[Epidemiology of multiple sclerosis in Germany: regional differences and drug prescription in the claims data of the statutory health insurance]. / Epidemiologie der Multiplen Sklerose in Deutschland : Regionale Unterschiede und Versorgungsstruktur in Abrechnungsdaten der gesetzlichen Krankenversicherung.

BACKGROUND: Nationwide population-based information on the prevalence of multiple sclerosis (MS) in Germany has so far not been available. In this study the prevalence of MS was determined with the help of the claims data of the health insurance funds underlying the morbidity-based risk adjustment scheme (M-RSA). MATERIAL AND METHODS: Health insurance funds reported inpatient and outpatient diagnoses, outpatient prescriptions, costs and enrolment data for all persons insured in the German statutory health insurance (SHI). The data reported for 2010 form the basis of this study which collated data on the 12-month prevalence, prevalence related to age and gender, drug therapy, regional distribution pattern, combinations of diagnoses and hospitalization. RESULTS: Nearly 200,000 people insured in the SHI have been diagnosed with MS. Hence, the prevalence seems to be considerably higher than was previously assumed. In addition, a slight west-east gradient was apparent. On average 49 % of all MS patients (with a slight east-west gradient) received MS-specific inpatient drug therapy. Insured patients living in the east received on average 30 daily doses per year less than patients living in the western part. CONCLUSION: For the first time MS prevalence has been determined nationwide for Germany with the help of SHI data. It appears that previously applied methods have underestimated the prevalence. The regional differences found with respect to prevalence and drug therapy need further clarification. The data underlying the M-RSA do not allow more causal research.

Fear of recurrence and disease progression in long-term (≥ 5 years) cancer survivors--a systematic review of quantitative studies.

BACKGROUND: Increasing proportions of patients diagnosed with cancer will become long-term survivors (≥ 5 years post-diagnosis). However, survivors may continue to experience negative effects of cancer and/or treatment, including fear of recurrence (FoR). This review aims to provide an overview of current knowledge on FoR, including determinants and consequences in long-term cancer survivors, and to outline methodological and conceptual challenges that should be addressed in future research. METHODS: Multiple databases including PUBMED, EMBASE, and PsycINFO were searched to identify relevant articles. Seventeen articles were included. Data were extracted by two reviewers and summarized following a systematic scheme. RESULTS: Even years after initial diagnosis, cancer survivors suffer from FoR. Most studies report low or moderate mean FoR scores, suggesting that FoR is experienced in modest intensity by most survivors. Studies including long-term and short-term survivors indicate no significant change of FoR over time. Lower level of education, lower level of optimism, and being Hispanic or White/Caucasian were found to be associated with higher levels of FoR. Significant negative associations were reported between FoR and quality of life as well as psychosocial well-being. All but three studies were conducted in the USA. General cut-offs for severity/clinical significance have not been defined yet. CONCLUSIONS: FoR at modest intensity is experienced by most long-term cancer survivors. Future studies should address determinants and consequences of FoR in more detail. Validated instruments providing cut-offs for severity/clinical significance of FoR should be developed and utilized. Efficient interventions should be implemented to reduce detrimental effects of FoR.

Creutzfeldt-Jakob disease and mad cows: lessons learnt from yeast cells.

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that affect mammals including humans. The proteinaceous nature of the infectious agent, the prion, and its propagation, challenge established dogmas in biology. It is now widely accepted that prion diseases are caused by unconventional agents principally composed of a misfolded host-encoded protein, PrP. Surprisingly, major break-throughs in prion research came from studies on functionally unrelated proteins in yeast and filamentous fungi. Aggregates composed of these proteins act as epigenetic elements of inheritance that can propagate their alternative states by a conformational switch into an ordered ß-sheet rich polymer just like mammalian prions. Since their discovery prions of lower eukaryotes have provided invaluable insights into all aspects of prion biogenesis. Importantly, yeast prions provide proof-of-principle that distinct protein conformers can be infectious and can serve as genetic elements that have the capacity to encipher strain specific information. As a powerful and tractable model system, yeast prions will continue to increase our understanding of prion-host cell interaction and potential mechanisms of protein-based epigenetic inheritance.

Benefit finding and post-traumatic growth in long-term colorectal cancer survivors: prevalence, determinants, and associations with quality of life.

BACKGROUND: As research on quality of life of colorectal cancer (CRC) survivors has mainly focused on downsides of cancer survivorship, the aim of this study is to investigate benefit finding (BF) and post-traumatic growth (PTG) in long-term CRC survivors. METHODS: Benefit finding, PTG, and quality of life were assessed 5 years after diagnosis in a population-based cohort of 483 CRC patients using the benefit finding scale, the post-traumatic growth inventory, and the EORTC QLQ-C30. Prevalence of BF and PTG, determinants of moderate-to-high BF and PTG, and the association between BF, PTG, and quality of life were investigated. RESULTS: Moderate to high levels of BF and PTG were experienced by 64% and 46% of the survivors, respectively. Survivors with the highest level of education and with higher depression scores reported less BF and PTG. The PTG increased with increasing stage and self-reported burden of diagnosis. Quality of life only correlated weakly with PTG (Pearson's r=0.1180, P=0.0112) and not with BF (r=0.0537, P=0.2456). CONCLUSION: Many long-term CRC survivors experience BF and PTG. As these constructs were not strongly correlated with quality of life, focusing solely on quality of life after cancer misses an important aspect of survivorship.

Quality of life among long-term (≥5 years) colorectal cancer survivors--systematic review.

BACKGROUND: Due to the growing number of long-term (≥5 years) colorectal cancer survivors, investigation of their quality of life (QoL) is important for an evaluation of chronic or late effects of the disease and treatment and to adjust treatment strategies to patients' needs. METHOD: To summarise current research results, multiple databases including PubMed, EMBASE and CINAHL were used to identify articles about long-term QoL of colorectal cancer survivors. The content of 10 included studies was independently extracted by two reviewers. RESULTS: Colorectal cancer survivors indicated a good overall QoL, but may have slightly lower physical QoL than the general population. Furthermore, survivors had worse depression scores and reported to suffer from long-term symptoms such as bowel problems and distress regarding cancer. Apart from stoma and recurrence of the disease, mainly general and health-related factors such as age, social network size, income, education, BMI and number of comorbidities were associated with QoL. Studies were mainly conducted in the United States (US) (n=7) and were heterogeneous with respect to the QoL instrument used and the adjustment to covariates. QoL assessment was cross-sectional in all studies. CONCLUSION: Despite an overall good QoL, colorectal cancer survivors have specific physical and psychological problems. The reported determinants of QoL may serve to identify survivors with special needs. But further studies are needed that focus on problems like distress, depression and bowel problems of long-term colorectal cancer survivors.

Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk.

BACKGROUND: In 1980, Garland hypothesized that lower levels of vitamin D resulting from much weaker UV-B radiation at higher latitudes may account for the striking geographical pattern of cancer mortality. Further research has been conducted over the past 20 years. AIM: To perform a systematic review and meta-analysis of longitudinal studies on the association between serum 25 hydroxyvitamin D (25(OH)D) and the risk of colorectal cancer (CRC). METHODS: Relevant studies published until September 2008 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase of serum 25(OH)D by 20 ng/mL. Summary odds ratios (ORs) were calculated using meta-analysis methods. RESULTS: Overall, eight original articles reporting on the association between serum 25(OH) D and CRC risk were included. In meta-analyses, summary ORs (95% confidence intervals) for the incidence of CRC, colon cancer and rectal cancer associated with an increase of 25(OH)D by 20 ng/mL were 0.57 (0.43-0.76), 0.78 (0.54-1.13) and 0.41 (0.11-1.49). No indication for publication bias was found. CONCLUSIONS: Our results support suggestions that serum 25(OH)D is inversely related to CRC risk.

Overweight, obesity and risk of work disability: a cohort study of construction workers in Germany.

OBJECTIVES: Although obesity and permanent work disability impose a great burden on the individual and are very costly for society, data on the impact of being overweight on occupational disability are sparse, especially in men who work hard physically. The aim of this study was to investigate the association of body mass index (BMI) with work disability among construction workers. METHODS: The association between BMI and work disability was examined during a mean follow-up period of 10.8 years in a cohort of 16,875 male construction workers in Württemberg, Germany, who participated in routine occupational health examinations from 1986 to 1992. Hazard ratios were calculated with normal weight (20.0-22.4 kg/m(2)) as reference using the Cox proportional hazards model, after adjustment for potential confounding factors. RESULTS: Overall, a U-shaped association of BMI with all-cause work disability (total number = 3064 cases) was observed, with the lowest risk of disabilities at BMI levels between 25 and 27.4 kg/m(2). Strong positive associations were observed between BMI and work disability due to osteoarthritis or cardiovascular diseases, whereas BMI was inversely related to work disability due to cancer, even after exclusion of the first 3 years of follow-up. CONCLUSIONS: Moderate overweight is not associated with increased risk of work disability among construction workers, but obesity increases the risk of work disability due to osteoarthritis and cardiovascular disease.

Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas.

BACKGROUND: Prognosis for most types of childhood tumours has improved during the last few decades. In this article we estimate up-to-date period survival for less common, but important childhood malignancies in Europe. METHODS: Using the database of the Automated Childhood Cancer Information System we calculated period estimates of 10-year survival for the 1995-1999 period for children aged 0-14 years diagnosed during 1985-1999 with tumours of the sympathetic nervous system (NS), retinoblastoma, renal tumours, bone tumours and soft tissue sarcomas in four European regions. RESULTS: Ten-year period survival for 1995-1999 was 66% in children with tumours of the sympathetic NS, 96% for retinoblastoma, 87% for renal tumours, 58% for bone tumours and 61% for soft tissue sarcomas. The higher period estimates, as compared with cohort and complete estimates indicate recent improvement in survival for tumours of the sympathetic NS and to a lesser extent for retinoblastoma and renal tumours. Region-specific period survival estimates were lowest for Eastern Europe for renal, bone and soft tissue tumours, but not for the other two tumour groups. CONCLUSION: There have been further improvements in the 1990s in long-term survival of children diagnosed with several malignancies, albeit to a different extent in different European regions.

Up-to-date monitoring of childhood cancer long-term survival in Europe: central nervous system tumours.

BACKGROUND: Tumours of the central nervous system (CNS) account for 15-20% of all malignant childhood tumours in developed countries. Steady improvement of survival of children with CNS tumours has been reported for the past decades. However, these results, obtained by cohort analysis of survival, do not reflect the full extent of recent improvement. METHODS: Using selected registries from the database of the Automated Childhood Cancer Information System (ACCIS), we calculated period survival estimates for the years 1995-99 for children diagnosed with a malignant CNS tumour. RESULTS: The overall 10-year period survival estimate for the years 1995-99 was 59% for children with all CNS tumours combined, 73% for children with astrocytoma, 53% for children with ependymoma and 45% for children with primitive neuroectodermal tumours. On average, estimates derived by cohort analysis (pertaining to children diagnosed in 1985-89) were around 4% units lower. Region-specific analysis revealed that recent progress was largest in Eastern Europe, where prognosis nevertheless remained lower than in other European regions. In Northern and Southern Europe, 10-year survival remained essentially unchanged. CONCLUSION: Although period survival of children with CNS tumours is higher than previously reported cohort survival, their long-term prognosis remains modest compared to other childhood malignancies.

Timely disclosure of progress in childhood cancer survival by 'period' analysis in the Automated Childhood Cancer Information System.

BACKGROUND: A few years ago, a new method of survival analysis, denoted 'period' analysis, was introduced to provide more up-to-date survival estimates of cancer patients. PATIENTS AND METHODS: We evaluated the period survival method using the large database of the Automated Childhood Cancer Information System (ACCIS). Our evaluation is based on data from 35 191 children diagnosed with cancer in 13 European countries between 1975 and 1989 and followed for vital status until around 1999. RESULTS: Using the follow-up data available in 1989, 10-year survival for all children with cancer calculated by the period method for the 1985-89 period was 58%, while it was 43% when calculated by traditional 'cohort' life-table analysis (based on children diagnosed in 1975-79). The period method provided a better estimate of the true 10-year survival of 62%, observed 10 years later in the cohort of patients diagnosed in 1985-89. Similar results were observed for each of the common groups of childhood cancer. CONCLUSION: Period analysis is especially useful for monitoring childhood cancer survival, because at a given point in time it provides more timely estimates of long-term survival expectations than the cohort life-table method. Using the ACCIS database, up-to-date estimates of period survival for childhood cancer are derived in subsequent papers in this journal.

Up-to-date monitoring of childhood cancer long-term survival in Europe: leukaemias and lymphomas.

BACKGROUND: In recent decades, following the introduction of effective chemotherapy, the prognosis of children with leukaemia and lymphoma has dramatically improved, but data reflecting further possible improvement achieved in the 1990s are scarce. METHODS: Using the Automated Childhood Cancer Information (ACCIS) database, we carried out a period analysis of 10-year survival for the 1995-99 period. Analyses were carried out by diagnostic groups, age-group at diagnosis, sex and four European regions. RESULTS: Ten-year survival estimates for the 1995-99 period were 73% for any type of leukaemia, 78% for acute lymphoid leukaemia and 52% for acute non-lymphocytic leukaemia. The corresponding 10-year survival rates for all types of lymphomas, Hodgkin lymphoma, and non-Hodgkin lymphoma were 84, 91 and 79%, respectively. These figures are much higher than those obtained by traditional (cohort-based) methods of survival analysis. A large difference in prognosis is still observed between the East and other parts of Europe. CONCLUSION: Major improvement in prognosis for children with leukaemia or lymphoma has been ongoing in Europe during the 1990s, but further monitoring and investments are required to remove the large regional differences between European regions.

To be, or not to be--molecular chaperones in protein degradation.

To be, or not to be--that is the question not only for Hamlet in Shakespeare's drama but also for a protein associated with molecular chaperones. While long viewed exclusively as cellular folding factors, molecular chaperones recently emerged as active participants in protein degradation. This places chaperones at the center of a life or death decision during protein triage. Here we highlight molecular mechanisms that underlie chaperone action at the folding/degradation interface in mammalian cells. We discuss the importance of chaperone-assisted degradation for the regulation of cellular processes and its emerging role as a target for therapeutic intervention in cancer and amyloid diseases.

Trends in population-based cancer survival in Germany: to what extent does progress reach older patients?

BACKGROUND: The ageing of populations makes outcome monitoring among elderly cancer patients particularly important. PATIENTS AND METHODS: Using data from the population-based Cancer Registry of Saarland, we examined age-specific trends in 5-year relative survival from 1979 to 2003 for patients with 15 common cancers in Germany. Model-based period analysis was applied to estimate 5-year relative survival for four age groups (15-54, 55-64, 65-74, 75+) in the periods 1979-1983, 1984-1988, 1989-1993, 1994-1998, and 1999-2003. RESULTS: Overall, 5-year relative survival improved steadily from 42.2% in 1979-1983 to 56.7% in 1999-2003. From the youngest to the oldest age group, 5-year relative survival increased by 14.5, 12.1, 12.5, and 8.4 percent units, respectively, after adjusting for changes in the spectrum of cancer sites, and survival significantly improved for 10, 12, 11, and 5 cancer sites, respectively. The age gradient particularly increased for cancer sites with major progress in chemotherapeutic treatment regimens, such as ovarian cancer, non-Hodgkin's lymphoma and leukemia. CONCLUSIONS: Relative survival of cancer patients increased considerably for many forms of cancer in Germany from 1979 to 2003. Increases were much less pronounced among elderly patients, leading to an increasing age gradient in prognosis.

Gender differences in colorectal cancer: implications for age at initiation of screening.

There is some variation regarding age at initiation of screening for colorectal cancer (CRC) between countries, but the same age of initiation is generally recommended for women and men within countries, despite important gender differences in the epidemiology of CRC. We have explored whether, and to what extent, these differences would be relevant regarding age at initiation of CRC screening. Using population-based cancer registry data from the US and national mortality statistics from different countries, we looked at cumulative 10-year incidence and mortality of CRC reached among men at ages 50, 55, and 60, and found that women mainly reached equivalent levels when 4 to 8 years older. The gender differences were remarkably constant across populations and over time. These patterns suggest that gender differentiation of age at initiation may be worthwhile to utilise CRC-screening resources more efficiently.

Construction work and risk of occupational disability: a ten year follow up of 14,474 male workers.

AIMS: Most industrialised countries have public income maintenance programmes to protect workers in case of disability but studies addressing disability risk of specific professional groups are rare. The objective of this study was to establish a detailed pattern of the nature and extent of occupational disability among construction workers. METHODS: A cohort study was set up including 14,474 male workers from the construction industry in Württemberg (Germany) aged 25-64 years who underwent occupational health exams between 1986 and 1992. The cohort was linked to the regional pension register of the manual workers' pension insurance institution to identify workers who were granted a disability pension during the 10 year follow up. All-cause and cause specific standardised incidence ratios (SIR) and 95% confidence intervals (CI) were calculated using disability rates from the general workforce and from all blue collar workers in Germany as references. RESULTS: In total, 2247 (16%) members of the cohort were granted a disability pension. Major causes of disability were musculoskeletal (45%) and cardiovascular diseases (19%). In comparison with the general workforce, construction workers experienced a higher risk of disability from cancer (SIR = 1.26; 95% CI 1.08 to 1.47), respiratory diseases (SIR = 1.27; 95% CI 1.03 to 1.55), musculoskeletal diseases (SIR = 2.16; 95% CI 2.03 to 2.30), injuries/poisoning (SIR = 2.52; 95% CI 2.06 to 3.05), and all causes combined (SIR = 1.47; 95% CI 1.41 to 1.53). When compared with the blue collar reference group, increased risks of disability among construction workers were found for musculoskeletal diseases (SIR = 1.53; 95% CI 1.44 to 1.63), injury/poisoning (SIR = 1.83; 95% CI 1.50 to 2.21), and all causes combined (SIR = 1.11; 95% CI 1.07 to 1.16). CONCLUSIONS: Musculoskeletal diseases and external causes are major factors limiting the work capability of construction workers and lead to an increased proportion of occupational disability.

Reduction of clinically manifest colorectal cancer by endoscopic screening: empirical evaluation and comparison of screening at various ages.

Endoscopic screening (sigmoidoscopy, colonoscopy) with removal of precancerous lesions can prevent a large proportion of colorectal cancers (CRCs). However, there is lack of data regarding optimal age, time intervals and numbers of screening examinations. We developed and applied modified techniques of epidemiological analysis to evaluate the impact of various endoscopy-based screening strategies on prevention of clinically manifest CRCs between the ages of 50 and 79 in a population-based case-control study (294 cases, 254 controls) conducted in Saarland, Germany. We found a strong potential for reduction of CRC occurrence even with a single screening endoscopy. The optimal age for a single screening endoscopy appears to be around 55 (estimated potential for prevention of cases between the ages of 55 and 79 in case of 100% compliance: 77% (95% confidence interval (CI) 46-90%)). A single screening endoscopy at age 50 would have a lower impact due to failure to prevent CRC at higher ages. Similarly, screening at ages 60 or older would have a lower impact because it would fail to prevent CRC at lower ages. Repeated offers of screening examinations could provide substantial additional benefit with the levels of compliance to be expected in practice, but they would have to be weighed against the increased risks and costs.

All-cause and cause specific mortality in a cohort of 20 000 construction workers; results from a 10 year follow up.

BACKGROUND: Construction workers are potentially exposed to many health hazards, including human carcinogens such as asbestos, silica, and other so-called "bystander" exposures from shared work places. The construction industry is also a high risk trade with respect to accidents. METHODS: A total of 19 943 male employees from the German construction industry who underwent occupational health examinations between 1986 and 1992 were followed up until 1999/2000. RESULTS: A total of 818 deaths occurred during the 10 year follow up (SMR 0.71; 95% CI 0.66 to 0.76). Among those were 299 deaths due to cancer (SMR 0.89; 95% CI 0.79 to 1.00) and 312 deaths due to cardiovascular diseases (SMR 0.59; 95% CI 0.51 to 0.68). Increased risk of mortality was found for non-transport accidents (SMR 1.61; 95% CI 1.15 to 2.27), especially due to falls (SMR 1.87; 95% CI 1.18 to 2.92) and being struck by falling objects (SMR 1.90; 95% CI 0.88 to 3.64). Excess mortality due to non-transport accidents was highest among labourers and young and middle-aged workers. Risk of getting killed by falling objects was especially high for foreign workers (SMR 4.28; 95% CI 1.17 to 11.01) and labourers (SMR 6.01; 95% CI 1.63 to 15.29). CONCLUSION: Fatal injuries due to falls and being struck by falling objects pose particular health hazards among construction workers. Further efforts are necessary to reduce the number of fatal accidents and should address young and middle-aged, semi-skilled and foreign workers, in particular. The lower than expected cancer mortality deserves careful interpretation and further follow up of the cohort.

Age-specific detriments to quality of life among breast cancer patients one year after diagnosis.

The aim of our study was to identify any differences in the quality of life (QOL) of breast cancer survivors one year after diagnosis when the acute treatment effects should not longer be apparent. QOL was assessed in a population-based cohort of 387 women with breast cancer from Saarland (Germany) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLC30). Functional and symptom QOL-scores were compared with published reference data from the general population. Breast cancer survivors and women from the general population reported similar scores of global health/QOL. However, major deficits among women with breast cancer were found, for emotional, social, role and cognitive functioning. Age-specific comparisons between breast cancer patients and the reference population revealed that these deficits are predominantly found in younger age groups. The overall QOL of life of breast cancer survivors one year after diagnosis is comparable to women from the general population. However, some differences exist that seem to predominantly affect younger women who show a poorer QOL in certain domains.

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer.

MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism.