An International Consensus List of Potentially Clinically Significant Drug-Drug Interactions in Older People.

Objectives We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. Design A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. Setting and Participants Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. Measures For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. Results Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. Conclusion and Implications We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies.pre-print896 K

Experience of hospital-initiated medication changes in older people with multimorbidity: a multicentre mixed-methods study embedded in the OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial.

BACKGROUND A patient-centred approach to medicines optimisation is considered essential. The OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial evaluated the effectiveness of medication review with shared decision-making (SDM) in older people with multimorbidity. Beyond evaluating the clinical effectiveness, exploring the patient experience facilitates a better understanding of contextual factors and mechanisms affecting medication review effectiveness. OBJECTIVE To explore experiences of hospital-initiated medication changes in older people with multimorbidity. METHODS We conducted a multicentre mixed-methods study, embedded in the OPERAM trial, combining semi-structured interviews and the Beliefs about Medicines Questionnaire (BMQ) with a purposive sample of 48 patients (70-94 years) from four European countries. Interviews were analysed using the Framework approach. Trial implementation data on SDM were collected and the 9-item SDM questionnaire was conducted with 17 clinicians. RESULTS Patients generally displayed positive attitudes towards medication review, yet emphasised the importance of long-term, trusting relationships such as with their general practitioners for medication review. Many patients reported a lack of information and communication about medication changes and predominantly experienced paternalistic decision-making. Patients' beliefs that 'doctors know best', 'blind trust', having limited opportunities for questions, use of jargon terms by clinicians, 'feeling too ill', dismissive clinicians, etc highlight the powerlessness some patients felt during hospitalisation, all representing barriers to SDM. Conversely, involvement of companions, health literacy, empathetic and trusting patient-doctor relationships, facilitated SDM. Paradoxical to patients' experiential accounts, clinicians reported high levels of SDM. The BMQ showed that most patients had high necessity and low concern beliefs about medicines. Beliefs about medicines, experiencing benefits or harms from medication changes, illness perception, trust and balancing advice between different healthcare professionals all affected acceptance of medication changes. CONCLUSION To meet patients' needs, future medicines optimisation interventions should enhance information exchange, better prepare patients and clinicians for partnership in care and foster collaborative medication reviews across care settings

Association between diabetes overtreatment in older multimorbid patients and clinical outcomes: an ancillary European multicentre study.

BACKGROUND Diabetes overtreatment is a frequent and severe issue in multimorbid older patients with type 2 diabetes (T2D). OBJECTIVE This study aimed at assessing the association between diabetes overtreatment and 1-year functional decline, hospitalisation and mortality in older inpatients with multimorbidity and polypharmacy. METHODS Ancillary study of the European multicentre OPERAM project on multimorbid patients aged ≥70 years with T2D and glucose-lowering treatment (GLT). Diabetes overtreatment was defined according to the 2019 Endocrine Society guideline using HbA1c target range individualised according to the patient's overall health status and the use of GLT with a high risk of hypoglycaemia. Multivariable regressions were used to assess the association between diabetes overtreatment and the three outcomes. RESULTS Among the 490 patients with T2D on GLT (median age: 78 years; 38% female), 168 (34.3%) had diabetes overtreatment. In patients with diabetes overtreatment as compared with those not overtreated, there was no difference in functional decline (29.3% vs 38.0%, P = 0.088) nor hospitalisation rates (107.3 vs 125.8/100 p-y, P = 0.115) but there was a higher mortality rate (32.8 vs 21.4/100 p-y, P = 0.033). In multivariable analyses, diabetes overtreatment was not associated with functional decline nor hospitalisation (hazard ratio, HR [95%CI]: 0.80 [0.63; 1.02]) but was associated with a higher mortality rate (HR [95%CI]: 1.64 [1.06; 2.52]). CONCLUSIONS Diabetes overtreatment was associated with a higher mortality rate but not with hospitalisation or functional decline. Interventional studies should be undertaken to test the effect of de-intensifying GLT on clinical outcomes in overtreated patients

Healthcare Costs and Health-Related Quality of Life in Older Multimorbid Patients After Hospitalization.

OBJECTIVES We identified factors associated with healthcare costs and health-related quality of life (HRQoL) of multimorbid older adults with polypharmacy. METHODS Using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid older people) trial, we described the magnitude and composition of healthcare costs, and time trends of HRQoL, during 1-year after an acute-care hospitalization. We performed a cluster analysis to identify groups with different cost and HRQoL trends. Using multilevel models, we also identified factors associated with costs and HRQoL. RESULTS Two months after hospitalization monthly mean costs peaked (CHF 7'124) and HRQoL was highest (0.67). They both decreased thereafter. Age, falls, and comorbidities were associated with higher 1-year costs. Being female and housebound were negatively associated with HRQoL, while moderate alcohol consumption had a positive association. Being independent in daily activities was associated with lower costs and higher HRQoL. CONCLUSION Although only some identified potential influences on costs and HRQoL are modifiable, our observations support the importance of prevention before health deterioration in older people with multimorbid illness and associated polypharmacy

Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial.

BACKGROUND Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016

Collaborative approach to Optimise MEdication use for Older people in Nursing homes (COME-ON): study protocol of a cluster controlled trial

BACKGROUND: Ageing has become a worldwide reality and presents new challenges for the health-care system. Research has shown that potentially inappropriate prescribing, both potentially inappropriate medications and potentially prescribing omissions, is highly prevalent in older people, especially in the nursing home setting. The presence of potentially inappropriate medications/potentially prescribing omissions is associated with adverse drug events, hospitalisations, mortality and health-care costs. The Collaborative approach to Optimise MEdication use for Older people in Nursing homes (COME-ON) study aims to evaluate the effect of a complex, multifaceted intervention, including interdisciplinary case conferences, on the appropriateness of prescribing of medicines for older people in Belgian nursing homes. METHODS/DESIGN: A multicentre cluster-controlled trial is set up in 63 Belgian nursing homes (30 intervention; 33 control). In each of these nursing homes, 35 residents (≥65 years) are selected for participation. The complex, multifaceted intervention comprises (i) health-care professional education and training, (ii) local concertation (discussion on the appropriate use of at least one medication class at the level of the nursing home) and (iii) repeated interdisciplinary case conferences between general practitioner, nurse and pharmacist to perform medication review for each included nursing home resident. The control group works as usual. The study period lasts 15 months. The primary outcome measures relate to the appropriateness of prescribing and are defined as (1) among residents who had at least one potentially inappropriate medication/potentially prescribing omission at baseline, the proportion of them for whom there is a decrease of at least one of these potentially inappropriate medications/potentially prescribing omissions at the end of study, and (2) among all residents, the proportion of them for whom at least one new potentially inappropriate medication/potentially prescribing omission is present at the end of the study, compared to baseline. The secondary outcome measures include individual components of appropriateness of prescribing, medication use, outcomes of the case conferences, clinical outcomes and costs. A process evaluation (focusing on implementation, causal mechanisms and contextual factors) will be conducted alongside the study. DISCUSSION: The COME-ON study will contribute to a growing body of knowledge concerning the effect of complex interventions on the use of medicines in the nursing home setting, and on factors influencing their effect. The results will inform policymakers on strategies to implement in the near future. TRIAL REGISTRATION: Current Controlled Trials ISRCTN66138978

Patient and public involvement in pragmatic trials : online survey of corresponding authors of published trials

Acknowledgements The authors acknowledge Dr. Paxton Montgomery Moon, Alison Howie, Hayden Nix and Dr. Merrick Zwarenstein for their contributions to the data extraction. They also thank Drs. Bruno Giraudeau and Agnes Caille (University of Tours), Dr. Laura Hanson (University of North Carolina School of Medicine) and Dr. Jill Harrison (Brown University) for assistance with pilot testing of the survey questionnaire. Funding: This work was supported by the Canadian Institutes of Health Research through the Project Grant competition (competitive, peer-reviewed), award number PJT-153045, and the National Institute of Aging ( NIA) of the National Institutes of Health under Award Number U54AG063546, which funds NIA Imbedded Pragmatic Alzheimer’s Disease and Related Dementias Clinical Trials Collaboratory ( NIA IMPACT Collaboratory). The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.Peer reviewedPublisher PD