Does residential exposure to air pollutants influence mortality and cardiovascular morbidity of older people from primary care?

BACKGROUND: Diseases affecting the cardiovascular system are the most common cause of death worldwide. In addition to classical risk factors of atherosclerosis, long-term exposure to particulate matter with particles of size up to 10 µm (PM10) in the atmosphere has become an increasing focus of scientific attention in recent decades. This study analyses the associations of residential-associated air pollutants exposure with all-cause mortality and cardiovascular morbidity of older patients in a primary care setting. METHODS: The "German Epidemiological Trial on Ankle Brachial Index" (getABI) is a prospective cohort study that started in 2001 and included 6,880 primary care patients with a follow-up of 7 years. The PM10 and nitrogen dioxide (NO2) concentrations in the atmosphere are interpolated values from the study "Mapping of background air pollution at a fine spatial scale across the European Union". The primary outcome in this analysis is death of any cause, a secondary outcome is onset of PAD. Cox proportional hazards regression was used in a two-step modelling, the first step with basic adjustment only for age, sex, and one or more air pollutants, the second with additional risk factors. RESULTS: A total of 6,819 getABI patients were included in this analysis. 1,243 of them died during the study period. The hazard ratio (HR) (1.218, 95%-confidence-interval (CI) 0.949-1.562) for the risk of death from any cause was elevated by 22% per 10 µg/m3 increase of PM10 in the fully adjusted model, although not statistically significant. Increased PM10 exposure in combination with the presence of PAD had a significantly increased risk (HR = 1.560, 95%-CI: 1.059-2.298) for this endpoint in the basic adjustment, but not in the fully adjusted model. 736 patients developed peripheral artery disease (PAD) during the course of the study. There was no association of air pollutants and the onset of PAD. CONCLUSIONS: Our analysis renders some hints for the impact of air pollutants (PM10, NO2, and proximity to major road) on mortality. Interaction of PAD with PM10 was found. There was no association of air pollutants and the onset of PAD. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00029733 (19/09/2022).

Socioeconomic factors and the onset of peripheral artery disease in older adults.

Background: As evidence concerning the impact of socioeconomic factors on the risk of peripheral artery disease (PAD) is sparse, we assessed the association of education and area-level factors (population density, type of municipality and local unemployment rate) on the onset of PAD in older adults. Patients and methods: The analysis used data of the getABI study, a prospective cohort study with seven years of follow-up. Onset of PAD was determined by ankle brachial index (<0.9) or PAD symptoms. Cox regression analysis was employed. Results: Out of 5,444 primary care attendees without PAD at baseline, there were 1,381 participants with PAD onset (cumulative observation time 31,739 years), yielding an event rate of 43.5 (0.95 confidence interval [0.95 CI] 41.2-45.8) per 1,000 person-years. Multivariable Cox regression analysis showed an association of PAD onset with low education (hazard ratio 1.29; 0.95 CI 1.14-1.46; P<0.001), high population density (0.93; 0.89-0.98; P=0.002), small cities (compared to large cities) (0.71; 0.53-0.96; P=0.027) and high local unemployment rate (1.04; 1.00-1.07; P=0.032). The impact of low education on PAD onset was higher for men (2.11; 1.64-2.72) than for women (1.22; 1.07-1.40) (interaction term P=0.013). Conclusions: Socioeconomic factors, education as well as area-level socioeconomic indicators, make independent contributions to PAD onset in older adults.

Gamma-glutamyl transferase as a risk factor for mortality and cardiovascular events in older adults - results from a prospective cohort study in a primary care setting (getABI).

Background: In primary care, the gamma-glutamyl transferase (GGT) activity is used for assessing hepatobiliary dysfunction, but is also known to be associated with the risk of cardiovascular events as well as overall mortality. As this knowledge is mainly based on cohorts with middle-aged participants, we aim to assess these associations in elderly patients in a primary care setting. Patients and methods: 6,880 unselected primary care patients, aged 65 years or older, were enrolled by 344 general practitioners all over Germany (getABI study). During seven years of follow-up, coronary heart disease (CHD) events (myocardial infarction or coronary revascularization), cerebrovascular events (stroke or carotid revascularization) and deaths were recorded. Event rates were calculated and Cox regression analysis with adjustment for age, gender, GGT, classical and other risk factors (e.g. education, homocysteine, C-reactive protein, vitamin D) was performed. Results: 1,243 patients died. 27.8 deaths per 1,000 patient years (0.95 confidence interval [0.95 CI]: 26.2-29.3) occurred in the whole cohort. 605 participants had a CHD event, i.e. 16.1 per 1,000 patient years (0.95 CI: 14.8-17.4). 296 cerebrovascular events were observed, i.e. 7.7 per 1,000 patient years (0.95 CI: 6.9-8.6). Cox regression analysis with adjustment for the above-mentioned risk factors showed a significant impact of baseline elevation of GGT above the 3rd quartile (women > 18 U/L, men > 26 U/L) compared to the rest on mortality (hazard ratio [HR] 1.38, 95% CI 1.22-1.56, p < 0.001) and cerebrovascular events (1.39, 95% CI: 1.08-1.79), p = 0.010), whereas the association with CHD events (HR: 1.16, 95% CI: 0.97-1.39, p = 0.103) showed no significance. Conclusions: In a primary care setting, GGT values have a significant association with overall mortality and cerebrovascular events, but not with CHD events in elderly patients.

Interactions between C-reactive protein and traditional risk factors in predicting mortality of older adults.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are known to be associated with cardiovascular (CV) morbidity and mortality in older adults, however, there seems to be heterogeneity of this association across subsets of individuals. We aim to assess the effects of interactions between CRP and one of the following traditional CV risk factors regarding all-cause mortality in unselected elderly men and women: age, sex, body mass index, diabetes, and hypertension. PATIENTS AND METHODS: Three hundred and forty-four general practitioners all over Germany enrolled 6,817 unselected participants, aged 65 years or older, and performed thorough examinations, including CRP measurement at baseline (getABI study). All-cause mortality was determined in the following seven years. Cox regression analyses were done using uni- and multivariable models. RESULTS: At baseline 4,172 participants of this cohort had a CRP value of ≤ 3 mg/L (low level CRP group), 2,645 participants had a CRP value of > 3 mg/L (high level CRP group). The unadjusted hazard ratio for all-cause death of the high level CRP group compared to the low level CRP group was 1.49 (95 % confidence interval [95 %CI] 1.34 to 1.66). After adjustment for sex, age, education, peripheral artery disease/media sclerosis, other prior vascular events, smoking status, diabetes, systolic blood pressure, antihypertensive medication, body mass index, cholesterol, and statin use, the hazard ratio was 1.34 (95 %CI 1.20 to 1.50). Significant interactions with CRP were found for sex (adjusted hazard ratio 1.38, 95 %CI 1.11 to 1.72), age (0.75, 95 %CI 0.60 to 0.94), and baseline systolic blood pressure (0.64, 95 % CI 0.51 to 0.81). The interactions of CRP with body mass index and of CRP with diabetes were not significant. CONCLUSIONS: In older German adults, there seem to be effect modifications by age, sex, and arterial hypertension regarding the effect of CRP in the prediction of all-cause mortality.

The risk of peripheral artery disease in older adults - seven-year results of the getABI study.

BACKGROUND: To assess the risk of peripheral artery disease (PAD) in older adults and the contribution of traditional and novel risk factors to the incidence of PAD. PATIENTS AND METHODS: 344 general practitioners (GPs), trained by vascular specialists all over Germany, enrolled 6,880 unselected participants aged 65 years or older (getABI study). The onset of PAD was determined by a regression method in the course of repeated measurements of the ankle brachial index (ABI) over seven years. PAD onset was defined by the declining linear regression ABI line reaching 0.9 or by PAD symptoms. RESULTS: The cumulative PAD incidence over seven years was 12.9%, corresponding to an incidence rate of 20.3 per 1000 person years (95% confidence interval [95%CI] 18.8 to 21.7). Logistic regression analysis showed that traditional risk factors contributed significantly to the risk of PAD: current smoker status (odds ratio 2.65, 95%CI 2.08 to 3.37), diabetes (1.35, 95%CI 1.13 to 1.62), and low-density lipoprotein >130 mg/dl (1.26, 95%CI 1.07 to 1.48). Three novel risk factor candidates showed significant impact on PAD incidence: elevated sensitive C-reactive protein level (1.23, 95%CI 1.05 to 1.45), impaired estimated glomerular filtration rate (1.27, 95%CI 1.03 to 1.56), and elevated homocysteine level (1.19, 95%CI 1.01 to 1.41). CONCLUSIONS: Older adults in Germany have a PAD risk of 12.9% per seven years. Potentially modifiable traditional PAD risk factors yield high impact on PAD incidence. Novel risk factor candidates may contribute to the risk of PAD.

Potentially inappropriate medication including drug-drug interaction and the risk of frequent falling, hospital admission, and death in older adults - results of a large cohort study (getABI).

Introduction: With growing age, multiple chronic diseases may result in polypharmacy. Drugs that should be avoided in older adults are called potentially inappropriate medications (PIM). Beyond PIM, drug-drug interactions (DDI) are known to be related to adverse drug events. This analysis examines the risk of frequent falling, hospital admission, and death in older adults associated with PIM and/or DDI (PIM/DDI) prescription. Materials and methods: This post hoc analysis used data of a subgroup of the getABI study participants, a large cohort of community-dwelling older adults. The subgroup comprised 2120 participants who provided a detailed medication report by telephone interview at the 5-year getABI follow-up. The risks of frequent falling, hospital admission, and death in the course of the following 2 years were analysed by logistic regression in uni- and multivariable models with adjustment for established risk factors. Results: Data of all 2,120 participants was available for the analysis of the endpoint death, of 1,799 participants for hospital admission, and of 1,349 participants for frequent falling. The multivariable models showed an association of PIM/DDI prescription with frequent falling (odds ratio (OR) 1.66, 95% confidence interval (CI) 1.06-2.60, p = 0.027) as well as with hospital admission (OR 1.29, 95% CI 1.04-1.58, p = 0.018), but not with death (OR 1.00, 95% CI 0.58-1.72, p = 0.999). Conclusion: PIM/DDI prescription was associated with the risk of hospital admission and frequent falling. No association was found with death by 2 years. This result should alert physicians to provide a closer look at PIM/DDI prescriptions.

Hospital-based, prospective, multicentre surveillance to determine the incidence of intussusception in children aged below 15 years in Germany.

BACKGROUND: A new vaccine against Rotavirus (RV) gastroenteritis was introduced in Germany in 2006. In 1997 the first RV vaccine was withdrawn due to an increased incidence in intussusception (IS). Thus, an accurate estimation of the incidence of IS is important for post-licensure surveillance. METHODS: IS-Data were obtained from the 'Erhebungseinheit für seltene pädiatrische Erkrankungen Deutschland' (ESPED, German surveillance unit for rare pediatric diseases) collaborations' central register where all cases of intussusception in Germany for the years 2006 and 2007 are collected (n = 1200). In order to obtain an unbiased estimate of the incidence, it is necessary to determine the population under risk out of which these cases originated, and the proportion of real cases not reported to the registry (underreporting). In order to assess underreporting, a random sample of 31 hospitals was re-assessed by an outside reviewer. The estimation of incidence was done using a single Maximum-Likelihood (ML) estimator based on data from both the registry and the sample. RESULTS: The uncorrected observed incidence was calculated to be 26.6/100,000 child-years for children below 1 year old, 23.8 for those below 2 years old, and 5.2 for those below 15 years old. The review revealed a mean reporting quota of about 41% and the ML approach yielded an incidence of 51.5/100,000 child-years (95%CI [41.7;61.1]) for children below 2 years of age. CONCLUSIONS: While substantial under-reporting led to very conservative estimates of the IS incidence, the approach described here allows an accurate estimation of IS incidence including corresponding confidence bands. Therefore, ML estimation is a straightforward instrument to derive stable, unbiased estimates in epidemiological studies with incomplete data.

Prospective observational cohort study on epidemiology, treatment and outcome of patients with traumatic brain injury (TBI) in German BG hospitals.

OBJECTIVES: Since 2000/2001, no large-scale prospective studies addressing traumatic brain injury (TBI) epidemiology in Germany have been published. Our aim was to look for a possible shift in TBI epidemiology described in other European countries, to look for possible changes in TBI management and to identify predictors of 1-year outcome especially in patients with mild TBI. DESIGN: Observational cohort study. SETTING: All patients suffering from a TBI of any degree between 1 October 2014 and 30 September 2015, and who arrived in one of the seven participating BG hospitals within 24 hours after trauma, were included. PARTICIPANTS: In total, 3514 patients were included. OUTCOME MEASURES: Initial care, acute hospital care and rehabilitation were documented using standardised documentation forms. A standardised telephone interview was conducted 3 and 12 months after TBI in order to obtain information on outcome. RESULTS: Peaks were identified in males in the early 20s and mid-50s, and in both sexes in the late 70s, with 25% of all patients aged 75 or older. A fall was the most frequent cause of TBI, followed by traffic accidents (especially bicyclists). The number of head CT scans increased, and the number of conventional X-rays of the skull decreased compared with 2000/2001. Besides, more patients were offered rehabilitation than before. Though most TBI were classified as mild, one-third of the patients participating in the telephone interview after 12 months still reported troubles attributed to TBI. Negative predictors in mild TBI were female gender, intracranial bleeding and Glasgow Coma Scale (GCS) 13/14. CONCLUSION: The observed epidemiologic shift in TBI (ie, elderly patients, more falls, more bicyclists) calls for targeted preventive measures. The heterogeneity behind the diagnosis 'mild TBI' emphasises the need for defining subgroups not only based on GCS.

Predicting negative health outcomes in older general practice patients with chronic illness: Rationale and development of the PROPERmed harmonized individual participant data database.

The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process.

A prognostic model predicted deterioration in health-related quality of life in older patients with multimorbidity and polypharmacy.

OBJECTIVES: To develop and validate a prognostic model to predict deterioration in health-related quality of life (dHRQoL) in older general practice patients with at least one chronic condition and one chronic prescription. STUDY DESIGN AND SETTING: We used individual participant data from five cluster-randomized trials conducted in the Netherlands and Germany to predict dHRQoL, defined as a decrease in EQ-5D-3 L index score of ≥5% after 6-month follow-up in logistic regression models with stratified intercepts to account for between-study heterogeneity. The model was validated internally and by using internal-external cross-validation (IECV). RESULTS: In 3,582 patients with complete data, of whom 1,046 (29.2%) showed deterioration in HRQoL, and 12/87 variables were selected that were related to single (chronic) conditions, inappropriate medication, medication underuse, functional status, well-being, and HRQoL. Bootstrap internal validation showed a C-statistic of 0.71 (0.69 to 0.72) and a calibration slope of 0.88 (0.78 to 0.98). In the IECV loop, the model provided a pooled C-statistic of 0.68 (0.65 to 0.70) and calibration-in-the-large of 0 (-0.13 to 0.13). HRQoL/functionality had the strongest prognostic value. CONCLUSION: The model performed well in terms of discrimination, calibration, and generalizability and might help clinicians identify older patients at high risk of dHRQoL. REGISTRATION: PROSPERO ID: CRD42018088129.

Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease.

BACKGROUND: Our aim was to assess the mortality and vascular morbidity risk of elderly individuals with asymptomatic versus symptomatic peripheral artery disease (PAD) in the primary care setting. METHODS AND RESULTS: This prospective cohort study included 6880 representative unselected patients >or=65 years of age with monitored follow-up over 5 years. According to physician diagnosis, 5392 patients had no PAD, 836 had asymptomatic PAD (ankle brachial index <0.9 without symptoms), and 593 had symptomatic PAD (lower-extremity peripheral revascularization, amputation as a result of PAD, or intermittent claudication symptoms regardless of ankle brachial index). The risk of symptomatic compared with asymptomatic PAD patients was significantly increased for the composite of all-cause death or severe vascular event (myocardial infarction, coronary revascularization, stroke, carotid revascularization, or lower-extremity peripheral vascular events; hazard ratio, 1.48; 95% confidence interval, 1.21 to 1.80) but not for all-cause death alone (hazard ratio, 1.13; 95% confidence interval, 0.89 to 1.43), all-cause death/myocardial infarction/stroke (excluding lower-extremity peripheral vascular events and any revascularizations; hazard ratio, 1.18; 95% confidence interval, 0.92 to 1.52), cardiovascular events alone (hazard ratio, 1.20; 95% confidence interval, 0.89 to 1.60), or cerebrovascular events alone (hazard ratio, 1.33; 95% confidence interval, 0.80 to 2.20). Lower ankle brachial index categories were associated with increased risk. PAD was a strong factor for the prediction of the composite end point in an adjusted model. CONCLUSIONS: Asymptomatic PAD diagnosed through routine screening in the offices of primary care physicians carries a high mortality and/or vascular event risk. Notably, the risk of mortality was similar in symptomatic and asymptomatic patients with PAD and was significantly higher than in those without PAD. In the primary care setting, the diagnosis of PAD has important prognostic value.

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.

Reduction of potentially inappropriate medication in the elderly: design of a cluster-randomised controlled trial in German primary care practices (RIME).

BACKGROUND: Potentially inappropriate medication (PIM) is considered to have potentially more harmful than beneficial health effects in elderly patients. A German example for a PIM list is the PRISCUS list that has been available since 2010. PIMs are associated with an increased risk of hospitalisation and adverse health outcomes. Furthermore, drug-drug interactions (DDI) may pose additional risks to patients. It is not yet clear how numbers of PIM and DDI can be reduced in community-dwelling seniors in primary care; nor is it clear whether patients would benefit from such deprescribing. METHODS: The cluster-randomised controlled study on the "Reduction of potentially Inappropriate Medication in the Elderly" (RIME study) is designed to examine whether an intervention based on the PRISCUS list can lower the proportion of community-dwelling people of ⩾70 years taking at least one PIM and/or medication inducing at least one dangerous DDI. The intervention consists of professional education and training on the reduction of PIM and DDI, and will be offered to either general practitioners (GPs) alone or GPs and their office staff in the experimental study arm. The control group will be offered professional education and training on more general issues of prescribing in the elderly, not specifically addressing PIM or DDI. The primary endpoint is the difference in the proportion of patients with at least one PIM or DDI between the start of the study and study closure after 12 months as compared between intervention and control group. Secondary endpoints include overall mortality, number of hospitalisations during the course of the study, quality of life and costs. Secondary analyses will be explorative, with the cluster randomisation being factored in. DISCUSSION: The RIME study will contribute to answering the question of whether an intervention based on the PRISCUS list can reduce the proportion of community-dwelling seniors aged ⩾70 years with at least one PIM and/or DDI, and whether this will result in positive health effects, for example, as regards hospitalisations. TRIAL REGISTRATION: The Study has been registered in the German Clinical Trials Register (DRKS) under the number DRKS00003610.

Are Anticholinergic Symptoms a Risk Factor for Falls in Older General Practice Patients With Polypharmacy? Study Protocol for the Development and Validation of a Prognostic Model.

Background: Cumulative anticholinergic exposure, also known as anticholinergic burden, is associated with a variety of adverse outcomes. However, studies show that anticholinergic effects tend to be underestimated by prescribers, and anticholinergics are the most frequently prescribed potentially inappropriate medication in older patients. The grading systems and drugs included in existing scales to quantify anticholinergic burden differ considerably and do not adequately account for patients' susceptibility to medications. Furthermore, their ability to link anticholinergic burden with adverse outcomes such as falls is unclear. This study aims to develop a prognostic model that predicts falls in older general practice patients, to assess the performance of several anticholinergic burden scales, and to quantify the added predictive value of anticholinergic symptoms in this context. Methods: Data from two cluster-randomized controlled trials investigating medication optimization in older general practice patients in Germany will be used. One trial (RIME, n = 1,197) will be used for the model development and the other trial (PRIMUM, n = 502) will be used to externally validate the model. A priori, candidate predictors will be selected based on a literature search, predictor availability, and clinical reasoning. Candidate predictors will include socio-demographics (e.g. age, sex), morbidity (e.g. single conditions), medication (e.g. polypharmacy, anticholinergic burden as defined by scales), and well-being (e.g. quality of life, physical function). A prognostic model including sociodemographic and lifestyle-related factors, as well as variables on morbidity, medication, health status, and well-being, will be developed, whereby the prognostic value of extending the model to include additional patient-reported symptoms will be also assessed. Logistic regression will be used for the binary outcome, which will be defined as "no falls" vs. "≥1 fall" within six months of baseline, as reported in patient interviews. Discussion: As the ability of different anticholinergic burden scales to predict falls in older patients is unclear, this study may provide insights into their relative importance as well as into the overall contribution of anticholinergic symptoms and other patient characteristics. The results may support general practitioners in their clinical decision-making and in prescribing fewer medications with anticholinergic properties.

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.

Profound influence of different methods for determination of the ankle brachial index on the prevalence estimate of peripheral arterial disease.

BACKGROUND: The ankle brachial index (ABI) is an efficient tool for objectively documenting the presence of lower extremity peripheral arterial disease (PAD). However, different methods exist for ABI calculation, which might result in varying PAD prevalence estimates. To address this question, we compared five different methods of ABI calculation using Doppler ultrasound in 6,880 consecutive, unselected primary care patients > or = 65 years in the observational get ABI study. METHODS: In all calculations, the average systolic pressure of the right and left brachial artery was used as the denominator (however, in case of discrepancies of > or = 10 mmHg, the higher reading was used). As nominators, the following pressures were used: the highest arterial ankle pressure of each leg (method #1), the lowest pressure (#2),only the systolic pressure of the tibial posterior artery (#3), only the systolic pressure of the tibial anterior artery (#4),and the systolic pressure of the tibial posterior artery after exercise (#5). An ABI < 0.9 was regarded as evidence of PAD. RESULTS: The estimated prevalence of PAD was lowest using method #1 (18.0%) and highest using method #2 (34.5%),while the differences in methods #3-#5 were less pronounced. Method #1 resulted in the most accurate estimation of PAD prevalence in the general population. Using the different approaches, the odds ratio for the association of PAD and cardiovascular (CV) events varied between 1.7 and 2.2. CONCLUSION: The data demonstrate that different methods for ABI determination clearly affect the estimation of PAD prevalence, but not substantially the strength of the associations between PAD and CV events. Nonetheless, to achieve improved comparability among different studies, one mode of calculation should be universally applied, preferentially method #1.

Acupuncture and knee osteoarthritis: a three-armed randomized trial.

BACKGROUND: Despite the popularity of acupuncture, evidence of its efficacy for reducing pain remains equivocal. OBJECTIVE: To assess the efficacy and safety of traditional Chinese acupuncture (TCA) compared with sham acupuncture (needling at defined nonacupuncture points) and conservative therapy in patients with chronic pain due to osteoarthritis of the knee. DESIGN: Randomized, controlled trial. SETTING: 315 primary care practices staffed by 320 practitioners with at least 2 years' experience in acupuncture. PATIENTS: 1007 patients who had had chronic pain for at least 6 months due to osteoarthritis of the knee (American College of Rheumatology [ACR] criteria and Kellgren-Lawrence score of 2 or 3). INTERVENTIONS: Up to 6 physiotherapy sessions and as-needed anti-inflammatory drugs plus 10 sessions of TCA, 10 sessions of sham acupuncture, or 10 physician visits within 6 weeks. Patients could request up to 5 additional sessions or visits if the initial treatment was viewed as being partially successful. MEASUREMENTS: Success rate, as defined by at least 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 26 weeks. Additional end points were WOMAC score and global patient assessment. RESULTS: Success rates were 53.1% for TCA, 51.0% for sham acupuncture, and 29.1% for conservative therapy. Acupuncture groups had higher success rates than conservative therapy groups (relative risk for TCA compared with conservative therapy, 1.75 [95% CI, 1.43 to 2.13]; relative risk for sham acupuncture compared with conservative therapy, 1.73 [CI, 1.42 to 2.11]). There was no difference between TCA and sham acupuncture (relative risk, 1.01 [CI, 0.87 to 1.17]). LIMITATIONS: There was no blinding between acupuncture and traditional therapy and no monitoring of acupuncture compliance with study protocol. In general, practitioner-patient contacts were less intense in the conservative therapy group than in the TCA and sham acupuncture groups. CONCLUSIONS: Compared with physiotherapy and as-needed anti-inflammatory drugs, addition of either TCA or sham acupuncture led to greater improvement in WOMAC score at 26 weeks. No statistically significant difference was observed between TCA and sham acupuncture, suggesting that the observed differences could be due to placebo effects, differences in intensity of provider contact, or a physiologic effect of needling regardless of whether it is done according to TCA principles.

Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial.

BACKGROUND: Our aim was to assess the efficacy of a part-standardised verum acupuncture procedure, in accordance with the rules of traditional Chinese medicine, compared with that of part-standardised sham acupuncture and standard migraine prophylaxis with beta blockers, calcium-channel blockers, or antiepileptic drugs in the reduction of migraine days 26 weeks after the start of treatment. METHODS: This study was a prospective, randomised, multicentre, double-blind, parallel-group, controlled, clinical trial, undertaken between April 2002 and July 2005. Patients who had two to six migraine attacks per month were randomly assigned verum acupuncture (n=313), sham acupuncture (n=339), or standard therapy (n=308). Patients received ten sessions of acupuncture treatment in 6 weeks or continuous prophylaxis with drugs. Primary outcome was the difference in migraine days between 4 weeks before randomisation and weeks 23-26 after randomisation. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN52683557. FINDINGS: Of 1295 patients screened, 960 were randomly assigned to a treatment group. Immediately after randomisation, 125 patients (106 from the standard group) withdrew their consent to study participation. 794 patients were analysed in the intention-to-treat popoulation and 443 in the per-protocol population. The primary outcome showed a mean reduction of 2 .3 days (95% CI 1.9-2.7) in the verum acupuncture group, 1.5 days (1.1-2.0) in the sham acupuncture group, and 2.1 days (1.5-2.7) in the standard therapy group. These differences were statistically significant compared with baseline (p<0.0001), but not across the treatment groups (p=0.09). The proportion of responders, defined as patients with a reduction of migraine days by at least 50%, 26 weeks after randomisation, was 47% in the verum group, 39% in the sham acupuncture group, and 40% in the standard group (p=0.133). INTERPRETATION: Treatment outcomes for migraine do not differ between patients treated with sham acupuncture, verum acupuncture, or standard therapy.

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.