Background: Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial.Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm.Method: This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention.Discussion: The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019.Trial registration: Universal Trial Number:U1111-1181-9400Clinicaltrials.gov:NCT02986425, Registered 08 December 2016.FOPH (Swiss national portal):SNCTP000002183. Netherlands Trial Register:NTR6012(07-10-2016).

Aims The Systematic Tool to Reduce Inappropriate Prescribing is a method to assess patient's medication and has been incorporated into a clinical decision support system: STRIP Assistant. Our aim was to evaluate the effect of recommendations generated using STRIP Assistant on appropriate prescribing and mortality in a preoperative setting. Methods This cluster‐randomized controlled trial was carried out at the preoperative geriatric outpatient clinic. Residents who performed a comprehensive geriatric assessment were randomized to the control group and intervention group in a 1:1 ratio. Visiting patients aged 70 years or older on 5 or more medications were included. Intervention: prescribing recommendations were generated by a physician using STRIP Assistant and given to the resident. Control group residents performed a medication review according to usual care. Primary outcome: number of medication changes made because of potential prescribing omissions (PPOs), potentially inappropriate medications (PIMs), and suboptimal dosages according to the prescribing recommendations. Secondary outcome: 3‐month postoperative mortality. Results 65 intervention and 59 control patients were included, attended by 34 residents. Significantly more medication changes because of PPOs and PIMs were made in the intervention group than in the control group (PPOs 26.2% vs 3.4%, odds ratio 0.04 [95% confidence interval 0.003–0.46] P < .05; PIMS 46.2% vs 15.3% odds ratio 0.14 [95% confidence interval 0.07–0.57] P < .005). There were no differences in dose adjustments or in postoperative mortality. Conclusion Prescribing recommendations generated with the help of STRIP Assistant improved appropriate prescribing in a preoperative geriatric outpatient clinic but did not affect postoperative mortality.

Objective: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. Methods: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. Results: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9–14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30–50 ml/min/1.73 m²; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients’ reluctance to discontinue or initiate medication. Conclusion: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. Clinical trial registration: Trial Registration Number NCT02986425.

Background/Objectives: Hyponatremia has been associated with mortality and hospital readmissions. Although multimorbid older patients are particularly affected, specific data on this group are lacking. Methods: A prospective cohort was used based on the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) trial, a European multicenter, cluster-randomized trial among hospitalized patients aged ≥70 years with ≥3 chronic medical conditions taking ≥5 long-term medications, with documented sodium values at admission, excluding participants with hypernatremia (>145 mmol/L). The primary outcome was all-cause 1-year mortality, and secondary outcomes were 30-day mortality and readmission at 1 year and at 30 days. We examined the association between hyponatremia and mortality in comparison to normonatremia using a mixed-effects survival model, with adjustment for age, sex, comorbidities, study intervention arm, study site and cluster; and the association between hyponatremia and readmission using competing risk models with death as the competing risk. Subgroup analyses were performed across sodium hyponatremia categories (mild 134–130 mmol/L, moderate 129–125 mmol/L, severe < 125 mmol/L). Results: Of 2008 OPERAM participants, 1968 had a sodium value at admission, and 33 were excluded due to hypernatremia. In the 1935 participants, the mean age was 79.4 years (standard deviation 6.3), 866 (44.8%) were female, the median number of comorbidities was 11 (IQR 8–16), the median number of drugs was 10 (IQR 7–13), and 401 (20.7%) had hyponatremia at admission. The multivariate-adjusted hazard ratio (HR) for 1-year mortality with hyponatremia was 1.41 (95% confidence interval [CI] 1.11–1.78, 364 deaths) and for 30-day mortality was 1.20 (95%CI 0.74–1.94, 89 deaths). The adjusted sub-HR for 1-year readmission was 0.94 (95%CI 0.79–1.11), and that for 30-day readmission was 1.1 (95%CI 0.78–1.59). There was a linear increase in 1-year mortality across hyponatremia categories (HR from 1.31 to 2.64, p for trend = 0.001). Conclusions: Hyponatremia at admission is associated with increased 1-year mortality in multimorbid older adults, with increasing risk for lower sodium values. These findings support sodium as a useful prognostic marker in this setting, while its potential independent impact on survival remains to be clarified in prospective studies.

OBJECTIVE: To evaluate agreement of hospital physicians and older patients with individualised STOPP/START based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥3 chronic conditions) older people (≥70 years) with polypharmacy (≥5 chronic medications). Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Determinants associated with higher agreement in multivariate analysis were: female gender (+17.1% [3.7;30.4]), ≥1 falls in the past year (+15.0% [1.5;28.5]) and eGFR 30-50 ml/min/1.73m2; (+18.0% [2.0;34.0]). The main reason for disagreement (40%) was patients’ reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid invalid recommendations, will likely result in higher agreement with future pharmacotherapy optimisation recommendations.