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Hospitalisation in older patients due to adverse drug reactions

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Parameswaran Nair, N ORCID: 0000-0002-0202-6453 2018 , 'Hospitalisation in older patients due to adverse drug reactions', PhD thesis, University of Tasmania.

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Abstract

Medication safety at various stages of the patient journey continues to be a significant problem. The increasingly ageing population worldwide, together with the growing use of multiple medications, leads to an increased risk of medication‐related problems. In Australia, the proportion of all hospital admissions that are medication-related is between 2% and 3%. Adverse drug reactions (ADRs) are the most common medication-related problems causing significant morbidity and mortality. Based on data collected from general practitioners’ encounters in 2003 and 2004 in Australia, ADRs represented the most common adverse drug event in the community (72%). Older patients are particularly susceptible to ADRs due to multiple comorbidities, cognitive and functional impairment, a high prevalence of polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics. Of particular concern are ADR-related hospital admissions which are one of the main reasons for hospitalisation in older patients living in the community. More than half of these ADR-related admissions are considered preventable. Even though several methods of ADR identification exist, prospective and intensive monitoring methods using patient interviews usually have the highest ADR detection rate and allow more accurate recording of both drug history and symptoms for assessing the causality of ADRs. A prospective cross-sectional survey in Australia (1998) estimated that 13.3% of elderly admissions to medical wards were ADR-related. A recent meta-analysis found that one in ten hospital admissions in older patients were due to ADRs. Despite the current efforts to identify and prevent ADRs, the burden of ADRs is continuing. A secondary data analysis of case series in Australia (1981-2002) found that hospital admissions due to ADRs in elderly patients had increased despite programs to promote rational and safer use of medicines. In addition to this burden, ADRs that result in hospitalisation in patients with a history of ADR-related hospitalisation, or ‘repeat ADRs’ are also increasingly common and an important contributor to the burden of ADRs. A population-based longitudinal study (1980-2003) in Australia found that repeat ADRrelated hospitalisations had increased faster than first-time ADRs in the elderly since 1980 and were responsible for 30.3% of all ADR-related admissions in 2003.
Hence, strategies to reduce the risk of ADR-related admissions, as well as repeat admissions due to ADRs, are required to reduce the global burden of ADR-related admissions, especially in the elderly. While various strategies including medication review, avoiding use of potentially inappropriate medications, computer-based prescribing systems, and comprehensive geriatric assessment have been suggested, health professionals are not able to easily identify elderly community-dwelling outpatients who are at high risk of being hospitalised due to an ADR. To our knowledge, there are no empirical data that allow stratification of community-dwelling older people according to the likelihood of ADRs leading to hospital admission. A tool that focusses on ADRs as a cause of hospitalisation could potentially be used in primary care and at the point of hospital discharge to prioritise primary care-based medication management services to prevent ADR-related morbidity and mortality in patients at the highest risk of such events. Furthermore, given the scarcity of ADR-related hospital admissions data in the elderly identified using prospective intensive monitoring, and the lack of recent data from Australia, more recent estimates of the burden of ADRs are needed.
The overall objective of the body of work contained in this thesis was to fill these gaps in the literature by developing a practical, efficient and simple method of identifying people 65 years and older who are at high risk of experiencing an ADR leading to hospitalisation. The specific aims were:
1. To investigate the proportion, clinical characteristics, causality, severity, preventability, and outcome of ADR-related admissions in older patients admitted to medical wards of two Tasmanian hospitals.
2. To develop and validate a prediction model for ADR-related hospitalisation in patients aged ≥65 years.
3. To investigate the occurrence of repeat ADR-related admissions in elderly patients within 12 months of a hospital admission to a medical ward due to an ADR.
4. To investigate the utility of a validated ADR score in identifying patients at higher risk of a repeat ADR-related hospitalisation.
5. To compare the rates of ADR-related hospitalisations using different methods of detection.
In order to achieve these aims, we conducted a prospective cross-sectional study in the medical wards of two hospitals in Tasmania, Australia: the Royal Hobart Hospital (RHH) and the Launceston General Hospital (LGH). ADR-related hospital admission was determined by clinical pharmacists through expert consensus from comprehensive reviews of medical records and patient interviews. The causality, preventability, and severity of each ADR-related admission were assessed. We pooled the data from both hospitals, which allowed us to investigate the extent of the problem by determining the proportion of ADR-related admissions in older patients admitted to Tasmanian hospitals, identifying commonly implicated drugs, and describing the clinical manifestations and outcomes of ADRs. Of 1008 admissions from the pooled analysis of the RHH and LGH data, 18.9% of admissions were potentially related to ADRs categorised as ‘definite, probable or possible’; 88.5% of these admissions were preventable. Cardiovascular complaints (29.3%) represented the most common ADRs, followed by neuropsychiatric (20%) and renal and genitourinary disorders (15.2%). The most frequently implicated drug classes were diuretics (23.9%), renin–angiotensin system inhibitors (16.4%), β-blocking agents (7.1%), antidepressants (6.9%), and antithrombotic agents (6.9%). ADR severity was rated moderate and severe in 97.9% and 2.1% of admissions, respectively.
A predictive score named the ‘PADR-EC score’ was developed using the data from the RHH (derivation cohort), and the score was validated using the data from the LGH (validation cohort). In the derivation sample at the RHH, 115 (15%) patients were admitted due to a ‘definite or probable’ ADR; 92.2% of these admissions were deemed preventable. In the validation sample at the LGH, 30 (12.5%) patients’ admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The predictive ability of the score in the derivation sample at the RHH was 0.70 (95% confidence interval (CI), 0.65–0.75) and 0.67 (95% CI 0.56–0.78) in the validation sample at the LGH. The PADR-EC score assigns points to five significant predictors of ADR-related hospitalisation: (i) antihypertensive use (three or five points if 1-2 or ≥3 antihypertensives, respectively), (ii) renal failure (two points), (iii) dementia (two points), (iv) inappropriate anticholinergic use (two points) and (v) drug changes in the preceding three months (two points). These points are summed to produce the final score, with the risk of ADR-related hospitalisation more than three times higher in those with a score ≥6.
After the development and validation of the ADR score, the occurrence of repeat ADR-related admissions was estimated using the data from the RHH participants who had an ADR-related admission and experienced a subsequent admission due to an ADR within 12 months of discharge from their initial index admission. Of the 112 definite or probable ADR-related admissions among the RHH cohort (three patients died during their index admission), repeat ADR-related admissions occurred in 13.4% (n=15). Patients with a repeat ADR-related admission had significantly higher PADR-EC scores at the discharge of their index admission (median PADR-EC score 7, interquartile range (IQR) 2-11) than patients who did not have a repeat admission due to ADRs (median PADREC score 7, IQR 5-7, P=0.034).
Finally, to compare the rates of ADR-related hospitalisations using different methods of detection, we linked the records of patients from the RHH cohort, where clinical pharmacists prospectively identified ADRs, to their hospital administrative data. We then identified patients in the prospective study whose admissions were coded as ADRs using the International Classification of Diseases 10th Revision Australian Modification (ICD-10 AM) codes. We found that only 2.7% of patients were identified as having been admitted due to ADRs using the ICD-10 AM codes compared to the 15% identified by the prospective review.
This body of work has resulted in the development and external validation of a simple and robust approach to identifying community-dwelling elderly patients at risk of hospitalisation due to preventable ADRs. To our knowledge, this approach has never been adopted before in the field of assessing ADR-related admissions in the elderly. Furthermore, our research has identified the extent of the current problem of ADR-related admissions as well as ADR-related repeat admissions in the elderly Tasmanian population. Our study found that almost one in five unplanned overnight hospital admissions to medical wards in elderly Australian patients were related to ADRs. Additionally, our study showed that one in eight elderly patients hospitalised due to an ADR had a repeat admission for ADR within 12 months of discharge. These findings update the existing information on the rate of ADR-related admissions and repeat admissions in the elderly. More detailed prospective review of admissions gave a clearer understanding of the true number of ADRs for directing appropriate medication management services towards addressing the problem. We suggest that the PADR-EC score has the potential to assist healthcare practitioners at the point of discharge and in primary care to identify those elderly patients for whom intervention may reduce the risk of ADRs and subsequent hospitalisation. Future studies are required to investigate the utility of the PADR-EC score in these settings and thereafter the effectiveness of interventions, such as deprescribing, in reducing the risk of ADR-related admissions in elderly populations.

Item Type: Thesis - PhD
Authors/Creators:Parameswaran Nair, N
Keywords: adverse drug reactions, hospital admission, prediction, elderly
Copyright Information:

Copyright 2017 the author

Additional Information:

Chapter 2 appears to be the equivalent of a post-print version of an article published as: Parameswaran Nair, N., Chalmers, L., Peterson, G. M., Bereznicki, B. J., Castelino, R. L., Bereznicki, L. R., 2016. Hospitalization in older patients due to adverse drug reactions – the need for a prediction tool, Clinical interventions in aging, 11, 497-505. © 2016 Parameswaran Nair et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/)

Chapter 3 appears to be the equivalent of a post-peer-review, pre-copyedit version of an article published in Drug safety. The final authenticated version is available online at: https://doi.org/10.1007/s40264-017-0528-z

Chapter 4 appears to be the equivalent of a post-print version of an article published as: Parameswaran Nair, N., Chalmers, L., Connolly, M., Bereznicki, B. J., Peterson, G. M., Curtain, C., Castelino, R. L., Bereznicki, L. R., 2016. Prediction of hospitalization due to adverse drug reactions in elderly community-dwelling patients (the PADR-EC score). PLoS One 11(10), e0165757. Copyright: © 2016 Parameswaran Nair et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Chapter 5 appears to be the equivalent of a pre-print version of an article published as: Parameswaran Nair, N., Chalmers, L., Bereznicki, B. J., Curtain, C. M., Bereznicki, L. R., 2017. Repeat adverse drug reaction-related hospital admissions in elderly Australians: a retrospective study at the Royal Hobart Hospital, Drugs and aging, 34(10), 777–783

Chapter 6 appears to be the equivalent of the pre-peer reviewed version of the following article: Parameswaran Nair, N., Chalmers, L., Peterson, G. M., Bereznicki, B. J., Curtain, C. M., Bereznicki, L. R., 2018. Prospective identification versus administrative coding of adverse drug reaction‐related hospitalizations in the elderly: A comparative analysis, Pharmacoepidemiology and drug safety, (27(11), 1281-1285, which has been published in final form at https://doi.org/10.1002/pds.4667. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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