Rationale and design of OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM): a cluster randomised controlled trial.

Multimorbidity and polypharmacy are important risk factors for drug-related hospital admissions (DRAs). DRAs are often linked to prescribing problems (overprescribing and underprescribing), as well as non-adherence with drug regimens for different reasons. In this trial, we aim to assess whether a structured medication review compared with standard care can reduce DRAs in multimorbid older patients with polypharmacy. OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people is a European multicentre, cluster randomised, controlled trial. Hospitalised patients ≥70 years with ≥3 chronic medical conditions and concurrent use of ≥5 chronic medications are included in the four participating study centres of Bern (Switzerland), Utrecht (The Netherlands), Brussels (Belgium) and Cork (Ireland). Patients treated by the same prescribing physician constitute a cluster, and clusters are randomised 1:1 to either standard care or Systematic Tool to Reduce Inappropriate Prescribing (STRIP) intervention with the help of a clinical decision support system, the STRIP Assistant. STRIP is a structured method performing customised medication reviews, based on Screening Tool of Older People's Prescriptions/Screening  Tool to Alert to Right Treatment criteria to detect potentially inappropriate prescribing. The primary endpoint is any DRA where the main reason or a contributory reason for the patient's admission is caused by overtreatment or undertreatment, and/or inappropriate treatment. Secondary endpoints include number of any hospitalisations, all-cause mortality, number of falls, quality of life, degree of polypharmacy, activities of daily living, patient's drug compliance, the number of significant drug-drug interactions, drug overuse and underuse and potentially inappropriate medication. The local Ethics Committees in Switzerland, Ireland, The Netherlands and Belgium approved this trial protocol. We will publish the results of this trial in a peer-reviewed journal. European Union's Horizon 2020 programme. NCT02986425 , SNCTP000002183 , NTR6012, U1111-1181-9400.

Adam L ，Moutzouri E ，Baumgartner C ，Loewe AL ，Feller M ，M'Rabet-Bensalah K ，Schwab N ，Hossmann S ，Schneider C ，Jegerlehner S ，Floriani C ，Limacher A ，Jungo KT ，Huibers CJA ，Streit S ，Schwenkglenks M ，Spruit M ，Van Dorland A ，Donzé J ，Kearney PM ，Jüni P ，Aujesky D ，Jansen P ，Boland B ，Dalleur O ，Byrne S ，Knol W ，Spinewine A ，O'Mahony D ，Trelle S ，Rodondi N ... -  《BMJ Open》

Intervention protocol: OPtimising thERapy to prevent avoidable hospital Admission in the Multi-morbid elderly (OPERAM): a structured medication review with support of a computerised decision support system.

Crowley EK ，Sallevelt BTGM ，Huibers CJA ，Murphy KD ，Spruit M ，Shen Z ，Boland B ，Spinewine A ，Dalleur O ，Moutzouri E ，Löwe A ，Feller M ，Schwab N ，Adam L ，Wilting I ，Knol W ，Rodondi N ，Byrne S ，O'Mahony D ... -  《BMC HEALTH SERVICES RESEARCH》

'Optimising PharmacoTherapy In the multimorbid elderly in primary CAre' (OPTICA) to improve medication appropriateness: study protocol of a cluster randomised controlled trial.

Multimorbidity and polypharmacy are major risk factors for potentially inappropriate prescribing (eg, overprescribing and underprescribing), and systematic medication reviews are complex and time consuming. In this trial, the investigators aim to determine if a systematic software-based medication review improves medication appropriateness more than standard care in older, multimorbid patients with polypharmacy. Optimising PharmacoTherapy In the multimorbid elderly in primary CAre is a cluster randomised controlled trial that will include outpatients from the Swiss primary care setting, aged ≥65 years with ≥three chronic medical conditions and concurrent use of ≥five chronic medications. Patients treated by the same general practitioner (GP) constitute a cluster, and clusters are randomised 1:1 to either a standard care sham intervention, in which the GP discusses with the patient if the medication list is complete, or a systematic medication review intervention based on the use of the 'Systematic Tool to Reduce Inappropriate Prescribing'-Assistant (STRIPA). STRIPA is a web-based clinical decision support system that helps customise medication reviews. It is based on the validated 'Screening Tool of Older Person's Prescriptions' (STOPP) and 'Screening Tool to Alert doctors to Right Treatment' (START) criteria to detect potentially inappropriate prescribing. The trial's follow-up period is 12 months. Outcomes will be assessed at baseline, 6 and 12 months. The primary endpoint is medication appropriateness, as measured jointly by the change in the Medication Appropriateness Index (MAI) and Assessment of Underutilisation (AOU). Secondary endpoints include the degree of polypharmacy, overprescribing and underprescribing, the number of falls and fractures, quality of life, the amount of formal and informal care received by patients, survival, patients' quality adjusted life years, patients' medical costs, cost-effectiveness of the intervention, percentage of recommendations accepted by GPs, percentage of recommendation rejected by GPs and patients' willingness to have medications deprescribed. The ethics committee of the canton of Bern in Switzerland approved the trial protocol. The results of this trial will be published in a peer-reviewed journal. Swiss National Science Foundation, National Research Programme (NRP 74) 'Smarter Healthcare'. Clinicaltrials.gov (NCT03724539), KOFAM (Swiss national portal) (SNCTP000003060), Universal Trial Number (U1111-1226-8013).

Jungo KT ，Rozsnyai Z ，Mantelli S ，Floriani C ，Löwe AL ，Lindemann F ，Schwab N ，Meier R ，Elloumi L ，Huibers CJA ，Sallevelt BTGM ，Meulendijk MC ，Reeve E ，Feller M ，Schneider C ，Bhend H ，Bürki PM ，Trelle S ，Spruit M ，Schwenkglenks M ，Rodondi N ，Streit S ... -  《BMJ Open》

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial.

To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. Cluster randomised controlled trial. 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. Primary outcome was first drug related hospital admission within 12 months. 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. ClinicalTrials.gov NCT02986425.

Blum MR ，Sallevelt BTGM ，Spinewine A ，O'Mahony D ，Moutzouri E ，Feller M ，Baumgartner C ，Roumet M ，Jungo KT ，Schwab N ，Bretagne L ，Beglinger S ，Aubert CE ，Wilting I ，Thevelin S ，Murphy K ，Huibers CJA ，Drenth-van Maanen AC ，Boland B ，Crowley E ，Eichenberger A ，Meulendijk M ，Jennings E ，Adam L ，Roos MJ ，Gleeson L ，Shen Z ，Marien S ，Meinders AJ ，Baretella O ，Netzer S ，de Montmollin M ，Fournier A ，Mouzon A ，O'Mahony C ，Aujesky D ，Mavridis D ，Byrne S ，Jansen PAF ，Schwenkglenks M ，Spruit M ，Dalleur O ，Knol W ，Trelle S ，Rodondi N ... -  《BMJ-British Medical Journal》

Methods to reduce prescribing errors in elderly patients with multimorbidity.

Lavan AH ，Gallagher PF ，O'Mahony D 《Clinical Interventions in Aging》