficacy. CONCLUSIONS: Various clinician characteristics have different effects on quality of communication and/or patient outcome. Research is needed to investigate the pathways leading to effective communication between clinicians and patients. Copyright © 2013 John Wiley & Sons, Ltd.

Contrôle de la qualité des soins: aspects épidémiologiques. [Quality control of health care: epidemiological aspects].

Quality control in health care should be performed by health professionals. To do so they must define indicators, set up studies aimed at measuring and analyzing quality of care, and implement quality assurance programs in health care systems. The elements of a quality improvement program of this kind are described, with special emphasis on the contribution of epidemiology in this field.

Alexithymia in cancer patients: review of the literature.

Objective: To summarize the literature on alexithymia in cancer patients. Methods: The empirical literature published between 1972 and January 2010 was searched through MEDLINE, PSYINFO, EMBASE and the Cochrane Library. Key words were: alexithymia, affective symptoms, cancer, neoplasms. Results: The search identified 16 relevant studies which are methodologically problematic and show conflicting results. However, several interesting hypotheses emerge such as a possible link between alexithymia and the immune system, between alexithymia and quality of life, or between alexithymia, anxiety and depression. The question to what degree alexithymia in cancer patients is a trait or a state cannot be answered by these studies. Conclusions: A lack of methodologically sound studies and the large variations of results among studies suggest that the role of alexithymia in patients with cancer deserves more systematic research. Consequently, studies are needed which investigate the nature (state or trait) of alexithymia, its impact on cancer development and progression, as well as its influence on compliance and on the underestimation of psychological distress and psychiatric outcome in cancer patients.

The effectiveness of brief alcohol interventions in primary care settings: a systematic review.

Issues. Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. We also hand-searched the reference lists of key articles and reviews. We included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted. Key Findings. The primary meta-analysis included 22 RCT and evaluated outcomes in over 5800 patients. At 1 year follow up, patients receiving brief intervention had a significant reduction in alcohol consumption compared with controls [mean difference: -38 g week(-1), 95%CI (confidence interval): -54 to -23], although there was substantial heterogeneity between trials (I(2) = 57%). Subgroup analysis confirmed the benefit of brief intervention in men but not in women. Extended intervention was associated with a non-significantly increased reduction in alcohol consumption compared with brief intervention. There was no significant difference in effect sizes for efficacy and effectiveness trials. Conclusions. Brief interventions can reduce alcohol consumption in men, with benefit at a year after intervention, but they are unproven in women for whom there is insufficient research data. Longer counselling has little additional effect over brief intervention. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature is relevant to routine primary care.

Paper 3: EUROCAT data quality indicators for population-based registries of congenital anomalies.

The European Surveillance of Congenital Anomalies (EUROCAT) network of population-based congenital anomaly registries is an important source of epidemiologic information on congenital anomalies in Europe covering live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. EUROCAT's policy is to strive for high-quality data, while ensuring consistency and transparency across all member registries. A set of 30 data quality indicators (DQIs) was developed to assess five key elements of data quality: completeness of case ascertainment, accuracy of diagnosis, completeness of information on EUROCAT variables, timeliness of data transmission, and availability of population denominator information. This article describes each of the individual DQIs and presents the output for each registry as well as the EUROCAT (unweighted) average, for 29 full member registries for 2004-2008. This information is also available on the EUROCAT website for previous years. The EUROCAT DQIs allow registries to evaluate their performance in relation to other registries and allows appropriate interpretations to be made of the data collected. The DQIs provide direction for improving data collection and ascertainment, and they allow annual assessment for monitoring continuous improvement. The DQI are constantly reviewed and refined to best document registry procedures and processes regarding data collection, to ensure appropriateness of DQI, and to ensure transparency so that the data collected can make a substantial and useful contribution to epidemiologic research on congenital anomalies.