Adverse drug reactions and targets for deprescribing in high risk older adults

Over the last twenty years, many prescribing tools have been developed and validated to identify inappropriate prescribing (IP) in older adults and assist physicians in medication optimisation. However, these prescribing tools have predominantly focused on identifying IP in the general older adult population, rather than targeting the population cohort that is growing at the fastest rate and that is at the highest risk of IP and adverse drug reactions (ADRs) i.e. older frailer multimorbid patients with a poor survival prognosis. Extensive research on the prevalence of ADRs has been published. However many different definitions of ADRs and many different ADR causality tools have been employed across different studies, making it difficult to compare the results of studies. To confound this area of investigation further, many ADR causality tools are not appropriate to use in older frail multimorbid adults. In addition, a limited amount of research has occurred identifying the morbidity associated with ADRs in older adults. To date, there is no standardized approach to identifying, assessing and reporting ADRs in older adults. This doctoral thesis was designed to (i) standardise the identification, assessment and reporting of ADRs in older adults, (ii) assess ADRs using this new methodology in high risk populations, and (iii) develop and validate a new usable set of criteria called STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy) to assist deprescribing in older frail multimorbid adults with a poor survival prognosis i.e. patients where the role of preventative therapy is questionable. This thesis comprises eleven chapters. The first chapter is an introduction, divided into four sections i.e. (i) demographic changes and the proportional increase in high risk older adults, (ii) prescribing considerations for older adults, (iii) consequences of IP including ADRs and (iv) potential targets for intervention. The second chapter proposes a methodologically robust way of identifying, assigning causality and reporting ADRs and tests this theory on physicians, pharmacists, biomedical scientists and nurses. The third chapter uses this new ADR methodology to identify the prevalence of ADRs in older adults presenting to hospital. The fourth chapter compares older and younger adults with cancer in terms of multimorbidity, medication use and ADRs using the same methodology proposed in Chapter 2. The fifth chapter develops and validates STOPPFrail criteria, an explicit prescribing tool to assist deprescribing in frail older adults with a poor one year survival prognosis. The sixth chapter describes the inter-rater reliability (IRR) of STOPPFrail criteria between physicians. The seventh chapter, applies STOPPFrail criteria to two representative populations i.e. a proportion of older adults deemed suitable for nursing home care and a proportion of older adults presenting for hospitalisation. Chapter eight considers the relevance of the research data developed in this thesis as well as questions any issues arising from these research studies. Chapter nine contains peer-reviewed articles that were published and awards received during the writing of this thesis. Finally, chapters ten and eleven list the references and appendices, respectively

Methods to reduce prescribing errors in elderly patients with multimorbidity

The global population of multimorbid older people is growing steadily. Multimorbidity is the principal cause of complex polypharmacy, which in turn is the prime risk factor for inappropriate prescribing and adverse drug reactions and events. Those who prescribe for older frailer multimorbid people are particularly prone to committing prescribing errors of various kinds. The causes of prescribing errors in this patient population are multifaceted and complex, including prescribers’ lack of knowledge of aging physiology, geriatric medicine, and geriatric pharmacotherapy, overprescribing that frequently leads to major polypharmacy, inappropriate prescribing, and inappropriate drug omission. This review examines the various ways of minimizing prescribing errors in multimorbid older people. The role of education in physician prescribers and clinical pharmacists, the use of implicit and explicit prescribing criteria designed to improve medication appropriateness in older people, and the application of information and communication-technology systems to minimize errors are discussed in detail. Although evidence to support any single intervention to prevent prescribing errors in multimorbid elderly people is inconclusive or lacking, published data support focused prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool of older people’s prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing, electronic prescribing, and close liaison between clinical pharmacists and physicians in relation to structured medication review and reconciliation. Carrying out a structured medication review aimed at optimizing pharmacotherapy in this vulnerable patient population presents a major challenge. Another challenge is to design, build, validate, and test by clinical trials suitably versatile and efficient software engines that can reliably and swiftly perform complex medication reviews in older multimorbid people. The European Union-funded SENATOR and OPERAM clinical trials commencing in 2016 will examine the impact of customized software engines in reducing medication-related morbidity, avoidable excess cost, and rehospitalization in older multimorbid people

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol

Background: The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients' current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. Methods: We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants' medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant's clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial's primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/- 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy

Advance care planning within survivorship care plans for older cancer survivors: a systematic review

Advances in the medical treatment of cancer have increased the number of survivors, particularly among older adults, who now represent the majority of these. Survivorship care plans (SCPs) are documents that cancer patients receive summarising their care, usually at the end of treatment but preferably from initial diagnosis. These may increase patient satisfaction and represent an opportunity to initiate preventative strategies and address future care needs. Advance care planning (ACP), incorporating advance healthcare decision-making, including formal written directives, increases satisfaction and end-of-life care. This paper systematically reviews evaluations of ACP within SCPs among older (≥65 years) cancer survivors. No studies meeting the inclusion criteria were identified by search strategies conducted in PubMed/MEDLINE and the Cochrane databases. One paper examined cancer survivors’ mainly positive views of ACP. Another discussed the use of a SCP supported by a ‘distress inventory’ that included an advance care directive (living will) as an issue, though no formal evaluation was reported. Although ACP is important for older adults, no study was found that evaluated its role within survivorship care planning. Despite the risk of recurrence and the potential for morbidity and mortality, especially among older cancer survivors, ACP is not yet a feature of SCPs

Deprescribing practices, habits and attitudes of geriatricians and geriatricians-in-training across Europe: a large web-based survey

Purpose To provide an overview of the current deprescribing attitudes, practices, and approaches of geriatricians and geriatricians-in-training across Europe. Methods An online survey was disseminated among European geriatricians and geriatricians-in-training. The survey comprised Likert scale and multiple-choice questions on deprescribing approaches and practices, deprescribing education and knowledge, and facilitators/barriers of deprescribing. Responses to the survey questions and participant characteristics were quantified and differences evaluated between geriatricians and geriatricians-in-training and between European regions. Results The 964 respondents (median age 42 years old; 64% female; 21% geriatricians-in-training) were generally willing to deprescribe (98%) and felt confident about deprescribing (85%). Despite differences across European regions, the most commonly reported reasons for deprescribing were functional impairment and occurrence of adverse drug reactions. The most important barriers for deprescribing were patients' unwillingness, fear of negative consequences, lack of time, and poor communication between multiple prescribers. Perceived risk of adverse drug reactions was highest for psychotropic drugs, nonsteroidal anti-inflammatory drugs, cardiovascular drugs, and opioid analgesics. Only one in four respondents (23% of geriatricians and 37% of geriatricians-in-training) think education in medical school had sufficiently prepared them for deprescribing in clinical practice. They reported that their future deprescribing activities would probably increase with improved information sharing between various prescribers, deprescribing recommendations in guidelines, and increased education and training. Approximately 90% think that a paradigm shift is required for prescribers and patients, increasing focus on the possible benefits of deprescribing (potentially) inappropriate medications. Conclusions Based on the outcomes of this survey, we recommend investing in improved inter-professional communication, better education and evidence-based recommendations to improve future patient-centered deprescribing practices

Deprescribing practices, habits and attitudes of geriatricians and geriatricians-in-training across Europe : a large web-based survey

Abstract: Purpose To provide an overview of the current deprescribing attitudes, practices, and approaches of geriatricians and geriatricians-in-training across Europe. Methods: An online survey was disseminated among European geriatricians and geriatricians-in-training. The survey comprised Likert scale and multiple-choice questions on deprescribing approaches and practices, deprescribing education and knowledge, and facilitators/barriers of deprescribing. Responses to the survey questions and participant characteristics were quantified and differences evaluated between geriatricians and geriatricians-in-training and between European regions. Results: The 964 respondents (median age 42 years old; 64% female; 21% geriatricians-in-training) were generally willing to deprescribe (98%) and felt confident about deprescribing (85%). Despite differences across European regions, the most commonly reported reasons for deprescribing were functional impairment and occurrence of adverse drug reactions. The most important barriers for deprescribing were patients’ unwillingness, fear of negative consequences, lack of time, and poor communication between multiple prescribers. Perceived risk of adverse drug reactions was highest for psychotropic drugs, nonsteroidal anti-inflammatory drugs, cardiovascular drugs, and opioid analgesics. Only one in four respondents (23% of geriatricians and 37% of geriatricians-in-training) think education in medical school had sufficiently prepared them for deprescribing in clinical practice. They reported that their future deprescribing activities would probably increase with improved information sharing between various prescribers, deprescribing recommendations in guidelines, and increased education and training. Approximately 90% think that a paradigm shift is required for prescribers and patients, increasing focus on the possible benefits of deprescribing (potentially) inappropriate medications. Conclusions: Based on the outcomes of this survey, we recommend investing in improved inter-professional communication, better education and evidence-based recommendations to improve future patient-centered deprescribing practices