Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial.

Purpose: We evaluated the feasibility of biomarker development in the context of multicenter clinical trials.

Experimental Design: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from a prospective adjuvant colon cancer trial (PETACC3). DNA was isolated from tumor as well as normal tissue and used for analysis of microsatellite instability, KRAS and BRAF genotyping, UGT1A1 genotyping, and loss of heterozygosity of 18 q loci. Immunohistochemistry was used to test expression of TERT, SMAD4, p53, and TYMS. Messenger RNA was retrieved and tested for use in expression profiling experiments.

Results: Of the 3,278 patients entered in the study, FFPE blocks were obtained from 1,564 patients coming from 368 different centers in 31 countries. In over 95% of the samples, genomic DNA tests yielded a reliable result. Of the immmunohistochemical tests, p53 and SMAD4 staining did best with reliable results in over 85% of the cases. TERT was the most problematic test with 46% of failures, mostly due to insufficient tissue processing quality. Good quality mRNA was obtained, usable in expression profiling experiments.

Conclusions: Prospective clinical trials can be used as framework for biomarker development using routinely processed FFPE tissues. Our results support the notion that as a rule, translational studies based on FFPE should be included in prospective clinical trials.

Establishing a minimum dataset for prospective registration of systematic reviews: an international consultation

Background: In response to growing recognition of the value of prospective registration of systematic review protocols, we planned to develop a web-based open access international register. In order for the register to fulfil its aims of reducing unplanned duplication, reducing publication bias, and providing greater transparency, it was important to ensure the appropriate data were collected. We therefore undertook a consultation process with experts in the field to identify a minimum dataset for registration. Methods and Findings: A two-round electronic modified Delphi survey design was used. The international panel surveyed included experts from areas relevant to systematic review including commissioners, clinical and academic researchers, methodologists, statisticians, information specialists, journal editors and users of systematic reviews. Direct invitations to participate were sent out to 315 people in the first round and 322 in the second round. Responses to an open invitation to participate were collected separately. There were 194 (143 invited and 51 open) respondents with a 100% completion rate in the first round and 209 (169 invited and 40 open) respondents with a 91% completion rate in the second round. In the second round, 113 (54%) of the participants reported having previously taken part in the first round. Participants were asked to indicate whether a series of potential items should be designated as optional or required registration items, or should not be included in the register. After the second round, a 70% or greater agreement was reached on the designation of 30 of 36 items. Conclusions: The results of the Delphi exercise have established a dataset of 22 required items for the prospective registration of systematic reviews, and 18 optional items. The dataset captures the key attributes of review design as well as the administrative details necessary for registration.

Lipoprotein-associated phospholipase A(2), inflammatory biomarkers, and risk of cardiovascular disease in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Objective: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an inflammatory biomarker that circulates mainly bound to LDL. We evaluated the association of Lp-PLA(2) with vascular events in the elderly where the importance of LDL is diminished as a risk factor for coronary disease.

Organisational merger and psychiatric morbidity: a prospective study in a changing work organisation

Background Prospective studies on the relationship between organisational merger and mental health have been conducted using subjective health indicators. The objective of this prospective occupational cohort study was to examine whether a negative change during an organisational merger is an independent predictive factor of psychiatric morbidity.

Prospective study of workplace social capital and depression: are vertical and horizontal components equally important?

Background Recent studies have emphasised the multidimensional nature of the social capital concept, but it is not known whether the health effects of social capital vary by dimension. The objective of this study was to examine the vertical component (ie, respectful and trusting relationships across power differentials at work) and the horizontal component of workplace social capital (trust and reciprocity between employees at the same hierarchical level) as risk factors for subsequent depression.

Burnout as a predictor of all-cause mortality among industrial employees: A 10-year prospective register-linkage study

Objective: Burnout, a psychological consequence of prolonged work stress, has been shown to coexist with physical and mental disorders. The aim of this study was to investigate whether burnout is related to all-cause mortality among employees. Methods: In 1996, of 15,466 Finnish forest industry employees, 9705 participated in the 'Still Working' study and 8371 were subsequently identified from the National Population Register. Those who had been treated in a hospital for the most common causes of death prior to the assessment of burnout were excluded on the basis of the Hospital Discharge Register, resulting in a final study population of 7396 people. Burnout was measured using the Maslach Burnout Inventory-General Survey. Dates of death from 1996 to 2006 were extracted from the National Mortality Register. Mortality was predicted with Cox hazard regression models, controlling for baseline sociodemographic factors and register-based health status according to entitled medical reimbursement and prescribed medication for mental health problems, cardiac risk factors, and pain problems. Results: During the 10-year 10-month follow-up, a total of 199 employees had died. The risk of mortality per one-unit increase in burnout was 35% higher (95% CI 1.07-1.71) for total score and 26% higher (0.99-1.60) for exhaustion, 29% higher for cynicism (1.03-1.62), and 22% higher for diminished professional efficacy (0.96-1.55) in participants who had been under 45 at baseline. After adjustments, only the associations regarding burnout and exhaustion were statistically significant. Burnout was not related to mortality among the older employees. Conclusion: Burnout, especially work-related exhaustion, may be a risk for overall survival. (C) 2010 Elsevier Inc. All rights reserved.

School Neighborhood Disadvantage as a Predictor of Long-Term Sick Leave Among Teachers: Prospective Cohort Study

This ongoing prospective study examined characteristics of school neighborhood and neighborhood of residence as predictors of sick leave among school teachers. School neighborhood income data for 226 lower-level comprehensive schools in 10 towns in Finland were derived from Statistics Finland and were linked to register-based data on 3,063 teachers with no long-term sick leave at study entry. Outcome was medically certified (> 9 days) sick leave spells during a mean follow-up of 4.3 years from data collection in 2000-2001. A multilevel, cross-classified Poisson regression model, adjusted for age, type of teaching job, length and type of job contract, school size, baseline health status, and income level of the teacher's residential area, showed a rate ratio of 1.30 (95% confidence interval: 1.03, 1.63) for sick leave among female teachers working in schools located in low-income neighborhoods compared with those working in high-income neighborhoods. A low income level of the teacher's residential area was also independently associated with sick leave among female teachers (rate ratio = 1.50, 95% confidence interval: 1.18, 1.91). Exposure to both low-income school neighborhoods and low-income residential neighborhoods was associated with the greatest risk of sick leave (rate ratio = 1.71, 95% confidence interval: 1.27, 2.30). This study indicates that working and living in a socioeconomically disadvantaged neighborhood is associated with increased risk of sick leave among female teachers.

Sense of coherence and psychiatric morbidity: a 19-year register-based prospective study

Background Most prospective studies on the relationship between sense of coherence (SOC) and mental health have been conducted using subjective health indicators and short-term follow-ups. The objective of this prospective occupational cohort study was to examine whether a strong sense of coherence is a protective factor against psychiatric disorders over a long period of time.

Engagement in cultural activities and cause-specific mortality: Prospective cohort study

Objective. To determine the relation between engagement in cultural activities and main causes of mortality among full-time employees.

Lack of Predictability at Work and Risk of Acute Myocardial Infarction: An 18-Year Prospective Study of Industrial Employees

Objectives. We examined whether the distinctive components of job control-decision authority, skill discretion, and predictability-were related to subsequent acute myocardial infarction (MI) events in a large population of initially heart disease-free industrial employees.

Sense of coherence and diabetes: A prospective occupational cohort study

Background: Sense of coherence (SOC) is an individual characteristic related to a positive life orientation leading to effective coping. A weak SOC has been associated with indicators of general morbidity and mortality. However, the relationship between SOC and diabetes has not been studied in prospective design. The present study prospectively examined the relationship between a weak SOC and the incidence of diabetes.