[Screening for dementia using telephone interviews. An evaluation and reliability study of the Telephone Interview for Cognitive Status (TICS) in its modified German version]. / Demenzscreening per Telefon. Eine Reliabilitäts- und Evaluationsstudie zum Telefoninterview für den kognitiven Status (TICS) in seiner modifizierten deutschen Fassung.

BACKGROUND: To assess cognitive impairment or dementia in epidemiologic studies using telephone interviews for data acquisition, valid, reliable and short instruments suitable for telephone administration are required. For the Telephone Interview for Cognitive Status (TICS) in its modified German version, the only instrument used in Germany so far, more data on reliability and practicability are needed. MATERIAL AND METHODS: Participants were recruited in the offices of nine primary care physicians. Data from 197 participants (115 females, mean age 78.5±4.1 years) who were tested by telephone and in the office by means of the Mini-Mental State Examination (MMSE) were used for the evaluation. For assessing reliability, a group of 91 participants (55 females, mean age 78.1±4.1 years) was contacted twice during 30 days to be tested during a telephone interview by means of the TICS in its modified German version. RESULTS: The intraclass correlation coefficient (ICC), a measure of reliability, was 0.67 [95% confidence interval (CI): 0.53; 0.77]. The Bland-Altman plot did not reveal any relationship between the variability of the difference between repeated measures and the total amount of the measure. For the overall TICS score, no differences were found between repeated measurements. However, the tasks recall of the word list and counting backwards showed some improvement in the repeated tests. TICS and MMSE showed only moderate correlation, with a correlation coefficient of 0.48 (95% CI: 0.36; 0.58). TICS values were dependent on age and educational level of the person tested. CONCLUSIONS: The TICS in its modified German version appears to be of acceptable reliability for the assessment of cognitive impairment during a telephone interview. TICS values depend on age and educational level of the person tested. TICS and MMSE correlate only moderately.

Prerequisites for a new health care model for elderly people with multimorbidity: the PRISCUS research consortium.

BACKGROUND: Multimorbidity, the concurrent manifestation or presence of multiple chronic conditions, poses huge challenges to affected patients, their relatives, physicians, and practitioners alike. The growing number of affected persons and the complexity of their needs places just as much of a burden on the health care system as does the plethora of often poorly coordinated interventions. The Chronic Care Model developed for different chronic diseases is suited for improving medical care. The PRISCUS research consortium was established to create the prerequisites for a new care model for multimorbid, elderly patients oriented along those lines. METHODS: The research consortium utilizes data gathered in a large-scale epidemiological study on peripheral arterial disease (getABI study) and from the Dortmund and Münster stroke registries, by extracting epidemiologic and health economic data, quality-of-life parameters, and data on the extent and quality of medication. Additional projects evaluate the implementation of a multidimensional geriatric assessment in primary care, the functional consequences of multimorbidity in stroke patients along with options for prevention and therapy afforded by physical activity. Systematic reviews of the literature are used to describe quality of life and patient preferences. Experts will work on an initial draft treatment standard for patients with multimorbidity and a list of potentially inappropriate medication for the elderly in Germany. CONCLUSION: The results of the PRISCUS research consortium will enable an epidemiologic characterization and description of consequences of multimorbidity, while illustrating new approaches towards prevention, diagnosis, and management of multimorbid patients. With this, some prerequisites for a new health care model for patients with multimorbidity comparable to the Chronic Care Model will be fulfilled.

[Prerequisites for a new health care model for elderly people with multiple morbidities: results and conclusions from 3 years of research in the PRISCUS consortium]. / Voraussetzungen für ein neues Versorgungsmodell für ältere Menschen mit Multimorbidität: Ergebnisse und Schlussfolgerungen aus 3-jähriger Forschung im PRISCUS-Verbund.

BACKGROUND: The concurrent presence or manifestation of multiple chronic conditions, i.e. multimorbidity, poses a challenge to affected patients and their relatives, physicians, and practitioners, and to the health care system in general. Aiming to improve medical care for different chronic diseases, the Chronic Care Model also appears to be suited for multimorbidity. The established research consortium PRISCUS is trying to create some of the prerequisites for a new care model for multimorbid, elderly patients oriented along the lines of the Chronic Care Model. METHODS AND RESULTS: Four out of seven subprojects of the research consortium provide an overview of some of their findings. Topics in a sports medicine subproject were the assessment of physical activity by means of a newly developed questionnaire and the development and feasibility testing of an exercise program for elderly people with chronic conditions and mobility impairment. Partners from family medicine implemented geriatric assessment in a primary care setting and evaluated its consequences. In a pharmacological subproject, potentially inappropriate medication as well as drug-drug interactions and dosing errors were addressed. The health economic subproject investigated quality of life impairment due to multiple chronic diseases and the effects of multimorbidity on costs. CONCLUSIONS: The results of the PRISCUS research consortium allow a better description of consequences of multimorbidity and illustrate at least some new approaches towards prevention, diagnosis, and treatment of patients suffering from multimorbidity. Ongoing projects will test the efficacy of a physical activity program and a new complex intervention to reduce potentially inappropriate medication in the elderly. With this, the research consortium will create some prerequisites for a new health care model for patients with multimorbidity comparable to the Chronic Care Model.

[Epidemiological methods for health services research]. / Epidemiologische Methoden für die Versorgungsforschung

On July 1, 2009, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal (Gesundheitswesen 2009; 71: 505-510). This is an in-depth publication on the "epidemiological methods for health services research". Legal, political and economic steps of intervention in the medical care system modify the health services structures and processes but the impact of such interventions on the medical care users has, so far and in general, not been examined scientifically. Due to this lack of evaluation, there is, also with regard to the economic situation within the health system, no transparency of potentially severe effects on healthy and, particularly, on ill people. For this very reason, the main questions and focuses of medical care research deal with prevalence, causes and effects of over, under and inappropriate supply of health services, the interaction between diagnostics and therapy, the processes across different sectors and the complex interdependences of health services. This part of the Memorandum of Deutsches Netzwerk für Versorgungsforschung e. V. (DNVF e. V., German Network for Health Services Research) will enumerate the methods and instruments that will be used for planned studies and that have been applied for finished studies of health services research and for the evaluation of its quality and value. Health services research takes advantage of the theories and the methods of the disciplines that are involved in its studies. It does not need a specific research methodology; its methods are adapted to the specific research question. It is rather to be expected that certain issues of this research branch and its access to data will lead to the development of new methods.

[Quality of care after distal radius fracture in Germany. Results of a fracture register of 1,201 elderly patients]. / Die stationäre Behandlungsqualität der distalen Radiusfraktur in Deutschland: Ergebnisse eines Frakturregisters mit 1201 älteren Patienten.

BACKGROUND: This study is the first to document the quality of inpatient care provided to elderly patients with distal radius fracture in Germany. PATIENTS AND METHODS: Inpatient care provided to 1,201 patients age 65 or older with isolated distal radius fracture was documented in a prospective cohort study conducted at 242 acute care clinics in Germany between January 2002 and September 2003. RESULTS: The median patient age was 75, and nearly 90% of patients were female. Approximately 71% of patients were classified as ASA I or II, and 28% were ASA III. The most common comorbidity was arterial hypertension (60%). Seventy-five percent of patients were admitted on the day of the accident; of these, 63% had surgery on the same day, and 20% on the following day. The primary form of anaesthesia was general anaesthesia (55%). The predominant fracture management procedure was percutaneous K-wire osteosynthesis (56% of cases), followed by plate osteosynthesis (44%). The length of hospital stay after plate osteosynthesis (median 8.5 days) was more than twice as long as after K-wire osteosynthesis (median 4 days). The rate of postoperative complications typical of each procedure was around 10%. Roughly 90% of patients were discharged to home. Although evidence of osteoporosis was observed in 62% of women and 50% of men, only 7.9% of patients were prescribed osteoporosis-specific medication. CONCLUSIONS: Unexpected findings were the predominance of general anaesthesia and percutaneous K-wire osteosynthesis. Osteoporosis, affecting a majority of elderly women, is neglected in clinical practice. Good quality of care is reflected by the low rate of complications.

[Comparison of two coronary risk equivalents: diabetes mellitus and peripheral arterial disease]. / Risiken der Koronaräquivalente Diabetes mellitus und Periphere Arterielle Verschlusskrankheit im Vergleich.

BACKGROUND AND OBJECTIVE: Diabetes mellitus (DM) and peripheral arterial disease (PAD) are both coronary artery disease equivalents ("coronary equivalents"). It was the aim of this study to ascertain (1) to what extent each of these diseases differs from the other in respect of early death, (2) how frequently DM and PAD occur together in elderly patients seen in general practice and (3) what risk patients with DM and concomitant PAD carry. PATIENTS AND METHODS: In the prospective non-interventional study--"German Epidemiological Trial on Ankle Brachial Index"--6,880 unselected patients, aged 65 years or more, from 344 general medical practices were followed over five years and the incidence of deaths and of cardiovascular events recorded. DM was defined according to the medical diagnosis and/or if the HbA1c was > or = 6.5% and the ankle brachial index (ABI), determined by Doppler sonography. PAD was defined as an ABI of < 0.9 or the presence of intermittent claudication or state after peripheral revascularization/amputation. Survival rates were obtained using Kaplan-Meier estimate curves and Cox's proportional hazard model. 59 patients with an ABI > 1.5 were excluded from the study. Hazard ratios (HR with 95% confidence intervals [CI]) were adjusted according to known risk factors. RESULTS: The overall observation period for all the patients amounted to nearly 33000 patient-years (PY). The risk of death of patients with DM but no PAD (n = 1,220; 17.9%) was 1.5 times the risk of death (HR, 95% CI 1.2-1.8) of persons with neither disease (n = 4 172; 61.2%) and the risk of those with PAD but no DM (n = 918, 13;5%) was 1.7 times of those persons without either disease (HR, 95% CI 1.4-2.0). The risk for persons with DM and PAD (n = 511; 7.5%) was nearly 3 times that of persons without either disease, after adjustment for other cardiovascular risk factors (HR 2.8, 95% CI 2.3-3.4). The lower the ABI in persons with or without DM the greater the number of deaths per 1000 PY. CONCLUSIONS: These results confirm that diabetics and patients with PAD have a clearly increased risk of early death. These patients need intensive treatment of the risk factors. This is especially true for patients who have DM and PAD concomitantly.

[Metabolic syndrome and peripheral arterial occlusive disease as indicators for increased cardiovascular risk]. / Metabolisches Syndrom und periphere arterielle Verschlusskrankeit als Indikatoren für erhöhtes kardiovaskuläres Risiko.

BACKGROUND AND AIMS: The usefulness of the metabolic syndrome (MetS) or a low ankle brachial index (ABI), respectively, to identify patients with high risk for cardiovascular events has repeatedly been postulated. However, robust data on the prevalence and prognosis of such patients are missing in the primary care setting. PATIENTS AND METHODS: In the prospective, non-interventional "German epidemiological trial on Ankle Brachial Index (getABI) at total of 6880 unselected patients > or = 65 years were observed by their General Practitioners over 3 years. Death and cardiovascular events were recorded. The definition of MetS was similar to the one of NCEP ATP III (National Cholesterol Education Program--Adult Treatment Panel III). ABI (ratio of the systolic blood pressures measured at the distal part of the calf and at the upper arm) was measured with Doppler sonography. Peripheral arterial disease (PAD) was defined as ABI <0.9 or peripheral revascularization/amputation owing to PAD. Survival analyses were conducted with a Cox proportional hazard model. Hazard rate ratios (HRR, 95 % confidence intervals, CI) were multvariate adjusted. RESULTS: The observation time for the total cohort was more than 20,000 patient years (PY). Cardiovascular mortality in patients with MetS (n = 3040, 44 %) compared to patients without MetS (n = 3795; 55 %) was doubled (8.5 vs. 4.0 per 1,000 PY; HRR: 2.0; CI 1.3 - 2.9). Concomitant presence of MetS and PAD (n = 651; 9.5 %) increased the mortality risk compared to patients without both conditions (n = 3194; 46.4 %) drastically (21.1 vs. 3.0 per 1000 PY; HRR: 5.7; CI: 3.5 - 9.4). Similar significant risk increases also were noted for all-cause mortality or a combined endpoint of mortality and vascular morbidity. Further, in lower ABI categories cardiovascular event rates increased. CONCLUSIONS: Patients with MetS carry a substantially increased risk of premature death, especially cardiovascular death, and therefore require intensive treatment of their risk factors. This holds especially true if concomitant PAD is present.

High prevalence of peripheral arterial disease and low treatment rates in elderly primary care patients with diabetes.

Representative data on peripheral arterial disease (PAD) in community-based office practice are scarce while at the same time of high interest. Thus, we aimed to determine the prevalence of peripheral arterial disease (PAD), comorbidity of atherothrombotic manifestations, and treatment intensity among elderly diabetic patients in primary care. In this monitored cross-sectional study, 344 general practitioners throughout Germany determined the ankle-brachial index (ABI) of 6880 consecutive, unselected patients aged 65 years or older with bilateral Doppler ultrasound measurements. PAD was defined according to the recent American Heart Association guidelines (using the higher of the 2 systolic ankle pressures: ABI < 0.9) or peripheral revascularisation, or amputation because of PAD. Coronary events (CAD) and cerebrovascular events (CVD) were taken from the patient's history without additional diagnostic measures. Diabetes was defined according to the clinical diagnosis of the physician and/or HbA1c > or = 6.5 % and/or intake of oral antidiabetic medication and/or application of insulin. 1.743 patients were classified as diabetics: the median disease duration was 6 years (1st; 3rd quartile: 2; 11), median HbA1c 6.6 % (5.9; 7.3), mean age 72.5 +/- 5.4 years, and 51.4 % were females. Diabetics had in comparison with non-diabetics a higher prevalence of PAD defined as ABI < 0.9 (26.3 % vs. 15.3 %, univariate odds ratio 2.0 [95 % confidence interval: 1.7; 2.3]), intermittent claudication (5.1 % vs. 2.1 %, OR: 2.5 [1.9; 3.4]), known CAD (16.1 % vs. 10.6 %, OR: 1.6 [1.4; 1.9]), and known CVD (6.8 % vs. 4.8 %; OR: 1.4 [1.2; 1.8]). 57.4 % of the diabetics with previously known PAD (as only atherothrombotic manifestation) received antiplatelet therapy (vs. 75.1 % with CAD and/or CVD only). The ABI was suitable as screening measure in the primary care setting. In elderly diabetics in comparison to non-diabetics, the prevalence of PAD was very high. Despite the known benefits of antiplatelet therapy, PAD patients were less intensively treated than patients with CAD or CVD.

An internal standard for verifying the accuracy of serious adverse event reporting: the example of an acupuncture study of 190,924 patients.

BACKGROUND: Reporting of all serious adverse events (SAEs) is a requirement for regulatory approval of a drug. Can equally rigorous reporting standards be expected in studies of non-drug treatments and how can underreporting, if any, be detected and proven? Using data from our large-scale prospective cohort study of acupuncture on outpatients, we examine the use of an internal standard, a principle taken from laboratory medicine, to quantify real event rates. METHODS: A total of 190,924 patients (68.6% women) seeking treatment for chronic pain (headache, low back pain, coxarthrosis or gonarthrosis) from 12,000 physicians in private practice in Germany were observed during a six-month period ending in May 2002. Most received ten sessions of body acupuncture. Mean treatment time was six weeks. All practitioners were certified in acupuncture and received written instructions on completing forms for basic patient data and SAE monitoring. They were also informed that payment by insurers would be made only upon return of the completed form. All SAEs occurring between start of the first acupuncture session and end of the last one were to be reported, whether causally related to the treatment or not. Multiple minor adverse events (AEs) per single patient were to be reported only once. As the internal standard we chose the expected number of deaths, based on the death rate for the German population, adjusted for age, sex distribution and mean observation time of our study patients. RESULTS: 45 SAEs and 14,404 AEs were reported (i.e. 2.4 SAEs and 754 AEs per 10,000 patients). The number of reported deaths (9) was only 5% of the statistically expected number (180). Applying the resulting correction factor of 20 to all reported SAEs, resulted in 900 expected SAEs (versus 45 reported) or 47 per 10,000 patients. CONCLUSIONS: Without verifying the accuracy of a measurement, results remain speculative. Our internal standard for the first time provides a means of verifying the accuracy of the reported SAE rate and correcting it to the statistically expected SAE rate.

Are elevated homocysteine plasma levels related to peripheral arterial disease? Results from a cross-sectional study of 6880 primary care patients.

BACKGROUND: It is still unclear whether the strength of the association between elevated plasma homocysteine (HC) levels and peripheral arterial disease (PAD), coronary artery disease (CAD) and cerebrovascular disease (CVD) is similar. METHODS: Fasting homocysteine plasma levels were measured in 6880 unselected primary care patients aged 65 years or older. Presence of PAD was determined with the ankle brachial index, and both CAD and CVD were recorded according to patient history. RESULTS: Median homocysteine levels in the total sample (58.0% females, mean age 72.5 years, mean body mass index 27.3 kg m-2) differed between patients with and without PAD: 15.2 micro mol L-1 (95% confidence interval [CI] 14.8; 15.7, vs. 13.9 micro mol L-1 (CI: 13.8; 14.1; P < 0.001). Peripheral arterial disease prevalence moderately increased from 13.0% in the lowest HC quintile to 24.3% in the highest quintile (crude odds ratio [OR], 2.1 [CI: 1.7; 2.6]). The frequency of atherothrombotic manifestations in the patients' history increased nearly linearly across the homocysteine quintiles in the univariate analysis. However, the association diminished substantially after adjusting for known interfering variables: the ORs between the HC highest fifth vs. lowest fifth (adjusted for age, gender, smoking status, diabetes, hypertension lipid disorders, and estimated glomerular filtration rate levels) for PAD decreased to 1.4, for CAD to 1.0 (NS), and for CVD to 1.1. (NS). CONCLUSIONS: Elevated HC is only slightly more related to PAD than to CAD and CVD. After adjustment for known risk factors, the effect size is small, and an association can no longer be observed between homocysteine and CAD and CVD.

Practical experience with the design and analysis of a three-armed equivalence study.

OBJECTIVE: While there is a lot of experience with the design, conduct and interpretation of bioequivalence studies, the methodology of trials concerning therapeutic equivalence is still at an early stage of development. Two-armed equivalence studies involve special problems of interpretation, which can be partly solved by the introduction of a third (placebo) arm. We describe a trial in which the therapeutic equivalence of horse chestnut seed extract (HCSE) and compression treatment was to be demonstrated in patients with chronic venous insufficiency (CVI). Compression is regarded as the standard therapy in this field. However, the efficacy of compression in terms of the variable of primary interest, namely oedema reduction, has never been demonstrated according to current methodological rules. Thus, the 'standard' had to be established in the trial itself. This can be achieved by demonstration of relevant superiority in comparison with placebo. METHODS: Two hypotheses had to be tested: (1) the relevant superiority of compression compared with placebo as a precondition for (2) the at most irrelevant inferiority of HCSE in comparison with compression ('equivalence'). For both corresponding statistical tests, the irrelevance criterion -- formulated as standardized difference -- was set to 0.5. RESULTS: Therapeutic equivalence could not be demonstrated following this design, because compression failed to be relevantly superior compared with placebo, even though HCSE was shown to be at most irrelevantly inferior compared with compression. Explorative analyses show that it is not possible to reject simultaneously both null hypotheses with the obtained data when using equal irrelevance limits for both tests. CONCLUSION: Although the primary objective of the trial could not be achieved, the results were encouraging. Thus, a new study was planned and started based on the observed data. The concept of a shifted null hypothesis may be applied to 'routine' clinical trials too; using 'no difference' as the null hypothesis in a trial does not seem to be meaningful when in fact an at least relevant difference is required.

Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency.

BACKGROUND: Diseases of the venous system are widespread disorders sometimes associated with modern civilisation and are among the major concerns of social and occupational medicine. This study was carried out to compare the efficacy (oedema reduction) and safety of compression stockings class II and dried horse chestnut seed extract (HCSE, 50 mg aescin, twice daily). METHODS: Equivalence of both therapies was examined in a novel hierarchical statistical design in 240 patients with chronic venous insufficiency. Patients were treated over a period of 12 weeks in a randomised, partially blinded, placebo-controlled, parallel study design. FINDINGS: Lower leg volume of the more severely affected limb decreased on average by 43.8 mL (n = 95) with HCSE and 46.7 mL (n = 99) with compression therapy, while it increased by 9.8 mL with placebo (n = 46) after 12 weeks therapy for the intention-to-treat group (95% CI: HCSE: 21.1-66.4; compression: 30.4-63.0; placebo: 40.0-20.4). Significant oedema reductions were achieved by HCSE (p = 0.005) and compression (p = 0.002) compared to placebo, and the two therapies were shown to be equivalent (p = 0.001); in this design, however, compression could not be proven as standard with regard to oedema reduction in the statistical test procedure. Both HCSE and compression therapy were well tolerated and no serious treatment-related events were reported. INTERPRETATION: These results indicate that compression stocking therapy and HCSE therapy are alternative therapies for the effective treatment of patients with oedema resulting from chronic venous insufficiency.

How to evaluate measuring methods in the case of non-defined external validity.

In the clinical routine of chronic diseases, a new measurement has to be compared to an established criterion to see whether there is agreement on assessing disease progress. Because of the nonexistence of established criteria for rheumatoid arthritis the evaluation of grading systems for radiological assessment needs an alternative approach. Using the measurement error as a measure for repeatability and rater agreement in comparison to the progress of the grading score might be a solution to this dilemma.

Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group.

Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.