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

Performance of a trigger tool for detecting adverse drug reactions in patients with polypharmacy acutely admitted to the geriatric ward

PURPOSE: Adverse drug reactions (ADRs) account for 10% of acute hospital admissions in older people, often under-recognised by physicians. The Dutch geriatric guideline recommends screening all acutely admitted older patients with polypharmacy with an ADR trigger tool comprising ten triggers and associated drugs frequently causing ADRs. This study investigated the performance of this tool and the recognition by usual care of ADRs detected with the tool. METHODS: A cross-sectional study was performed in patients ≥ 70 years with polypharmacy acutely admitted to the geriatric ward of the University Medical Centre Utrecht. Electronic health records (EHRs) were screened for trigger-drug combinations listed in the ADR trigger tool. Two independent appraisers assessed causal probability with the WHO-UMC algorithm and screened EHRs for recognition of ADRs by attending physicians. Performance of the tool was defined as the positive predictive value (PPV) for ADRs with a possible, probable or certain causal relation. RESULTS: In total, 941 trigger-drug combinations were present in 73% (n = 253/345) of the patients. The triggers fall, delirium, renal insufficiency and hyponatraemia covered 86% (n = 810/941) of all trigger-drug combinations. The overall PPV was 41.8% (n = 393/941), but the PPV for individual triggers was highly variable ranging from 0 to 100%. Usual care recognised the majority of ADRs (83.5%), increasing to 97.1% when restricted to possible and certain ADRs. CONCLUSION: The ADR trigger tool has predictive value; however, its implementation is unlikely to improve the detection of unrecognised ADRs in older patients acutely admitted to our geriatric ward. Future research is needed to investigate the tool's clinical value when applied to older patients acutely admitted to non-geriatric wards

Performance of a trigger tool for detecting adverse drug reactions in patients with polypharmacy acutely admitted to the geriatric ward

Key summary pointsAim To investigate the performance of an adverse drug reaction (ADR) trigger tool in patients with polypharmacy acutely admitted to our geriatric ward. Findings The ADR trigger tool had a positive predictive value (PPV) of 41.8%. Usual care recognised 83.5% of ADRs considered as possible, probable or certain, increasing to 97.1% when restricted to probable and certain ADRs. Message It is unlikely that implementation of the ADR trigger tool will improve detection of unrecognised ADRs in older patients acutely admitted to our geriatric ward.Purpose Adverse drug reactions (ADRs) account for 10% of acute hospital admissions in older people, often under-recognised by physicians. The Dutch geriatric guideline recommends screening all acutely admitted older patients with polypharmacy with an ADR trigger tool comprising ten triggers and associated drugs frequently causing ADRs. This study investigated the performance of this tool and the recognition by usual care of ADRs detected with the tool. Methods A cross-sectional study was performed in patients >= 70 years with polypharmacy acutely admitted to the geriatric ward of the University Medical Centre Utrecht. Electronic health records (EHRs) were screened for trigger-drug combinations listed in the ADR trigger tool. Two independent appraisers assessed causal probability with the WHO-UMC algorithm and screened EHRs for recognition of ADRs by attending physicians. Performance of the tool was defined as the positive predictive value (PPV) for ADRs with a possible, probable or certain causal relation. Results In total, 941 trigger-drug combinations were present in 73% (n = 253/345) of the patients. The triggers fall, delirium, renal insufficiency and hyponatraemia covered 86% (n = 810/941) of all trigger-drug combinations. The overall PPV was 41.8% (n = 393/941), but the PPV for individual triggers was highly variable ranging from 0 to 100%. Usual care recognised the majority of ADRs (83.5%), increasing to 97.1% when restricted to possible and certain ADRs. Conclusion The ADR trigger tool has predictive value; however, its implementation is unlikely to improve the detection of unrecognised ADRs in older patients acutely admitted to our geriatric ward. Future research is needed to investigate the tool's clinical value when applied to older patients acutely admitted to non-geriatric wards

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

INTRODUCTION Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. OBJECTIVE The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. METHODS Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. RESULTS In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. CONCLUSION MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. FUNDING European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF)

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission

Introduction Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people.Objective The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA.Methods Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in- hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review.Results In total, 84 of 963 OPERAM intervention patients ( 8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% ( n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented.Conclusion MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (similar to 50%), or no recommendation was given during the medication review (similar to 25%), or the recommendation was not implemented (similar to 25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations

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

OBJECTIVE To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. DESIGN Cluster randomised controlled trial. SETTING 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. PARTICIPANTS 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). INTERVENTION 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. MAIN OUTCOME MEASURE Primary outcome was first drug related hospital admission within 12 months. RESULTS 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). CONCLUSIONS 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. TRIAL REGISTRATION ClinicalTrials.gov NCT02986425

Medication optimisation in hospitalised older people with polypharmacy and multimorbidity

The prevalence of multimorbidity and polypharmacy is increasing in the ageing population, and both are important risk factors for drug-related harm, such as drug-related hospital admissions. Previous studies have reported that 10%–30% of all hospital admissions in older people are drug-related, half of which are potentially preventable. Several tools, such as the Screening Tool of Older Person’s Prescriptions (STOPP) and the Screening Tool to Alert to the Right Treatment (START) criteria, have been developed to detect potentially inappropriate prescribing in multimorbid older people to improve medication appropriateness and prevent adverse outcomes. To incorporate such tools into daily clinical practice, the application of software assistance has gained attention in facilitating medication optimisation. However, previous studies investigating pharmacotherapy optimisation interventions in older people reported inconsistent results on improved clinical outcomes. In this thesis, we focus on strategies for medication optimisation in hospitalised, multimorbid older people with polypharmacy and evaluate the effectiveness of a software-assisted in-hospital medication review on clinical outcomes. Key messages - Current clinical practice guidelines (CPGs) include screening tools to identify patients at risk for drug-related harm. For future development of explicit drug optimisation tools, such as STOPP/START, the clarity on a language level can be improved to enhance clinical applicability. - Screening tools recommended by CPGs have predictive value (~40%) to identify patients at risk for adverse drug reactions (ADRs) and for potentially inappropriate prescribing. However, when screening tools are integrated as clinical decision support in electronic health systems, their clinical applicability depends on the availability of structured patient information, the setting in which these tools will be used, and their intended end-users. (Chapter 2, 4.1) - A structured in-hospital medication review, performed jointly by a physician and a pharmacist with the support of a clinical decision software system, reduced inappropriate prescribing without causing detriment to patient outcomes, however, it did not significantly affect drug-related hospital admissions. (Chapter 3) - We found that medication errors identified at readmission were not addressed by the prior in-hospital medication review because either these medication errors occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). (Chapter 4.3) Conclusion The interaction between attending physicians, patients and healthcare professionals with expertise in geriatric care remains essential in translating evidence-based signals for potentially inappropriate prescribing to the most appropriate pharmacotherapy at the individual patient level. Barriers to the non-implementation of proposed recommendations differed between prescribers and patients and varied per drug class. Future research should focus on optimising the medication review timing, setting and frequency and implementing of proposed medication recommendations across health care settings. Overall, we learned that the association between a patient-specific medication review and the clinical outcome ‘drug-related hospital admission’ is difficult to establish with a randomised controlled trial because both the intervention and outcome are highly variable. To further explore the potential clinical benefits of medication optimisation interventions in older people, we recommend exploring research designs based on large, real-world data rather than randomised clinical trials

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

Objective: To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. Design: Cluster randomised controlled trial. Setting: 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. Participants: 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). Intervention: 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. Main outcome measure: Primary outcome was first drug related hospital admission within 12 months. Results: 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). Conclusions: 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. Trial registration: ClinicalTrials.gov NCT02986425

Evaluation of clarity of the STOPP/START criteria for clinical applicability in prescribing for older people : a quality appraisal study

OBJECTIVES: Appropriate prescribing in older people continues to be challenging. Studies still report a high prevalence of inappropriate prescribing in older people. To reduce the problem of underprescribing and overprescribing in this population, explicit drug optimisation tools like Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) have been developed. The aim of this study was to evaluate the clinical applicability of STOPP/START criteria in daily patient care by assessing the clarity of singular criteria. DESIGN: Quality appraisal study. METHODS: For each of the 114 STOPP/START criteria V.2, elements describing the action (what/how to do), condition (when to do) and explanation (why to do) were identified. Next, the clarity of these three elements was quantified on a 7-point Likert scale using tools provided by the Appraisal of Guidelines for Research and Evaluation (AGREE) Consortium. PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was the clarity rating per element, categorised into high (>67.7%), moderate (33.3%-67.7%) or low (<33.3%). Secondary, factors that positively or negatively affected clarity most were identified. Additionally, the nature of the conditions was further classified into five descriptive components: disease, sign, symptom, laboratory finding and medication. RESULTS: STOPP recommendations had an average clarity rating of 64%, 60% and 69% for actions, conditions and explanations, respectively. The average clarity rating in START recommendations was 60% and 57% for actions and conditions, respectively. There were no statements present to substantiate the prescription of potential omissions for the 34 START criteria. CONCLUSIONS: Our results show that the clarity of the STOPP/START criteria can be improved. For future development of explicit drug optimisation tools, such as STOPP/START, our findings identified facilitators (high clarity) and barriers (low clarity) that can be used to improve the clarity of clinical practice guidelines on a language level and therefore enhance clinical applicability

Evaluation of clarity of the STOPP/START criteria for clinical applicability in prescribing for older people : a quality appraisal study

OBJECTIVES: Appropriate prescribing in older people continues to be challenging. Studies still report a high prevalence of inappropriate prescribing in older people. To reduce the problem of underprescribing and overprescribing in this population, explicit drug optimisation tools like Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) have been developed. The aim of this study was to evaluate the clinical applicability of STOPP/START criteria in daily patient care by assessing the clarity of singular criteria. DESIGN: Quality appraisal study. METHODS: For each of the 114 STOPP/START criteria V.2, elements describing the action (what/how to do), condition (when to do) and explanation (why to do) were identified. Next, the clarity of these three elements was quantified on a 7-point Likert scale using tools provided by the Appraisal of Guidelines for Research and Evaluation (AGREE) Consortium. PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was the clarity rating per element, categorised into high (>67.7%), moderate (33.3%-67.7%) or low (<33.3%). Secondary, factors that positively or negatively affected clarity most were identified. Additionally, the nature of the conditions was further classified into five descriptive components: disease, sign, symptom, laboratory finding and medication. RESULTS: STOPP recommendations had an average clarity rating of 64%, 60% and 69% for actions, conditions and explanations, respectively. The average clarity rating in START recommendations was 60% and 57% for actions and conditions, respectively. There were no statements present to substantiate the prescription of potential omissions for the 34 START criteria. CONCLUSIONS: Our results show that the clarity of the STOPP/START criteria can be improved. For future development of explicit drug optimisation tools, such as STOPP/START, our findings identified facilitators (high clarity) and barriers (low clarity) that can be used to improve the clarity of clinical practice guidelines on a language level and therefore enhance clinical applicability