Funnel plots for population‐based cancer survival: principles,methods and applications

Funnel plots are graphical tools designed to detect excessive variation in performance indicators by simple visual inspection of the data. Their main use in the biomedical domain so far has been to detect publication bias in meta‐analyses, but they have also been recommended as the most appropriate way to display performance indicators for a vast range of health‐related outcomes. Here, we extend the use of funnel plots to population‐based cancer survival and several related measures. We present three applications to familiarise the reader with their interpretation. We propose funnel plots for various cancer survival measures, as well as age‐standardised survival, trends in survival and excess hazard ratios. We describe the components of a funnel plot and the formulae for the construction of the control limits for each of these survival measures. We include three transformations to construct the control limits for the survival function: complementary log–log, logit and logarithmic transformations. We present applications of funnel plots to explore the following: (i) small‐area and temporal variation in cancer survival; (ii) racial and geographical variation in cancer survival; and (iii) geographical variation in the excess hazard of death. Funnel plots provide a simple and informative graphical tool to display geographical variation and trend in a range of cancer survival measures. We recommend their use as a routine instrument for cancer survival comparisons, to inform health policy makers in planning and assessing cancer policies. We advocate the use of the complementary log–log or logit transformation to construct the control limits for the survival function. Copyright © 2013 John Wiley & Sons, Ltd.     

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA)/Shoenfeld’s syndrome: descriptive analysis of 300 patients from the international ASIA syndrome registry

Clinical Rheumatology - The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a recently identified condition in which the exposure to an adjuvant leads to an aberrant autoimmune...     

bcl-1 REARRANGEMENT AND CYCLIN D1 PROTEIN EXPRESSION IN MANTLE CELL LYMPHOMA

Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1–S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas ( n =40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL.     

Prevalence of viral hepatitis B and C in riverside communities of the Tucuruí Dam,Pará, Brazil

Epidemiologically, the relevance of infection caused by hepatitis viruses is related mainly to their wide geographic distribution and the large number of infected individuals in all parts of the world. In this study, 668 residents from the islands around the Tucuruí Dam were selected. Blood samples were collected for investigation of serological markers (HBsAg, total anti‐HBc, anti‐HBS, and anti‐HCV) by enzyme immunoassays. HCV‐positive subjects were tested using RT‐PCR and RFLP for the identification of viral genotypes. Among the 668 subjects studied, 1.9% were HBsAg positive, 28% were total anti‐HBc positive, and 41.9% were anti‐HBs positive. The anti‐HBs marker alone (vaccine response) was detected in 25.7% of the volunteers. Anti‐HCV antibody was detected in 2.2% of the subjects and genotype 1 was the predominant genotype (70%). The results indicate an intermediate level of HBV and HCV endemicity in the region studied, as well as low HBV vaccination coverage. J. Med. Virol. 84:1907–1912, 2012. © 2012 Wiley Periodicals, Inc.     

Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.      

Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology

Background

Patients under haemodialysis are considered at high risk to acquire hepatitis B virus (HBV) infection. Since few data are reported from Brazil, our aim was to assess the frequency and risk factors for HBV infection in haemodialysis patients from 22 Dialysis Centres from Santa Catarina State, south of Brazil.

Methods

This study includes 813 patients, 149 haemodialysis workers and 772 healthy controls matched by sex and age. Serum samples were assayed for HBV markers and viraemia was detected by nested PCR. HBV was genotyped by partial S gene sequencing. Univariate and multivariate statistical analyses with stepwise logistic regression analysis were carried out to analyse the relationship between HBV infection and the characteristics of patients and their Dialysis Units.

Results

Frequency of HBV infection was 10.0%, 2.7% and 2.7% among patients, haemodialysis workers and controls, respectively. Amidst patients, the most frequent HBV genotypes were A (30.6%), D (57.1%) and F (12.2%). Univariate analysis showed association between HBV infection and total time in haemodialysis, type of dialysis equipment, hygiene and sterilization of equipment, number of times reusing the dialysis lines and filters, number of patients per care-worker and current HCV infection. The logistic regression model showed that total time in haemodialysis, number of times of reusing the dialysis lines and filters, and number of patients per worker were significantly related to HBV infection.

Conclusions

Frequency of HBV infection among haemodialysis patients at Santa Catarina state is very high. The most frequent HBV genotypes were A, D and F. The risk for a patient to become HBV positive increase 1.47 times each month of haemodialysis; 1.96 times if the dialysis unit reuses the lines and filters ≥ 10 times compared with haemodialysis units which reuse < 10 times; 3.42 times if the number of patients per worker is more than five. Sequence similarity among the HBV S gene from isolates of different patients pointed out to nosocomial transmission.