[Which factors are associated with the use of potentially inadequate medications (PIM) in the elderly? : Results from the German health interview and examination survey (DEGS1)]. / Welche Faktoren begünstigen die Anwendung potenziell ungeeigneter Medikamente bei älteren Menschen? : Ergebnisse aus der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1).

BACKGROUND: Recent studies demonstrate a relationship between the prescription of potentially inappropriate medications (PIM) for patients 65 years or older and an increased risk for adverse events, in particular hospitalisations. The RKI conducted DEGS1-Survey ("German health interview and examination survey for adults") provides a representative sample of the target population to identify determinants for PIM use. OBJECTIVE: The aim of this study was to determine characteristics of older persons in Germany, who currently use PIM, and if there are subpopulations among older persons with a particularly high PIM use. METHODS: Within the DEGS1-Survey a total of 175 variables regarding health and social aspects were documented from 1392 community-dwelling persons between 65 and 79 years of age, and medication intake during the last seven days was recorded. PIM drugs were identified according to the PRISCUS list. Associations between PIM use and variables recorded were evaluated by means of multivariate statistical models. RESULTS: Within seven days before the survey PIM drugs were used by 13.0% (95%-CI: 10.7-15.6) of the respondents. The following factors significantly increase the risk for receiving a PIM: number of drugs taken in the last seven days; number of visits to different physician specialists during the last 12 months; sleep disorders; psychiatric condition, and diseases affecting the musculoskeletal system. The majority of PIMs were antidepressants and anxiolytics/sedatives. Elderly women with depression, sleep disorders, and a need for analgesics are particularly affected by increased PIM use. They deserve special attention in this regard.

Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the ASA low-response prevalence in CVD, CAD and PAD.

Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events in patients with atherosclerosis, a substantial number of incidents continue to occur. As only limited data exist we evaluated the antiplatelet effectiveness of ASA in patients with different manifestations of atherosclerosis as in cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD). For the evaluation of the antiplatelet effectiveness of ASA we used whole blood aggregometry (Chrono-log Model 590). The patients in the different subgroups received ASA 100, 200 or 500 mg daily. We analysed 737 consecutive patients: 47.5 % with CVD, 33.6 % with CAD, and 18.9 % with PAD. We identified 28.0 % of the CVD, 18.1 % of the CAD and 21.6 % of the PAD patients to be ASA low-responder (ALR). Comparing subgroups treated with 100 mg ASA, 36.4 % were ALR in the CVD group as were 13.1 % of the CAD and 21.6 % of the PAD patients. Multivariate regression analysis revealed an odds ratio for being ALR of 4.50 (95 % confidence interval (CI) 1.70-11.9) when 100 mg and of 2.97 (95 % CI 1.58-5.60) when 200 mg ASA was taken compared to a dose of 500 mg. Despite the proven benefits of antiplatelet therapy in the secondary prevention of atherosclerotic disease, current antiplatelet management is suboptimal as up to 36 % of patients failed to achieve an adequate platelet inhibitory effect. Our findings may explain, at least in part, the high rates of cardiovascular events observed in the course of atherothrombotic disease and support the need to improve antiplatelet therapy.

Tailored antiplatelet therapy can overcome clopidogrel and aspirin resistance--the BOchum CLopidogrel and Aspirin Plan (BOCLA-Plan) to improve antiplatelet therapy.

BACKGROUND: Dual antiplatelet therapy using acetylsalicylic acid (ASA, aspirin) and clopidogrel is of great importance following coronary stenting. However, the variable platelet inhibitory effectiveness compromises the antithrombotic advantages provided by dual antiplatelet therapy. The aim of this single-center prospective study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel according to a prespecified therapy algorithm. METHODS: Platelet function testing using whole blood aggregometry (Chronolog 590) was performed 48 hours following coronary stenting (for either acute coronary syndromes or stable coronary artery disease) on 504 patients. The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low responders (CLR: >5 ohm; adenosine diphosphate (ADP) 5 µM) and/or ASA low responders (ALR: >0 ohm; arachidonic acid 10 µM) were treated according to a structured therapy plan: in the case of CLR, the maintenance + dose was doubled (repeated loading dose followed by 150 mg daily), and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ALR was treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification did not take effect sufficiently. In addition, ADP receptor antagonist 2-methylthioadenosine 5'-monophosphate triethylammonium salt (MeSAMP) testing and ASA incubation were performed to rule out either a platelet ADP-receptor defect or an ASA pharmacokinetic resistance. RESULTS: Of the total cohort of 504 patients, we detected 30.8% clopidogrel low-responders and 19.4% aspirin low-responders. For ALR, with a dose adjustment of 300 mg ASA daily, 94.6% of ALR were effectively treated and the residual 5.4% by administration of daily dosages of 500 mg ASA. This means that after modification of the ASA maintenance dose, all initial ALRs had an adequate antiplatelet response. The results for clopidogrel revealed that 69% of the CLR were treated effectively by increasing the clopidogrel dose to 150 mg daily. When prasugrel was not available or contraindicated, 12.7% of the remaining low responders showed an adequate result after being switched to ticlopidine. Consequently, by applying the therapy algorithm, we were able to reduce the CLR prevalence by 86.6%. On including prasugrel in the therapy plan, we were finally able to eliminate thienopyridine low response. In addition, no ADP receptor defect was found in this study as a potential reason for CLR. We identified the following factors associated with both CLR and ALR status: acute coronary syndromes, positive troponin values as well as diabetes mellitus and elevated HbA1C values and a higher platelet count. Furthermore, our data revealed for CLR elevated C-reactive protein values and a high PREDICT-score (including an age >65 years, acute coronary syndrome, diabetes mellitus, renal failure, and reduced left ventricular function) as risk factors. The following factors correlated with the risk of ASA low response: patients with elevated hemoglobin, serum creatinine and C-reactive protein values. In addition, medication with nitrates reduced the risk of being CLR. As also holds true for CLR, we found the PREDICT-score to be correlated to the risk of being ALR. However, by far the strongest risk factor for CLR or ALR was the fact of dual resistance. CONCLUSION: Following a structured therapy plan based on a "test and treat" strategy, the prevalence of clopidogrel or aspirin low response can be significantly reduced and the risk of inadequate dual antiplatelet therapy minimized.

BAPA, a synthetic dual inhibitor of Factor Xa and Thrombin, extends the storage-time to a maximum of 12 hours in ADP- and 24 hours in arachidonic acid-induced impedance aggregometry.

Impedance aggregometry is mainly limited by the time-dependent instability of platelets in whole blood samples, caused by the influence of ex-vivo anticoagulants. The synthesis of a new anticoagulant, Benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA), has recently been introduced. Data from recent studies suggest stable results for up to 32 h. In view of this data we were interested in the results of ADP- and arachidonic acid (AA)-induced measurements after a prolonged storage time depending on the use of citrate or BAPA. Blood samples from 24 healthy individuals were anticoagulated with either citrate or BAPA. ADP- and AA-induced measurements were carried out between 2 h and up to 48 h after blood samples were taken. Results of ADP-induced measurements remained stable for 8 h in citrated and for a maximum of 12 h in BAPA-anticoagulated samples. AA-induced measurements yielded stable results up to 12 h in citrated and up to 24 h in BAPA anticoagulated blood. These data demonstrate that the storage time for whole blood impedance aggregometry can be prolonged when BAPA is used as an anticoagulant. However, in contrast to previous studies implicating considerably longer potential storage times we could not see a clear overall purpose in using BAPA. Further studies including blood samples of patients and the comparison of BAPA to other anticoagulants are necessary to define the potential role of BAPA anticoagulated samples.

Peripheral arterial disease as an independent predictor for excess stroke morbidity and mortality in primary-care patients: 5-year results of the getABI study.

BACKGROUND: There is controversial evidence with regard to the significance of peripheral arterial disease (PAD) as an indicator for future stroke risk. We aimed to quantify the risk increase for mortality and morbidity associated with PAD. METHODS: In an open, prospective, noninterventional cohort study in the primary care setting, a total of 6,880 unselected patients > or =65 years were categorized according to the presence or absence of PAD and followed up for vascular events or deaths over 5 years. PAD was defined as ankle-brachial index (ABI) <0.9 or history of previous peripheral revascularization and/or limb amputation and/or intermittent claudication. Associations between known cardiovascular risk factors including PAD and cerebrovascular mortality/events were analyzed in a multivariate Cox regression model. RESULTS: During the 5-year follow-up [29,915 patient-years (PY)], 183 patients had a stroke (incidence per 1,000 PY: 6.1 cases). In patients with PAD (n = 1,429) compared to those without PAD (n = 5,392), the incidence of all stroke types standardized per 1,000 PY, with the exception of hemorrhagic stroke, was about doubled (for fatal stroke tripled). The corresponding adjusted hazard ratios were 1.6 (95% confidence interval, CI, 1.1-2.2) for total stroke, 1.7 (95% CI 1.2-2.5) for ischemic stroke, 0.7 (95% CI 0.2-2.2) for hemorrhagic stroke, 2.5 (95% CI 1.2-5.2) for fatal stroke and 1.4 (95% CI 0.9-2.1) for nonfatal stroke. Lower ABI categories were associated with higher stroke rates. Besides high age, previous stroke and diabetes mellitus, PAD was a significant independent predictor for ischemic stroke. CONCLUSIONS: The risk of stroke is substantially increased in PAD patients, and PAD is a strong independent predictor for stroke.

Pantoprazole does not influence the antiplatelet effect of clopidogrel-a whole blood aggregometry study after coronary stenting.

Recent attention has been drawn to a potential drug-drug interaction observed between clopidogrel and proton pump inhibitors (PPIs). However, this potential interaction may not be a class effect of PPIs. We investigated if pantoprazole, which has a different metabolism than omeprazole, diminishes the effectiveness of clopidogrel. Our study included 336 patients (mean age 64.6 years; 106 women) 48 hours after percutaneous coronary stent implantation with a loading dose of 600 mg clopidogrel hydrogensulfate and 500 mg aspirin, followed by 75 mg clopidogrel and 100 mg aspirin daily. Whereas 188 patients (59 women) were not given any PPI comedication, 122 patients received pantoprazole and 26 either omeprazole or esomeprazole. The platelet aggregation followed by impedance aggregometry (in Ohm) was induced by 5 mmol/L adenosine diphosphate. The percentage of clopidogrel low-response (CLR) was similar between the non-PPI group [2.75 Ohm (confidence interval, CI: 2.25-3.26); 21.9% CLR] and the pantoprazole group [2.33 Ohm (CI: 1.79-2.87); 16.4% CLR] but higher in patients treated with omeprazole/esomeprazole (3.00 Ohm (CI: 1.49-4.51); 30.8% CLR). Multivariate regression analysis reveals that the risk of CLR in the pantoprazole comedication group was not increased compared with the group without any PPI [odds ratio 0.59 (CI: 0.31-1.13) 0.11]. Our data suggest that pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel early after coronary stenting. Therefore, the use of pantoprazole seems preferable in patients treated with clopidogrel when a concomitant medication with a PPI is indicated.

Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: study protocol of a single arm trial preparing an RCT [ISRCTN58562962].

BACKGROUND: Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted. METHODS: The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs. CONCLUSION: A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58562962.

German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups.

BACKGROUND: To our knowledge, verum acupuncture has never been directly compared with sham acupuncture and guideline-based conventional therapy in patients with chronic low back pain. METHODS: A patient- and observer-blinded randomized controlled trial conducted in Germany involving 340 outpatient practices, including 1162 patients aged 18 to 86 years (mean +/- SD age, 50 +/- 15 years) with a history of chronic low back pain for a mean of 8 years. Patients underwent ten 30-minute sessions, generally 2 sessions per week, of verum acupuncture (n = 387) according to principles of traditional Chinese medicine; sham acupuncture (n = 387) consisting of superficial needling at nonacupuncture points; or conventional therapy, a combination of drugs, physical therapy, and exercise (n = 388). Five additional sessions were offered to patients who had a partial response to treatment (10%-50% reduction in pain intensity). Primary outcome was response after 6 months, defined as 33% improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale questionnaire or 12% improvement or better on the back-specific Hanover Functional Ability Questionnaire. Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement. RESULTS: At 6 months, response rate was 47.6% in the verum acupuncture group, 44.2% in the sham acupuncture group, and 27.4% in the conventional therapy group. Differences among groups were as follows: verum vs sham, 3.4% (95% confidence interval, -3.7% to 10.3%; P = .39); verum vs conventional therapy, 20.2% (95% confidence interval, 13.4% to 26.7%; P < .001); and sham vs conventional therapy, 16.8% (95% confidence interval, 10.1% to 23.4%; P < .001. CONCLUSIONS: Low back pain improved after acupuncture treatment for at least 6 months. Effectiveness of acupuncture, either verum or sham, was almost twice that of conventional therapy.

The effect of time-to-surgery on outcome in elderly patients with proximal femoral fractures.

BACKGROUND: Whether reducing time-to-surgery for elderly patients suffering from hip fracture results in better outcomes remains subject to controversial debates. METHODS: As part of a prospective observational study conducted between January 2002 and September 2003 on hip-fracture patients from 268 acute-care hospitals all over Germany, we investigated the relationship of time-to-surgery with frequency of post-operative complications and one-year mortality in elderly patients (age > or =65) with isolated proximal femoral fracture (femoral neck fracture or pertrochanteric femoral fracture). Patients with short (< or =12 h), medium (> 12 h to < or =36 h) and long (> 36 h) times-to-surgery, counting from the time of the fracture event, were compared for patient characteristics, operative procedures, post-operative complications and one-year mortality. RESULTS: Hospital data were available for 2916 hip-fracture patients (mean age (SD) in years: 82.1 (7.4), median age: 82; 79.7% women). Comparison of groups with short (n = 802), medium (n = 1191) and long (n = 923) time-to-surgery revealed statistically significant differences in a few patient characteristics (age, American Society of Anesthesiologists ratings classification and type of admission) and in operative procedures (total hip endoprosthesis, hemi-endoprosthetic implants, other osteosynthetic procedures). However, comparison of these same groups for frequency of postoperative complications revealed only some non-significant associations with certain complications such as post-operative bleeding requiring treatment (early surgery patients) and urinary tract infections (delayed surgery patients). Both unadjusted rates of one-year all-cause mortality (between 18.1% and 20.5%), and the multivariate-adjusted hazard ratios (HR for time-to-surgery: 1.04; p = 0.55) showed no association between mortality and time-to-surgery. CONCLUSION: Although this study found a trend toward more frequent post-operative complications in the longest time-to-surgery group, there was no effect of time-to-surgery on mortality. Shorter time-to-surgery may be associated with somewhat lower rates of post-operative complications such as decubitus ulcers, urinary tract infections, thromboses, pneumonia and cardiovascular events, and with somewhat higher rates of others such as post-operative bleeding or implant complications.

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

BACKGROUND: The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews. METHODS: A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes. RESULTS: Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points). CONCLUSION: Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires.

A new efficient trial design for assessing reliability of ankle-brachial index measures by three different observer groups.

BACKGROUND: The usual method of assessing the variability of a measure such as the ankle brachial index (ABI) as a function of different observer groups is to obtain repeated measurements. Because the number of possible observer-subject combinations is impractically large, only a few small studies on inter- and intraobserver variability of ABI measures have been carried out to date. The present study proposes a new and efficient study design. This paper describes the study methodology. METHODS: Using a partially balanced incomplete block design, six angiologists, six primary-care physicians and six trained medical office assistants performed two ABI measurements each on six individuals from a group of 36 unselected subjects aged 65-70 years. Each test subject is measured by one observer from each of the three observer groups, and each observer measures exactly six of the 36 subjects in the group. Each possible combination of two observers occurs exactly once per patient and is not repeated on a second subject. The study involved four groups of 36 subjects (144), plus standbys. RESULTS: The 192 volunteers present at the study day were similar in terms of demographic characteristics and vascular risk factors: mean age 68.6 +/- 1.7; mean BMI 29.1 +/- 4.6; mean waist-hip ratio 0.92 +/- 0.09; active smokers 12%; hypertension 60.9%; hypercholesterolemia 53.4%; diabetic 17.2%. A complete set of ABI measurements (three observers performing two Doppler measurements each) was obtained from 108 subjects. From all other subjects at least one ABI measurement was obtained. The mean ABI was 1.08 (+/- 0.13), 15 (7.9%) volunteers had an ABI < 0.9, and none had an ABI > 1.4, i.e. a ratio that may be associated with increased stiffening of the arterial walls. CONCLUSION: This is the first large-scale study investigating the components of variability and thus reliability in ABI measurements. The advantage of the new study design introduced here is that only one sixth of the number of theoretically possible measurements is required to obtain information about measurement errors. Bland-Altman plots show that there are only small differences and no systematic bias between the observers from three occupational groups with different training backgrounds.

Patients with femoral or distal forearm fracture in Germany: a prospective observational study on health care situation and outcome.

BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in later life, predominantly due to simple falls, but modulated by other relevant factors such as osteoporosis. Fracture incidence rates rise with age. Because of the growing proportion of elderly people in Western industrialized societies, the number of these fractures can be expected to increase further in the coming years, and with it the burden on healthcare resources. Our study therefore assessed the effects of these injuries on the health status of older people over time. The purpose of this paper is to describe the study method, clinical parameters of fracture patients during hospitalization, mortality up to one and a half years after discharge in relation to various factors such as type of fracture, and to describe changes in mobility and living situation. METHODS: Data were collected from all consecutive patients (no age limit) admitted to 423 hospitals throughout Germany with distal radius or femoral fractures (57% acute-care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only) between January 2002 and September 2003. Polytrauma and coma patients were excluded. Demographic characteristics, exact fracture location, mobility and living situation, clinical and laboratory parameters were examined. Current health status was assessed in telephone interviews conducted on average 6-7 months after discharge. Where telephone contact could not be established, at least survival status (living/deceased/date of death) was determined. RESULTS: The study population consisted of 12,520 femoral fracture patients (86.8% hip fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture patients, average age 67.6 years, 81.6% female. Women's average age was 6.6 (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001). Only 4.6% of femoral fracture patients experienced changes in their living situation post-discharge (53% because of the fracture event), although less than half of subjects who were able to walk without assistive devices prior to the fracture event (76.7%) could still do so at time of interview (34.9%). At time of interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm fracture patients reported no change in living situation at all. Of the femoral fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%) died during hospital stay. Post-discharge (follow-up one and a half years) 1,463 femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation patients), but only 60 forearm fracture patients (3.0%). Ninety percent of femoral fracture deaths happened within the first year, approximately 66% within the first 6 months. More acute-care patients with a pertrochanteric fracture died within one year post-discharge (20.6%) than patients with a cervical fracture (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still alarmingly high and highest after pertrochanteric fracture. Although at time of interview more than half of femoral fracture patients reported reduced mobility, most patients (96%) attempt to live at home. Since forearm fracture patients were on average 10 years younger than femoral fracture patients, forearm fractures may be a means of diagnosing an increased risk of later hip fractures.

Designing an acupuncture study: the nationwide, randomized, controlled, German acupuncture trials on migraine and tension-type headache.

BACKGROUND: In the nationwide German Acupuncture Trials (GERAC) verum acupuncture, based on Traditional Chinese Medicine (TCM), was to be tested against sham acupuncture for the entities classified in the West as "migraine" (MIG) and "tension-type headache" (TTH). However, there were no generally accepted guidelines on how to perform a consistent verum or sham treatment. OBJECTIVE: To design broadly consensual verum and sham acupuncture treatment protocols for MIG and TTH for the GERAC. METHODOLOGY: Extensive literature study and consultation with acupuncture experts. Personal interviews, both free and structured, e-mail discussions, and phone conferences were used. RESULTS: Broadly consensual acupuncture protocols for MIG and TTH for verum and sham acupuncture were developed. They included semi-standardized point combinations with clearly described point selection rules based on TCM acupuncture diagnoses. A procedure was developed to help ensure homogenous treatment quality in a large multicenter trial. CONCLUSIONS: The GERAC study design allowed acupuncture to be tested in a naturalistic environment. The rigorous study design and the large number of physician investigators guaranteed a high external validity for the results. The results will help determine the significance of Chinese acupuncture in the context of Western medicine for the treatment of MIG and TTH.

Association between Potentially Inappropriate Medication (PIM) Use and Risk of Hospitalization in Older Adults: An Observational Study Based on Routine Data Comparing PIM Use with Use of PIM Alternatives.

OBJECTIVE: The safety of potentially inappropriate medications (PIMs) in elderly patients is still debated. Using the PRISCUS list, we examined the incident all-cause hospitalization risk associated with PIMs compared to PIM alternatives during the 180 days post individual first pharmacy dispensing (index date). METHODS: Routine claims data from a German health insurer on 392,337 ambulatory patients aged ≥65 years, were used to estimate adjusted hazard ratios (HRs) for hospitalization associated with incident PIM use. Observation period was January 2009 -December 2010. Users of PIM alternatives, as defined by the PRISCUS list, were the reference group. Patients with PIM dispensing or hospital stay in a six month "washout" period (second half of 2008) were excluded. All potential confounders were determined in the half year before the individual index date. RESULTS: In the total cohort 60.7% were female. Median age was 73 years. Of 79,041 incident PIM users, 58.4% had PIMs dispensed in one quarter of 2009 or 2010, 19.3% in two quarters, and 22.3% in three or more quarters. There were 126,535 hospitalizations during the observation period, and 47,470 of them occurred within 180 days post first dispensing. Multivariable Cox regression analysis revealed PIM use as a significant risk factor for hospitalization (HR 1.378; 95% CI 1.349-1.407) compared to use of PIM alternatives. CONCLUSIONS: PIM use compared to use of PIM alternatives is associated with an increased risk of all-cause hospitalization in the 180 days following individual index date. Future analyses comparing a single PIM with its corresponding alternative may help identify those PIMs responsible for this.

Clopidogrel high-on-treatment platelet reactivity in acute ischemic stroke patients.

BACKGROUND: During the first days following an acute ischemic stroke, a consistently good antiplatelet effect of clopidogrel is important due to the increased risk of recurrent ischemia. However, the platelet inhibitory effectiveness of clopidogrel is variable for multifactorial reasons. We investigated the prevalence and risk factors for clopidogrel high-on-treatment platelet reactivity (clopidogrel-HTPR) in acute ischemic stroke patients. METHODS: Using multiple-electrode impedance aggregometry (MEA), the antiplatelet effectiveness of clopidogrel in patients with acute ischemic stroke was prospectively evaluated. Measurements were performed 48 h after therapy was either initiated or continued after hospital admission. Clopidogrel-HTPR was defined as ADP-induced values>47 U. RESULTS: A total of 159 patients (71.8 ± 9.8 years, 69 female) were enrolled and 44% (n=70) patients were clopidogrel-HTPR. 35 of the clopidogrel-HTPR were retested within one week and 57.1% (n=20) showed a good clopidogrel response during subsequent testing. We identified diabetes mellitus (36.3% vs. 54.4%, p-value=0.003) and higher HbA1c values (6.3% vs. 6.8%, p=0.007) as risk factors for clopidogrel-HTPR. Multivariate regression analysis revealed that diabetes mellitus more than doubled the risk of clopidogrel-HTPR (OR 2.41; 95%-CI 1.19-4.88; p=0.015). CONCLUSIONS: Clopidogrel-HTPR was found in 44% of the patients with acute ischemic stroke. Besides time-dependency of the clopidogrel effect, major risk factors for clopidogrel-HTPR were diabetes mellitus and higher HbA1c values. Further investigations are required to analyse if a function test guided strategy has the potential to optimize the antiplatelet therapy of acute stroke patients.

Prevalence of self-reported pain, joint complaints and knee or hip complaints in adults aged ≥ 40 years: a cross-sectional survey in Herne, Germany.

BACKGROUND: Pain and musculoskeletal complaints are among the most common symptoms in the general population. Despite their epidemiological, clinical and health economic importance, prevalence data on pain and musculoskeletal complaints for Germany are scarce. METHODS: A cross-sectional survey of a random sample of citizens of Herne, Germany, aged ≥ 40 years was performed. A detailed self-complete postal questionnaire was used, followed by a short reminder questionnaire and telephone contacts for those not responding. The questionnaire contained 66 items, mainly addressing pain of any site, musculoskeletal complaints of any site and of knee and hip, pain intensities, the Western Ontario MacMaster Universities (WOMAC) index, medication, health care utilization, comorbidities, and quality of life. RESULTS: The response rate was 57.8% (4,527 of 7,828 individuals). Survey participants were on average 1.3 years older, and the proportion of women among responders tended to be greater than in the population sample. There was no age difference between the population sample and 2,221 participants filling out the detailed questionnaire. The following standardized prevalences were assessed: current pain: 59.7%, pain within the past four weeks: 74.5%, current joint complaints: 49.3%, joint complaints within the past four weeks and twelve month: 62.8% and 67.4%, respectively, knee as the site predominantly affected: 30.9%, knee bilateral: 9.7%, hip: 15.2%, hip bilateral: 3.5%, knee and hip: 5.5%. Pain and musculoskeletal complaints were significantly more often reported by women. A typical relationship of pain and joint complaints to age could be found, i.e. increasing prevalences with increasing age categories, with a drop in the highest age groups. In general, pain and joint pain were associated with comorbidity and body mass index as well as quality of life. CONCLUSIONS: Our data confirm findings of other recent national as well as European surveys. The high site specific prevalences of knee and hip complaints underline the necessity to further investigate characteristics and consequences of pain and symptomatic osteoarthritis of these joints in adults in Germany.

Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke.

Antiplatelet agents are essential in treating patients with acute ischaemic stroke (AIS) to prevent recurrent ischaemic events. The aim of this study was to evaluate the effectiveness of early antiplatelet therapy with different aspirin (ASA) dosages in patients with AIS. This observational study included 454 patients with AIS in whom antiplatelet treatment was initiated. The antiplatelet effect was determined by whole blood aggregometry within 48 hours after antplatelet therapy was initiated. An impedance change exceeding 0 W after stimulation with arachidonic acid was defined as ASA low response (ALR) and ≥5 Ω in ADP-stimulated specimen as clopidogrel LR. Of the study group 53.5% patients were treated with 200 mg ASA orally, 27.5% with 500 mg ASA intravenously, 8.6% with 100 mg ASA orally, and 7.7% with 75 mg clopidogrel. A dose-dependent antiplatelet effect of ASA treatment was found: 18.4% of patients with 500 mg ASA intravenously were ALR, in contrast to 32.5% on 200 mg and 35.9% on 100 mg ASA orally. Clopidogrel treatment without a loading dose resulted in a high proportion of LR (45.7%). Using the propensity score method revealed a three times higher risk for ALR for patients treated with ASA 200 mg [odds ratio 2.99 (1.55-5.79)] compared to treatment with ASA 500 mg. In conclusion, initiating antiplatelet therapy in patients with AIS resulted in a dose-dependent insufficient platelet inhibitory effect. Our findings suggest using a loading dose of 500 mg ASA intravenously as this seems to be favourable when a sufficient early platelet inhibitory effect is wanted.

Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry.

BACKGROUND: Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. METHODS: Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. RESULTS: Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. CONCLUSION: Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin.

Prevalence of anemia in elderly patients in primary care: impact on 5-year mortality risk and differences between men and women.

BACKGROUND: Increased mortality in patients with anemia has been demonstrated in disabled, seriously ill or hospitalized patients. In industrialized nations with their aging societies, however, elderly but apparently healthy family-physician patients are an important demographic group from a public-health perspective. We therefore set out to evaluate the prevalence of anemia in this group and associations between anemia and 5-year all-cause mortality, adjusted for multiple other established risk factors and chronic diseases. METHODS: This was a monitored, prospective cohort study in Germany with 344 representative family physicians who documented, consecutively, elderly patients (aged >or= 65 years). Extensive fasting plasma parameters were collected at baseline. Anemia at inclusion was defined according to World Health Organization criteria (hemoglobin below 12 g/dl in women and 13 g/dl in men). All participants were followed up for death of any cause for 5.3 years. RESULTS: Among the 6880 individuals, 2905 men and 3975 women, aged 65-95 (mean age 72.5), mild anemia (hemoglobin levels >or=10 g/dl) was found in 6.1% of women and 8.1% of men. Among those patients, 36.1% of anemic men and 15.0% of anemic women died. In a Cox proportional hazards analysis, multiple adjusted for potential confounders including major comorbidities, a near doubling of the 5-year mortality risk in anemic men (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.5-2.4) was found, while in anemic women there was no risk increase at all (HR 1.1; 95% CI 0.8-1.6). Even if patients with the lowest hemoglobin concentration (<11 g/dl for women, <12 g/dl for men) are singled out for multiple-adjusted analysis, anemia in men was related to a significant mortality risk (HR 3.3; 95% CI 2.1-5.1), but not in women (HR 1.85; 95% CI 0.97-3.53). CONCLUSION: In typical elderly patients without severe comorbidities, mild anemia was significantly associated with greater mortality in men but not in women. Given the impact of sex on outcomes of older subjects with mild anemia, the current definition of anemia should be adjusted for elderly males towards a higher hemoglobin threshold. Interventional trials will be needed to determine whether a consistent correction of anemia improves mortality of older men.