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.

Factors affecting physician implementation of hospital pharmacists' medication appropriateness recommendations in older adults.

AIMS: Non-implementation of pharmacist recommendations by physician prescribers may prolong potentially inappropriate prescribing in hospitalised older adults, increasing the risk of adverse clinical outcomes. The aim of this study was to ascertain the key factors affecting physician prescriber implementation of pharmacists' medication appropriateness recommendations in hospitalised older adults. METHODS: Semi-structured interviews were conducted with hospital pharmacists and physicians who provided care to older adults (≥65 years) in 2 acute university teaching hospitals in Ireland. Content analysis was employed to identify the key themes that influence physician prescriber implementation of pharmacist recommendations. RESULTS: Fourteen interviews were conducted with 6 hospital pharmacists and 8 hospital physicians between August 2018 and August 2019. Five key factors were found to affect physician implementation of pharmacist recommendations: (i) the clinical relevance and complexity of the recommendation-recommendations of higher priority and those that do not require complex decision-making are implemented more readily; (ii) interprofessional communication-recommendations provided verbally, particularly those communicated face to face with confidence and assertion, are more likely to be implemented than written recommendations; (iii) physician role and identity-the grade, specialty, and personality of the physician significantly affect implementation; (iv) knowing each other and developing trusting relationships-personal acquaintance and the development of interprofessional trust and rapport greatly facilitate recommendation implementation; and (v) the hospital environment-organisational issues such as documentation in the patient notes, having the opportunity to intervene, and the clinical pharmacy model all affect implementation. CONCLUSION: This study provides a deeper understanding of the underlying behavioural determinants affecting physician prescriber implementation of pharmacist recommendations and will aid in the development of theoretically-informed interventions to improve medication appropriateness in hospitalised older adults.

Prescribing cascades: we see only what we look for, we look for only what we know.

Prescribing cascades are increasingly recognized since they were described in the mid-1990s. Cascades are more likely in older people with multimorbidity and associated polypharmacy where multiple medications can induce a variety of side effects that manifest with various non-specific symptoms that may be misidentified as new geriatric syndromes such as falls, dizziness and new-onset incontinence. Geriatricians encounter medication side effects frequently and will usually consider if an older patient presenting with new symptoms could be experiencing an adverse drug reaction or event. However, most medications prescribed to multimorbid older patients are initiated and continued by prescribers without specialist geriatric training who may not detect medication-induced morbidity. Therefore, novel approaches to the detection and management of prescribing cascades in older people are needed. Currently, the knowledge base surrounding prescribing cascades in older people is evolving towards better methods for cascade detection and secondary prevention. However, the large number of cascades described in the literature, the wide-ranging symptomatology of cascades and the rapidly increasing number of multimorbid older people at risk of cascades represent major challenges for prescribers. Furthermore, prospective prevalence studies of prescribing cascades in older people are lacking. To detect and correct prescribing cascades during routine medication review in multimorbid older people, awareness of cascades is essential. Prescribing cascade awareness in turn requires novel explicit ways of defining cascades to facilitate their rapid detection and correction during medication review. Given that prescribing cascades represent another aspect of inappropriate prescribing (IP), explicit cascades criteria should be integrated with other explicit IP criteria.

Inappropriate prescribing: hazards and solutions.

With population ageing, the number of older people is growing, which results in increasing number of people with multimorbidity and related polypharmacy. Polypharmacy in its turn leads to drug-related problems (DRPs) and potentially inappropriate prescribing (IP) in older people. In this commentary, susceptibility of older people to DRPs due to changes in pharmacokinetics and pharmacodynamics, plurality of prescribing physicians, inadequate consideration of patients' characteristics, polypharmacy and its consequences such as prescribing cascades, drug interactions and potentially IP have been discussed respectively. Consecutively, identifying DRPs and optimizing of IP, including drug reconciliation, application of criteria for identifying and preventing IP, implementation of computer-based prescribing systems, and comprehensive geriatric assessment and management have been elaborated as well. One of the main challenges regarding appropriate and tailored prescribing in older people is to evaluate whether the expected benefits of pharmacotherapy are bigger than the risks in a population with multimorbidity, decreased tolerance to vulnerability and limited life expectancy. Comprehensive geriatric assessment enables informed prescribing decisions in the context of such variables. A challenge for future research is how to integrate important clinical information obtained by existing methods into a comprehensive and wide-reaching approach targeting all potential factors involved in causing DRPs. Good prescribing in late life accommodates the needs of older patients with multimorbidity. Individualized, interactive, multidisciplinary, and multifaceted approach to geriatric pharmacotherapy should be promoted and encouraged. How to optimize pharmacological prescription in complex older patients is a major legacy of geriatrics to contemporary medicine/medical practice.

Performance of a trigger tool for detecting drug-related hospital admissions in older people: analysis from the OPERAM trial.

BACKGROUND: identifying drug-related hospital admissions (DRAs) in older people is difficult. A standardised chart review procedure has recently been developed. It includes an adjudication team (physician and pharmacist) screening using 26 triggers and then performing causality assessment to determine whether an adverse drug event (ADE) occurred (secondary to an adverse drug reaction, overuse, misuse or underuse) and whether the ADE contributed to hospital admission (DRA). OBJECTIVE: to assess the performance of those triggers in detecting DRA. DESIGN: retrospective study using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people) trial. SETTINGS: four European medical centres. SUBJECTS: multimorbid (≥ 3 chronic medical conditions) older (≥ 70 years) inpatients with polypharmacy (≥ 5 chronic medications) were enrolled in the OPERAM trial (N = 2,008) and followed for 12 months. We included patients with ≥1 adjudicated hospitalisation during the follow-up. METHODS: the positive predictive value (PPV; number of DRAs identified by trigger/number of triggers) was calculated for each trigger and for the tool as a whole. RESULTS: of 1,235 hospitalisations adjudicated for 832 patients, 716 (58%) had at least one trigger; an ADE was identified in 673 (54%) and 518 (42%) were adjudicated as DRAs. The overall PPV of the trigger tool for detecting DRAs was 0.66 [0.62-0.69]. CONCLUSIONS: this tool performs well for identifying DRAs in older people. Based on our results, a revised version of the tool was proposed but will require external validation before it can be incorporated into research and clinical practice.

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

Deprescribing in older people approaching end-of-life: development and validation of STOPPFrail version 2.

BACKGROUND: Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy (STOPPFrail) criteria were developed in 2017 to assist physicians with deprescribing decisions in older people approaching end-of-life. Updating was required to make the tool more practical, patient-centred and complete. METHODS: a thorough literature review was conducted to, first, devise a practical method for identifying older people who are likely to be approaching end-of-life, and second, reassess and update the existing deprescribing criteria. An eight-member panel with a wide-ranging experience in geriatric pharmacotherapy reviewed a new draft of STOPPFrail and were invited to propose new deprescribing criteria. STOPPFrail version 2 was then validated using Delphi consensus methodology. RESULTS: STOPPFrail version 2 emphasises the importance of shared decision-making in the deprescribing process. A new method for identifying older people who are likely to be approaching end-of-life is included along with 25 deprescribing criteria. Guidance relating to the deprescribing of antihypertensive therapies, anti-anginal medications and vitamin D preparations comprises the new criteria. CONCLUSIONS: STOPPFrail criteria have been updated to assist physicians in efforts to reduce drug-related morbidity and burden for their frailest older patients. Version 2 is based on an up-to-date literature review and consensus validation by a panel of experts.

STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

BACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

Prevalence of drug-drug interactions in older people before and after hospital admission: analysis from the OPERAM trial.

BACKGROUND: Drug-drug interactions (DDIs) are highly prevalent in older patients but little is known about prevalence of DDIs over time. Our main objective was to assess changes in the prevalence and characteristics of drug-drug interactions (DDIs) during a one-year period after hospital admission in older people, and associated risk factors. METHODS: We conducted a sub-study of the European OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people), which assessed the effects of a structured medication review (experimental arm) compared to usual care (control arm) on reducing drug-related hospital readmissions. All OPERAM patients (≥70 years, with multimorbidity and polypharmacy, hospitalized in four centers in Bern, Brussels, Cork and Utrecht between December 2016 and October 2018, followed over 1 year) who were alive at hospital discharge and had full medication data during the index hospitalization (at baseline i.e., enrolment at admission, and at discharge) were included. DDIs were assessed using an international consensus list of potentially clinically significant DDIs in older people. The point-prevalence of DDIs was evaluated at baseline, discharge, and at 2, 6 and 12 months after hospitalization. Logistic regression models were performed to assess independent variables associated with changes in DDIs 2 months after baseline. RESULTS: Of the 1950 patients (median age 79 years) included, 1045 (54%) had at least one potentially clinically significant DDI at baseline; point-prevalence rates were 58, 57, 56 and 57% at discharge, and 2, 6 and 12 months, respectively. The prevalence increased significantly from baseline to discharge (P < .001 [significant only in the control group]), then remained stable over time (P for trend .31). The five most common DDIs -all pharmacodynamic in nature- accounted for 80% of all DDIs and involved drugs that affect potassium concentrations, centrally-acting drugs and antithrombotics. At 2 months, DDIs had increased in 459 (27%) patients and decreased in 331 (19%). The main factor predictive of a change in the prevalence of DDIs was hyperpolypharmacy (≥10 medications). CONCLUSIONS: DDIs were very common; their prevalence increased during hospitalization and tended to remain stable thereafter. Medication review may help control this increase and minimize the risk of adverse drug events.

Measurement properties of EQ-5D-3L and EQ-5D-5L in recording self-reported health status in older patients with substantial multimorbidity and polypharmacy.

BACKGROUND: The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. METHODS: Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person's EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. RESULTS: 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon's evenness index score of 0.86) than the EQ-5D-3L (Shannon's evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. CONCLUSION: Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

In-hospital adverse drug reactions in older adults; prevalence, presentation and associated drugs-a systematic review and meta-analysis.

BACKGROUND: the prevalence of adverse drug reactions (ADRs) in hospitalised older patients, their clinical presentations, causative drugs, severity, preventability and measurable outcomes are unclear, ADRs being an increasing challenge to older patient safety. METHODS: we systematically searched PubMed, Embase, EBSCO-CINAHL, the Cochrane Library, 'rey' literature and relevant systematic review bibliographies, published from database inception to March 2020. We included any study reporting occurrence of in-hospital ADRs as primary or secondary outcomes in hospitalised older adults (mean age ≥ 65 years). Two authors independently extracted relevant information and appraised studies for bias. Study characteristics, ADR clinical presentations, causative drugs, severity, preventability and clinical outcomes were analysed. Study estimates were pooled using random-effects meta-analytic models. RESULTS: from 2,399 abstracts, we undertook full-text screening in 286, identifying 27 studies (29 papers). Final analysis yielded a pooled ADR prevalence of 16% (95%CI 12-22%, I2 98%,τ2 0.8585), in a population of 20,153 hospitalised patients aged ≥65 years of whom 2,479 patients experienced ≥ one ADR. ADR ascertainment was highly heterogeneous. Almost 48.3% of all ADRs involved five presentations: fluid/electrolyte disturbances (17.3%), gastrointestinal motility/defaecation disorders (13.3%), renal disorders (8.2%), hypotension/blood pressure dysregulation disorders/shock (5.5%) and delirium (4.1%). Four drug classes accounted for 57.8% of causative medications i.e. diuretics (19.8%), anti-bacterials (14.8%), antithrombotic agents (12.2%) and analgesics (10.9%). Pooled analysis of severity was not feasible. Four studies reported the majority of ADRs as preventable (55-95%). CONCLUSIONS: on average, 16% of hospitalised older patients experience significant ADRs, varying in severity and mostly preventable, with commonly prescribed drug classes accounting for most ADRs.

Computer-generated STOPP/START recommendations for hospitalised older adults: evaluation of the relationship between clinical relevance and rate of implementation in the SENATOR trial.

BACKGROUND: findings from a recent qualitative study indicate that the perceived clinical relevance of computer-generated STOPP/START recommendations was a key factor affecting their implementation by physician prescribers caring for hospitalised older adults in the SENATOR trial. AIM: to systematically evaluate the clinical relevance of these recommendations and to establish if clinical relevance significantly affected the implementation rate. METHODS: a pharmacist-physician pair retrospectively reviewed the case records for all SENATOR trial intervention patients at Cork University Hospital and assigned a degree of clinical relevance for each STOPP/START recommendation based on a previously validated six-point scale. The chi-square test was used to quantify the differences in prescriber implementation rates between recommendations of varying clinical relevance, with statistical significance set at P < 0.05. RESULTS: in 204 intervention patients, the SENATOR software produced 925 STOPP/START recommendations. Nearly three quarters of recommendations were judged to be clinically relevant (73.6%); however, nearly half of these were deemed of 'possibly low relevance' (320/681; 47%). Recommendations deemed of higher clinical relevance were significantly more likely to be implemented than those of lower clinical relevance (P < 0.05). CONCLUSIONS: a large proportion (61%) of the computer-generated STOPP/START recommendations provided were of potential 'adverse significance', of 'no clinical relevance' or of 'possibly low relevance'. The adjudicated clinical relevance of computer-generated medication recommendations significantly affects their implementation. Meticulous software refinement is required for future interventions of this type to increase the proportion of recommendations that are of high clinical relevance. This should facilitate their implementation, resulting in prescribing optimisation and improved clinical outcomes for multimorbid older adults.

Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

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.

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: U1111-1181-9400 Clinicaltrials.gov: NCT02986425, Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183. Netherlands Trial Register: NTR6012 (07-10-2016).

Adverse Drug Reactions in an Oncological Population: Prevalence, Predictability, and Preventability.

BACKGROUND: Our goal was to determine (a) the prevalence of multimorbidity and polypharmacy in patients with cancer and (b) the prevalence, predictability, and preventability of adverse drug reactions (ADRs) causing/contributing to hospitalization. MATERIALS AND METHODS: We conducted a 12-month prospective observational study of patients aged ≥16 years admitted to an oncology center. Older adults were aged ≥70 years. RESULTS: We enrolled 350 patients: 52.3% (n = 183) female, mean age 63.6 years (SD 12.1), 36.6% (n = 121) aged ≥70 years. Multimorbidity (≥2 conditions) was identified in 96.9%; 68% had ≥5 conditions. The median number of medications was 6 (interquartile range [IQR] 4-8); 47% were prescribed ≥6 medications and 11.4% ≥11 medications. Older adults had higher numbers of comorbid conditions (7 [IQR 5-10] vs. 5 [IQR 3-7]) and were prescribed more medications (median 7 [IQR 4-9] vs. 4 [IQR 2-7]). ADRs caused/contributed to hospitalization in 21.5% (n = 75): 35.8% (n = 72) of emergency admissions and 4.7% (n = 3) of elective admissions. The most common ADRs were neutropenia with infection (25.3%), dyspepsia/nausea/vomiting (20%), and constipation (20%). Causative medications included systemic anticancer therapies (SACTs; 53.3%), opioids (17.3%), corticosteroids (6.7%), and nonsteroidal anti-inflammatory drugs (5.3%). ADR prevalence was similar in older and younger adults secondary to SACTs (8.3% vs. 13.1%), non-cancer medications (10.7% vs. 8.3%), and both (0% vs. 1.3%). ADRs were predictable in 89.3% (n = 67), definitely avoidable in 29.3% (n = 22), and possibly avoidable in 33.3% (n = 25). No association was identified between ADRs and age, gender, daily medication number, length of stay, or death. No ADR predictor variables were identified by logistic regression. CONCLUSION: More than 21% of admissions to an oncology service are ADR-related. ADRs are caused by both SACTs and non-cancer-specific medications. The majority are predictable; ≥60% may be preventable. Patients with cancer have high levels of multimorbidity and polypharmacy, which require vigilance for related adverse outcomes. IMPLICATIONS FOR PRACTICE: A diagnosis of cancer often occurs in patients with multimorbidity and polypharmacy. Cancer can cause an altered physiological environment, placing patients at risk of drug-drug interactions, drug-disease interactions, and adverse drug reactions (ADRs). This study identified that ADRs caused or contributed to one in five hospital admissions of patients with cancer. ADRs were caused by systemic anticancer therapies (SACTs) in 53.3% of cases and non-cancer medications in 45.4% of cases, and a combination of both in 1.3%. ADRs occurred in similar frequencies in older and younger patients secondary to SACTs (8.3% vs. 13.1%, p = .295), non-SACTs (10.7% vs. 8.3%, p = .107), and a combination of both (0% vs. 1.3%, p = .240). The majority of ADRs were predictable (89.3%) and potentially preventable (62.6%). These findings support the need for increased awareness of medication-related adversity in patients with cancer and interventions to minimize their occurrence, thus supporting the American Society of Clinical Oncology guidelines that recommend adults ≥65 years of age receiving chemotherapy have geriatric assessment to identify medical and medication issues.

STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with a limited life expectancy) criteria: application to a representative population awaiting long-term nursing care.

PURPOSE: STOPPFrail criteria highlight instances of potentially inappropriate medications (PIMs) in frailer older adults with poor 1-year survival prognosis. The objectives of this study were to (i) determine the proportion of older adults requiring long-term nursing care in whom STOPPFrail criteria are applicable, (ii) measure the prevalence of STOPPFrail PIMs, and (iii) identify risk factors for PIMs in this cohort. METHODS: We retrospectively reviewed applications for long-term nursing care to nursing homes in the Cork area over a 6-month period. We recorded diagnoses, medications, functional status, cognitive ability, frailty status, and applied STOPPFrail criteria as appropriate. RESULTS: We reviewed 464 applications; 38 were excluded due to incomplete information and 274 patients (64.3%) met STOPPFrail eligibility criteria (median age 83 years (IQR 77.25-88); 233 (54.7%) female). Those STOPPFrail eligible were prescribed 2194 medications (mean 8, (SD 4)), of which 828 (37.7%) were PIMs. At least one PIM was identified in 250 eligible patients (91.2%). The median number of PIMs was 3 (IQR 2-4), the most common being (i) medications without clear indication identified in 47.0% (n = 129) of patients, (ii) long-term high-dose proton pump inhibitors in 31.4% (n = 86), and (iii) statins in 29.6% (n = 81). For every additional medication prescribed, the odds of identifying a PIM increased by 58% (odds ratio 1.58, 95% CI 1.32-1.89, p < 0.001). CONCLUSION: Almost 65% of patients awaiting long-term care are eligible for the application of STOPPFrail criteria with over 90% prescribed at least one PIM. Transition to nursing home care represents an opportunity to review therapeutic appropriateness and goals of prescribed medications.

Qualitative analysis of community pharmacists' opinions on their involvement in reducing potentially inappropriate prescribing.

PURPOSE: Older people are at risk of potentially inappropriate prescribing (PIP) due to polypharmacy arising from multi-morbidity. Despite available explicit criteria to reduce PIP, it is highly prevalent. Whilst community pharmacists have the required knowledge to help reduce PIP, they are not currently engaged with the problem. This study explores the views of community pharmacists on their potential involvement in reducing PIP and determines the challenges to its implementation. METHODS: Semi-structured interviews with pharmacists working in community pharmacies in Ireland. The theoretical domains framework (TDF) was used to develop the topic guide and to analyse the transcripts. Domains of highest relevance for PIP reduction were identified based on their frequency or whether the participants emphasised the impact of constructs within a domain. Local ethical approval was obtained. RESULTS: Of 18 participants, 12 were female, median age was 30 years (IQR, 27-35) with a median of 6 years (IQR, 3-8) of experience. Seven TDF domains were identified as relevant to PIP reduction. Pharmacists were uncertain about their role in reducing PIP and reluctant to challenge physicians' prescribing decisions. Challenges pertained to the environment, knowledge, social influences, professional role and identity. CONCLUSIONS: Pharmacists welcomed new responsibilities in reducing PIP as part of their daily practice but expressed a need for removal of social and environmental barriers as well as, provision of relevant guidelines and education about PIP. This study provides useful insights into the target domains for overcoming barriers of pharmacist involvement in reducing PIP.

Deprescribing in multi-morbid older people with polypharmacy: agreement between STOPPFrail explicit criteria and gold standard deprescribing using 100 standardized clinical cases.

PURPOSE: Older people with advanced frailty are among the highest consumers of medications. When life expectancy is limited, some of these medications are likely to be inappropriate. The aim of this study was to compare STOPPFrail, a concise, easy-to-use, deprescribing tool based on explicit criteria, with gold standard, systematic geriatrician-led deprescribing. METHODS: One hundred standardized clinical cases involving 1024 medications were prepared. Clinical cases were based on anonymized hospitalized patients aged ≥ 65 years, with advanced frailty (Clinical Frailty Scale ≥ 6), receiving ≥ 5 regular medications, who were selected from a recent observational study. Level of agreement between deprescribing methods was measured by Cohen's kappa coefficient. Sensitivity and positive predictive value of STOPPFrail-guided deprescribing relative to gold standard deprescribing was also measured. RESULTS: Overall, 524 medications (51.2%) of medications prescribed to this frail, elderly cohort were potentially inappropriate by gold standard criteria. STOPPFrail-guided deprescribing led to the identification of 70.2% of the potentially inappropriate medications. Cohen's kappa was 0.60 (95% confidence interval 0.55-0.65; p < 0.001) indicating moderate agreement between STOPPFrail-guided and gold standard deprescribing. The positive predictive value of STOPPFrail was 89.3% indicating that the great majority of deprescribing decisions aligned with gold standard care. CONCLUSIONS: STOPPFrail removes an important barrier to deprescribing by explicitly highlighting circumstances where commonly used medications can be safely deprescribed in older people with advanced frailty. Our results suggest that in multi-morbid older patients with advanced frailty, the use of STOPPFrail criteria to address inappropriate polypharmacy may be reasonable alternative to specialist medication review.

Detection and prevention of adverse drug reactions in multi-morbid older patients.

Adverse drug reactions (ADRs) are a recognised unintentional form of iatrogenic harm, which commonly occur in older adults who have high levels of multi-morbidity and associated polypharmacy. Previous studies estimate that at least one in 10 hospitalised older patients will experience an ADR. While recent research indicates that this could be as high as 39% in hospitalised multi-morbid, older adults, up to two-thirds of these ADRs can be considered preventable and therefore potentially avoidable. In addition to increasing patient morbidity and contributing to avoidable mortality, there is an associated cost implication with ADR occurrence. This commentary summarises current mainstream research in terms of ADR detection, prediction and prevention in multi-morbid older patients. At present, the biggest barrier to understanding and comparing ADRs in the literature is the large heterogeneity that exists in the population and study methods. Furthermore, there is the lack of standardised universally accepted methodology for ADR prediction, detection, causality assessment and subsequent prevention in older people. Standard available methods of ADR prediction applied to a heterogeneous multi-morbid population are generally unsatisfactory. Without an instrument that consistently and reliably predicts ADR risk in a reproducible manner, ADR prevention in multi-morbid older patients is challenging. Further attention should be focused on the culprit drugs that commonly lead to major ADRs in older multi-morbid hospitalised patients with polypharmacy. Risk associated with particular drug classes may possibly predict ADR occurrence better than patient characteristics alone. Current research is examining this drug class focus for ADR prevention in multi-morbid older people.