Recruiting former melanoma patients via hospitals in comparison to office-based dermatologists in a register-based cohort study that required indirect contact.

BACKGROUND: There are detailed reviews about different recruitment strategies, but not with regard to differences between recruitment of hospital-based versus office-based physicians. Within this study, the two different recruitment schemes are compared. Advantages and disadvantages of different ways of recruitment in registry-based studies are discussed. METHODS: In a cross-sectional cancer-registry-based study, long-term melanoma patients were contacted by dermatologists rather than directly by the registry on the basis of the legal situation. Logistic regression models and generalized estimating equations were used to assess effects of various patient and physician characteristics on participation and data quality. Especially differences between hospital-based versus office-based dermatologists are evaluated. RESULTS: Seventy two out of 112 contacted dermatologists took part in the study (64.3%). The cooperation proportion was 52.2% (689 participants/1320 contacted patients). Participants and non-participants differed regarding age and sex, but not regarding other social demographic factors and cancer stage. We did not observe a difference in patient participation between hospital-based versus office-based dermatologists (OR 1.08 [CI 0.84-1.39]; p = 0.57). However, medical data provided by the cancer registry were better for participants registered and recruited by hospitals. CONCLUSIONS: In cohort studies with epidemiological cancer registries, recruitment via physicians has potential disadvantages and is more complex. If this indirect way of contact is mandatory, we recommend recruitment procedures including hospital-based rather than office-based physicians. However, physician characteristics were not associated with outcome.

Cardiac MR enables diagnosis in 90% of patients with acute chest pain, elevated biomarkers and unobstructed coronary arteries.

OBJECTIVE: To assess the diagnostic value of cardiac MRI (CMR) in patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram. METHODS: This study included a total of 125 patients treated in the chest pain unit during a 39-month period. Each included patient underwent MRI within a median of 3 days after cardiac catheterization. The MRI protocol comprised cine, oedema-sensitive and late gadolinium-enhancement imaging. The standard of reference was a consensus diagnosis based on clinical follow-up and the synopsis of all clinical, laboratory and imaging data. RESULTS: MRI revealed a multitude of diagnoses, including ischaemic cardiomyopathy (CM), dilated CM, myocarditis, Takotsubo CM, hypertensive heart disease, hypertrophic CM, cardiac amyloidosis and non-compaction CM. MRI-based diagnoses were the same as the final reference diagnoses in 113/125 patients (90%), with the two diagnoses differing in only 12/125 patients. In two patients, no final diagnosis could be established. CONCLUSION: CMR performed early after the onset of symptoms revealed a broad spectrum of diseases. CMR delivered a correct final diagnosis in 90% of patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram. ADVANCES IN KNOWLEDGE: Diagnosing patients with acute coronary syndrome but unobstructed coronary arteries remains a challenge for cardiologists. CMR performed early after catheterization reveals a broad spectrum of diseases with only a simple and quick examination protocol, and there is a high concordance between MRI-based diagnoses and final reference diagnoses.

[Changes in Incidence and Mortality Trends of Head and Neck Cancer in Rhineland-Palatinate, 2000-2009]. / Veränderung von Inzidenz und Mortalität von Kopf-Hals-Malignomen in Rheinland-Pfalz, 2000-2009.

BACKGROUND: Epidemiological data on HNC are often reported aggregated despite their anatomical and histological heterogeneity. In Germany, few studies have analyzed incidence and mortality trends separately for specific anatomic sites. Furthermore, little is known about whether the incidence of HPV-associated tumour entities of the head and neck region has increased. METHODS: Based on cancer registry data from Rhineland-Palatinate from 2000 to 2009, age-standardized incidence and mortality rates were calculated for all HNC sites and localisation groups that might be HPV-associated according to the literature. Trends were analyzed by Joinpoint regression and reported as the annual percentage change (APC). RESULTS: Throughout the study period, 8 055 incident cases and 3 177 deaths were identified. The incidence rates of overall HNC increased among women (APC:+2.2%) and declined slightly among men (- 0.9%). Significantly increasing incidence rates among women were seen for tumours of the oral cavity (+2.7%) and the oropharynx (+3.6%). Among men, a significant decrease in incidence rates for tumours of the hypopharynx (-3.4%) and the larynx (-2.7%) are noteworthy. Cancers at HPV-associated sites showed increased incidence rates in men (+3.3%) and women (+4.3%). A decrease in mortality was found for tumours of the larynx in both sexes (-5.8% men,-9.1% women). CONCLUSIONS: A detailed analysis by localisation of HNC showed significant and often opposing trends for men and women regarding incidence and mortality.

Survival after a diagnosis of testicular germ cell cancers in Germany and the United States, 2002-2006: a high resolution study by histology and age.

INTRODUCTION: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002-2006 and to compare these estimates between countries. METHODS: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997-2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. RESULTS: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. DISCUSSION: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients.

[Data quality or differences in oncological care? - standards of reporting for cancer survival analyses based on registry data]. / Datenqualität oder Unterschiede in der onkologischen Versorgung? - Berichtsstandards für Überlebenszeitanalysen mit Krebsregisterdaten.

BACKGROUND: The results of population-based cancer survival analyses are essential criteria with regard to the evaluation of oncological care. Their use and their interpretation as such require knowledge and transparency with regard to the data basis in order to avoid inadequate conclusions. METHOD: The working group 'survival analysis' of the Association of Population-Based Cancer Registries in Germany (GEKID) has identified factors within cancer registration and data evaluation which may distort population-based cancer survival analyses to a relevant degree. Recommendations in terms of standards of reporting were developed by mutual consent following empirical studies and discussions within GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and to be presented within the scope of population-based survival analyses. CONCLUSIONS: Referring to the "standards of reporting concerning population-based cancer survival analyses" introduced by GEKID there is a proposal on data transparency on hand, which might contribute substantially to the assessability of outcome quality in oncological care.

Survival from colorectal cancer in Germany in the early 21st century.

BACKGROUND: Colorectal cancer is the most common cancer in Germany and the second most common cause of cancer-related deaths in both men and women. The aim of this study is to provide detailed analysis of recent developments in survival of colorectal cancer patients using newly available data on a national basis. METHODS: We included data from 11 German cancer registries covering a population of 33 million inhabitants. Period analysis and modelled period analysis were used to provide most up-to-date estimates of 5-year relative survival in 2002-2006. RESULTS: The analysis was based on records of 164 996 colorectal cancer patients. Five-year relative survival was 63.0% overall, decreased with age and was significantly higher among women than among men in patients under 75 years. Overall age-adjusted 5-year relative survival increased from 60.6 to 65.0% over the period 2002-2006. Significant increase in survival was only observed in patients with localised or regional disease. Highest subsite-specific survival was observed in patients with cancer in descending (67.7%) and ascending (66.5%) colon. CONCLUSION: Survival of patients with colorectal cancer continued to increase in the early 21st century in Germany, with 5-year relative survival reaching 65% in 2006. However, lack of progress still persisted in patients with advanced disease.

Up-to-date results on survival of patients with melanoma in Germany.

BACKGROUND: Prior analyses of survival of patients with primary cutaneous malignant melanoma from Germany were based only on small populations and need to be updated. OBJECTIVES: We give a detailed overview of relative 5-year survival by sex, age group, histology, tumour stage and body site, and of time trends in a population of 33 million (40% of Germany), and compare survival in the federal states. METHODS: Conventional and model-based period analysis using the Ederer II method was applied to patients with melanoma diagnosed during 1997-2006 in Germany to assess 5-year relative survival (RS) rates and time trends. RESULTS: In total, 37,155 melanoma cases were included. Overall age-adjusted 5-year RS for the time period 2002-2006 was 91·9% for women and 87·0% for men. Survival differences by age group, histology, tumour stage and body site were found. No significant overall trend (2002-2006) was seen either in women or in men. Differences in survival between federal states were small; no clear pattern was seen. CONCLUSIONS: Based on the most recent and high-quality data from population-based cancer registries a comprehensive picture on melanoma survival in Germany was given. Survival from cutaneous malignant melanoma was high compared with other cancer sites and did not change during the analysed period 2002-2006. Patterns in melanoma survival by sex, age, tumour stage, histology and body site were in good agreement with previously published findings. No relevant differences between federal states were found.

Survival from common and rare cancers in Germany in the early 21st century.

BACKGROUND: Until recently, population-based data of cancer survival in Germany mostly relied on one registry covering ∼1 million people (1.3% of the German population). Here, we provide up-to-date cancer survival estimates for Germany based on data from 11 population-based cancer registries, covering 33 million people and compare them to survival estimates from the United States. PATIENTS AND METHODS: Cancer patients diagnosed in 1997-2006 were included. Period analysis was employed to calculate 5-year relative survival for 38 cancers for 2002-2006. German and USA survival rates were compared utilizing the Surveillance, Epidemiology and End Results 13 database. RESULTS: Five-year relative survival >80% was observed for testicular cancer (93.5%), skin melanoma (89.4%), cancers of the prostate (89.1%) and thyroid (87.8%), Hodgkin's lymphoma (84.5%) and cancers of the breast (83.7%) and endometrium (81.0%), which together account for almost 40% of cases. For the majority of cancers, German survival estimates were close to or below those in the United States. Exceptions with higher survival in Germany were cancers of the stomach, pancreas and kidney and Hodgkin's lymphoma. CONCLUSIONS: German cancer survival estimates are mostly higher than the 2000-2002 pan-European estimates. Further research is needed to investigate causes responsible for differences between German and USA cancer survival rates.

Meta-analysis of the relative efficiency of methionine-hydroxy-analogue-free-acid compared with DL-methionine in broilers using nonlinear mixed models.

The purpose of this paper was to perform a meta-analysis to compare the biological efficiency of DL-methionine with methionine-hydroxy-analogue-free-acid in broiler chickens. A database was developed which contained dose-response studies of these 2 methionine sources. Criteria for entry into the database were defined before the meta-analysis was initiated. Data from 46 dose-response experiments, extracted from a total of 27 peer-reviewed papers, were used for the analysis with the Statistical Analysis System. Initially, the NLIN procedure was applied to fit an exponential model of the form y = alpha + beta*[1 - exp (-Gamma*dose)] + e. Thereafter, meta-analysis was conducted by means of nonlinear mixed models, which were fitted by a full maximum likelihood method as implemented in the NLMIXED procedure. The nonlinear model used for the analysis allowed for separate plateaus or different efficiencies of the methionine sources. Mixed modeling was applied to account for heterogeneity among the studies in all regression parameters for both sources of methionine via random effects. Statistical hypotheses were tested by the asymptotic Wald test. In addition, potential co-variables were tested for inclusion as linear regressors for the nonlinear model parameters. In conclusion, the null hypothesis of equal plateaus of the 2 methionine sources was not rejected. The analyses of the response variables average daily gain (ADG) and gain to feed ratio (GF) showed a highly significant difference between the tested methionine sources. The covariate age at start of experiment significantly affected the intercept term alpha for the response variables ADG and GF, respectively. The meta-analysis showed that biological efficiencies of DL-methionine-hydroxy-analogue-free-acid were 81 and 79% of the values for DL-methionine, on an equimolar basis, for ADG and GF, respectively.

REML approach for adjusting the Fusarium head blight rating to a phenological date in inoculated selection experiments of wheat.

Fusarium head blight is one of the most important wheat diseases causing grain yield and quality losses as well as mycotoxin contamination all over the world. Since Fusarium cannot be reliably controlled with fungicides, breeding has become a favorable tool to decrease the infection severity. In most cases, selection for Fusarium resistance is done by artificial infection in the field. However, there is a risk in preferring late heading genotypes, because heading of wheat is negatively correlated to head blight severity. Because an indirect selection for late maturity is not intended, we considered a statistical approach to avoid this problem. In this paper, we propose a mixed model to analyze extensive Fusarium head blight rating in resistance breeding experiments of wheat. The objective of the analysis was to select for Fusarium resistance, while at the same time ensuring that late heading genotypes, which show less head blight over the shorter vegetation period, are not preferred. Thus, selection was to be done such that genetic variability for heading date was retained. Therefore, the statistical model contained a covariate to adjust for differences in the heading date. The use of covariate adjustment is an easily handled alternative to a bivariate analysis. Covariate adjustment will in practice often work almost equally well as bivariate analysis. Any statistical software with powerful mixed model analysis tools can be used for this type of analysis. We propose an ad hoc method to obtain heritability estimates and a form of LSD (least significance difference) as a measure of accuracy on the basis of the proposed model and under special consideration of the experimental design. The ad hoc LSD was used as a rough measure to judge rankings of genotypic means (BLUPs). Friedman's super smoother was used to compare smoothed rank estimates for adjusted and unadjusted genotypes against increasing smoothed heading dates. Traits were transformed to meet the model assumptions, especially homogeneity of errors and normality, and back-transformation of means and standard errors was conducted by using the delta method.

Evaluation of biological and economic efficiency of smallholder pig production systems in North Vietnam.

This study evaluates smallholder pig production systems in North Vietnam, comparing a semi-intensive system near a town with good market access, where a Vietnamese improved breed has replaced the indigenous pig breed, and an extensive system away from town, where the indigenous breed still prevails. Fieldwork was conducted in 64 households in four villages. Repeated farm visits yielded 234 structured interviews. Data were analysed by linear models and non-parametric tests. Production inputs and outputs were quantified, and feed use efficiency and economic efficiency were assessed. The gross margin was higher for semi-intensive production with the improved breed, while the benefit-cost ratio was higher under extensive conditions with the indigenous breed. The net benefit did not differ between systems. Twenty-four per cent of farmers yielded a negative net benefit. In one village under extensive conditions, live weight output from indigenous sows with crossbred offspring compared positively with the output from semi-intensive production with improved genotypes, but was associated with high inputs, making production inefficient. Results indicate that improved genotypes might not be an efficient production alternative for saving-oriented production with limited resource supply. Suitability of evaluation parameters, farmers' production aims, and factors impacting the production success in different systems are discussed.

Assessing the importance of genotype x environment interaction for root traits in rice using a mapping population II: conventional QTL analysis.

Modifying plant root systems is considered a means of crop improvement targeted to low-resource environments, particularly low nutrient and drought-prone agriculture. The identification of quantitative trait loci (QTLs) for root traits has stimulated marker-assisted breeding to this end, but different QTLs have been detected in different populations of the same species, and importantly, in the same population when grown in different experimental environments. The presence of QTL x environment interaction is implicated, and this must be characterised if the utility of the target QTLs is to be realised. Previous attempts to do this suffer from a lack of control over replicate environments and inadequate statistical rigour. The Bala x Azucena mapping population was grown in two replicate experiments of four treatment environments, a control, a low light, a low soil nitrogen and a low soil water treatment. After a 4 weeks growth, maximum root length, maximum root thickness, root mass below 50 cm, total plant dry mass, % root mass and shoot length were measured. A summary of the overall results is presented in an accompanying paper. Here, QTL analysis by composite interval mapping is presented. A total of 145 QTLs were detected, mapping to 37 discrete loci on all chromosomes. Superficial evidence of QTL x E (great difference in LOD score) was tested by single-marker analysis which confirmed QTL x E for five loci representing only five individual trait-loci interactions. Some loci appeared to be stable across environments. Some QTLs were clearly more or less active under low light, low nitrogen or drought. A few notable loci on chromosomes 1, 2, 3, 5, 7 and 9 are briefly discussed. Also discussed are some remaining statistical shortcomings that will be addressed in another companion paper.

Assessing the importance of genotype x environment interaction for root traits in rice using a mapping population. I: a soil-filled box screen.

Altering root system architecture is considered a method of improving crop water and soil nutrient capture. The analysis of quantitative trait loci (QTLs) for root traits has revealed inconsistency in the same population evaluated in different environments. It must be clarified if this is due to genotype x environment interaction or considerations of statistics if the value of QTLs for marker-assisted breeding is to be estimated. A modified split-plot design was used where a main plot corresponded to a separate experiment. The main plot factor had four treatments (environments), which were completely randomized among eight trials, so that each treatment was replicated twice. The sub-plot factor consisted of 168 recombinant inbreed lines of the Bala x Azucena rice mapping population, randomly allocated to the seven soil-filled boxes. The aim of the trial was to quantify QTL x environment interaction. The treatments were chosen to alter partitioning to roots; consisting of a control treatment (high-soil nitrogen, high light and high-water content) and further treatments where light, soil nitrogen or soil water was reduced singly. After 4 weeks growth, maximum root length (MRL), maximum root thickness, root mass below 50 cm, total plant dry mass (%), root mass and shoot length were measured. The treatments affected plant growth as predicted; low nitrogen and drought increased relative root partitioning, low-light decreased it. The parental varieties Bala and Azucena differed significantly for all traits. Broad-sense heritability of most traits was high (57-86%). Variation due to treatment was the most important influence on the variance, while genotype was next. Genotype x environment interaction was detected for all traits except MRL, although the proportion of variation due to this interaction was generally small. It is concluded that genotype x environment interaction is present but less important than genotypic variation. A companion paper presents QTL x environment analysis of data.

Designing a microarray experiment to estimate dominance in maize (Zea mays L.).

Experiments using cDNA microarrays for the identification of genes with certain expression patterns require a thoughtfully planned design. This study was conducted to determine an optimal design for a microarray experiment to estimate differential gene expression between hybrids and their parental inbred lines in maize (i.e. dominance). It has two features: the contrasts of interest contain more than two genotypes and the procedure may be customised to other microarray experiments where different effects may influence hybridisation signals. A mixed model was used to include all important effects. Impacts during growth of the plant material were taken into consideration as well as those occurring during hybridisation. The results of a preliminary experiment were used to determine which effects were to be included in the model, and data from another microarray experiment were used to estimate variance components. In order to select good designs, an optimality criterion adapted to the problem of differential gene expression between hybrids and their parental inbred lines was defined. Two approaches were used to determine an optimal design: the first one simplifies the problem by dividing it into several subproblems, whereas the second is more sophisticated and uses a simulated annealing (SA) algorithm. We found that the first approach constitutes a useful means for designing microarray experiments to study this problem. Using the more sophisticated SA approach the design can be further improved.