Bayesian spatio-temporal modelling of tobacco-related cancer data in Switzerland

Tobacco use is the leading cause of preventable death worldwide. Each year the tobacco epidemic accounts for 6 million deaths and costs hundreds of billions of dollars to the economy. Cigarette smoking accounts for more deaths than AIDS, murder, legal and illegal drugs, road accidents and suicide combined. Around 85–90% of all lung cancer deaths are estimated to be attributed to active or passive smoking. In Switzerland, lung cancer is the first cause of cancer mortality in men and second in women (after breast cancer). Gender-specific smoking patterns differ essentially in time as well as in space. In the 19th and the beginning of the following century, smoking was restricted to the male population, finding its peak in the 1970s in most European countries. In the past, the image of female tobacco use experienced an essential turn. In the middle of the 20th century the smoking prevalence among women increased due to the changes in gender roles and the subsequent effect on female smoking reputation. Before, female smoking had not been socially accepted. After strong gender-related developments, female smoking was associated with independence, emancipation and freedom. This movement was exploited to a great extent by the tobacco industry by adjusting their marketing strategies regarding this new target audience. In many developed countries the gap between gender and smoking prevalence is closing since the last decades, as males are smoking less, while female tobacco smoking is increasing steadily. Information on spatial as well as temporal patterns and trends of a disease are essential for health planning and intervention purposes. The Swiss Federal Office of Public Health (FOPH) has launched the National Programme Tobacco 2008–2012 aiming to reduce the proportion of smokers, targeting a decline of tobacco-related morbidity and mortality in the country as a final result. Cancer mapping visualizes geographical and temporal patterns and trends. Maps of estimated mortality serve as helpful tools to identify high risk areas and therefore enable focused intervention planning at a higher geographical scale than the national one. Disease maps of crude rates can be non-informative and might even lead to misinterpretation, as rare diseases or small populations might dominate the map and result in large variability in the estimated rates. Distinction between chance and real difference of the obtained variability is challenging. Spatial modelling of the rates enables the assessment of covariate effects to explain observed patterns and highlight them by obtaining smooth maps. Bayesian methods are the state-of-the-art modelling approach for spatio-temporal analysis. They allow flexible modelling and inference and provide computational advantages via the implementation of Markov chain Monte Carlo (MCMC). Model formulations improve the estimates sparse, unstable rates by borrowing strength from their neighbours. In addition, they allow risk factor analysis which takes into account potential spatial correlation. Apart flexible modelling, Bayesian inference provide computational advantages via the implementation of Markov chain Monte Carlo simulation methods. This thesis aimed (i) to assess geographical differences and trends of age- and gender-specific lung and all tobacco-related cancer mortality in Switzerland; (ii) to project tobacco-related cancer mortality in Switzerland at different geographical levels accounting for spatial variation; (iii) to develop Bayesian age-period-cohort (APC) models for projecting cancer mortality data; (iv) to develop Bayesian back-calculation models to estimate age- and gender-specific incidence from sparse mortality data; and (v) to develop models to indirectly approximate gender-specific smoking patterns in space and time by unadjusted and adjusted lung cancer mortality rates with non-smoking risk factors

General practitioners' approaches to prostate-specific antigen testing in the north-east of the Netherlands

BACKGROUND: There is wide variation in clinical practice for the early detection of prostate cancer, not least because of the ongoing debate about the benefits of prostate-specific antigen (PSA) testing. In this study, we aimed to assess the approaches, attitudes, and knowledge of general practitioners (GPs) regarding PSA testing in primary care in the Netherlands, particularly regarding recommendations for prostate cancer. METHODS: Questionnaire surveys were sent to 179 GPs in the north-east of the Netherlands, of which 65 (36%) were completed and returned. We also surveyed 23 GPs attending a postgraduate train-the-trainer day (100%). In addition to demographic data and practice characteristics, the 31-item questionnaire covered the attitudes, clinical practice, adherence to PSA screening recommendations, and knowledge concerning the recommendations for prostate cancer early detection. Statistical analysis was limited to the descriptive level. RESULTS: Most GPs (95%; n = 82) stated that they had at least read the Dutch GP guideline, but just half (50%; n = 43) also stated that they knew the content. Almost half (46%; n = 39) stated they would offer detailed counseling before ordering a PSA test to an asymptomatic man requesting a test. Overall, prostate cancer screening was reported to be of minor importance compared to other types of cancer screening. CONCLUSIONS: Clinical PSA testing in primary care in this region of the Netherlands seems generally to be consistent with the relevant guideline for Dutch GPs that is restrictive to PSA testing. The next step will be to further evaluate the effects of the several PSA testing strategies

Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

BACKGROUND: Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. METHODS/DESIGN: The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. DISCUSSION: It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. TRIAL REGISTRATION: Clinical trials gov. number: NCT0111766

A Bayesian generalized age-period-cohort power model for cancer projections

Age-period-cohort (APC) models are the state of art in cancer projections, assessing past and recent trends and extrapolating mortality or incidence data into the future. Nordpred is a well-established software, assuming a Poisson distribution for the counts and a log-link or power-link function with fixed power; however, its predictive performance is poor for sparse data. Bayesian models with log-link function have been applied, but they can lead to extreme estimates. In this paper, we address criticisms of the aforementioned models by providing Bayesian formulations based on a power-link and develop a generalized APC power-link model, which assumes a random rather than fixed power parameter. In addition, a power model with a fixed power parameter of five was formulated in the Bayesian framework. The predictive performance of the new models was evaluated on Swiss lung cancer mortality data using model-based estimates of observed periods. Results indicated that the generalized APC power-link model provides best estimates for male and female lung cancer mortality. The gender-specific models were further applied to project lung cancer mortality in Switzerland during the periods 2009-2013 and 2014-2018. Copyright © 2014 John Wiley & Sons, Ltd

Sequential tests for monitoring methods to detect elevated incidence – a simulation study

BACKGROUND: Common cancer monitoring practice is seldom prospective and rather driven by public requests. This study aims to assess the performance of a recently developed prospective cancer monitoring method and the statistical tools used, in particular the sequential probability ratio test in regard to specificity, sensitivity, observation time and heterogeneity of size of the geographical unit. METHODS: A simulation study based on a predefined selection of cancer types, geographical unit and time period was set up. Based on the population structure of Lower Saxony the mean number of cases of three diagnoses were randomly assigned to the geographical units during 2008–2012. A two-stage monitoring procedure was then executed considering the standardized incidence ratio and sequential probability ratio test. Scenarios were constructed differing by the simulation of clusters, significance level and test parameter indicating a risk to be elevated. RESULTS: Performance strongly depended on the choice of the test parameter. If the expected numbers of cases were low, the significance level was not fully exhausted. Hence, the number of false positives was lower than the chosen significance level suggested, leading to a high specificity. Sensitivity increased with the expected number of cases and the amount of risk and decreased with the size of the geographical unit. CONCLUSIONS: The procedure showed some desirable properties and is ready to use for a few settings but demands adjustments for others. Future work might consider refinements of the geographical structure. Inhomogeneous unit size could be addressed by a flexible choice of the test parameter related to the observation time

Tobacco-related cancer mortality: projections for different geographical regions in Switzerland

PRINCIPLES: Switzerland is divided into 26 cantons of variable population size and cultural characteristics. Although a federal law to protect against passive smoking and a national tobacco control programme exist, details of tobacco-related policies are canton-specific. This study aimed to project gender-specific tobacco-related cancer mortality in Switzerland at different geographical levels for the periods 2009-2013 and 2014-2018. METHODS: In this analysis, data on Swiss tobacco-related cancer mortality from 1984 until 2008 were used. Bayesian age-period-cohort models were formulated to assess past trends of gender-specific tobacco-related cancer mortality and to project them up to 2018 at cantonal and language region levels. Furthermore, estimates are provided on a national scale by age categories of 50-69 and ≥70 years. RESULTS: Model-based estimates at cantonal level identified regions with low and high tobacco-related cancer mortality rates for the observed and projected periods. Our analysis based on language regions showed the lowest mortality in the German-speaking part. Projections at national level, between younger (age 50-69) and older (age ≥70) males, indicated an ongoing decreasing trend for males but an upward trend for females. The gap in tobacco-related cancer mortality rates between younger and older males seems to be shrinking. In females, a stronger rise was obtained for the younger age group. CONCLUSION: Our findings indicate region-, sex- and age-related differences in tobacco-related cancer mortality in Switzerland and this could be useful for healthcare planning and for evaluating the impact of canton-specific tobacco-related policies and interventions

Using lung cancer mortality to indirectly approximate smoking patterns in space

Smoking is the leading cause of lung cancer. Non-smoking factors have been associated with the disease. Existing Swiss survey data only capture the country partially and temporal coverage does not allow for a time lag between exposure to tobacco and lung cancer outbreak. Knowledge about the distribution of tobacco-use is essential to estimate its contribution to disease burden. Bayesian regression models were applied to estimate spatial smoking patterns. Data were provided from the Swiss Health Survey (14521 participants). Regression models with spatial random effects (SREs) were employed to obtain smoking proxies based on mortality rates and SREs adjusted for environmental exposures. Population attributable fractions were estimated to assess the burden of tobacco-use on lung cancer mortality. Correlation between observed smoking prevalence with smoking proxies was moderate and stronger in females. In the absence of sufficient survey data, smooth unadjusted mortality rates can be used to assess smoking patterns in Switzerland

Tinnitus and Headache

Background. Tinnitus and headache are frequent disorders. Here, we aimed to investigate whether the occurrence of headache among tinnitus patients is purely coincidental or whether tinnitus and headache are pathophysiologically linked. We investigated a large sample of patients with tinnitus and headache to estimate prevalence rates of different headache forms, to determine the relationship between tinnitus laterality and headache laterality, and to explore the relationship between tinnitus and headache over time. Method. Patients who presented at a tertiary referral center because of tinnitus and reported comorbid headache were asked to complete validated questionnaires to determine the prevalence of migraine and tension-type headache and to assess tinnitus severity. In addition, several questions about the relationship between headache and tinnitus were asked. Results. Datasets of 193 patients with tinnitus and headache were analysed. 44.6% suffered from migraine, 13% from tension-type headache, and 5.7% from both. Headache laterality was significantly related to tinnitus laterality and in the majority of patients fluctuations in symptom severity of tinnitus and headache were interrelated. Conclusion. These findings suggest a significant relationship between tinnitus and headache laterality and symptom interaction over time and argue against a purely coincidental cooccurrence of tinnitus and headache. Both disorders may be linked by common pathophysiological mechanisms