Machine Learning Models Predict the Need of Amputation and/or Peripheral Artery Revascularization in Hypertensive Patients Within 7-Years Follow-Up.

Lower extremity amputation and requirement of peripheral artery revascularization are common outcomes of undiagnosed peripheral artery disease patients. In the current work, prediction models for the need of amputation or peripheral revascularization focused on hypertensive patients within seven years follow up are employed. We applied machine learning (ML) models using classifiers such as Extreme Gradient Boost (XGBoost), Random Forest (RF) and Adaptive Boost (AdaBoost), that will allow clinicians to identify the patients at risk of these two endpoints using simple clinical data. We used the non-interventional cohort of the getABI study in the primary care setting, selecting 4,191 hypertensive patients out of 6,474 patients with age over 65 years old and followed up for vascular events or death up to 7 years. During this follow up period, 150 patients underwent either amputation or peripheral revascularization or both. Accuracy, Specificity, Sensitivity and Area under the receiver operating characteristic curve (AUC) were estimated for each machine learning model. The results demonstrate Random Forest as the most accurate model for the prediction of the composite endpoint in hypertensive patients within 7 years follow-up, achieving 73.27 % accuracy.Clinical Relevance-This study assists clinicians to better predict and treat these serious outcomes, amputation and peripheral revascularization in hypertensive patients.

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).

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.

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.

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.

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).

Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity.

OBJECTIVE: To explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients. STUDY DESIGN AND SETTING: Using individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV). RESULTS: Prior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions. CONCLUSIONS: Predictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully. TRIAL REGISTRATION NUMBER: PROSPERO id: CRD42018088129.

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.

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.

NT-proBNP for risk prediction of cardiovascular events and all-cause mortality: The getABI-study.

BACKGROUND: Beside their role in the diagnosis of heart failure in symptomatic patients with dyspnea, natriuretic peptides have been suggested to improve risk prediction of cardiac events and mortality in asymptomatic cohorts. We aimed to evaluate the prognostic value of NT-proBNP for cardiovascular and all-cause mortality above traditional risk factors in a prospective cohort study of unselected elderly patients in a representative primary care setting. METHODS: We followed 6382 patients of the getABI-study for 7 years. Associations of NT-proBNP levels (≤125; 125-300; >300pg/ml for all) with all-cause and cardiovascular mortality were assessed using cox regression analysis. RESULTS: The incidence of all-cause and cardiovascular mortality was higher in subjects with higher levels of NT-proBNP (all-cause mortality/cardiovascular mortality: 35.4%/6% for NT-proBNP > 300 pg/ml; 16.2%/40% for NT-proBNP 125-300 pg/ml vs. 11.4%/4% for NT-proBNP ≤ 125 pg/ml. Participants with a NT-proBNP levels > 300pg/ml had increased incidence of hard endpoint (hazard ratio (HR) (95% confidence interval (CI)): 3.62 (3.15-4.17) for all-cause mortality, and 6.38 (4.84-8.41) for cardiovascular mortality). These associations remained after adjustment for traditional risk factors and cardiac medications and diseases (HR = 2.64 (2.26-3.08) for all-cause mortality, and HR = 3.93 (2.90-5.32) for cardiovascular mortality). CONCLUSION: Our results show strong associations of higher NT-proBNP levels with cardiovascular and all-cause mortality in an unselected, large population of elderly patients in the primary care setting independent of traditional risk factors indicating that NT-proBNP can help identifying subjects at high risk for cardiac events.

Bisphosphonate drug holidays: Risk of fractures and mortality in a prospective cohort study.

PURPOSE: This study examined osteoporotic fractures and mortality in patients pretreated with bisphosphonates (BPs) during BP holidays and ongoing BP use. METHODS: Interview-based prospective observational study in a cohort of 1973 patients with BP treatment for at least 80% of the total time of the preceding 4 years. Patients were recruited from 146 primarily endocrinological, orthopedic and rheumatological practices and clinics across Germany between May 2013 and June 2015. Outcomes were analyzed by Cox proportional hazards regression in relation to treatment status at the time of the first interview (model 1) or using time-dependent treatment variables (model 2). Temporal changes in fracture risk during BP holidays were evaluated by comparisons among 3 incremental levels of simple moving averages of BP treatment during the preceding 12 months (BP-SMA levels 0%, >0% to <50%, and ≥50%). RESULTS: For an observation period of up to 25 months, the adjusted hazard ratios (HRs) in model 1 for BP holidays compared to ongoing BP use were 0.87 (95% confidence interval [CI] 0.59-1.28) for major osteoporotic fractures (MOFs), 0.95 (95% CI 0.70-1.28) for any clinical osteoporotic fracture, 0.96 (95% CI 0.55-1.68) for clinical vertebral fractures, and 0.86 (95% CI 0.50-1.48) for mortality. The risk of MOFs was higher for the BP-SMA level 0%, corresponding to a time >12 months since the start of a BP holiday, than for the BP-SMA level >0% to <50%, corresponding mainly to a time >6 to ≤12 months since the start of a BP holiday (adjusted HR 2.28, 95% CI 1.07-4.86). We found an interaction between prevalent vertebral fractures (PVFs) and BP-SMA-related time to first MOF for BP-SMA as a continuous variable (p for interaction 0.046 in the adjusted model). The adjusted HR for MOFs for the BP-SMA level 0% compared to the BP-SMA level >0% to <50% was 3.53 (95% CI 1.19-10.51) with a PVF but was 1.44 (95% CI 0.49-4.22) without a PVF. CONCLUSIONS: Fracture risk and mortality in patients with preceding BP treatment did not significantly differ between BP holidays and ongoing BP use for an observation period up to 25 months when outcomes were analyzed in relation to treatment at the time of the first interview. However, in the presence of a PVF, the risk of MOFs was higher for a BP-SMA level corresponding to a time >12 months since the start of a BP holiday than for a BP-SMA level corresponding mainly to a time >6 to ≤12 months since the start of a BP holiday. The presence of a PVF may increase the relative risk of MOFs associated with a longer BP holiday.

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.

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.

Social Gradients in Myocardial Infarction and Stroke Diagnoses in Emergency Medicine.

BACKGROUND: Persons of lower socio-economic status are at higher risk of disease, especially with respect to severe and chronic illnesses. To date, there have not been any studies with large case numbers regarding acute medical emergencies in this population. METHODS: In a retrospective study, data were obtained on all cases treated by emergency physicians in Bochum, Germany, in 2014/2015, including the diagnoses that were made by the emergency physicians. There were a total of 16 767 cases. The local unemployment rate was taken as an indicator of the socioeconomic situation of a neighborhood; it was defined as the percentage of registered unemployed persons among persons aged 15 to 64 with their domicile in the neighborhood. 12 168 cases were grouped by emergency medical diagnosis and analyzed with respect to the three most heavily represented diagnostic categories (cardiovascular, neurological, and pulmonary emergencies), which accounted for nearly two-thirds of all diagnoses. RESULTS: The overall rates of deployment involving emergency physicians were found to be positively correlated with the unemployment rate. After adjustment for age, sex, and possible confounders, this correlation was statistically significant (p<0.01). The indirectly standardized rate ratio (IRR) for the overall case-activity rate ranged from 0.841 (95% confidence interval: [0.808; 0.875]) with less than 5% unemployment to 1.212 [1.168; 1.256] with 9.5% unemployment or higher. The same finding was obtained with respect to diagnosis-specific case activity in each of the three main diagnostic categories (cardiovascular, neurological, and pulmonary emergencies), as well as for the respective commonest individual diagnoses (acute coronary syndrome/circulatory arrest [1498 cases], transient ischemic attack/ischemic stroke/intracerebral hemorrhage [1274 cases], and asthma/chronic obstructive pulmonary disease [663 cases]). CONCLUSION: This study shows that the case-activity rate of the emergency medical services is significantly higher in socially disadvantaged neighborhoods, both with respect to total numbers and with respect to individual diseases. It demonstrates a problem affecting society as a whole, which should be taken into account in the organization of medical rescue services.