Identifying Tools that Assess Factors that may lead to Adverse Effects in Australian Aged-Care Facilities: A Scoping Review

: Aim: this scoping review was designed to identify studies that assess the adverse drug reactions (ADRs) for older people in Australian aged-care facilities. This review critically evaluated each published study to identify the risk of, or actual adverse drug events in older people. Inclusion criteria: This review considered any clinical studies that examined the adverse effects of medications in older people who were living in aged-care facilities. This review considered qualitative studies, analytical studies, RCTs, descriptive cross-sectional studies, and analytic observational studies that explored the use of medications and their adverse effects on older people in clinical settings (including aged care facilities). Methods : An initial search of the PubMed, OvidSP, EBSCOHost, MEDLINE, ScienceDirect, Wiley Online, SAGE, and SCOPUS databases, with full text was performed, followed by an analysis of the article’s title and abstract. Additionally, MeSH was used to describe the article. The initial round of the database search was based on inclusion criteria from studies that assessed tools or protocols aiming to identify the adverse effects of medications on the elderly population suffering chronic conditions or multiple co-morbidities. Two reviewers screened the retrieved papers for inclusion. The data presented in this review are in tabular forms and a narrative summary which aligns with the review’s objectives. Results: Seven studies were identified, and the extracted data from these studies were grouped according their characteristics and the auditing results of each study. Conclusion : There was no comprehensive or broadly adverse drug reaction assessment tool derived from Australian data that has been used on the elderly in an Australian healthcare setting.

medication in aged-care facilities. However, they are often specific to certain medical conditions and do not provide a comprehensive assessment of the medication's side effects [1]. Adverse drug reactions (ADRs) defined as an unwanted harmful reaction, resulted from an intervention related to the use of one or more medicinal products. The ADRs usually require warrant prevention, specific treatment, the alteration of a dosage regimen, or drug(s) discontinuation [3]. One of the major causes of ADRs is arising from inappropriate prescribing cascades, whereby a new medication is given to manage the adverse effect of that inappropriate drug(s), thus exposing the patient to continuing risks of ADRs from culprit drugs and newly prescribed drug [3]. In some cases, the adverse reactions (ADR) symptoms may be incorrectly interpreted as a primary diagnosis rather than as side effects of the medications [3]. This added complication in distinguishing between drug-induced symptoms and definitive medical conditions, which may result in additional medications being prescribed [3].
A scoping review was selected over a systematic review because the concepts of a scoping review is ideal to determine the depth and breadth of a body of literature on a given topic, such as the adverse effect of drugs in older people; it also gives a clear indication of the volume of the literature and studies that are available on this topic and provides more detail to the focus. A scoping review is a useful approach to examine each piece of evidence in detail and concerns more specific questions and gives more illustration about the inclusion and exclusion criteria. A scoping review is applicable in our topic to identify: (1) the types of available evidence about the effects of medications on older people; (2) to clarify key concepts and definitions in the published papers; (3) to examine how the research or study was done or conducted on our topic; (4) to identify the characteristics of each included study; (5) and to identify and analyse the gap needing to be covered in clinical practice.
This scoping review searched the current academic literature for ADR assessment in Australian agedcare facilities to identify studies that were summarized, and a critical evaluation was undertaken for each study. We completed and updated our search of the database literature from March 2017 to February 2020, with MeSH terms updated to reflect narrower subheadings that were added since and O (medication management in nursing homes or hospitals) was used to frame the data extraction.
In addition to PICO, the following study selection criteria were formulated: RCTs (randomized controlled trials) and only fully-length articles were considered for inclusion in this review. Two reviewers (HS and YG) independently selected titles and abstracts and the corresponding full text • What evaluation outcomes measures have been reported for the tools in primary care settings?
• Does the tool or protocol minimise the adverse effects of medications without compromising the benefits of medications?
• Do the tools improve patient's clinical outcomes by identifying inappropriate medication prescribed or medication errors?
• Do the tools or protocols support multi-disciplinary interventions through optimising dayto-day patient care?

Inclusion criteria:
The selected studies were based on the following: • The study was intended for patients aged 65 years or older • The study included older patients who were experienced adverse effects of medications • The study included older patients suffering from the adverse effects of polypharmacy and living in aged care facilities or admitted in hospitals • The study investigated tools that were/are currently being used in Australia.

Exclusion criteria (Round one):
Studies will be excluded if one or more of the following determined: • No data on the adverse effects • Indeterminate as to whether the measure has been accepted in practice

Methods
We designed and conducted our systematic scoping review by following guidelines published by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRIMSA) [17].

Search strategy
The titles, abstracts, methods, results, discussion and finding for all published papers were screened by two reviewers against the agreed upon inclusion criteria. Disagreements between reviewers were resolved by further discussion of the reason for exclusion and a consensus was approached [14]. The search strategy and subsequent selection criteria of the identified published papers are displayed in

Types of participants:
This review considered studies for the identification of the adverse effects that medications have had on older people in the primary care settings of Australia (regardless of whether the study is designed in Australia or overseas). Only studies that had their abstract in English were selected. There was no limitation in considering the date of acceptance for publication.

Concept
This review explored and identified the characteristics of each study and critically measures their effectiveness on a patient's health and wellbeing. Data from each study include: the number of participants in each study, drugs identified as contributing to major ADRs, rates of primary outcomes, drugs most frequently associated with outcomes, the most frequent body system affected by ADRs, acceptable low rates of loss to follow-up, binding outcome, and potential bias.

Context
In this systematic review, no limit will be set for the study setting or time frame. All studies, including the selected studies are conducted in clinical settings (hospitals and nursing facilities). Appendix II is the summary of the selected studies.

Information sources:
Our source of information was based on electronic databases. These databases are obtained through PubMed, PMC, OvidSP, EBSCOHost, MEDLINE, ScienceDirect, Wiley Online, SAGE, and SCOPUS.
Moreover, the searching strategy by Medical Subject Headings (MeSH) terms in popular and commonly used keywords and phrases was also through PubMed. ScienceDirect and OvidSP searched for literature and dissertations, and abstracts were reached through SCOPUS.

Study selection:
The studies were identified through electronic databases and manual searches. A full set of the selected studies were exported from the databases into the reference manager software, EndNote X8 (Clarivate Analytics, PA, USA). Duplications were removed. Before formal screening and finalising the selection processes, a calibration exercise for the identified studies was performed by two reviewers (HQ and YG) independently. The purpose of this review was to refine the screening questions and to ensure consistency across reviewers for screening and to select eligible studies according to the inclusion criteria. Every article passed through a two-step process by two reviewers working independently: Step 1: the two reviewers (HQ and YG) screened all the titles and abstracts and they selected those that were relevant. Each reviewer independently assessed the article against from. The study selection process was determined and presented in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram format.

Extraction and data presentation
The data extracted from the included studies was based on the guides of the systematic review questions. The extracted data had tabulated according to the author's name, location, number of patients, number of drugs, rate of primary outcomes, drugs most frequently associated with outcomes, validation, most frequent body system affected by the adverse effects of medications, whether the selection was biased or not, acceptable low rate of loss to follow-up, and blinding outcome. Furthermore, the extracted data was audited and critically appraised by comparing data regarding their use in clinical practice, which health profession it was used by, if the study had been evaluated or not, which condition(s) were not used and why, and to determine if there are any limitations in practice. A summary table illustrating the audited and critically appraised data in Appendix IV.

Results
The database searches yielded a total of 337 citations after duplicates were removed. The titles and abstracts for these 337 articles were screened by the first author, and 239 article titles and abstracts were excluded in round one due to having the following issues: the studies with no data on adverse effects (42 articles), the studies included paediatrics (24 articles), the duplicated studies (45 articles), the studies with single medications only (51 articles), the studies included younger than 65 years old (28 articles), primary objective was not adverse effects of medication (31 articles), studies were not in English (7 articles), the studies focuses on experimental medicines (9 articles), and the studies were within the stages of phase III of clinical trials (2 articles). The remaining 98 articles were considered for further detailed assessment of the full paper in round two, and 91 were excluded due to having the following issues: the model designs were not well described (52 articles), the methodologies were ambiguous (19 articles), the design and measures were not fully detailed (2 articles), and whether the measure has been accepted in practice (18 articles). The search yielded a total of seven citations for inclusion in this review.

Outcome measured
The seven studies that reported on the rate of adverse effects from prescribed medications in older people are summarised in Appendix III. They identified which medications were involved in causing major adverse effects and worsened patient's health conditions. However, none of these measures were able to predict the risk or rate of adverse drug effects to prevent health deterioration in older people.
Nishtala and colleagues [13] conducted a drug burden index (DBI) study in 62 aged-care facilities in New South Wales (NSW). DBI measures the effect of cumulative exposure to both anticholinergic and sedative medications on cognitive and physical functions in older adults [15]. DBI scores in older people were calculated, and the impact of medication review on the DBI score after the uptake of . This tool has been designed to identify the barriers to medication adherence due to the side effects of medications. This tool asks the following "Do your medications give you side effects that make you NOT want to take it". If so, further assessment of why the medications have side effects and the changed doses or changing medication(s) will start from that point. This tool uses Likert scales for the responses (4-point scales of frequency) from 1 representing 'never' to 4 representing 'often'. A pre and post-interview design was established with a total of 172 participants. Based on their response, they were categorised into three adherence subdivisions: intentional non-adherence (INA), partial non-adherence (PNA), and adherers.
Participants within INA and PNA groups were assigned to the intervention groups, while the adherer participants were assigned to the control group [11]. M-DRAW could provide recommendations to clinicians by giving them a systematic approach to overcome each identified barrier to adherence, especially non-adherence due to ADR [11]. The criteria were based on the following: prescriptions may introduce the patient to clinically significant risks of adverse effects, equally effective or more effective alternatives with less risk are available, and any clinical intervention that is reasonable enough to change the existing prescription to decrease morbidity [12]. The final list contained 71 inappropriate prescriptions for older people.
Each item includes a clinical situation and each situation contains recommendations for alternative therapy and/or further investigations [12].

Discussion
The current scoping review included a total of seven studies that met the inclusion criteria, so they Basger's criteria has been designed due to the deficiencies of the older Beers criteria in order to better suit the Australian health care system [9]. It is similar to Beers criteria, but it is a list of indicators based on, and derived from, Australian data sources rather than US sources [9]. The medications expressed in the collected sources have greater potential relevance in the Australian healthcare setting [9]. Additionally, it is developed from an analysis of the most commonly dispensed PBS medications and the most common conditions for which the elderly receive medical care [9].
For the Harrison study outcome, further studies would be suggested to examine whether deprescribing of medications included in the drug burden index (DBI) or Beers criteria may improve quality of life outcomes for these individuals, as well as to improve other consequences associated with reduced exposure to these medications, such as reduced hospitalisation and mortality [7].
The M-DRAW tool is acceptable and reliable to identify barriers to medication adherence and the causes behind non-adherence [11]. However, the validity of this tool is still uncertain, and further study needs to be done with a larger sample size and follow-up with patients [11].
The McLeod tool includes substantial information about the severity of the adverse effect of medications and ranking of the clinical importance of the medication risks [12]. The suggestions of alternative therapeutic options were based on the concept of more effective and less risky therapy [12]. This tool will help establish specific evidence-based guidelines for geriatric pharmacotherapy.
Therefore, it would be advisable to revise the McLeod list of medications regularly, such as by further validation or validation in the Australian setting [12].
Further studies are needed to establish the efficacy of the FRID tools and to rationalize or simplify medication regimens for elderly patients who are prescribed medications associated with orthostatic Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 29 February 2020 doi:10.20944/preprints202002.0451.v1 hypotension and psychotropics [8]. Further research will be required to determine whether deprescribing fall risk-inducing medications will effectively reduce the risk of falls in older people [8].
The findings by Nishtala's study reinforce the importance of careful clinical assessment and management of older people who are at risk of increased anticholinergic burdens due to the use multiple neuropsychotropic drugs [13].
Generally, the idea of designing ADR assessment tools is essential at all stages of the medication management pathway. The designed tool needs to be derived from validated Australian data and be applicable to the Australian health care system. The designed tool needs to adopt the concept of multidisciplinary corporation, a structured approach to identify potential risks related to the risk of adverse effects of medicines and help to develop a framework for improvement strategies, and it can be a reliable resource to assist in reducing medication errors, overuse, and potential risky adverse effects. Thus, it may help clinicians to make the most appropriate clinical decisions for their patients.

Conclusions
To the best of our knowledge, numerous studies were done in Australia and overseas to assess the side effects of medication in older people. However, they are often specific to certain medical conditions and do not provide a comprehensive assessment of the medication's adverse effects. This is of concern, given the increasing prevalence of age-related chronic diseases and associated disability, as well as the increasing number of Australians living in aged-care facilities, leading to an increase in age-related disabilities and chronicity. Adverse medication-related incidents, unplanned medication related admission to hospital and inappropriate prescribing patterns are commonly observed in Australian elderly people [16]. Moreover, these studies do not provide guidelines for alternative therapeutic options, nor do they provide recommendations that avoid interactions and ADRs.
Therefore, it would be beneficial if Australian clinician researchers designed a predictive tool that integrates the information reported in this review to minimize the risks of ADRs.

Appendix I: Search strategies
Our initial search was syntax for MeSH terms in PubMed as the following:

Full-texts articles excluded (total) N = 91
Model designs of study didn't well described