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).

Collaborative Ambulatory Orthopaedic Care in Patients with Hip and Knee Osteoarthritis: A Retrospective Comparative Cohort Study on Health Utilisation and Economic Outcomes.

Objective: To evaluate a novel healthcare programme for the treatment of patients with hip and knee osteoarthritis in southern Germany in terms of clinical and health economic outcomes. The study is based on claims data from 2014 to 2017. Methods: We conducted a retrospective comparative cohort study of 9768 patients with hip and knee osteoarthritis, of whom 9231 were enrolled in a collaborative ambulatory orthopaedic care programme (intervention group), and 537 patients received usual orthopaedic care (control group). Key features of the programme are coordinated care, morbidity-adapted reimbursement and extended consultation times. Multivariable analysis was performed to determine effects on health utilisation outcomes. The economic analysis considered annual costs per patient from a healthcare payer perspective, stratified by healthcare service sector. Besides multivariable regression analyses, bootstrapping was used to estimate confidence intervals for predicted mean costs by group. Results: Musculoskeletal-disease-related hospitalisation was much less likely among intervention group patients than control group patients [odds ratio (OR): 0.079; 95% CI: 0.062-0.099]. The number of physiotherapy prescriptions per patient was significantly lower in the intervention group (RR: 0.814; 95% CI: 0.721-0.919), while the likelihood of participation in exercise programmes over one year was significantly higher (OR: 3.126; 95% CI: 1.604-6.094). Enrolment in the programme was associated with significantly higher ambulatory costs (€1048 vs. €925), but costs for inpatient care, including hospital stays, were significantly lower (€1003 vs. €1497 and €928 vs. €1300 respectively). Overall annual cost-savings were €195 per patient. Conclusions: Collaborative ambulatory orthopaedic care was associated with reduced hospitalisation in patients with hip and knee osteoarthritis. Health costs for programme participants were lower overall, despite higher costs for ambulatory care.

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.

A comparison of different methods to adjust survival curves for confounders.

Treatment specific survival curves are an important tool to illustrate the treatment effect in studies with time-to-event outcomes. In non-randomized studies, unadjusted estimates can lead to biased depictions due to confounding. Multiple methods to adjust survival curves for confounders exist. However, it is currently unclear which method is the most appropriate in which situation. Our goal is to compare forms of inverse probability of treatment weighting, the G-Formula, propensity score matching, empirical likelihood estimation and augmented estimators as well as their pseudo-values based counterparts in different scenarios with a focus on their bias and goodness-of-fit. We provide a short review of all methods and illustrate their usage by contrasting the survival of smokers and non-smokers, using data from the German Epidemiological Trial on Ankle-Brachial-Index. Subsequently, we compare the methods using a Monte-Carlo simulation. We consider scenarios in which correctly or incorrectly specified models for describing the treatment assignment and the time-to-event outcome are used with varying sample sizes. The bias and goodness-of-fit is determined by taking the entire survival curve into account. When used properly, all methods showed no systematic bias in medium to large samples. Cox regression based methods, however, showed systematic bias in small samples. The goodness-of-fit varied greatly between different methods and scenarios. Methods utilizing an outcome model were more efficient than other techniques, while augmented estimators using an additional treatment assignment model were unbiased when either model was correct with a goodness-of-fit comparable to other methods. These "doubly-robust" methods have important advantages in every considered scenario.

[Positive experiences of specialist assistants and physicians with respect to the delegation research project StaerkeR : Evaluation of the training and experiences within the framework of this project]. / Positive Erfahrungen von Fachassistent:innen und Ärzt:innen hinsichtlich des Delegations-Forschungsprojekts StärkeR : Evaluation der Schulung und Erfahrungen im Rahmen dieses Projekts.

INTRODUCTION: The delegation of medical services to rheumatology assistants (RFA) has proven to be safe and effective in the evaluation of the research project "StaerkeR". Afterwards, the experiences of the participating RFAs and rheumatologists with delegation were surveyed and discussed within the framework of an opinion research project. METHODS: At the end of the project, the participating RFAs and rheumatologists were surveyed via an online questionnaire (quantitative analysis) (21 questions for physicians and 44 questions for RFAs). In addition, focus group meetings were held for the RFAs, which were led by a moderator and a secretary. The results of the focus group sessions (qualitative analyses) were analyzed according to the structured method of Kuckartz. RESULTS: All 31 RFAs and 25 rheumatologists involved in the project participated in the online surveys and 9 RFAs took part in the 2 focus groups. In the online surveys, both the RFAs and the rheumatologists gave predominantly good to very good ratings with respect to RFA training, the implementation of delegation in the practices and outpatient clinics, the role of the RFAs and the overall evaluation of the delegation concept. In the focus group discussions, many possible limitations regarding acceptance and implementation of the delegation concept were mentioned. CONCLUSION: The delegation of medical tasks to RFAs is a concept that is positively assessed and highly accepted by both sides, the rheumatologists and the RFAs. In a comparison between the individual practices and hospital outpatient departments, there is still a clear heterogeneity with respect to the willingness and logistical possibilities in the implementation of the delegation concept.

Differences in opioid prescription rates between patients with musculoskeletal disorders enrolled in coordinated ambulatory healthcare and patients receiving usual care: a retrospective observational cohort study.

OBJECTIVES: To compare opioid prescription rates between patients enrolled in coordinated ambulatory care and patients receiving usual care. DESIGN: In this retrospective cohort study, we analysed claims data for insured patients with non-specific/specific back pain or osteoarthritis of hip or knee from 2014 to 2017. SETTING: The study was based on administrative data provided by the statutory health insurance fund 'Allgemeine Ortskrankenkasse', in the state of Baden-Wurttemberg, Germany. PARTICIPANTS: The intervention group consisted of patients enrolled in a coordinated ambulatory healthcare model; the control group included patients receiving usual care. Outcomes were overall strong and weak opioid prescriptions. Generalised linear regression models were used to analyse the effect of the intervention. RESULTS: Overall, 46 001 (non-specific 18 787/specific 27 214) patients with back pain and 19 366 patients with osteoarthritis belonged to the intervention group, and 7038 (2803/4235) and 963 patients to the control group, respectively. No significant difference in opioid prescriptions existed between the groups. However, the chance of being prescribed strong opioids was significantly lower in the intervention group (non-specific back pain: Odds Ratio (OR) 0.735, 95% Confidential Interval (CI) 0.563 to 0.960; specific back pain: OR 0.702, 95% CI 0.577 to 0.852; osteoarthritis: OR 0.644, 95% CI 0.464 to 0.892). The chance of being prescribed weak opioids was significantly higher in patients with specific back pain (OR 1.243, 95% CI 1.032 to 1.497) and osteoarthritis (OR 1.493, 95% CI 1.037 to 2.149) in the intervention group. CONCLUSION: Coordinated ambulatory healthcare appears to be associated with a lower prescription rate for strong opioids in patients with chronic musculoskeletal disorders. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS00017548).

Evaluation of a collaborative ambulatory orthopedic care program for patients with hip and knee osteoarthritis: a comparative observational cohort study.

BACKGROUND: In 2014, the novel orthopedic care program was established by the AOK health insurance fund in southern Germany to improve ambulatory care for patients with musculoskeletal disorders. The program offers extended consultation times, structured collaboration between general practitioners and specialists, as well as a renewed focus on guideline-recommended therapies and patient empowerment. The aim of this study was to assess the impact of the program on health service utilization in patients with hip and knee osteoarthritis (OA). METHODS: This retrospective cohort study, which is based on claims data, evaluated health service utilization in patients with hip and knee OA from 2014 to 2017. The intervention group comprised OA patients enrolled in collaborative ambulatory orthopedic care, and the control group received usual care. The outcomes were participation in exercise interventions, prescription of physical therapy, OA-related hospitalization, and endoprosthetic surgery rates. Generalized linear regression models were used to analyze the effect of the intervention. RESULTS: Claims data for 24,170 patients were analyzed. Data for the 23,042 patients in the intervention group were compared with data for the 1,128 patients in the control group. Participation in exercise interventions (Odds Ratio (OR): 1.781; 95% Confidence Interval (CI): 1.230-2.577; p = 0.0022), and overall prescriptions of physical therapy (Rate Ratio (RR): 1.126; 95% CI: 1.025-1.236; p = 0.0128) were significantly higher in the intervention group. The intervention group had a significantly lower risk of OA -related hospitalization (OR: 0.375; 95% CI: 0.290-0.485; p < 0.0001). Endoprosthetic surgery of the knee was performed in 53.8% of hospitalized patients in the intervention group vs. 57.5% in the control group; 27.7% of hospitalized patients underwent endoprosthetic surgery of the hip in the intervention group versus 37.0% in the control group. CONCLUSIONS: In patients with hip and knee OA, collaborative ambulatory orthopedic care is associated with a lower risk of OA-related hospitalization, higher participation in exercise interventions, and more frequently prescribed physical therapy.

The Efficacy of Short-Term Bridging Strategies With High- and Low-Dose Prednisolone on Radiographic and Clinical Outcomes in Active Early Rheumatoid Arthritis: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. This study was undertaken to compare the effect of 3 bridging strategies, including high-dose and low-dose prednisolone, on radiographic and clinical outcomes. METHODS: Adult RA patients from 1 rheumatology hospital and 23 rheumatology practices who presented with moderate/high disease activity were randomized (1:1:1) to receive 60 mg prednisolone (high-dose prednisolone [HDP]) or 10 mg prednisolone (low-dose prednisolone [LDP]) daily (tapered to 0 mg within 12 weeks) or placebo. The 12-week intervention period was followed by 40 weeks of therapy at the physicians' discretion. The primary outcome measure was radiographic change at 1 year measured using the total modified Sharp/van der Heijde score (SHS). Disease activity was assessed with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). RESULTS: Of 395 randomized patients (HDP, n = 132; LDP, n = 131; placebo, n = 132), 375 (95%) remained in the modified intention-to-treat analysis. Mean ± SD changes in SHS scores in the 3 groups after 1 year were comparable: mean ± SD 1.0 ± 2.0 units in the HDP group, 1.1 ± 2.2 units in the LDP group, and 1.1 ± 1.5 units in the placebo group. The primary analysis showed no superiority of HDP compared to placebo (estimated difference of the mean change -0.04 [95% confidence interval (95% CI) -0.5, 0.4]). At week 12, the mean DAS28-ESR differed: -0.6 (95% CI -1.0, -0.2) for HDP versus placebo; -0.8 (95% CI -1.2, -0.5) for LDP versus placebo. At week 52, there was no significant difference in DAS28-ESR between the 3 groups (range 2.6-2.8). Serious adverse events occurred similarly often. CONCLUSION: Short-term glucocorticoid bridging therapy at a high dose showed no benefit with regard to progression of radiographic damage at 1 year.

General practitioner-centred paediatric primary care reduces risk of hospitalisation for mental disorders in children and adolescents with ADHD: findings from a retrospective cohort study.

BACKGROUND: General practitioners (GPs) play an essential role in the sustainable management of attention-deficit/hyperactivity disorder (ADHD). To our knowledge, the healthcare programme described here is the first integrated care programme for paediatric ambulatory care embedded in GP-centred-healthcare in Germany. OBJECTIVES: To compare the health-service-utilisation of patients with ADHD enrolled in a GP-centred-paediatric-primary-care-programme with usual care in terms of disease-related hospitalisation, pharmacotherapy and psychotherapy. METHODS: In 2018, we conducted a retrospective cohort study of 3- to 18-year-old patients with ADHD in Baden-Wuerttemberg, southern Germany. The intervention group (IG) comprised patients enrolled in a GP-centred-paediatric-primary-healthcare-programme and consulted a participating GP for ADHD at least once. GP-centred-paediatric-primary-care provides high continuity of care, facilitated access to specialist care, extended routine examinations and enhanced transition to adult healthcare. Patients in the control group (CG) received usual care, meaning they consulted a non-participating GP for ADHD at least once. Main outcomes were disease-related hospitalisation, pharmacotherapy and psychotherapy. Multivariable logistic regression was performed to compare groups. RESULTS: A total of 2317 patients were included in IG and 4177 patients in CG. Mean age was 8.9 ± 4.4. The risk of mental-disorder-related hospitalisations was lower in IG than CG (odds ratio (OR): 0.666, 95% confidence interval (CI): 0.509-0.871). The prescription rate for stimulants was lower in IG (OR: 0.817; 95% CI: 0.732-0.912). There was no statistically significant difference in the participation rate of patients in cognitive behavioural therapy between groups (OR: 0.752; 95% CI: 0.523-1.080). CONCLUSION: Children and adolescents with ADHD enrolled in GP-centred-paediatric-primary-care are at lower risk of mental-disorder-related hospitalisation and less likely to receive stimulants.

The Structured Delegation of Medical Care Services for Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: In some areas of Germany, there is a shortage of specialist physicians for patients with inflammatory rheumatic diseases. Delegating certain medical care services to qualified, specialized rheumatological assistants (SRAs) might be an effective way to supplement the available capacity for specialized medical care. METHODS: Patients under stable treatment for rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were included in this trial, which was designed to demonstrate, in a first step, the non-inferiority of a form of care involving delegation of physicians' tasks to SRAs (team-based care), in comparison to standard care, with respect to changes in disease activity at one year. "Non-inferiority," in this context, means either superiority or else an irrelevant extent of inferiority. In a second step, in case non-inferiority could be shown, the superiority of team-based care with respect to changes in patients' health-related quality of life would be tested as well. Disease activity was measured with the Disease Activity Score 28, and health-related quality of life with the EQ-5D-5L. This was a randomized, multicenter, rater-blinded trial with two treatment arms (team-based care and standard care). The statistical analysis was performed with mixed linear models (DRKS00015526). RESULTS: From September 2018 to June 2019, 601 patients from 14 rheumatological practices and 3 outpatient rheumatological clinics in the German states of North Rhine-Westphalia and Lower Saxony were randomized to either team-based or standard care. Team-based care was found to be non-inferior to standard care with respect to changes in disease activity (adjusted difference = -0.19; 95% confidence interval [-0.36; -0.02]; p <0.001 for non-inferiority). Superiority with respect to health-related quality of life was not demonstrated (adjusted difference = 0.02 [-0.02; 0.05], p = 0.285). CONCLUSION: Team-based care, with greater integration of SRAs, is just as good as standard care in important respects. Trained SRAs can effectively support rheumatologists in the care of stable patients with RA or PsA.

Reduction of Potentially Inappropriate Medication in the Elderly.

BACKGROUND: Medications with an unfavorable risk-benefit profile in the elderly, and for which there are safer alternatives, are designated as potentially inappropriate medications (PIM). The RIME trial (Reduction of Potentially Inappropriate Medication in the Elderly) was based on PRISCUS, a list of PIM that was developed in 2010 for the German pharmaceuticals market. In this trial, it was studied whether special training and the PRISCUS card could lessen PIM and undesired drug-drug interactions (DDI) among elderly patients in primary care. METHODS: A three-armed, cluster-randomized, controlled trial was carried out in two regions of Germany. 137 primary care practices were randomized in equal numbers to one of two intervention groups-in which either the primary care physicians alone or the entire practice team received special training-or to a control group with general instructions about medication. The primary endpoint was the percentage of patients with at least one PIM or DDI (PIM/DDI) per practice. The primary hypothesis was that at 1 year this endpoint would be more effectively lowered in the intervention groups compared to the control group. RESULTS: Among 1138 patients regularly taking more than five drugs, 453 (39.8%) had at least one PIM/DDI at the beginning of the trial. The percent - ages of PIM/DDI at the beginning of the trial and 1 year later were 43.0% and 41.3% in the intervention groups and 37.0% and 37.6% in the control group. The estimated intervention effect of any intervention (69 practices) versus control (68 practices) was 2.3% (p = 0.36), while that of team training (35 practices) versus physician training (34 practices) was 4.3% (p = 0.22). CONCLUSION: The interventions in the RIME trial did not significantly lower the percentage of patients with PIM or DDI.

[Secondary Data-based Trend Analysis of How Quality Differences in Two Forms of Healthcare Develop Over Time]. / Eine Trendanalyse zur zeitlichen Entwicklung von Qualitätsunterschieden zweier Versorgungsformen auf Basis von Sekundärdaten.

AIM OF THE STUDY: The evaluation of complex interventions such as different forms of healthcare are methodologically challenging. The aim of this study was to use generalized estimating equations (GEE) to investigate how quality differences between family practitioner-based healthcare (HZV) and standard care develop over time. METHODS: A longitudinal secondary data analysis for 2011-2018 was conducted using routine data from the AOK Baden Wuerttemberg health insurer. A dynamic cohort of insured persons that fulfilled the inclusion criteria were included in the analysis at the beginning of each year of observation, so the size and composition of the cohorts varied from year to year. Quality differences between HZV and standard care were investigated, whereby an autoregressive covariance structure (AR1) was assumed for multiple measurements. Under observation were a group variable for healthcare type, a variable for year of observation, and any interaction between the two. The resulting estimates provided information on the relationship between the two groups at the beginning of the observation period, and on how the groups developed both individually and in relation to one another over time. RESULTS: The GEE were used exemplarily on the quality indicator prescription of potentially inappropriate medication (PIM) in elderly insured patients. At the beginning of the observation period, the chance of PIM in those over 65 years of age (year 2018; N=628,523) was significantly lower in the HZV group than in the group receiving standard care (odds ratio 0.978; 95% confidence interval: 0.968-0.987). The chance of a PIM in the following seven years declined in both groups, but faster in the HZV group than the group receiving standard care. CONCLUSION: A secondary data-based trend analysis with GEE of quality differences in comparison groups over time has considerable potential in the evaluation of new and existing forms of healthcare.

Effectiveness of the application of an electronic medication management support system in patients with polypharmacy in general practice: a study protocol of cluster-randomised controlled trial (AdAM).

INTRODUCTION: Clinically complex patients often require multiple medications. Polypharmacy is associated with inappropriate prescriptions, which may lead to negative outcomes. Few effective tools are available to help physicians optimise patient medication. This study assesses whether an electronic medication management support system (eMMa) reduces hospitalisation and mortality and improves prescription quality/safety in patients with polypharmacy. METHODS AND ANALYSIS: Planned design: pragmatic, parallel cluster-randomised controlled trial; general practices as randomisation unit; patients as analysis unit. As practice recruitment was poor, we included additional data to our primary endpoint analysis for practices and quarters from October 2017 to March 2021. Since randomisation was performed in waves, final study design corresponds to a stepped-wedge design with open cohort and step-length of one quarter. SCOPE: general practices, Westphalia-Lippe (Germany), caring for BARMER health fund-covered patients. POPULATION: patients (≥18 years) with polypharmacy (≥5 prescriptions). SAMPLE SIZE: initially, 32 patients from each of 539 practices were required for each study arm (17 200 patients/arm), but only 688 practices were randomised after 2 years of recruitment. Design change ensures that 80% power is nonetheless achieved. INTERVENTION: complex intervention eMMa. FOLLOW-UP: at least five quarters/cluster (practice). recruitment: practices recruited/randomised at different times; after follow-up, control group practices may access eMMa. OUTCOMES: primary endpoint is all-cause mortality and hospitalisation; secondary endpoints are number of potentially inappropriate medications, cause-specific hospitalisation preceded by high-risk prescribing and medication underuse. STATISTICAL ANALYSIS: primary and secondary outcomes are measured quarterly at patient level. A generalised linear mixed-effect model and repeated patient measurements are used to consider patient clusters within practices. Time and intervention group are considered fixed factors; variation between practices and patients is fitted as random effects. Intention-to-treat principle is used to analyse primary and key secondary endpoints. ETHICS AND DISSEMINATION: Trial approved by Ethics Commission of North-Rhine Medical Association. Results will be disseminated through workshops, peer-reviewed publications, local and international conferences. TRIAL REGISTRATION: NCT03430336. ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03430336).

Effects of Three Different Methods Defining Onset of Peripheral Artery Disease on the Assessments of Incidence and Important Predictors - Results from the German Epidemiological Trial on Ankle Brachial Index (getABI).

PURPOSE: The common definition of asymptomatic peripheral artery disease (PAD) by a single determination of the ankle brachial index (ABI) has some uncertainty due to measurement errors. This may impact estimates of PAD incidence and assessment of PAD risk factors. To investigate this issue, we used three methods to define asymptomatic PAD and made use of data from the German Epidemiological Trial on Ankle Brachial Index (getABI). PATIENTS AND METHODS: A total of 6,880 unselected subjects aged ≥65 years, enrolled by 344 trained general practitioners, had ABI assessments at baseline and four visits during follow-up. The first approach defined asymptomatic PAD onset as soon as a single ABI value was below 0.9 (single ABI). The second approach employed a regression method using all available ABI values (regression A), while for the third approach (regression B), an extended regression beyond the last valid ABI value for the observation time of the study was allowed. For each approach, we calculated PAD incidence rates and assessed the effect of important PAD predictors using multivariable Cox proportional hazards regression. RESULTS: The regression method A showed the lowest (25.0 events per 1,000 person years) and the single ABI method the highest incidence rate (41.2). The regression methods assigned greater impact to several risk factors of incident PAD. Using regression A, the hazard ratios (HR) of active smoking (2.36; 95% CI 1.92 to 2.90) and of diabetes (1.33; 95% CI 1.13 to 1.56), using regression B the HR of older age (1.72; 95% CI 1.50 to 1.97) were about twice as high as the corresponding HR of the single ABI approach. CONCLUSION: Use of the single ABI method leads to higher PAD incidence rates and to lower impact of important PAD predictors compared to regression methods. For an alert risk factor management, multiple ABI determination may be useful.

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.

Strong and sustainable primary healthcare is associated with a lower risk of hospitalization in high risk patients.

In 2004, Germany introduced a program based on voluntary contracting to strengthen the role of general practice care in the healthcare system. Key components include structured management of chronic diseases, coordinated access to secondary care, data-driven quality improvement, computerized clinical decision-support, and capitation-based reimbursement. Our aim was to determine the long-term effects of this program on the risk of hospitalization of specific categories of high-risk patients. Based on insurance claims data, we conducted a longitudinal observational study from 2011 to 2018 in Baden-Wuerttemberg, Germany. Patients were assigned to one or more of four open cohorts (in 2011, elderly, n = 575,363; diabetes mellitus, n = 163,709; chronic heart failure, n = 82,513; coronary heart disease, n = 125,758). Adjusted for key patient characteristics, logistic regression models were used to compare the hospitalization risk of the enrolled patients (intervention group) with patients receiving usual primary care (control group). At the start of the study and throughout long-term follow-up, enrolled patients in the four cohorts had a lower risk of all-cause hospitalization and ambulatory, care-sensitive hospitalization. Among patients with chronic heart failure and coronary heart disease, the program was associated with significantly reduced risk of cardiovascular-related hospitalizations across the eight observed years. The effect of the program also increased over time. Over the longer term, the results indicate that strengthening primary care could be associated with a substantial reduction in hospital utilization among high-risk patients.

Use of an electronic decision support tool to reduce polypharmacy in elderly people with chronic diseases: cluster randomised controlled trial.

OBJECTIVE: To evaluate the effects of a computerised decision support tool for comprehensive drug review in elderly people with polypharmacy. DESIGN: Pragmatic, multicentre, cluster randomised controlled trial. SETTING: 359 general practices in Austria, Germany, Italy, and the United Kingdom. PARTICIPANTS: 3904 adults aged 75 years and older using eight or more drugs on a regular basis, recruited by their general practitioner. INTERVENTION: A newly developed electronic decision support tool comprising a comprehensive drug review to support general practitioners in deprescribing potentially inappropriate and non-evidence based drugs. Doctors were randomly allocated to either the electronic decision support tool or to provide treatment as usual. MAIN OUTCOME MEASURES: The primary outcome was the composite of unplanned hospital admission or death by 24 months. The key secondary outcome was reduction in the number of drugs. RESULTS: 3904 adults were enrolled between January and October 2015. 181 practices and 1953 participants were assigned to electronic decision support (intervention group) and 178 practices and 1951 participants to treatment as usual (control group). The primary outcome (composite of unplanned hospital admission or death by 24 months) occurred in 871 (44.6%) participants in the intervention group and 944 (48.4%) in the control group. In an intention-to-treat analysis the odds ratio of the composite outcome was 0.88 (95% confidence interval 0.73 to 1.07; P=0.19, 997 of 1953 v 1055 of 1951). In an analysis restricted to participants attending practice according to protocol, a difference was found favouring the intervention (odds ratio 0.82, 95% confidence interval 0.68 to 0.98; 774 of 1682 v 873 of 1712, P=0.03). By 24 months the number of prescribed drugs had decreased in the intervention group compared with control group (uncontrolled mean change -0.42 v 0.06: adjusted mean difference -0.45, 95% confidence interval -0.63 to -0.26; P<0.001). CONCLUSIONS: In intention-to-treat analysis, a computerised decision support tool for comprehensive drug review of elderly people with polypharmacy showed no conclusive effects on the composite of unplanned hospital admission or death by 24 months. Nonetheless, a reduction in drugs was achieved without detriment to patient outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10137559.

High microsatellite instability (MSI-H) is associated with distinct clinical and molecular characteristics and an improved survival in early Colon cancer (CC); real world data from the AIO molecular registry Colopredict Plus.

Colorectal cancer is one of the leading malignancies and still accounts for almost 25 000 deaths in Germany each year. Although there is accumulating data on the molecular basis, treatment and clinical outcome of patients within clinical trials evidence from the real-world setting is mostly lacking. We started the molecular registry trial Colopredict Plus in 2013 to collect clinical and molecular data from a real-world cohort of patients with early colon cancer stage II and III in 70 German colon cancer centers focusing on the prognostic impact of high microsatellite instability. In this interim report, we characterize a clinical cohort of 2615 patients, of whom 1787 tissue probes were analyzed. Microsatellite status was assessed using immunhistochemistry and fragment length analysis, with a concordance of 91.4 %. These established histopathological methods are sensitive and cost-effective. The median age was 72 years, significantly higher compared to clinical trial populations, with a median Charlson Comorbidity Index of 3. The stage-dependent incidence of microsatellite instability was 23.7 % and was associated with female gender, BRAF-mutation, UICC stage II and localization in the right colon. Survival calculated in disease free, relapse free and overall survival significantly differed between MSI-H and MSS, in favor of MSI-H patients. Multivariate age-adjusted analyses of relapse-free survival, disease-free survival, and overall survival highlighted microsatellite instability as a robust and positive prognostic marker for early colon cancer independent of age.

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.

Nurse-led care versus physician-led care in the management of rheumatoid arthritis and psoriatic arthritis (StaerkeR): study protocol for a multi-center randomized controlled trial.

BACKGROUND: In Germany, the care of patients with inflammatory arthritis could be improved. Although specialized rheumatology nurses could take over substantial aspects of patient care, this hardly occurs in Germany. Thus, the aim of the study is to examine structured nursing consultation in rheumatology practices. METHODS/DESIGN: In total, 800 patients with a stable course of rheumatoid arthritis or psoriatic arthritis in 20 centers in North Rhine-Westphalia and Lower Saxony will be randomized to either nurse-led care or standard care. Participating nurses will study for a special qualification in rheumatology and trial-specific issues. It is hypothesized that nurse-led care is non-inferior to standard care provided by rheumatologists with regard to a reduction of disease activity (DAS28) while it is hypothesized to be superior regarding changes in health-related quality of life (EQ-5D-5L) after 1 year. Secondary outcomes include functional capacity, patient satisfaction with treatment, and resource consumption. DISCUSSION: Since there is insufficient care of rheumatology patients in Germany, the study may be able to suggest improvements. Nurse-led care has the potential to provide more efficient and effective patient care. This includes a more stringent implementation of the treat-to-target concept, which may lead to a higher percentage of patients reaching their treatment targets, thereby improving patient-related outcomes, such as quality of life, functional capacity, and participation. Additionally, nurse-led care may be highly cost-effective. Finally, this project may form the basis for a sustainable implementation of nurse-led care in standard rheumatology care in Germany. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00015526. Registered on 11 January 2019.