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Semiquantitative immunohistochemical assessment of estrogen receptor (ER) is used to predict the likelihood of response to antiestrogen therapy in breast carcinoma. If semiquantitative immunohistochemical analysis leads to therapeutic decisions, the importance of standardization and quality control increases. ER assessment reproducibility was studied among 172 laboratories using tissue microarray slides with 20 tissue spots negative and 10 tissue spots expressing ER at low, medium, or high levels. More than 80% of the laboratories demonstrated ER positivity in the medium- and high-expressing tissue spots, but only about 43% succeeded with tissue spots with low expression. Poor interlaboratory agreement was based on insufficient retrieval efficacy as shown by additional tests using autoclave pretreatment. The immunohistochemical scores used to quantify therapeutic target molecules remain inconclusive as long as progress toward standardized immunohistochemical procedures and evaluation is not achieved. Tissue microarray technology has proved its suitability for large-scale immunohistochemical trials, giving rise to new dimensions in control assessment. Immunohistochemical stains have become an indispensable part of laboratory procedures in pathology, both for diagnostic and research purposes. In the past, immunohistochemical analysis was used mostly for qualitative assessments, eg, lineage-specific markers such as antibodies against keratin were applied to determine the epithelial origin of a tumor. Today, a growing number of markers are used that identify cell cycle–dependent proteins, receptors, oncogenes, and antioncogenes, even in fixed tissue. However, many of these require a semiquantitative evaluation to establish the degree of expression. Antiestrogen receptor antibodies were among the first markers introducing such a semiquantitative immunohistochemical assessment, followed by others such as progesterone receptor (PR) or HER2 (c-erbB2). Several methods are known (eg, immunoreactive score [IRS], H score, quick score) for reporting estrogen receptor (ER) and PR results to clinicians. The IRS system is widely used in Germany. It is calculated by multiplication of the number of positively labeled cells (4 percentage groups) with the intensity of the staining

Thirty-four alcoholics were treated with acupuncture to the ear and the body in a randomized single-blind placebo-controlled design over 14 days. Orthodox points and placebo needles to orthodox points were used daily for a total of 10 treatments starting on the first day of admission as add-on therapy to standard medication with carbamazepine. The primary outcome was the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) assessed on days 1-6, 9 and 14. No initial differences were found regarding sociodemographic data, drinking history and alcohol-related data, indicating successful randomization. Longitudinal analysis of the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) data showed that patients assigned to acupuncture had a general tendency towards better outcome results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon-W=177.500, Z=-2.009, p = 0.045). No significant differences were found in the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI X1 and X2) and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an adjunctive treatment to carbamazepine medication shows promise for the treatment of alcohol withdrawal symptoms. Further investigation of this treatment modality appears to be warranted.

Proliferative activity of tumour cells, as assessed by the Ki-67 labelling index, has been suggested as a potential prognostic indicator in many neoplastic diseases. Meaningful application of the immunohistochemically determined tumour cell growth fraction in clinical decision-making requires information about its inter-laboratory reproducibility. To assess the reproducibility of Ki-67 determined growth fraction, a multi-centre immunohistochemical trial was performed with 172 participating laboratories, each testing 30 different tissue samples. Evaluating 5160 Ki-67 labelling indices with a newly developed tissue microarray, good inter-observer reproducibility but high inter-laboratory variability was found. Reassessment of all stainings revealed considerable inter-laboratory differences in the intensity and frequency of labelled nuclei, suggesting that antigen retrieval or staining techniques are predominantly responsible for the inter-laboratory variability found in this trial. Consequently, cut-off levels for Ki-67, suggested to distinguish prognostic subgroups in tumours, appear to have limited reproducibility in a multi-centre approach. It is concluded that there is a need to standardize the immunohistochemical determination of the Ki-67 labelling index when it is used as a prognostic indicator in surgical pathology.

© 2017 Stewart et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Inappropriate use of multiple medicines (inappropriate polypharmacy) is a major challenge in older people with consequences of increased prevalence and severity of adverse drug reactions and interactions, and reduced medicines adherence. The aim of this study was to determine the levels of consensus amongst key stakeholders in the European Union (EU) in relation to aspects of the management of polypharmacy in older people. Methods: Forty-six statements were developed on aspects of healthcare structures, processes and desired outcomes, with consensus defined at ≥ 80% agreement. Panel members were strategists (e.g. directors, leading clinicians and commissioners) from each of the 28 EU member states, with a target recruitment of five per member state. Three Delphi rounds were conducted via email, with panel members being provided with summative results and collated, anonymised comments at the commencement of Rounds 2 and 3. Results: Ninety panel members were recruited (64.3% of target), with high participation levels throughout the three Delphi rounds (91.1%, 83.3%, 72.2%). During Round 1, consensus was obtained for 27/46 statements (58.7%), with an additional two statements in Round 2 and none in Round 3. Consensus was obtained for statements relating to: potential gain arising from polypharmacy management (3/4 statements); strategic development (7/7); change management (5/7) indicator measures (4/6); legislation (0/3); awareness raising (5/5); polypharmacy reviews (5/7); and EU vision (0/7). Analysis of free text comments indicated that the vision statements were too ambitious and not achievable by the specified timeframe of 2025. Conclusion: Consensus was obtained amongst key EU strategists around many aspects of polypharmacy management in older people. Notably, no consensus was achieved in relation to statements relating to the need to alter legislation in areas of healthcare delivery, remuneration and practitioner scope of practice. While the vision for the EU by 2025 was considered rather ambitious, there is great potential and clear opportunity to advance polypharmacy management throughout the EU and beyond.

Context: The administration of pharmabiotics is a promising alternative to antimicrobial drugs for the treatment and/or prevention of female urogenital infections. Objective: To design pharmabiotic formulations including bioactive ingredients of microbial origin combined with non-microbial substances and then to evaluate the stability of the combinations during freeze-drying and storage. Materials and Methods: Different formulations including Lactobacillus gasseri CRL 1263, Lactobacillus salivarius CRL 1328, salivaricin CRL 1328 (a bacteriocin) and non-microbial compounds (lactose, inulin and ascorbic acid) were assayed and the ingredients were freeze-dried together or separately. The formulations were stored in gelatin capsules at 4ºC for 360 days. Results: The viability of lactobacilli was affected to different extents depending on the strains and on the formulations assayed. L. salivarius and ascorbic acid were successfully combined only after the freeze-drying process. Salivaricin activity was not detected in formulations containing L. gasseri. However, when combined with ascorbic acid, lactose, inulin or L. salivarius, the bacteriocin maintained its activity for 360 days. The selected microorganisms proved to be compatible for their inclusion in multi-strain formulations together with lactose, inulin and ascorbic acid. Salivaricin could be included only in a L. salivarius CRL 1328 single-strain formulation together with non-microbial substances. Conclusions: This study provides new insights into the design of urogenital pharmabiotics combining beneficial lactobacilli, salivaricin CRL 1328 and compounds with different functionalities. Fil: Vera Pingitore, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Juárez Tomás, María Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Weise, Birgitt. Hannover Medical School. Institute of Biometry; Alemania Fil: Nader, Maria Elena Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

ObjectiveThe objective of this study was to describe and analyze the effects of depression on health care utilization and costs in a sample of multimorbid elderly patients.MethodThis cross-sectional analysis used data of a prospective cohort study, consisting of 1,050 randomly selected multimorbid primary care patients aged 65 to 85 years. Depression was defined as a score of six points or more on the Geriatric Depression Scale (GDS-15). Subjects passed a geriatric assessment, including a questionnaire for health care utilization. The impact of depression on health care costs was analyzed using multiple linear regression models. A societal perspective was adopted.ResultsPrevalence of depression was 10.7%. Mean total costs per six-month period were €8,144 (95% CI: €6,199-€10,090) in patients with depression as compared to €3,137 (95% CI: €2,735-€3,538; pConclusionAmong multimorbid elderly patients, depression was associated with significantly higher health care utilization and costs. The effect of depression on costs was even greater than reported by previous studies conducted in less morbid patients.

The impact of self-efficacy on pain-related disability in multimorbid elderly patients in primary care is not known. The aim of our study was to analyze the influence of self-efficacy on the relation between pain intensity and pain-related disability, controlled for age and disease count, in aged multimorbid primary care patients with osteoarthritis and chronic pain. Patients were recruited in the German MultiCare study (trial registration: ISRCTN89818205). Pain was assessed using the Graded Chronic Pain Scale, and self-efficacy using the General Self-Efficacy Scale. We employed SPSS for statistical analysis. One thousand eighteen primary care patients were included in the study. Correlation analyses showed significant correlations between pain intensity and pain-related disability (r = 0.591, p

PURPOSE The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edi- tion (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determi- nants of the future course of MCI in the AgeCoDe study (German Study on Age- ing, Cognition, and Dementia in Primary Care Patients). METHODS We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospec- tively split into 4 groups representing remittent, fluctuating, stable, and progres - sive courses of MCI. We performed ordinal logistic regression analysis and clas- sification and regression tree (CART) analysis. RESULTS Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spec- trum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis. CONCLUSIONS In primary care, about one-quarter of patients with MCI have pro- gression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.

A study with needle acupuncture was performed in tension-type headache employing a new placebo acupuncture method. Sixty-nine patients (mean age 48.1 years, sd = 14.1) fulfilling the International Headache Society criteria for tension-type headache were randomly assigned to verum or placebo condition. No significant differences between placebo and verum with respect to visual analogue scale and frequency of headache attacks could be observed immediately, 6 weeks and 5 months after the end of treatment. There was a significant but weak improvement in quality of life parameters (clinical global impressions, Nottingham Health Profile) after verum treatment. In decision tree analyses, the changes in clinical global impressions and headache frequency depended significantly on primary headache frequency with a limit value of 24.5 days headache per month. High values in the von Zerssen Depression Score resulted in high mean visual analogue scale values.

The correlation between extent and severity of coronary artery disease as documented by quantitative coronary angiography and the incidence of cardiac events within 3 years was analyzed from a prospective study. In 73 out of 419 patients, 89 events occurred comprising 10 cardiac deaths, 15 non-fatal myocardial infarcts, 26 cases of unstable angina, and 38 coronary revascularization procedures (bypass graft operation or angioplasty). The incidence of any event correlated with the baseline number of all stenoses and high-grade stenoses (≥20% and ≥50% diameter stenosis, respectively) (P

Background In the revised version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) the Mood Disorder Workgroup for DSM-V the bereavement exclusion criterion for the diagnosis of major depression has been eliminated. Aim To investigate the impact of bereavement on the incidence of depression and depressive symptoms in the elderly. Method Participants over 75 years from the longitudinal German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) that were still married at baseline were investigated ( n =1,193). Data from four follow-ups (time frame: 6 years) were investigated. The response rate at baseline was 50.3%. Three clinical endpoints were analyzed: depressive symptoms according to Geriatric Depression Scale (1) GDS≥6, (2) GDS≥10, and (3) Major Depression (MD). The effect of loss was investigated using random-effects regression models. Results Experiencing a loss of spouse was predictive of a higher incidence in GDS≥6 (OR 4.52, 95% CI 2.6–7.9) and 10 (OR 5.59, 95% CI 1.8–17.0) even after adjusting for age, gender, impairment at baseline, and GDS score at baseline. Associations with MD were not significant (OR 1.77, 96% CI 0.9–3.5). Conclusions Older adults experiencing the loss of their spouse are more likely to display elevated levels of depressive symptoms, that may reach a concerning level of severity.

On the basis of data from one German Sickness Fund we analyzed which medical discipline coded the incident diagnosis of dementia in ambulatory medical care in Germany, which type of dementia was coded and how the initial code eventually changed during the year of incidence.Claims data of 1,848 insured people aged ≥ 65 years in 2004 with incident dementia were analyzed by means of descriptive statistics.The diagnosis within the first quarter of the incidence year was coded by the GP in 71%, by a psychiatrist or neurologist in 14%, by both in 6% and by other disciplines in 9% of the cases. The percentage of unspecified diagnoses was 62% among GPs and 46% among psychiatrists or neurologists, a number differing largely from epidemiological studies. In 27% of the cases patients received two or more different dementia diagnoses during the incidence year.Studies and care concepts regarding dementia on the basis of diagnosis codes in ambulatory claims data should be interpreted with great caution.

Background Multimorbidity is a common phenomenon in primary care. Until now, no clinical guidelines for multimorbidity exist. For the development of these guidelines, it is necessary to know whether or not patients are aware of their diseases and to what extent they agree with their doctor. The objectives of this paper are to analyze the agreement of self-reported and general practitioner-reported chronic conditions among multimorbid patients in primary care, and to discover which patient characteristics are associated with positive agreement. Methods The MultiCare Cohort Study is a multicenter, prospective, observational cohort study of 3,189 multimorbid patients, ages 65 to 85. Data was collected in personal interviews with patients and GPs. The prevalence proportions for 32 diagnosis groups, kappa coefficients and proportions of specific agreement were calculated in order to examine the agreement of patient self-reported and general practitioner-reported chronic conditions. Logistic regression models were calculated to analyze which patient characteristics can be associated with positive agreement. Results We identified four chronic conditions with good agreement (e.g. diabetes mellitus κ = 0.80;PA = 0,87), seven with moderate agreement (e.g. cerebral ischemia/chronic stroke κ = 0.55;PA = 0.60), seventeen with fair agreement (e.g. cardiac insufficiency κ = 0.24;PA = 0.36) and four with poor agreement (e.g. gynecological problems κ = 0.05;PA = 0.10). Factors associated with positive agreement concerning different chronic diseases were sex, age, education, income, disease count, depression, EQ VAS score and nursing care dependency. For example: Women had higher odds ratios for positive agreement with their GP regarding osteoporosis (OR = 7.16). The odds ratios for positive agreement increase with increasing multimorbidity in almost all of the observed chronic conditions (OR = 1.22-2.41). Conclusions For multimorbidity research, the knowledge of diseases with high disagreement levels between the patients’ perceived illnesses and their physicians’ reports is important. The analysis shows that different patient characteristics have an impact on the agreement. Findings from this study should be included in the development of clinical guidelines for multimorbidity aiming to optimize health care. Further research is needed to identify more reasons for disagreement and their consequences in health care. Trial registration ISRCTN89818205

Patient education is a compulsory element of the nationwide disease management program (DMP) for type 2 diabetes mellitus in Germany. However, a considerable proportion of patients do not attend diabetes self-management education courses. Therefore, the purpose of this study was to describe patient-reported reasons for nonparticipation and to identify typical subgroups of nonparticipants in order to improve recruitment strategies.The authors performed a cross-sectional observational study on 165 participants and 132 nonparticipants in diabetes education using a postal survey and chart review.Participants and nonparticipants were compared using 2-sided t tests and χ2 tests. Nonparticipants were grouped by cluster analysis based on the reasons for nonparticipation.A total of 95% of participants and 36% of nonparticipants reported to have received a recommendation for diabetes education from their physician. The authors identified 4 typical subgroups of nonparticipants: the "informed and responsible," the "unconcerned without desire for more information," the "uninformed but responsible," and the "anxious and burdened with psychosocial problems and functional limitations."The physician's recommendation seems to influence participation in diabetes education and should be used intentionally to increase participation rates. Also, differentiating barriers of nonparticipants can be determined by the degree of feeling informed and responsible for diabetes management. Physicians should more clearly explore patients' perception of their knowledge of diabetes and their attribution of responsibility for diabetes management. Starting from this patient perspective might help physicians motivate patients to participate in diabetes education.

Since the beginning of the 21st century, serious adverse events and an increased risk of mortality have been documented in patients with dementia treated with antipsychotics. The aim of this study was to assess antipsychotic prescribing in patients with incident dementia compared with a non-demented control group.We analysed the claims data of a German health insurance company for incident dementia patients and age-matched and sex-matched non-demented controls aged 65 years and older in 2004 to 2006. The data were used to analyse the prescribing patterns of antipsychotics in the year of dementia incidence. We estimated odds ratios stratified by age, sex, care setting and care dependence and in a multivariate logistic regression.The 1848 patients with and 7385 persons without dementia were on average 78.8 years old (standard deviation: 7.4), and 47.6% were women. A total of 25.4% of the dementia patients received antipsychotics compared with 4.3% of the controls (ORcrude : 7.61; 95%CI: 6.52-8.87). An increase in care level, age, female gender and living in a nursing home is associated with a considerably higher prevalence of at least one prescription for antipsychotics. After adjusting for all these variables, a significant influence of age could no longer be found.The results show that antipsychotics play an important role in dementia care-despite the risk of adverse events. Further research is needed with regard to safe pharmacological and non-pharmacological approaches for the behavioural and psychological symptoms of dementia in this vulnerable group.

Background: S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment. Patients and Methods: We analyzed CSF of 45 patients with CJD and of 45 patients with other neurological diseases for tau protein and S-100B in a follow-up setting. All diagnoses of CJD were later neuropathologically verified. A ratio between tau protein differences and the time between lumbar puncture was calculated. The same was done for S-100B. Results: Tau protein levels of 34 cases were above the cut-off level for CJD (>1,300 pg/ml) in the first CSF sample. In 7 of 11 patients with lower tau levels in the first CSF sample, tau levels rose. The above-mentioned ratio was significantly higher in the CJD group than in the group with other neurological diseases. Similar results were obtained for S-100B. Conclusion: We conclude that follow-up investigations and calculation of ratios is a useful tool in the differential diagnosis of CJD. Variations in this pattern were observed in single cases.

Objective: to determine incidence and predictors of late-life depression. Methods: this is a 3-year observational cohort study of 3,214 non-demented patients aged 75 and over completing three waves of assessment. The patients were recruited in 138 primary care practices in six urban areas in Germany. Depressive symptoms were measured at baseline, and 18 months and 36 months later using the GDS-15 Geriatric Depression Scale with a cut-off 0–5/6–15. Cox proportional hazard regression models were applied to examine predictors of incident depression, adjusting for sex, age, education, living situation, activities of daily living - and instrumental activities of daily living impairment, somatic comorbidity, alcohol consumption, smoking, mild cognitive impairment and apoE4 status. Results: the incidence of depression was 36.8 (95% CI: 29.6–45.3) per 1,000 person-years in men and 46.0 (95% CI: 39.9–52.8) in women (sex difference P= 0.069). The incidence increased from 35.4 (95% CI: 29.7–41.9) per 1000 personyears between the ages of 75 and 79 to 75.2 (95% CI: 53.2–103.2) for subjects 85 years and older. After full adjustment for confounding variables, hazard ratios (HR) for incident depression were significantly higher for subjects 85 years and older (HR: 1.83, 95% CI: 1.24–2.70) and those with mobility impairment (HR: 2.53, 95% CI: 1.97–3.25), vision impairment (HR: 1.41, 95% CI: 1.04–1.91), mild cognitive impairment (HR: 1.52, 95% CI: 1.10–2.10), subjective memory impairment (HR: 1.33, 95% CI: 1.01–1.74) and current smoking (HR: 1.69, 95% CI: 1.13–2.53). Conclusions: the incidence of depression increased significantly with age. In designing prevention programmes, it is important to call more attention on functional impairment, cognitive impairment and smoking.

The number of angiographically documented coronary occlusions and the incidence of Q-wave myocardial infarcts were retrospectively compared in 348 patients with moderate coronary artery disease from the INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy). In only 68 out of 118 infarcts (58%) an occlusion of the respective coronary artery was found, suggesting a spontaneous recanalization rate of 42%. On the other hand, only 68 out of 150 coronary occlusions (45%) had resulted in a Q-wave infarct. Considering the high spontaneous recanalization rate of the occlusions, it seemed possible that roughly only every fourth coronary occlusion might result in a myocardial infarct. This hypothesis was confirmed in the prospective 3 years follow-up of the identical patients during which 41 new occlusions developed causing only 10 myocardial infarcts (24%). These findings might contribute to explain the relatively low incidence of clinically apparent coronary heart disease in the general population despite a high prevalence of coronary artery disease.

Background This study investigates the efficacy of a complex multifaceted intervention aiming at increasing the quality of care of GPs for patients with multimorbidity. In its core, the intervention aims at enhancing the doctor-patient-dialogue and identifying the patient’s agenda and needs. Also, a medication check is embedded. Our primary hypothesis is that a more patient-centred communication will reduce the number of active pharmaceuticals taken without impairing the patients’ quality of life. Secondary hypotheses include a better knowledge of GPs about their patients’ medication, a higher patient satisfaction and a more effective and/or efficient health care utilization. Methods/design Multi-center, parallel group, cluster randomized controlled clinical trial in GP surgeries. Inclusion criteria: Patients aged 65–84 years with at least 3 chronic conditions. Intervention: GPs allocated to this group will receive a multifaceted educational intervention on performing a narrative doctor-patient dialogue reflecting treatment targets and priorities of the patient and on performing a narrative patient-centred medication review. During the one year intervention GPs will have a total of three conversations à 30 minutes with the enrolled patients. Control: Care as usual. Follow-up per patient: 14 months after baseline interview. Primary efficacy endpoints: Differences in medication intake and health related quality of life between baseline and follow-up in the intervention compared to the control group. Randomization: Computer-generated by an independent institute. It will be performed successively when patient recruitment in the respective surgery is finished. Blinding: Participants (GPs and patients) will not be blinded to their assignment but will be unaware of the study hypotheses or outcome measures. Discussion There is growing evidence that the phenomenon of polypharmacy and low quality of drug use is substantially due to mis-communication (or non-communication) in the doctor patient interaction. We assume that the number of pharmaceutical agents taken can be reduced by a communicational intervention and that this will not impair the patients’ health-related quality of life. Improving communication is a core issue of future interventions, especially for patients with multimorbidity. Trial registration Current Controlled Trials ISRCTN46272088.

In recent years follow-up trials on coronary artery disease with angiographic end points analyzed quantitatively have gained increasing relevance and popularity. There is no consensus, however, on the method of calculation of progression or regression from multiple angiographic projections. Therefore the influence of the selection of angiographic projections on the outcomes of such trials was investigated with the data of the International Nifedipine Trial on Antiatherosclerotic Therapy. In 348 patients with coronary artery disease, repeated coronary angiograms were compared in multiple identical angiographic projections. Changes in angiographic parameters were averaged over the 1063 stenoses analyzed. Five methods of evaluation of multiple projections in the individual stenoses were applied, resulting in different extents of overall progression or even regression of coronary artery disease ( p

General Practitioners (GPs) often have to simultaneously tackle multiple health problems of older patients. A patient-centred process that engages the patient in setting health priorities for treatment is needed. We investigated whether a structured priority-setting consultation reconciles the often-differing doctor-patient views on the importance of problems.Cluster randomised controlled trial with 40 GPs and their 317 consecutively recruited older patients.Following a geriatric assessment, patients and doctors independently rated the importance of each uncovered problem. GPs then selected priorities with their patients in a consultation. Trained intervention GPs held a structured consultation and utilised the list of uncovered patient problems with their importance ratings to agree priorities. Untrained control GPs only used the patient's problem list without importance ratings.Doctor-patient agreement on independent importance ratings two weeks after the priority-setting consultation.Weighted kappa (κw) and multilevel logistic regression model.Intervention GPs and their patients determined mutual priorities for 20% of individual problems. In this process, GPs often succeeded in convincing their patients of the importance of vaccinations, lifestyle and cognitive issues. Likewise, patients convinced their GPs to prioritise their social and functional problems. Further treatment plans ensued in 84% of these priority areas. The regression model adjusting for clusters and baseline characteristics did not demonstrate significant differences in doctor-patient agreement on problems between groups a two weeks later.Differing views on the importance of health problems between GPs and older patients were not sustainably reconciled. The special consultation facilitated identification of priority problems for treatment despite differences in perceived importance of problems between patients and GPs. German clinical trials register drks 00000792.

Background GPs increasingly deal with multiple health problems of their older patients. They have to apply a hierarchical management approach that considers priorities to balance competing needs for treatment. Yet, the practice of setting individual priorities in older patients is largely unexplored. This paper analyses the GPs’ perceptions on important and unimportant health problems and how these affect their treatment. Methods GPs appraised the importance of health problems for a purposive sample of their older patients in semi-structured interviews. Prior to the interviews, the GPs had received a list of their patients’ health problems resulting from a geriatric assessment and were asked to rate the importance of each identified problem. In the interviews the GPs subsequently explained why they considered certain health problems important or not and how this affected treatment. Data was analysed using qualitative content analysis and quantitative methods. Results The problems GPs perceive as important are those that are medical and require active treatment or monitoring, or that induce empathy or awareness but cannot be assisted further. Unimportant problems are those that are well managed problems and need no further attention as well as age-related conditions or functional disabilities that provoke fatalism, or those considered outside the GPs’ responsibility. Statements of professional actions are closely linked to explanations of important problems and relate to physical problems rather than functional and social patient issues. Conclusions GPs tend to prioritise treatable clinical conditions. Treatment approaches are, however, vague or missing for complex chronic illnesses and disabilities. Here, patient empowerment strategies are of value and need to be developed and implemented. The professional concepts of ageing and disability should not impede but rather foster treatment and care. To this end, GPs need to be able to delegate care to a functioning primary care team. Trial Registration German Trial Register (DRKS): 00000792

Background/Aims: In the past few decades, a number of studies investigated risk factors of nursing home placement (NHP) in dementia patients. The aim of the study was to investigate risk factors of NHP in incident dementia cases, considering characteristics at the time of the dementia diagnosis. Methods: 254 incident dementia cases from a German general practice sample aged 75 years and older which were assessed every 1.5 years over 4 waves were included. A Cox proportional hazard regression model was used to determine predictors of NHP. Kaplan-Meier survival curves were used to evaluate the time until NHP. Results: Of the 254 incident dementia cases, 77 (30%) were institutionalised over the study course. The mean time until NHP was 4.1 years. Significant characteristics of NHP at the time of the dementia diagnosis were marital status (being single or widowed), higher severity of cognitive impairment and mobility impairment. Conclusion: Marital status seems to play adecisive role in NHP. Early initiation of support of sufferers may ensure remaining in the familiar surroundings as long as possible.

Background Multimorbidity is a phenomenon with high burden and high prevalence in the elderly. Our previous research has shown that multimorbidity can be divided into the multimorbidity patterns of 1) anxiety, depression, somatoform disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However, it is not yet known, how these patterns are influenced by patient characteristics. The objective of this paper is to analyze the association of socio-demographic variables, and especially socio-economic status with multimorbidity in general and with each multimorbidity pattern. Methods The MultiCare Cohort Study is a multicentre, prospective, observational cohort study of 3.189 multimorbid patients aged 65+ randomly selected from 158 GP practices. Data were collected in GP interviews and comprehensive patient interviews. Missing values have been imputed by hot deck imputation based on Gower distance in morbidity and other variables. The association of patient characteristics with the number of chronic conditions is analysed by multilevel mixed-effects linear regression analyses. Results Multimorbidity in general is associated with age (+0.07 chronic conditions per year), gender (-0.27 conditions for female), education (-0.26 conditions for medium and -0.29 conditions for high level vs. low level) and income (-0.27 conditions per logarithmic unit). The pattern of cardiovascular and metabolic disorders shows comparable associations with a higher coefficient for gender (-1.29 conditions for female), while multimorbidity within the pattern of ADS and pain correlates with gender (+0.79 conditions for female), but not with age or socioeconomic status. Conclusions Our study confirms that the morbidity load of multimorbid patients is associated with age, gender and the socioeconomic status of the patients, but there were no effects of living arrangements and marital status. We could also show that the influence of patient characteristics is dependent on the multimorbidity pattern concerned, i.e. there seem to be at least two types of elderly multimorbid patients. First, there are patients with mainly cardiovascular and metabolic disorders, who are more often male, have an older age and a lower socio-economic status. Second, there are patients mainly with ADS and pain-related morbidity, who are more often female and equally distributed across age and socio-economic groups. Trial registration ISRCTN89818205

Background: Dementia is an important disease in older age. Existing studies on dementia mortality face limitations. For instance, they are based on prevalent, small, or geographically limited samples or do not include controls. We aimed to study survival after the first diagnosis of dementia compared with a control group.Methods: We analyzed claims data of a German health insurance company, including 1,818 incident dementia cases and 7,235 age- and sex-matched non-dementia controls (53% male; mean age 78.8 years). The follow-up was five years. We assessed survival with the Kaplan–Meier curves and performed Cox proportional hazard regression, also including nursing care dependency and comorbidities.Results: The cumulative five-year mortality was 53.5% in the dementia cases and 31.1% in the control group (hazard ratio: 2.1). Even after adjusting for comorbidities and nursing care, the mortality risk was 1.5 times higher for patients with incident dementia than for controls. Nursing care dependency showed high influence on mortality, likewise in dementia patients and controls.Conclusions: Although some factors, such as education or the type and severity of dementia, could not be included in the analyses, our study shows a clear influence of dementia on mortality irrespective of age, sex, care dependency, and comorbidities. The strongest influence on mortality was found for dementia patients with nursing care dependency. Taking into account their mortality of around 70% in care level 1 and up to 80% in care levels 2 and 3, healthcare delivery to these patient groups should strongly consider elements of palliative care focusing on the quality of life.

Objective: We investigated the degree of comparability of the prevalence of chronic diseases and disease combinations in the elderly in two databases comparable with regard to diseases included, sex and age of the patients (65e85 years), and cutoff score for case definition. Study Design and Setting: One study is based on chart-supported interviews with the primary care physicians within a cohort study of 3,189 multimorbid elderly patients. The second study analyzed claims data from ambulatory care delivered to the multimorbid members of one German Health Insurance (n 5 70,031). Multimorbidity was defined by the presence of three or more chronic conditions from an identical list of 46 diseases. Results: The difference of the median number of chronic conditions was 1 (mean 6.7 vs. 5.7). The prevalences of individual conditions were approximately one-third lower in the claims data, but the relative rank order corresponded well between the two databases. These relatively small prevalence differences cumulate when combinations of chronic conditions are investigated, for example, the prevalence differences between the two databases increased to nearly 100% for triadic combinations and nearly 170% for quartets. Conclusion: The study shows that conclusions regarding the prevalence of combinations of diseases should be drawn with caution

A correlation of the angiographic evolution of coronary stenoses (stenosis diameter > or = 20%) with morphological stenosis parameters at baseline could help to identify the risk of progressive stenoses. Therefore, the data of the prospective INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy) were reviewed. In 348 patients with moderate coronary artery disease, standardized coronary angiograms were taken 3 years apart and were quantitatively analysed. Changes in the minimal diameter of the 1063 preexisting coronary stenoses compared between both angiograms were set in relation to a number of conventional stenosis parameters at baseline. Regression analysis demonstrated a significant correlation of the changes in minimal diameter with baseline % diameter stenosis (r = 0.30; P < 0.001), minimal diameter (r = -0.28; P < 0.001) and reference diameter of stenoses (r = -0.14; P < 0.001). The changes were not correlated with stenosis length and plaque area. The baseline parameters of 22 preexisting stenoses progressing to occlusions differed from those remaining patent only with regard to the % diameter stenosis (43 +/- 9% vs 39 +/- 11%; P < 0.05). Additional progression of coronary disease became manifest through development of 228 stenoses and 19 occlusions at arterial sites free from definitive stenoses in the baseline angiograms. Thus, progression of atherosclerosis predominantly occurred in mild preexisting coronary stenoses and developed at previously angiographically normal sites. Since the conventional angiographic parameters analysed in this study failed to identify individual arterial sites with an increased risk for progression, definition of new angiographic parameters or application of new techniques seem mandatory to this end.

In this paper, a statistical model for clinical trials is presented for the special situation that a varying and unstructered number of binary responses is obtained from each subject. The assumptions of the model are the following: 1.) For each subject there is a (constant) individual Bernoulli parameter determining the distribution of the binary responses of this subject. 2.) The Bernoulli parameters associated with the subjects are realizations of independent random variables with distributions Pg in treatment group g(g = 1, 2, …, G). 3.) Given the value of the Bernoulli parameter, the observations are stochastically independent within each subject. Under these assumptions, a test statistic is derived to test the hypothesis H0:E(P1) = E(P2) = … = E(PG). It is proven and demonstrated by simulations, that the test statistic asymptotically (i.e. for a large number of subjects) follows the X2-distribution.

Objectives The Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological (CERAD-NP) battery represents a commonly used neuropsychological instrument to measure cognitive functioning in the elderly. This study provides normative data for changes in cognitive function that normally occur in cognitively healthy individuals to interpret changes in CERAD-NP test scores over longer time periods. Design Longitudinal cohort study with three assessments at 1.5-year intervals over a period of 3 years. Setting Primary care medical record registry sample. Participants As part of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients, a sample of 1,450 cognitively healthy general practitioner patients, age 75 years and older, was assessed. Measurements Age-, education-, and gender-specific Reliable Change Indices (RCIs) were computed for a 90% confidence interval for selected subtests of the CERAD-NP battery. Results Across different age, education, and gender subgroups, changes from at least six to nine points in Verbal Fluency, four to eight points in Word List Memory, two to four points in Word List Recall, and one to four points in Word List Recognition indicated significant (i.e. reliable) changes in CERAD-NP test scores at the 90% confidence level. Furthermore, the calculation of RCIs for individual patients is demonstrated. Conclusions Smaller changes in CERAD-NP test scores can be interpreted with only high uncertainty because of probable measurement error, practice effects, and normal age-related cognitive decline. This study, for the first time, provides age-, education-, and gender-specific CERAD-NP reference values on the basis of RCI methods for the interpretation of cognitive changes in older-age groups.

A variant within the clusterin gene has been recently associated with increased risk for Alzheimer's disease (AD) in genome wide association studies. Here we tested the association of the respective single nucleotide polymorphisms (rs11136000) with plasma concentration of clusterin in 67 AD subjects and 191 cognitively unimpaired elderly individuals. We observed an association of the rs11136000 AD-risk variant with low clusterin plasma levels in an allele-dose dependent manner in the healthy individuals (p = 0.011). This effect was numerically also present in the AD patients. We conclude that the rs11136000 AD-risk variant is associated with low clusterin plasma levels.

Objectives. This study represents the first prospective, quantitative analysis of the association of progression of coronary atherosclerosis with anatomic site and diameter.Background. The progressive course of coronary artery disease has been documented in many angiographic follow-up trials.Methods. The data of 348 patients with coronary artery disease from the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) were reviewed. Standardized coronary angiograms were taken 3 years apart and were analyzed quantitatively. The coronary tree was subdivided into 25 segments. The progression of 1,063 preexisting coronary stenoses and the appearance of 247 newly formed stenoses was assessed in relation to the mean diameter of segments (3 mm) and to their position in the coronary tree (proximal, mid, distal) and in the three major coronary arteries.Results. Decreases in the minimal diameter of preexisting stenoses were largest in segments that were >3 mm in diameter (mean ± SD 0.23 ± 0.5 mm vs. 0.10 ± 0.4 mm and 0.02 ± 0.3 mm, p < 0.001), in a proximal position (0.14 ± 0.5 mm vs. 0.09 ± 0.4 mm and 0.06 ± 0.3 mm, p = 0.081) and in the right coronary artery (0.14 ± 0.4 mm vs. 0.07 ± 0.4 mm and 0.07 ± 0.3 mm, p < 0.01). Changes in percent diameter stenosis of preexisting stenoses were lowest in segments that were 2 mm in diameter, in a proximal or midartery position and in the right coronary artery.

Background: Maintaining independence in instrumental activities of daily living (IADL) is crucial for older adults. This study explored the association between cognitive and functional performance in general and in single IADL domains. Also, risk factors for developing IADL impairment were assessed. Methods: Here, 3,215 patients aged 75–98 years were included. Data were collected during home visits. Results: Cognitive functioning was associated with IADL both cross-sectionally and longitudinally. Regarding the single IADL domains cross-sectionally, executive functioning was especially associated with shopping, while episodic memory was associated with responsibility for own medication. Conclusion: Reduced performance in neuropsychological tests is associated with a greater risk of current and subsequent functional impairment. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background Due to demographic changes and an un-equal distribution of physicians, regional analyses of service utilization of elderly patients are crucial, especially for diseases with an impact like dementia. This paper focuses on dementia patients. The aim of the study is to identify differences in service utilization of incident dementia patients in urban and rural areas. Methods Basis for the analysis were all insured persons of a German Health Insurance fund (the GEK) aged 65 years and older living in rural and urban areas. We focussed on physician contacts in the outpatient sector during the first year after an incidence diagnosis of dementia. Special attention was given to contacts with primary care physicians and neurologists/psychiatrists. The dementia cohort was analyzed together with a non-dementia control group drawn according to age, gender and amount of physician contacts. Uni- and bivariate as well as multivariate analysis were performed to estimate the influences on service utilization. Results Results show that the provision of primary care seems to be equally given in urban and rural areas. For specialists contacts however, rural patients are less likely to consult neurologists or psychiatrists. This trend can already be seen before the incident diagnosis of dementia. All consultations rise in the quarter of the incident dementia diagnosis compared to the control group. The results were also tested in a linear and a logistic regression, showing a higher chance for persons living in urban areas to visit a specialist and an overall higher rate in service utilization for dementia patients. Conclusions Because of a probable increase in the number of dementia patients, service provision has to be accessible even in rural areas. Due to this and the fact that demographic change is happening at different paces in different regions, regional variations have to be considered to ensure the future service provision.

An increasing number of longitudinal cohort studies have identified a risk increase for dementia by the chronic use of drugs with anticholinergic properties. The respective data from the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) also showing risk increase (hazard ratio = 2.081) are reported here. The mechanisms by which the risk increase is transported are still unknown. Irritation of compensated alterations of cholinergic transmission at the pre-dementia stage of Alzheimer's disease (AD) or acceleration of neuroinflammation by disturbance of the anti-inflammatory effect of cholinergic innervation are discussed. In terms of dementia prevention, centrally acting anticholinergic drugs should be strictly avoided, because of long-term dementia risk increase in addition to acute negative effects on cognition.

The growing tendency of opioid addicts to misuse multiple other drugs leads to the investigation of new pharmacostrategies to prevent patients from suffering life-threatening complications and minimize the withdrawal symptoms. The short-term efficacy of a 10-day low-dose buprenorphine/19-day carbamazepine regime (n = 15) to a 14-day oxazepam/19-day carbamazepine regime (n = 12) in an open-labelled 21-day inpatient detoxification treatment was compared. Twenty-seven men and women dependent on opioids and misusing other drugs admitted to a detoxification unit were included in this protocol. Eighteen of 27 patients (67%) completed the study. Four non-completers (27%) received buprenorphine/carbamazepine (four of 15) and five non-completers (42%) were treated with oxazepam/carbamzepine (five of 12), but the difference in the dropout rate between the two treatment strategies was not significant.The buprenorphine/carbamazepine regime provided significantly more effective relief of withdrawal symptoms during the first week of treatment. No severe side effects occurred during treatment in both groups. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than oxazepam/carbamazepine in rapid opioid detoxification in patients with additional multiple drug misuse and both regimens were safe with no unexpected side effects.

Androgen receptor (AR) expression profile in the different Gleason patterns (GP) of primary prostate cancers and nodal metastases is unknown. More information about AR distribution is needed to optimize evaluation methods and to better understand the role of AR in development and progression of prostate cancer.A tissue microarray was constructed from 119 hormone-naïve nodal positive, surgically treated prostate cancers containing tissues from all GP present in every primary tumor and the matched metastases. ARs were evaluated immunohistochemically and an expression score (intensity × percentage of positive cells) was assigned for each tissue spot.ARs were up-regulated in primary tumors compared to normal glands and significantly different expressed in the GP (mean AR scores: GP 3=128.7, GP 4=159.1, GP 5=123.5; P=0.016). A similar expression profile was observed in metastases, however, on significantly (P0.001) lower level (mean AR scores: GP 3=70.5, GP 4=90.4, GP 5=71.7; P=0.114). High AR expression in metastases was associated with larger total size of metastases (P=0.008). All other correlations of AR expression in primary tumors and metastases with quantitative (age, prostate cancer volume, number of metastases) or categorical (tumor stage, Gleason score of the primary tumor and metastases) tumor characteristics or with survival were insignificant.ARs are differentially expressed in GP what should be considered in prognostic models which include AR. In nodal metastases, ARs are significantly down-regulated suggesting decreased dependence on androgens already under hormone-naïve conditions. AR expression level is not prognostic in nodal positive disease.

Aims: To analyze how the diagnosis of dementia changes the utilization of the ambulatory medical care services in the German statutory health insurance. Methods: In this case-control study, claims data of 1,848 insurants aged ≧65 years with incident dementia and 7,392 matched controls were compared regarding their utilization of ambulatory medical care services. Results: We found an increase in the utilization of ambulatory medical care services by demented patients of 50% in the year before and of 40% in the year after the incidence, predominantly in primary care and neurology/psychiatry settings. A negative interaction effect of age and gender (p ≤ 0.000) was found regarding the number of visited physicians. Conclusion: Service utilization by demented patients increases already within the year before the first diagnosis and stays on a relatively high level within the year after. Especially (female) patients aged 80 years and older at dementia onset ought to be observed to prevent a possible undersupply.

Background and Objectives: With the Cyberspace's exponential growth of influence questions arise about its mental impacts. The presented study examines the question whether the dependent use of the Internet can be understood as an impulse con- trol disorder, an addiction or as a symptom of other psychiatric conditions. Methods: Internet dependent patients seeking for psychiatric assistance and fulfilling the criteria for pathological Internet use (PIU) were examined with the Structured Clinical Inter- view according to DSM-IV (SCID), and a variety of questionnaires including the Barratt Im- pulsiveness Scale (BIS), the Beck Depression Inventory (BDI) and the Dissociative Experi- ence Scale (DES). The patient group was compared to a matched group of healthy controls. Results: The adult patient-group consisted of 25 subjects, 76% male, with a mean age of 29.36 years. Average time spent in Cyberspace was 6.47 h/d, mostly in online-role- playing games. According to SCID I and BDI, 19 patients (76%) suffered from a depres- sive syndrome, with 10 cases of major depressive disorder (40%) and 8 cases of adjust- ment disorder with depression (32%). Six patients (24%) suffered from a comorbid anxiety disorder. Compared to controls, the patient group presented significantly higher levels of depression (BDI), impulsivity (BIS) and dissociation (DES). Conclusions: PIU shares common psychopathological features and comorbidities with substance related disorders. Therefore, it might be seen as a diagnostic entity in itself in a spectrum of behavioural and substance dependencies. Especially Internet role play may contain an addictive potential for adolescents and adults with subclinical psychopathology.

BACKGROUND At present, there is extensive knowledge on the clinical course of coronary artery disease (CAD), whereas data on the underlying anatomical changes and their relation to clinical events are still limited. METHODS AND RESULTS We investigated progression and regression of CAD prospectively over 3 years in 230 patients (average age, 53.2 years) with mild to moderate disease by applying quantitated, repeated coronary angiography. Minimal stenotic diameters, segment diameters, and percent stenosis were analyzed by the computer-assisted Coronary Angiography Analysis System (CAAS). Progression was defined either as an increase in percent stenosis of preexisting stenoses by greater than or equal to 20% including occlusions or as formation of new stenoses greater than or equal to 20% and new occlusions in previously angiographically "normal" segments. At first angiography, we found 838 stenoses greater than or equal to 20% (average degree, 39.3%) and 135 occlusions in the four major coronary branches (4.23 lesions per patient). At second angiography, 82 (9.8%) of the preexisting stenoses had progressed, 15 of them up to occlusion (1.8%; preocclusion degree averaging 46.6%; 29.7-65.6%). In addition, there were 144 newly formed stenoses (average degree, 39.2%) and 10 new occlusions. Hence, 25 (2.6%) of all stenoses had become occluded. Altogether, 129 patients (56.1%) showed progression: 68 (29.6%) with new lesions only, 27 (11.7%) with preexisting lesions, and 34 (14.8%) with both types. Regression (decrease in degree of stenoses greater than or equal to 20%) was present in 29 stenoses (3.6%) and 28 patients (12%). The incidence of new myocardial infarctions was low, with three originating from occluding preexisting stenoses and one from new stenoses; hence, only four (16%) of the 25 new occlusions led to myocardial infarctions. Risk factor analysis showed that cigarette smoking correlated significantly with the formation of new lesions (p = 0.001), whereas total cholesterol correlated with the further progression of preexisting stenoses (p = 0.017) but not with the incidence of new lesions. CONCLUSIONS In patients with mild to moderate CAD, the angiographic progression is slow (in this study 18.7% of patients and 7% of stenoses per year) but exceeds regression (4.1% of patients and 1.2% of stenoses per year). Progression is predominantly seen in the formation of new coronary stenoses and less in growth of preexisting ones. Most of the stenoses were of a low degree (less than 50%), clinically not manifest including those going into occlusion and leading to myocardial infarction. Progression was influenced by risk factors, especially cigarette smoking (formation of new lesions) and high cholesterol levels (progression of preexisting stenoses).

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers.

Background Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects. Methods/Design The study is designed as a multicentre prospective, observational cohort study of 3.050 patients aged 65 to 85 at baseline with at least three different diagnoses out of a list of 29 illnesses and syndromes. The patients will be recruited in approx. 120 to 150 GP surgeries in 8 study centres distributed across Germany. Information about the patients' morbidity will be collected mainly in GP interviews and from chart reviews. Functional status, resources/risk factors, health care utilization and additional morbidity data will be assessed in patient interviews, in which a multitude of well established standardized questionnaires and tests will be performed. Discussion The main aim of the cohort study is to monitor the course of the illness process and to analyse for which reasons medical conditions are stable, deteriorating or only temporarily present. First, clusters of combinations of diseases/disorders (multimorbidity patterns) with a comparable impact (e.g. on quality of life and/or functional status) will be identified. Then the development of these clusters over time will be analysed, especially with regard to prognostic variables and the somatic, psychological and social consequences as well as the utilization of health care resources. The results will allow the development of an instrument for prediction of the deterioration of the illness process and point at possibilities of prevention. The practical consequences of the study results for primary care will be analysed in expert focus groups in order to develop strategies for the inclusion of the aspects of multimorbidity in primary care guidelines.

Cognitive functions show large variation in elderly people and are substantially heritable. Animal studies revealed that dynorphins influence cognition and memory, especially in aged animals. Thus, we tested the effect of four SNPs (rs7272891, rs1997794, rs2235751 and rs910080) and the VNTR promoter polymorphism in the prodynorphin gene (PDYN) on episodic memory and verbal fluency in a large (n = 1619) sample of elderly people (mean age: 80 ± 3.39 years; range 75–90 years) recruited through the German study on ageing, cognition and dementia in primary care patients (AgeCoDe). We found that carriers of the minor alleles of rs1997794 (P

Angioplasty of single total, subacute, or chronic coronary occlusions was performed in 90 patients. It was successful in 54 occlusions (60%), in 77% of those less than 6 weeks old, and in 44% of those of greater than 6 weeks' duration (p less than 0.005). All procedures were uneventful. Control angiography was performed in 53 (98%) patients with successful angioplasty after an average interval of 97 +/- 53 days. Stenosis had recurred in 16 patients (30%). During a follow-up period of 36 +/- 13 months, three patients died, five patients underwent coronary bypass operation, and 10 had reangioplasty. Despite an additional late angiographic recurrence of stenosis in seven patients, 36 patients revealed angiographic long-term success. In the 46 nonoperated patients, angina pectoris and exercise stress tests were substantially improved. Thus angioplasty of subacute and chronic total coronary occlusions is an uneventful procedure, the success rate depending on the duration of the occlusions. Despite a high angiographic recurrence rate, the angiographic and clinical long-term results are favorable.

Background: Individuals with Mild Cognitive Impairment (MCI) are at high risk to develop dementia and are a target group for preventive interventions. Therefore, research aims at diagnosing MCI at an early stage with short, simple and easily administrable screening tests. Due to the fact that the Cl[for full text, please go to the a.m. URL], 10. Deutscher Kongress für Versorgungsforschung; 18. GAA-Jahrestagung

Dedifferentiation of hepatocellular carcinoma implies aggressive clinical behavior and is associated with an increasing number of genomic alterations, eg deletion of 13q. Genes directly or indirectly deregulated due to these genomic alterations are mainly unknown. Therefore this study compares array comparative genomic hybridization and whole genome gene expression data of 23 well, moderately, or poorly dedifferentiated hepatocellular carcinoma, using unsupervised hierarchical clustering. Dedifferentiated carcinoma clearly branched off from well and moderately differentiated carcinoma (P