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.

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).

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.

[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.

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.

[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.

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.

Potentially inappropriate medication among people with dementia in eight European countries.

Objectives: to evaluate the frequency of potentially inappropriate medication (PIM) prescription among older people with dementia (PwD) from eight countries participating in the European study 'RightTimePlaceCare', and to evaluate factors and adverse outcomes associated with PIM prescription. Methods: survey of 2,004 PwD including a baseline assessment and follow-up after 3 months. Interviewers gathered data on age, sex, prescription of medication, cognitive status, functional status, comorbidity, setting and admission to hospital, fall-related injuries and mortality in the time between baseline and follow-up. The European Union(7)-PIM list was used to evaluate PIM prescription. Multivariate regression analysis was used to investigate factors and adverse outcomes associated with PIM prescription. Results: overall, 60% of the participants had at least one PIM prescription and 26.4% at least two. The PIM therapeutic subgroups most frequently prescribed were psycholeptics (26% of all PIM prescriptions) and 'drugs for acid-related disorders' (21%). PwD who were 80 years and older, lived in institutional long-term care settings, had higher comorbidity and were more functionally impaired were at higher risk of being prescribed two PIM or more. The prescription of two or more PIM was associated with higher chance of suffering from at least one fall-related injury and at least one episode of hospitalisation in the time between baseline and follow-up. Conclusions: PIM use among PwD is frequent and is associated with institutional long-term care, age, advanced morbidity and functional impairment. It also appears to be associated with adverse outcomes. Special attention should be paid to psycholeptics and drugs for acid-related disorders.

Polypharmacy in older patients with chronic diseases: a cross-sectional analysis of factors associated with excessive polypharmacy.

BACKGROUND: Polypharmacy is common in older people and associated with potential harms. The aim of this study was to analyse the characteristics of an older multimorbid population with polypharmacy and to identify factors contributing to excessive polypharmacy in these patients. METHODS: This cross-sectional analysis is based on the PRIMA-eDS trial, a large randomised controlled multicentre study of polypharmacy in primary care. Patients' baseline data were used for analysis. A number of socioeconomic and medical data as well as SF-12-scores were entered into a generalized linear mixed model to identify variables associated with excessive polypharmacy (taking ≥10 substances daily). RESULTS: Three thousand nine hundred four participants were recruited. Risk factors significantly associated with excessive polypharmacy were frailty (OR 1.45; 95% CI 1.22-1.71), > 8 diagnoses (OR 2.64; 95% CI 2.24-3.11), BMI ≥30 (OR 1.18; 95% CI 1.02-1.38), a lower SF-12 physical health composite score (OR 1.47; 95% CI 1.26-1.72), and a lower SF-12 mental health composite score (OR 1.33; 95% CI 1.17-1.59) than the median of the study population (≤36.6 and ≤ 48.7, respectively). Age ≥ 85 years (OR 0.83; 95% CI 0.70-0.99) led to a significantly lower risk for excessive polypharmacy. No association with excessive polypharmacy could be found for female sex, low educational level, and smoking. Regarding the study centres, being recruited in the UK led to a significantly higher risk for excessive polypharmacy compared to being recruited in Germany 1/Rostock (OR 1.71; 95% CI 1.27-2.30). Being recruited in Germany 2/Witten led to a slightly significant lower risk for excessive polypharmacy compared to Germany 1/Rostock (OR 0.74; 95% CI 0.56-0.97). CONCLUSIONS: Frailty, multimorbidity, obesity, and decreased physical as well as mental health status are risk factors for excessive polypharmacy. Sex, educational level, and smoking apparently do not seem to be related to excessive polypharmacy. Physicians should especially pay attention to their frail, obese patients who have multiple diagnoses and a decreased health-related quality of life, to check carefully whether all the drugs prescribed are evidence-based, safe, and do not interact in an unfavourable way. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

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.

Falls and EQ-5D rated quality of life in community-dwelling seniors with concurrent chronic diseases: a cross-sectional study.

BACKGROUND: Although recommended for use in studies investigating falls in the elderly, the European Quality of Life Group instrument, EQ-5D, has not been widely used to assess the impact of falls on quality of life. The aim of this study was to investigate the association of single and frequent falls with EQ-5D rated quality of life in a sample of German community-dwelling seniors in primary care suffering a variety of concurrent chronic diseases and conditions. METHODS: In a cross-sectional study, a sample of community-dwelling seniors aged ≥ 72 years was interviewed by means of a standardised telephone interview. According to the number of self-reported falls within twelve months prior to interview, participants were categorised into one of three fall categories: no fall vs. one fall vs. two or more falls within twelve months. EQ-5D values as well as other characteristics were compared across the fall categories. Adjustments for a variety of concurrent chronic diseases and conditions and further variables were made by using multiple linear regression analysis, with EQ-5D being the target variable. RESULTS: In total, 1,792 participants (median age 77 years; 53% female) were analysed. The EQ-5D differed between fall categories. Participants reporting no fall had a mean EQ-5D score of 81.1 (standard deviation [s.d.]: 15.4, median: 78.3), while participants reporting one fall (n = 265; 14.8%) and participants with two or more falls (n = 117; 6.5%) had mean total scores of 77.0 (s.d.: 15.8, median: 78.3; mean difference to participants without a fall: -4.1, p < 0.05) and 72.1 (s.d.: 17.6, median: 72.5; mean difference: -9.0, p < 0.05), respectively. The mean difference between participants with one fall and participants with two or more falls was -4.9 (p < 0.05). Under adjustment for a variety of chronic diseases and conditions, the mean decrease in the total EQ-5D score was about -1.0 score point for one fall and about -2.5 points for two or more falls within twelve months. In quantity, this decrease is comparable to other chronic diseases adjusted for. Among the variables with the greatest negative association with EQ-5D ratings in multivariate analysis were depression and fear of falling. CONCLUSIONS: The findings suggest that falls are negatively associated with EQ-5D rated quality of life independent of a variety of chronic diseases and conditions.

Diurnal profiles of pedometer-determined physical activity in chronically ill and mobility-limited older adults: a cross-sectional study.

BACKGROUND: The aim of this study was to analyze diurnal profiles of physical activity for community-dwelling adults aged 70 years and over, and to explore the moderating effect of sex, age, morbidity, mobility limitation, and season on physical activity throughout the day. METHODS: A sample of 149 primary health care patients (mean age 79.5 ± 5.2 years, 74.5% females) was included in the analyses. Participants' physical activity was measured on up to six consecutive days via Omron Walking Style Pro HJ-720IT-E2 pedometer. Step count per day and per hour, and pedometer wear time were descriptively analyzed. A repeated measures ANOVA with physical activity per hour as dependent variable was performed to analyze the moderating effect of sex, age, morbidity, mobility limitation, and season on diurnal profiles of physical activity. The diurnal profile for the total sample and adjusted diurnal profiles for subgroups are presented. RESULTS: Participants' daily step count averaged 3280 ± 1873 steps/day. They wore the pedometer for 14.2 ± 1.7 hours per day and walked on average 234 ± 139 steps per hour. With respect to diurnal profiles, there were two peaks at 10-11 AM (mean [95%-confidence interval]: 382 [329-435] steps) and at 3-4 pm (313 [261-365] steps) interrupted by a period of lower activity with a low point at 1-2 pm (229 [190-268] steps). A mobility limitation, defined by use of a cane or a rollator, had a significant moderating effect (p = 0.0237) on diurnal physical activity. CONCLUSIONS: This is the first study to explore pedometer-determined diurnal profiles of physical activity in chronically ill and mobility-limited older adults. Prolonging periods of elevated physical activity in the afternoon while respecting individual daily routine and commitments could be one option for facilitating the integration of physical activity and for making it a habit in older adults' daily lives. The use of a walking aid seems to be an indicator for a quite low activity plateau during the second half of the day. People who use walking aids should be motivated to increase their physical activity during afternoon; this might help to increase the overall low physical activity level of this vulnerable subgroup of older adults.

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.

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.

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.

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).

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.