Comparison of four tumor markers at the RNA and protein level for the detection of micrometastases and disseminated tumor cells in lymph nodes of patients with cervical carcinoma

Lymph node status is the key prognostic factor for disease recurrence and patient mortality among cervical cancer patients. Patients with positive lymph nodes (pN1) have a high risk for recurrence. However, 15% of treated patients suffer recurrent disease although their lymph nodes have no evident metastases or micrometastases (pN0). The presence of occult tumor cells or tumor cell clusters smaller than micrometastases (<0.2mm) in lymph nodes could be the reason for poor prognosis of these patients. The goal of this dissertation is the detection of occult tumor cells and clusters in lymph nodes by using different molecular tumor markers and the measurement of the reliability on each marker by comparing them to each other. A highly sensitive, and at the same time, specific detection of these tumor cells is a prerequisite for further research confirming the clinical importance of occult tumor cells in lymph nodes. In this study, immunohistochemical staining (IHC) and reverse transcription nested PCR (RT-PCR) were used to detect metastatic tumor cells or clusters in sentinel lymph nodes (SLN) of 48 patients with primary cervical cancer. 120 lymph nodes were evaluated. IHC was performed with a pan-reactive antibody against cytokeratins (AE1/3), an antibody against CK19 and an antibody against p16INK4a. The latter protein, which is a surrogate marker of viral oncogene activity, is invariably upregulated in cervical cancers. Moreover, the viral oncogene (HPV-mRNA) activity was directly detected by RT-PCR

Determinants of Sickness Absence and Return to Work Among Employees with Common Mental Disorders:A Scoping Review

Purpose To present an overview of the existing evidence on prognostic factors of (recurrent) sickness absence (SA) and return to work (RTW) among workers with a common mental disorder (CMD). This scoping review provides information about determinants for SA and RTW, which could be used to develop better interventions aimed at the prevention of SA and promotion of RTW among workers with a CMD. Methods Relevant articles were identified in PubMed, Embase, PsycINFO, PSYNDEX, and SINGLE up to October 2016. In order to be included, studies should provide insight into prognostic factors of SA or RTW of workers with a CMD. We classified all factors according to the domains of the International Classification of Functioning, Disability and Health. Results Our searches identified 2447 possible relevant articles, of which 71 were included for data extraction. There is consistent evidence in >= 3 studies that previous episodes of CMD, higher symptom severity, previous absenteeism, co-morbidity, high job demands, low job control, high job strain, female gender, lower educational level, smoking behavior, and low perceived general health are predictors of SA in people with CMDs. Earlier RTW is consistently predicted by lower symptom severity, having no previous absenteeism, younger age, and positive expectations concerning sick-leave duration or RTW. Conclusions The amount of research on determinants for SA and RTW in workers with CMD has increased dramatically in recent years, although most studies are from the Netherlands and Scandinavia. There are some research gaps identified in this scoping review that need further attention in primary and secondary studies. Based on the summary of the evidence, we provide guidance for policy, practice and research

Resuming the discussion of AMSTAR: What can (should) be made better?

Abstract Background Evidence syntheses, and in particular systematic reviews (SRs), have become one of the cornerstones of evidence-based health care. The Assessment of Multiple Systematic Reviews (AMSTAR) tool has become the most widely used tool for investigating the methodological quality of SRs and is currently undergoing revision. The objective of this paper is to present insights, challenges and potential solutions from the point of view of a group of assessors, while referring to earlier methodological discussions and debates with respect to AMSTAR. Discussion One major drawback of AMSTAR is that it relies heavily on reporting quality rather than on methodological quality. This can be found in several items. Furthermore, it should be acknowledged that there are now new methods and procedures that did not exist when AMSTAR was developed. For example, the note to item 1 should now refer to the International Prospective Register of Ongoing Systematic Reviews (PROSPERO). Furthermore, item 3 should consider the definition of hand-searching, as the process of reviewing conference proceedings using the search function (e.g. in Microsoft Word or in a PDF file) does not meet the definition set out by the Cochrane Collaboration. Moreover, methods for assessing the quality of the body of evidence have evolved since AMSTAR was developed and should be incorporated into a revised AMSTAR tool. Summary Potential solutions are presented for each AMSTAR item with the aim of allowing a more thorough assessment of SRs. As the AMSTAR tool is currently undergoing further development, our paper hopes to add to preceding discussions and papers regarding this tool and stimulate further discussion

Inter-rater reliability of AMSTAR is dependent on the pair of reviewers

Abstract Background Inter-rater reliability (IRR) is mainly assessed based on only two reviewers of unknown expertise. The aim of this paper is to examine differences in the IRR of the Assessment of Multiple Systematic Reviews (AMSTAR) and R(evised)-AMSTAR depending on the pair of reviewers. Methods Five reviewers independently applied AMSTAR and R-AMSTAR to 16 systematic reviews (eight Cochrane reviews and eight non-Cochrane reviews) from the field of occupational health. Responses were dichotomized and reliability measures were calculated by applying Holsti’s method (r) and Cohen’s kappa (κ) to all potential pairs of reviewers. Given that five reviewers participated in the study, there were ten possible pairs of reviewers. Results Inter-rater reliability varied for AMSTAR between r = 0.82 and r = 0.98 (median r = 0.88) using Holsti’s method and κ = 0.41 and κ = 0.69 (median κ = 0.52) using Cohen’s kappa and for R-AMSTAR between r = 0.77 and r = 0.89 (median r = 0.82) and κ = 0.32 and κ = 0.67 (median κ = 0.45) depending on the pair of reviewers. The same pair of reviewers yielded the highest IRR for both instruments. Pairwise Cohen’s kappa reliability measures showed a moderate correlation between AMSTAR and R-AMSTAR (Spearman’s ρ =0.50). The mean inter-rater reliability for AMSTAR was highest for item 1 (κ = 1.00) and item 5 (κ = 0.78), while lowest values were found for items 3, 8, 9 and 11, which showed only fair agreement. Conclusions Inter-rater reliability varies widely depending on the pair of reviewers. There may be some shortcomings associated with conducting reliability studies with only two reviewers. Further studies should include additional reviewers and should probably also take account of their level of expertise

Additional file 1: of Inter-rater reliability of AMSTAR is dependent on the pair of reviewers

Appendix 1 Search strategy in PubMed. (DOCX 11 kb

Additional file 2: of Inter-rater reliability of AMSTAR is dependent on the pair of reviewers

Appendix 2: overview of included systematic reviews. (DOCX 17 kb