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.

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).

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.

Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support (PRIMA-eDS): study protocol for a randomized controlled trial.

BACKGROUND: Multimorbidity is increasing in aging populations with a corresponding increase in polypharmacy as well as inappropriate prescribing. Depending on definitions, 25-50 % of patients aged 75 years or older are exposed to at least five drugs. Evidence is increasing that polypharmacy, even when guidelines advise the prescribing of each drug individually, can potentially cause more harm than benefit to older patients, due to factors such as drug-drug and drug-disease interactions. Several approaches reducing polypharmacy and inappropriate prescribing have been proposed, but evidence showing a benefit of these measures regarding clinically relevant endpoints is scarce. There is an urgent need to implement more effective strategies. We therefore set out to develop an evidence-based electronic decision support (eDS) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-randomized controlled trial. METHODS: The "Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations" (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic reviews and guidelines, the European list of inappropriate medications for older people, the SFINX-database of interactions, the PHARAO-database on adverse effects, and the RENBASE-database on renal dosing. The tool will be evaluated in a cluster-randomized controlled trial involving 325 general practitioners (GPs) and around 3500 patients across five study centres in the United Kingdom, Germany, Austria and Italy. GP practices will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-randomized after completion of patient recruitment. Intervention GPs will have access to the PRIMA-eDS tool, while control GPs will treat their patients according to current guidelines (usual care) without access to the PRIMA-eDS tool. After an observation time of 2 years, intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death. DISCUSSION: The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death. A positive result of the trial will contribute substantially to the improvement of care in multimorbidity. The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome, but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis (CORRA): study protocol for a randomized controlled trial.

BACKGROUND: Although glucocorticoids are widely used in the treatment of patients with early rheumatoid arthritis, the best dosage of glucocorticoids with regards to efficacy and safety is not known.The aim of the study 'Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis' (CORRA) is to compare two standard glucocorticoid starting dosages and the non-use of glucocorticoids in the treatment of patients with early active rheumatoid arthritis on the background of the established 'anchor' therapy with methotrexate. METHODS/DESIGN: CORRA is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial with two treatment arms, starting with 60 mg or 10 mg prednisolone per day, tapered down to 5 mg prednisolone within eight weeks, and one placebo arm, each arm comprising 150 patients. The duration of the intervention is 12 weeks. In parallel, all patients will be treated with methotrexate (usual dosage 15 mg/week). The primary efficacy endpoint is the progression of radiographic joint damage after one year compared to baseline. Important secondary endpoints are the percentage of patients in remission, patient global assessment of disease activity, and changes of functional capacity. Safety monitoring is performed.The statistical analysis is performed in three hierarchical steps. The first step is an analysis of covariance (α = 0.05) to compare the group with the initial prednisolone dosage of 60 mg and the placebo group. In case of a statistically significant result, the comparison of the group starting with 10 mg prednisolone with the placebo group will be performed as a second step (α = 0.05). In case of superiority of the 10 mg prednisolone group versus the placebo group, the third step will be a non-inferiority test for the 10 mg prednisolone group versus the 60 mg prednisolone group (α = 0.025). DISCUSSION: The CORRA trial will yield information concerning the optimal glucocorticoid dosage schedule in the treatment of patients with early rheumatoid arthritis. TRIAL REGISTRATION: This trial was registered on 19 November 2013 at ClinicalTrials.gov. REGISTRATION NUMBER: NCT02000336.