Personalized medicine in screening for malignant disease: a review of methods and applications.

Personalized medicine (PM) is currently a hot topic in the professional world. It is often called the medicine of the future and has already achieved resounding success in the area of targeted therapy. Nevertheless, integration of the concepts of PM into routine clinical practice is slow. This review is intended to give an overview of current and potential applications of PM in oncology. PM could soon play a decisive role, especially in screening. The relevance of PM in screening was examined in the case of four common cancers (colorectal cancer, lung cancer, breast cancer, and prostate cancer). A literature search was performed. This showed that biomarkers in particular play a crucial role in screening. In summary, it can be emphasized that there are already numerous known promising biomarkers in malignant disease. This results in several possibilities for individualizing and revolutionizing screening.

Impact of low mini-mental status on health outcome up to 5 years after stroke: the Erlangen Stroke Project.

Cognitive deficits are frequent stroke sequelae. Data from population-based stroke cohorts on the impact of cognitive deficits on long-term outcome are scarce. The purpose of this study was to investigate the impact of low mini-mental status on health outcome up to 5 years after first-ever stroke. Data were collected from the Erlangen Stroke Project, a population-based stroke registry covering a source population of 103,000 inhabitants. The Mini-Mental State Examination (MMSE) was used to assess global cognitive function. Health outcome included limitations in instrumental activities of daily living (IADL, Frenchay Activities Index), low independence in activities of daily living (ADL, Barthel Index), depressive symptoms (Zung Self Rating Depression Scale), and institutionalization. Using multivariate logistic regression analysis, association of an education-adjusted MMSE score ≤ 24 with these health outcomes was investigated within distinct models at 12, 36, and 60 months after stroke as well as predictors at 3 months for low IADL. A total of 705 patients with first-ever stroke were included. Institutionalization, low levels of ADL and IADL (p < 0.001) are associated with a MMSE score ≤ 24 over 5 years after stroke. Predictors at 3 months for low IADL are low mini-mental status up to 3 years after stroke (OR 2.69, 95% CI 1.2-5.8) as well as older age (p < 0.001), and stroke severity (p < 0.001) up to 5 years. A low mini-mental status has an independent impact on long-term health outcome after stroke. Our results emphasize the importance of cognitive status screening to identify stroke survivors at risk and manage and treat these patients more efficiently.

Changes in cognitive function over 3 years after first-ever stroke and predictors of cognitive impairment and long-term cognitive stability: the Erlangen Stroke Project.

BACKGROUND AND PURPOSE: Cognitive impairment (CI) is frequent after stroke, but data from population-based stroke cohorts on the natural course of CI are limited. The purpose of this study was to determine changes in cognitive status over 3 years after stroke. METHODS: Data were collected from the Erlangen Stroke Project, an ongoing population-based stroke registry. The Mini-Mental State Examination (MMSE) for assessing global cognitive function was used; CI was defined as an MMSE score <24. RESULTS: From February 1998 to January 2006, 630 patients with first-ever stroke were included. Prevalence rates of CI at 3 months, 1 and 3 years were 15, 13, and 12%. In multivariable analysis, stroke severity, i.e. Barthel index (p < 0.001), age (OR = 1.03; 95% CI = 1.00-1.05) and diabetes mellitus (OR = 2.03; 95% CI = 1.13-3.67) were associated with CI at 3 months. Recovery rate from CI at 3 months after stroke was found to be 31% over the following 3 years. Intact cognitive function rate was 71% over 3 years and inversely associated with age (OR = 0.96; 95% CI = 0.96-0.94) and stroke severity (p < 0.001). CONCLUSION: CI is frequent among stroke survivors and associated with age, stroke severity, and diabetes mellitus, but recovery occurs in approximately one third of the patients over the course of 3 years. Factors affecting intact cognitive function over time are increasing age and stroke severity.

Care needs and economic consequences after acute ischemic stroke: the Erlangen Stroke Project.

The objective was to determine the functional outcome, location of care and economic consequences in the first 3 months after ischemic stroke. As part of the Erlangen Stroke Project, (ESPro) information was collected on patients suffering a first-ever ischemic stroke. Three months after the stroke, location of care, dependence on caregivers and function based on Barthel Index: poor (0-55), moderate (60-90) or good function (95-100) were recorded. Data about health services used were combined with cost estimates for Germany (2000 Euros, undiscounted). Of 491 patients hospitalized, 383 were alive 3 months afterwards, 79% residing in the community. The majority of patients with poor function (60%) were still in institutional care. Patients with good function typically accrued the lowest costs, whether in an institution (17 965) or not (11 032) compared with poorer function who were living in an institution (poor: 26 370; moderate: 28,121), or community (poor: 27,207; moderate: 19,350). Hospitalization and rehabilitation services were the major costs accrued at each level of function. Many patients were left requiring a substantial amount of care and the costs associated with providing institutional care has a major impact on the economic consequences of a stroke.

[The reliability of the german version of the barthel-index and the development of a postal and telephone version for the application on stroke patients]. / Untersuchung der Reliabilität der deutschen Version des Barthel-Index sowie Entwicklung einer postalischen und telefonischen Fassung für den Einsatz bei Schlaganfall-Patienten.

BACKGROUND AND PURPOSES: Aim of the study was to translate the original version of the Barthel-Index (BI) into German and to investigate the reliability of the German version. In addition, a German version of the BI for postal and telephone use was developed. METHODS: Data were collected in four neurological hospitals in Germany. The translation of the BI followed the protocol of the Medical Outcomes Trust. The interrater reliability of the German version of the BI was investigated in 72 patients after acute stroke. The reliability of the postal and telephone version of the BI was compared with face-to-face interview in 147 patients three months after stroke. Reliability was assessed using simple weighted kappa-statistics. RESULTS: The interrater reliability of the German version of the BI was excellent (mean kappa 0.93). The mean kappa coefficient was 0.79 for the postal version of the BI and 0.80 for the telephone version. Thus, the agreement between the postal and the telephone administration of the BI compared to the face-to-face interview was substantial to excellent. CONCLUSIONS: Our study published the first German version of the BI which was investigated for interrater reliability in a standardized way. The development of a postal and a telephone version allows the widespread use of the German BI for the follow up of stroke patients in different access paths.

[Telemedicine stroke department network. Introduction of a telemedicine pilot project for integrated stroke management in South Bavaria and analysis of its efficiency]. / Telemedizinisch vernetzte Schlaganfallstationen. Vorstellung des telemedizinischen Pilotprojekts zur integrierten Schlaganfallversorgung in Südostbayern und seiner Effizienzanalyse.

More than 100 stroke units have been established in Germany. In rural areas, however, acute stroke care needs to be improved. In order to advance clinical stroke therapy, two specialized stroke centers founded a telemedicine network (TEMPiS) among 12 community hospitals in eastern Bavaria. Each network hospital established specialized stroke wards where qualified teams manage acute stroke patients. Twenty-four hours daily, physicians in local hospitals are able to contact the stroke centers via videoconferencing including transmission of digital DICOM data. To study the efficacy of this network, a controlled trial will be performed. Five TEMPiS-network hospitals will be matched with five other hospitals equal in size, catchment area, and diagnostic techniques. For about 1 year, all consecutive stroke cases in the matched study hospitals will be prospectively recorded in a database. Neurological deficits will be quantified on the National Institute of Health Stroke Scale within 24 h after stroke onset. Mortality and institutional care as a combined primary endpoint will be assessed after 3 and 12 months. Furthermore, functional outcome according to the modified Rankin scale, Barthel score, and quality of life will be assessed using a standard telephone interview. Data acquisition started in July 2003, and final results are expected in 2005.

[Factors influencing duration of hospitalization after stroke in Germany]. / Einflussfaktoren auf die stationäre Liegezeit nach Schlaganfall in Deutschland.

BACKGROUND: In Germany up-to-date data within community settings about factors influencing length of stay in acute hospitals are lacking. We, therefore, identified predictors for length of stay in acute hospital after ischemic stroke in a pooled analysis of large German stroke registers. METHODS: Ischemic stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000 and December 31, 2000 were analysed. The influence of patients' demographic and clinical characteristics as well as the characteristics of the treating hospitals on length of stay were analysed by multivariate linear regression. RESULTS: Overall, 13 440 patients after ischemic stroke were included in the analyses. Their mean age was 70 years, 53 % were men. Median length of stay in acute hospitals was 12 days. In multivariate analyses younger age, an increasing number of co-morbidities, and an increasing number of neurological deficits were identified as predictors of prolonged stay in hospital. Patients were more likely to stay longer in an acute hospital if they were to be discharged to a rehabilitation unit or to a nursing home. Length of stay was independently decreased for patients treated in hospitals providing acute stroke unit services and for hospitals treating more than 250 stroke patients per year. CONCLUSION: In addition to patients' demographic and clinical characteristics, length of stay in hospital was influenced by the hospitals' characteristics. Especially the volume of treated patients and the organisation of services within the hospital may play the key role.

[Incidence, etiology and long-term prognosis of stroke]. / Inzidenz, Atiologie und Langzeitprognose des Schlaganfalls.

BACKGROUND AND PURPOSE: In Germany, basic data on stroke morbidity are lacking. So far only routine mortality statistics have provided information on epidemiology of stroke. Therefore, a population-based register of stroke was set up in Germany to determine incidence and case fatality in a defined German population. METHODS: The Erlangen Stroke Register is a prospective community-based study among the 101,450 residents of the city of Erlangen, Bavaria, Germany. All identified cases of first-ever strokes were followed-up to 12 months from onset of stroke. RESULTS: During 2 years of registration, 354 first-ever-in-a-lifetime strokes (FELS) were registered. The diagnosis and stroke type were confirmed by CT scan in 95 % of cases. Fifty-one percent of all FELS occurred in the age group > 75 years of age. After age-adjustment to the German standard population, the incidence rate was 182 per 100,000 (200 per 100,000 for men and 170 per 100,000 for women). Overall case fatality at 28 days was 19.4 %, at 3 months it was 28.5 %, and at 1 year 37.3 %. CONCLUSIONS: The first prospective community-based stroke register in Germany including all age groups revealed incidence rates of stroke similar to those reported from other population-based studies in western industrialized countries.

Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence, recurrence, and long-term survival rates of ischemic stroke subtypes by a mechanism-based classification scheme (Trial of ORG 10172 in Acute Stroke Treatment, or TOAST). METHODS: We identified all 583 residents of the city of Erlangen, Bavaria, Germany, with a first ischemic stroke between 1994 and 1998. Multiple overlapping sources of information were used to ensure completeness of case ascertainment. The cause of ischemic stroke was classified according to the TOAST criteria. Patients were followed up at 3 months and 1 and 2 years after stroke onset. RESULTS: The age-standardized incidence rates for the European population (per 100 000) regarding ischemic stroke subtypes were as follows: cardioembolism, 30.2 (95% CI 25.6 to 35.7); small-artery occlusion, 25.8 (95% CI 21.5 to 30.9); and large-artery atherosclerosis, 15.3 (95% CI 12 to 19.3). When age-adjusted to the European population, the incidence rate for large-artery atherosclerosis was more than twice as high for men than for women (23.6/100 000 versus 9.2/100 000). Two years after onset, patients in the small-artery occlusion subgroup were 3 times more likely to be alive than those with cardioembolism. Ischemic stroke subtype according to the TOAST criteria was a significant predictor for long-term survival, whereas subtype was not a significant predictor of long-term recurrence up to 2 years, both before and after adjustment for age and sex. CONCLUSIONS: Epidemiological observational studies that possess wide access to appropriate diagnostic technologies and apply standardized etiologic classifications provide a much better understanding of underlying risk factors for initial stroke, recurrence, and mortality.

Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: Results from a population-based case-control study.

BACKGROUND AND PURPOSE: Helicobacter pylori and Chlamydia pneumoniae have been associated epidemiologically and pathogenetically with coronary atherosclerosis. However, population-based data on chronic infection and stroke are lacking. Therefore, we investigated the association of both bacterial pathogens and ischemic stroke subtypes in a population-based case-control study. METHODS: Patients with first ischemic stroke in the population-based Erlangen Stroke Project were collected as cases. Neighborhood controls were drawn from the study population, matched for age, sex, and place of residence. IgG antibodies to H pylori were measured by enzyme immunoassay, and IgG antibodies to C pneumoniae were measured by microimmunofluorescence technique. Conditional logistic regression was used. Analyses were stratified for etiologic stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: A total of 145 case and 260 control subjects were included. Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke. CONCLUSIONS: Our population-based study does not provide evidence of any strong association between the immune response to C pneumoniae as a marker of prior infection and ischemic stroke. Further studies are required to reveal the role of chronic H pylori infection as an independent risk factor for the subgroup small-artery occlusion.

Acute stroke management in the local general hospital.

BACKGROUND AND PURPOSE: The majority of stroke patients are treated in local general hospitals. Despite this fact, little is known about stroke care in these institutions. We sought to investigate the status quo of acute stroke management in nonspecialized facilities with limited equipment and resources. METHODS: Four general hospitals located in smaller cities of a rural area in Germany participated in this study. The 4 hospitals were similar in structure and technical equipment; none had a CT scanner in-house. We reviewed the medical records of every stroke patient hospitalized in 1 of the 4 hospitals within a period of 8 weeks within 1 year. RESULTS: We collected data of a total of 95 patients at all 4 hospitals. The frequency of diagnostic tests was low: at least 1 CT scan was obtained in only 36.8% of all cases, whereas diagnostic methods available in-house were used more frequently, such as Doppler ultrasound (49.0%), echocardiography (42.3%), and 24-hour ECG registration (48.4%). Each hospital had a different therapeutic approach. Main therapeutic options were the use of pentoxyfilline (0% to 90.5%), osmodiuretics (0% to 90%), piracetam (0% to 93.3%), and hydroxyethylstarch (4.8% to 30%). Medication for long-term secondary prevention was given to 69.8% of all patients. CONCLUSIONS: This study provides one of the few data samples reflecting stroke care in smaller general hospitals. The findings demonstrate a partially suboptimal level of care in these institutions. To achieve future improvements, extended human and technical resources as well as research for stroke care should not be restricted to academic stroke centers.

[Quality assurance in treatment of stroke: basic module of the German Stroke Registry Study Group]. / Qualitätssicherung in der Schlaganfall-Behandlung: das Basismodul der Arbeitsgemeinschaft Deutscher Schlaganfall-Register (ADSR).

BACKGROUND AND PURPOSE: Comparable, standardised data on the quality and efficiency of stroke care in Germany are lacking. The Arbeitsgemeinschaft Deutscher Schlaganfall-Register (ADSR--German Stroke Registries Study Group) has defined a "Minimum DataSet" for the evaluation of quality indicators of stroke treatment in Germany. METHODS: The ADSR is a voluntary network of current regional stroke registries aiming at a standardisation in the use of stroke terminology and methods of data collection for German stroke databases. Currently six regional stroke registries are cooperating in the ADSR, combining data from about 18,000 stroke patients in 110 hospitals annually. RESULTS: In the design of the ADSR DataSet a modular approach was chosen. The ADSR "Minimum DataSet" was adapted for a wide use in different health care facilities. In addition to the "Minimum DataSet" an "Advanced DataSet" will be developed to document additional items of stroke care in specialised stroke centres. The ADSR DataSet collection will be completed by special "Extended DataSets", designed for answering centre-specific and research questions. CONCLUSION: The ADSR "Minimum DataSet" allows a standardised assessment of stroke care in Germany. It is the first questionnaire that provides valid and reliable comparisons between different clinical settings as well as regional stroke databases. The ADSR "Minimum DataSet" defines core items for a future National German Health Report on stroke care.

A prospective community-based study of stroke in Germany--the Erlangen Stroke Project (ESPro): incidence and case fatality at 1, 3, and 12 months.

BACKGROUND AND PURPOSE: In Germany, basic data on stroke morbidity are lacking. If a population-based register in former East Germany is excluded, only routine mortality statistics have thus far provided information on epidemiology of stroke. Therefore, a population-based register of stroke was set up in Southern Germany to determine incidence and case fatality in a defined German population. METHODS: The Erlangen Stroke Project (ESPro) is a prospective community-based study among the 101 450 residents of the city of Erlangen, Bavaria, Germany. Standard definitions and overlapping case-finding methods were used to identify all cases of first-ever stroke in all age-groups, occurring in the 2 years of registration (April 1, 1994, to March 31, 1996). All identified cases of first-ever strokes were followed up at 3 and 12 months from onset. RESULTS: During 2 years of registration, 354 first-ever-in-a-lifetime strokes (FELS) were registered. The diagnosis and stroke type were confirmed by CT scan in 95% of cases. Fifty-one percent of all FELS occurred in the age group >/=75 years of age. The crude annual incidence rate was 1.74 per 1000 (1.47 for men and 2.01 for women). After age-adjustment to the European population, the incidence rate was 1.34 per 1000 (1.48 for men and 1. 25 for women). The annual crude incidence rate of cerebral infarction was 1.37/1000, intracerebral hemorrhage 0.24/1000, subarachnoid hemorrhage 0.06/1000, and unspecified stroke 0.08/1000. Overall case fatality at 28 days was 19.4%, at 3 months it was 28.5%, and at 1 year 37.3%. CONCLUSIONS: The first prospective community-based stroke register including all age groups in Germany revealed incidence rates of stroke similar to those reported from other population-based studies in western industrialized countries, but lower than that observed in former East Germany.