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REVIEW ARTICLE
Year : 2022  |  Volume : 49  |  Issue : 2  |  Page : 91-102

Incidence of adverse drug reactions among elderly patients: A systematic review and meta-analysis


1 Department of Pharmacy Practice, Sumandeep Vidyapeeth Deemed to be University, Vadodara, India
2 Department of Pharmacy Practice, Maliba Pharmacy College, Bardoli, Gujarat, India
3 Department of Paediatrics, SBKS Medical Institute and Research Center, Sumandeep Vidyapeeth Deemed to be University, Vadodara, India

Date of Submission24-Mar-2022
Date of Acceptance23-May-2022
Date of Web Publication23-Aug-2022

Correspondence Address:
Rajesh Hadia
Department of Pharmacy Practice, Sumandeep Vidyapeeth Deemed to be University, Vadodara - 391 760, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.jss_50_22

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  Abstract 


Background: Several studies suggest that adverse drug reactions (ADRs) are commonly seen among hospitalized elderly and found common causes of hospital admission leading to substantial morbidity and mortality among elderly. However, no meta-analysis was conducted till date to estimate the overall incidence of ADRs among elderly. Objectives: To estimate the overall incidence of ADRs in elderly patients, incidence of ADRs in elderly in different health-care settings, incidence of serious ADRs in elderly patients, and the continent-wise incidence of ADRs in elderly patients. Design: Meta-analysis and systematic review. Methodology: Studies were identified through searching different databases such as MEDLINE, Cochrane Database of Systematic Reviews, Google Scholar, Clinical Key, and Scopus (published from 1980 to October, 2015) and by hand searching the reputed journals on geriatrics and gerontology and references of the included articles. Original peer-reviewed research articles published in English, defined ADRs according to the WHO's or similar definition and assessed the incidence of ADRs in elderly or having sufficient raw data to determine the incidence were included. Disease- or treatment-specific studies were excluded. Before meta-analysis, the studies were evaluated for heterogeneity using Chi-square and I2 statistics. The overall incidence of ADRs among the elderly with 95% confidence interval (CI) was determined using a random-effects model (DerSimonian and Laird method). Subgroup analyses were performed based on study settings and continent where the studies conducted. All the analyses were carried out using Review Manager (RevMan, version: 5.3) software. Results: Of the 5747 articles retrieved, only 56 and 54 articles were included for systematic review and meta-analysis, respectively. The overall incidence (95% CI) of ADRs among elderly population was 12.94%. The health-care setting-wise overall incidences of ADRs in the elderly were 17.53%, 19.54%, and 6.92% in inpatients, outpatients, and patients hospitalized due to ADRs, respectively. The continent-wise overall incidences of ADRs in elderly were 12.15%, 22.94%, 12.34%, and 18.76% in Asia, Australia, Europe, and USA, respectively. Electrolyte disorders and skin rashes were the common manifestations of the drugs. Cardiovascular drugs and NSAIDs were the most common causative drugs for the ADRs among elderly. Polypharmacy was the major risk factor for ADRs in elderly population, irrespective of the type of health-care settings and continents. Conclusions: The incidence of ADRs in the elderly was higher and is a significant health-care burden in the elderly. Appropriate prescribing, proper compliance, and monitoring for ADRs are needed to decrease the incidence of ADRs in elderly patients.

Keywords: Adverse drug reactions, elderly, systematic review and meta-analysis


How to cite this article:
Hadia R, Joshi D, Bhil D, Maheshwari R. Incidence of adverse drug reactions among elderly patients: A systematic review and meta-analysis. J Sci Soc 2022;49:91-102

How to cite this URL:
Hadia R, Joshi D, Bhil D, Maheshwari R. Incidence of adverse drug reactions among elderly patients: A systematic review and meta-analysis. J Sci Soc [serial online] 2022 [cited 2022 Oct 6];49:91-102. Available from: https://www.jscisociety.com/text.asp?2022/49/2/91/354276




  Introduction Top


At present, elderly people are the most rapidly growing part of the patient population worldwide.[1] According to the World Health Organization (WHO), world's elderly population, i.e., people with 60 years of age and older, is approximately 650 million at present, and by 2050, it is forecast to reach 2 billion.[2] In addition, 70% of all older people now live in low- or middle-income countries,[3] where sustainable pharmacovigilance systems have not developed yet. As per the report jointly brought by the United Nations Population Fund and Help Age International, “India has around 100 million elderly at present and the number is expected to increase to 323 million by 2050.”[4] Individuals aged 80 years or more are the fastest growing section of the population and are expected to reach nearly 30% of the overall population in the richest nations by 2050.[5],[6] It is not surprising that older persons in general have the highest prevalence of chronic and multiple diseases. Although the elderly account for 15% of the population in Western countries, they consume one-third of total volume of prescription medications.[7] However, benefits of medication use are always accompanied by potential harm. Even when medication is prescribed in the recommended doses according to the guidelines, adverse drug reactions (ADRs) can occur.[8] ADRs are regarded as top of the pyramid containing all drug-related problems (DRPs) and are a major public health concern.[9],[10],[11] In the USA, more than 90% of adults aged 65 years and older use one medication per week and 10%–25% experience ADRs. These ADRs are responsible for 3.4%–7.0% of hospital admissions.[12] The average rate of ADR-related hospital admission is 16.6% in the elderly compared to 4.1% in younger patients, with 88% considered preventable.[13] Recently, the Centers for Disease Control and Prevention revealed that older adults (65 years or older) are twice as likely as others to come to emergency departments for adverse drug events (ADEs) (over 177,000 emergency visits each year) and nearly seven times more likely to be hospitalized after an emergency visit.[14] A study conducted in an Indian tertiary care hospital showed ADR incidence of 16.5% in elderly inpatients, while the similar studies conducted in Europe and USA showed incidence of 42.45% and 54.18%, respectively.[15],[16],[17] Similar differences are present in the incidence of ADR in ambulatory care elderly and ADR leads to hospitalization in the elderly among different countries and continents.[18],[19],[20],[21] Considering the severity and clinical importance of ADRs in elderly, it is worthful to know the overall incidence of ADRs in the elderly among different settings and among different continents. By conducting a systematic review and meta-analysis of ADRs in the elderly, a comprehensive result regarding ADRs in elderly population can be obtained. As per our knowledge, there is no systematic review or meta-analysis to find out the overall incidence of ADRs in the elderly. Hence, this study aimed to assess the overall incidence of ADRs among elderly as well as the incidence of ADRs in different health-care setting and different continents by conducting a systematic review and meta-analysis.


  Methodology Top


Search strategy

A comprehensive literature search was carried out using various databases such as MEDLINE, Cochrane Database of Systematic Reviews, Google Scholar, Clinical Key, and Scopus for articles published on ADRs among the elderly from 1980 to August 2016 considering the inclusion of the latest data of ADRs along with the support of previous studies in the past 35 years. The studies conducted before 1980 were excluded as many of the drugs and dosing regimens used during that era are outdated now. Some reputed journals on the elderly and gerontology, references of the included articles, and previous systematic reviews and meta-analyses on ADRs were also reviewed to identify additional relevant articles. The databases were searched for commonly utilized terminology on ADRs among elderly patients in titles, abstracts, and index terms of the articles [Table 1] and [Table 2].
Table 1: Search strategy used in the search of bibliographic databases

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Table 2: Flowchart of results of search strategy

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Selection criteria

The titles and abstracts of all the citations retrieved were screened initially by two investigators to identify their suitability for inclusion. Studies were selected for inclusion after the careful reviewing of full-text articles based on the following inclusion and exclusion criteria. A third investigator participated in the review process when uncertainty about eligibility criteria arose. To avoid inconsistent estimates on the incidence of ADRs, studies that adopted WHO's definition, defining ADR as “a response which is noxious and unintended, and which occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function”,[22] or those studies which adopted Edwards and Aronson's definition[23] were selected. Small changes in wording were overlooked if the two researchers agreed that the functional meaning remained the same. Observational studies (prospective, retrospective, epidemiologic, database survey, registry, cohort, case–control, etc.) conducted on elderly patients to find the incidence of ADRs and studies conducted on general population, but determined the incidence of ADRs in elderly patients, were included. The studies which had sufficient information to calculate the incidence of ADRs in elderly patients, adopted the definition of ADR coincided with definition adopted in this study, and published in English were selected. The studies in which the patients were selected for particular conditions or specific drug exposures were excluded. The studies in which ADRs caused by errors in administration, noncompliance, overdose, drug abuse, and therapeutic failures were not considered. We also excluded the studies that assessed neither incidence nor having enough data available to estimate the incidence, summarizing previous results without original assessment of ADRs, and studies focusing only on specific types of or life-threatening or fatal ADRs. Review articles, letters to editor which were published without original data, editorials, and/or case reports were not considered. Multiple publications of the same study were carefully reviewed and included only the most-relevant studies and the remaining were excluded. In order to maximize the number of articles, paid articles were sourced through all possible access available with institution. Furthermore, in all cases, where there was no source of retrieval of paid articles, corresponding authors were contacted for full-text articles through E-mail communication. After exploring all the possible resources, if full-text was not available, abstract of that particular study was included.

Data extraction

One investigator extracted the data from all the included studies, and the accuracy and completeness of the extraction were confirmed by the second investigator. Any disagreements were noted and resolved by consensus with the third investigator. The extracted data were based on information reported in or calculated from the included articles, and where required, the authors were contacted for additional information. In order to increase the reliability and efficiency of data extraction, Excel sheet was used to extract the data by adopting the checklist for the Strengthening the Reporting of Observational Studies in Epidemiology.[24] When studies have details on more than one setting and more than one continent (e.g., information on ADR incidence for inpatients as well ADRs leading to hospitalization and information on incidence of ADRs in America and Asia), data were extracted separately for each setting and each continent.

Data assessment

The overall incidence of ADRs among the elderly was estimated based on the data available in all studies. Whereas, the incidences of ADRs among the elderly in different settings such as inpatients, outpatients, and EDs and the incidences of ADRs among the elderly in different continents such as Asia, Australia, Europe, and USA were determined based on a prespecified subgroup analysis. Where direct values for considered parameters were not available, values were calculated based on available information. When studies showed large number of causative drugs and/or common manifestations, topmost causative drugs and/or manifestations were extracted for systematic review.

Statistical analysis

The incidence of ADRs among the elderly was determined by dividing the number of elderly patients experienced at least one ADR by the total number of elderly patients included in the study. The incidence was determined only if the study has not provided the value and the raw data were available to calculate the incidence. Standard error (SE) for the reported or calculated incidence was calculated using the following formula.

SEp = sqrt (p [1-p]/n)

(SEp: Standard Error, sqrt: Square root, p: Proportion of successes in the sample, n: Number of observations in the sample).

Heterogeneity among the studies was assessed using the Chi-square and I2 statistics; for the Chi-square statistic, P < 0.10 was considered statistically significant for heterogeneity; for I2, 50% is considered a measure of severe heterogeneity.[25] Meta-analysis was performed to assess the overall incidence of ADRs among the elderly using the random-effects model (DerSimonian and Laird method), which accounts for heterogeneity among the studies. 95% confidence intervals (CIs) for each summary measure were calculated. All analyses were performed using RevMan version 5.3. All statistical tests were two-sided, and P < 0.05 was considered statistically significant, unless otherwise specified. The present study was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [Table 3].
Table 3: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 checklist: Recommended items to include in a systematic review protocol

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  Results Top



  Search results Top


A total of 4947 citations were found from electronic database searches and additional 800 records were identified from search in individual journals and reference lists of the retrieved articles. After removal of 2505 duplicate records, there were 3242 unique citations available for reviewing the titles and abstracts to identify the relevance. A total of 2920 citations were excluded by reviewing the titles and abstracts and it leaves 322 articles to assess the eligibility as per the inclusion and exclusion criteria. After reading full-text articles, 272 articles were excluded for various reasons. Finally, 56 studies were included for systematic review (qualitative synthesis) and 54 studies for meta-analysis (quantitative synthesis). The excluded articles commonly focused on studies on ADEs having insufficient information on ADRs and studies on ADRs in general population only. Many of the studies were excluded as they had information on ADRs on specific diseases which are more prevalent in the elderly and specific drugs which are commonly used by the elderly. Among the included studies, two studies[26],[27] have reported the incidence of ADR in elderly patients, but there was a lack of information on the total number of elderly patients included in the study and/or total number of patients developed ADRs. Thus, for these studies, it was not possible to calculate SE, which is necessary to include the study in forest plot. For this reason, these two studies were not included in the meta-analysis to estimate the overall incidence of ADRs among elderly. However, these two studies were included for systematic review as they matched for inclusion criteria and provided useful information on ADRs in elderly patients. Thus, 56 and 54 studies were considered for systematic review and meta-analysis, respectively. Among all the included studies, a total of 25 studies had details on the incidence of ADRs in elderly inpatients, but in one study,[26] there was not sufficient information on raw data to calculate SE and it was not included for meta-analysis but included for systematic review. Ten studies had information on the incidence of ADRs among elderly outpatients and all these studies were included for both meta-analysis and systematic review. Of the 28 studies on ADRs leading to hospitalization in the elderly, 27 studies were included for meta-analysis. Under continent-wise subgroup analysis, studies were grouped as per continent where the study was conducted. For meta-analysis, 11 studies[15],[21],[28],[29],[30],[31],[32],[33],[34],[35],[36] from Asia, 3 studies[37],[38],[39] from Australia, 24 studies[19],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62] from Europe, and 16 studies[17],[18],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74],[75],[76] from USA were included. Two more studies were included only for systematic review. Among them, one study[26] was on ADRs in elderly inpatients conducted in Asia (China) and another[27] was on ADRs leading to hospitalization in elderly which was conducted in Europe (Netherland) [Table 2].

Study characteristics

Among all the included studies, 21 studies followed WHO definition of ADR, and 2 studies[19],[21] followed Edward and Aronsan's definition of ADR. One study each followed Karch and Lasagna's definition,[34] Kramer's Definition,[49] and Rawlins and Thompson's definition.[61] Other studies have followed definition of ADRs reviewed and approved by the Hospital's Pharmacy and Therapeutics Committee and/or derived from the WHO definition of ADRs. Some of the studies were conducted in more than one setting. Four studies[28],[29],[41],[45] were reviewed for both ADRs in inpatients and ADRs leading to hospitalization in the elderly. In a similar way, one study[15] was reviewed for both ADRs in elderly inpatients and outpatients. Among all the included studies, 46 were specified on ADRs, while the others[30],[32],[33],[35],[36],[37],[38],[42],[58],[63],[65] were specifically focused on ADEs, DRPs, or MEs. Since they have enough information for calculating ADRs in the elderly, they were not excluded from our study-analysis. For the same reason, 15 studies[19],[26],[28],[29],[32],[33],[35],[36],[40],[41],[45],[54],[56],[59],[68] which were focused on general population were included for the systematic review and meta-analysis. Most of the studies included for the analysis were of prospective type (28 studies). The studies were conducted between 1980[62] and 2014.[26] The study periods ranged from 4 days[33] to 27 years.[27] The age group of the elderly considered among the included studies was ≥60 to ≥80 years. The total number of elderly patients among all the studies included for meta-analysis was 5,759,576 and the total number of elderly patients experienced ADRs were 86,730. The characteristics on the included studies, based on the study settings, are presented in [Figure 2],[Figure 3],[Figure 4].
Figure 1: Forest plot for overall incidence of ADRs in elderly patients. ADRs: Adverse drug reactions

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Figure 2: Forest plot for incidence of ADRs in elderly inpatients. ADRs: Adverse drug reactions

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Figure 3: Forest plot for incidence of ADRs in elderly outpatients. ADRs: Adverse drug reactions

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Figure 4: Forest plot for incidence of ADRs leads to hospitalization in elderly patients. ADRs: Adverse drug reactions

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Overall incidence of adverse drug reactions in the elderly

Because heterogeneity (Pheterogeneity < 0.001 and I2 = 100%) was observed, a random-effects model was chosen over a fixed-effects model and it was found that the overall incidence of ADRs in elderly was 12.94% [95% CI: 12.29, 13.60%]. Both incidences with 95% CIs of each study and pooled incidence are shown in [Figure 1].

Subgroup analysis (continent-wise incidence of adverse drug reactions in elderly)

The continent-wise overall incidences of ADR were found to be 12.15% (95% CI: 10.51, 13.80), 22.94% (95% CI: 1.1, 46.98), 12.34% (95% CI: 11.20, 13.48), and 18.76% (95% CI: 16.25, 21.27) in Asia, Australia, Europe, and USA, respectively. In subgroup analysis also, significant heterogeneity was found [Figure 2].

Overall incidence of adverse drug reactions in elderly inpatients

The overall incidence of ADRs in elderly inpatients was found to be 17.53% [95% CI: 16.31, 18.74]. The heterogeneity was found (Pheterogeneity < 0.001 and I2 = 99%) [Figure 3].

Subgroup analysis (continent-wise incidence of adverse drug reactions in elderly inpatients)

The continent-wise overall incidences of ADR in inpatients were found to be 11.42% (95% CI: 10.12, 12.72), 21.40% (95% CI: 15.92, 26.88), and 43.32% (95% CI: 27.52, 59.13) in Asia, Europe, and USA, respectively. In subgroup analysis also, significant heterogeneity was found [Figure 3].

Overall incidence of adverse drug reactions in elderly outpatients

The overall incidence of ADRs in elderly outpatients was found to be 19.54% (95% CI: 14.31, 24.78). The heterogeneity was found.(Pheterogeneity < 0.001 and I2 = 99%) [Figure 4].

Subgroup analysis (continent-wise incidence of adverse drug reactions in elderly outpatients)

The continent-wise overall incidences of ADR in elderly outpatients were found to be 9.05% (95% CI: 6.12, 11.98), 51.18% (95% CI: 45.8, 56.49), 5.72% (95% CI: 4.76, 6.68), and 20.74% (95% CI: 10.15, 31.33) in Asia, Australia, Europe, and USA, respectively. In subgroup analysis also, significant heterogeneity was found [Figure 4].

Overall incidence of adverse drug reactions leading to hospitalization in elderly

The overall incidence of ADRs leading to hospitalization in elderly was found to be 6.92% (95% CI: 5.93, 7.91). The heterogeneity was found (Pheterogeneity < 0.001 and I2 = 99%).

Subgroup analysis (continent-wise incidence of adverse drug reactions leading to hospitalization in elderly)

The overall continent-wise incidences of ADRs leading o hospitalization were found to be 4.6% (95% CI: 0.37, 9.57), 8.72% (95% CI: 0.24, 17.20), 6.94% (95% CI: 5.80, 8.07), and 7.47% (95% CI: 5.10, 9.85) in Asia, Australia, Europe, and USA, respectively. In subgroup analysis also, significant heterogeneity was found.


  Discussion Top


As per our knowledge, till date, there is no meta-analysis to find continent-wise incidence of ADR in elderly. We have explored in our study to obtain the pooled ADR incidence in elderly population in each of the continents. The ADR incidence in elderly, as calculated in each study, could have not been originated from one common population, so from the proportions, as calculated in each individual study, no common estimator should be calculated. The best resolution for this problem is to choose for the weighted average. From all the included studies, arithmetic mean of ADR incidence in elderly was found to be 53.01%, which is almost four times more than the pooled ADR incidence (12.94%) calculated by considering weighted incidence of each study. The studies having larger population have been given more weightage compared to studies having smaller population. The data on ADRs in elderly are found to be heterogeneous. As large number of studies with different countries, population, and study designs are included, heterogeneity is quite expected. In this meta-analysis, we found the highest heterogeneity (Pheterogeneity < 0.001 and I2 = 100%). However, to minimize the effect of heterogeneity on the results, we carried out setting-wise and continent-wise subgroup analysis. The overall incidence of ADRs was found to be 12.94% in our findings, which included reports from elderly inpatients and outpatients as well ADRs leading to hospitalization in the elderly. Effective comparisons of this incidence with data in other studies could not be done since most of the studies report incidence of ADRs in the elderly in either one or two of the above-mentioned categories. Meta-analysis conducted by Miguel et al.[77] indicated that ADRs occur in 16.88% (95% CI: 13.56%–20.21%) of patients (general population) during hospitalization. Our finding shows 17.53% of the ADR incidence in elderly inpatients. This finding shows that the incidence of ADRs in elderly patients is slightly higher than the incidence of ADRs in general population. A systematic review conducted by Kongkaew et al.[78] represented approximately 5.3% of hospital admissions associated with ADRs in general population. Our finding shows 6.92% of hospital admissions associated with ADRs in elderly population. These findings show that the incidence of ADR in elderly patients is slightly higher than the incidence of ADRs in general population. A meta-analysis conducted by Beijer and de Blaey[13] reported the incidence of 16.6% for hospitalization of the elderly due to ADRs, while our finding shows incidence of 6.92% for hospitalization due to ADRs in the elderly. As we have included a greater number of studies with larger population, significant difference in incidence compared to this previous study has been observed as a result of decreased heterogeneity.

In the elderly, 87.9% of hospital admissions were found to be preventable in previous study.[79] In contrast, we could identify preventability with lesser incidence of 36.8% for ADRs leading to hospitalization in the elderly. One meta-analysis[13] conducted on hospitalized children shows the overall incidence of ADRs of 9.53%, which is lesser than the overall incidence of ADRs in the elderly (17.53%) found in our study. This indicates higher incidence of ADR in the elderly compared to pediatrics in hospital setting. In elderly inpatients, the major clinical manifestation found in our systematic-review was skin rash, which is consistent with the most of the studies on ADRs on general and/or elderly inpatients. Moreover, our findings show electrolyte imbalance (mainly hypokalemia) as another major clinical manifestation in elderly inpatients. In our systematic review, NSAIDs, antimicrobials, cardiovascular drugs, antithrombotic, and antidiabetics were the most commonly implicated drug classes, which probably reflects their widespread use in elderly population. Previous meta-analysis[13] identified cardiovascular drugs and NSAIDs as major causative drug classes for hospitalization. In our study, we could able to identify specific drugs, digitalis, digoxin, and aspirin, as major causative agents in these classes. Moreover, from the two studies conducted on elderly outpatients, we could identify heparin and warfarin as major causative agents for ADRs in the elderly in ambulatory setting. By combining the results of five studies from inpatient elderly, we could identify furosemide, insulin, and aspirin as major causative agents for inpatient elderly. Our finding shows polypharmacy as a major risk factor for ADRs in the elderly, which is consistent to the previous study results. One study[80] shows a positive correlation between ≥9 medications and occurrence of ADRs in elderly. Our result (average medications consumed by elderly experienced ADRs, mean: 15.8 and median: 10) is consistent with this finding. Another study[60] conducted on elderly outpatients reported that the elderly who experienced ADRs used more different drugs (14.4 ± 6 drugs) than the other elderly patients (8.14 ± 5.7 drugs). In contrast, in our study, the average number of drugs consumed by the elderly outpatients who experienced ADRs was found to be in the range of 6.45–8.7. Other than polypharmacy, inappropriate medications in the elderly inpatients and more numbers of concurrent diseases in elderly outpatients are identified as major risk factors for ADRs in the elderly. In this manner, the specific risk factors by different settings were not identified by previous studies. One systematic review and meta-analysis[81] on general population shows women at a greater risk for ADRs (68%). Similarly, our systematic review could able to identify female gender as a risk factor for ADRs in the elderly. We observed no positive association between a variety of geriatric conditions and risk of developing an ADR, which is consistent with previous study results.[76] In our systematic review, we observed that one study[45] has reported the details on fatal ADRs in elderly inpatients. Based on the information available, we determined the incidence of fatal ADRs, which was found to be 19.57%. One study[82] conducted on general population shows that 6.4% of the deaths were suspected to be caused by ADRs in the hospital. This difference shows that elderly is more prone to mortality secondary to ADRs compared to general population. In our systematic review, only one study[45] mentioned details of fatal ADRs. The main ADRs and causative drugs were digitalis toxicity, dehydration aggravated by diuretics, hyperkalemia by spironolactone and amiloride, acute renal failure by lisinopril, hemorrhage with an anticoagulant or antiplatelet drug (heparin, acenocoumarol, fluindione, and ticlopidine), cytopenia by cytarabine, cyclophosphamide, and etoposide, and severe hypoglycemia by glipizide. For analyzing and preventing fatal ADRs in the elderly, much more research is needed especially focusing on fatality of ADRs in elderly with details of causative drugs. In our study, the range of hospital stay was found to be 11.1–25 days for elderly hospitalized patients experienced ADRs. One study[83] mentioned average length of stay of 5.5 days in elderly hospitalized patients. This difference clearly shows an increase in length of stay due to ADRs in elderly. In our systematic review, the range of hospital stay was found to be 7.4–25 for elderly hospitalized due to ADR, which is more than a previous finding of 8.7 days by Goettler et al.[84] on general population.

In our study, we identified the range of 48.5%–80.4% for preventable ADRs in elderly, which is more than the incidence (45%) of preventable ADRs in elderly identified by previous meta-analysis.[79] In a systematic review, we identified the range of 22%–36.84% for definitely preventable ADRs and 6%–17.54% for probably preventable ADRs, which is lesser than 71% of preventability found in previous meta-analysis[79] on preventability of ADRs for general outpatients. This finding shows that most of ADRs in elderly outpatients are not preventable. The main contribution of the present study was identification of drugs that are considered to be mainly responsible for ADRs in elderly populations. This finding is useful for continuous education programs, therapeutic committees, and policy makers, because adverse effects complicate the course of diseases in aged patients, cause hospitalization, and/or require the prescription of additional drugs. In addition to contributing to education in health-care costs, continuous efforts to promote rational drug use could also benefit elderly patients by preventing some avoidable drug toxicity. Through this study, we were able to identify the overall, continent-wise, and setting-wise ADR incidence in the elderly. Moreover, systematic review of ADR will help the reader to identify all general characteristics of ADRs in elderly patients. As mentioned earlier, there are very few studies focused on severe and fatal ADRs in the elderly. To prevent morbidities and mortalities secondary to ADRs, more studies focused on severe and fatal ADRs should be conducted.


  Conclusion Top


The overall incidence of ADRs in elderly population is very significant (12.94%). Appropriate prescribing, proper compliance, and monitoring for ADRs are needed to decrease ADRs and their life-threatening outcomes in elderly population. The overall continent-wise incidence of ADRs in elderly inpatients was highest in Australia (22.94%), followed by USA (18.76%) and Europe (12.34%), while the overall incidence was the least in Asian countries (12.15%), yet it is significant. In health-care setting wise, the incidence of ADR is highest in elderly outpatients (19.54%) and polypharmacy was found to be the main risk factor in elderly for developing ADRs. The range of percentage of severe ADRs was found to be 10%–11.11% for elderly experiencing ADRs. For assessment of incidence of serious ADRs, sufficient data on elderly patients experiencing ADRs were not available. Hence, pooled incidence of serious ADR was not obtained.

Moher et al. Systematic Reviews 2015, 4:1. Available on: http://www.systematicreviewsjournal.com/content/4/1/1.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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