Inappropriate prescribing among ambulatory elderly patients in a geriatric centre in Southwestern Nigeria CURRENT

Background: Inappropriate medication prescribing is a common, major global health concern among the elderly. There are no guidelines to detect potentially inappropriate prescribing in Nigeria among the elderly. Therefore, this study compared the appropriateness of Beers' and Screening Tool of Older Person’s Prescription (STOPP)/ Screening Tool to Alert Right Treatment (START) criteria to identify potentially inappropriate prescribing in ambulatory elderly patients in Nigeria. Methods: A retrospective study at the geriatric centre, University College Hospital, Ibadan was conducted using systematically selected case files of 335 elderly patients aged ≥ 60 years between 1st January and 31st December 2016. With the aid of a data extraction sheet, information on the socio-demographic characteristics, drug utilisation pattern and morbidities were obtained from the most recent prescription in the case files. The 2015 American Geriatrics Society (AGS)-Beers Criteria, and version 2 of the STOPP and START were subsequently used to identify the Potentially Inappropriate Prescribing (PIP) and Potential Prescribing Omissions (PPOs). Associations between polypharmacy (≥ 5 medications) and multimorbidity (presence of 2 or more diseases), and AGS Beers and STOPP/START criteria were determined with Chi-square test at p <0.05. Results: Mean age of patients was 69 ± 0.4 years (range 60-85 years) and 219 (65.4%) were females. An average of 4.2 medications per patient prescription was found. The Beers criteria identified 26.5% PIMs, while STOPP criteria identified 57.1% PIMs. START detected 29 PPOs in 15 (4.4%) of the patient’s prescription. The most prevalent disease conditions were hypertension 235 (70.1%) and osteoarthritis 64 (19.3%). Polypharmacy was significantly associated with PIMs use in both Beers (p=0.002) and STOPP (p=0.001) criteria. Conclusions: The prevalence of PIP is high among the elderly patients. The STOPP/START criteria identified a higher proportion of PIMs among elderly patients compared with Beers criteria. The frequency of PIP should stimulate efforts to curtail potentially inappropriate prescribing and may require the need for advocating for a national criteria to be adopted by health care professionals in Nigeria.

developing countries [1]. According to United Nation projection, the elderly population aged from 60 years and above in Nigeria is expected to increase to approximately 26 million from the 6.98 million by 2050 [2], and in Africa, from the 68.7 million to 228.5 million by 2050 [3]. Nigeria is at the lead of this growing age bracket, with approximately 7.0% of Nigerians in the elderly age group in 2014 [4].
The elderly usually has multiple disease conditions, the management of which frequently leads to polypharmacy. The consequences of polypharmacy are poor health outcomes and hospitalization due to adverse drug reactions [5][6][7]. Similarly, polypharmacy is also known to lead to the use of potentially inappropriate medications (PIMs) [8,9]. These are medications with greater risk of intolerance related to adverse pharmacodynamics, pharmacokinetics or drug-disease interactions when used in the elderly [10].
Potentially inappropriate medications are consequences of inappropriate prescribing among the elderly. Inappropriate prescribing is a prominent challenge in the management of multiple diseases in the elderly owing to its direct correlation with morbidity, mortality and utilization of health funds globally. To address this problem, the American Geriatrics Society Beers criteria (AGS/Beers) [10,11] and the Screening Tool of Older Persons' Prescription (STOPP)/Screening Tool to Alert Right Treatment (START) [12,13] were developed. These tools/criteria are commonly used by physicians to target risk management strategies of potential inappropriate prescribing (PIP) among the elderly. The AGS/Beers criteria was originally developed about two decades ago, with the most updated version 2019 AGS/Beers published after experts reviewed the 2015 AGS/Beers criteria based on most recent available evidence [14]. These criteria include three classification of PIMs; namely potentially inappropriate medication use in older adults, potentially inappropriate medication use in older adults due to drug-disease or drug-syndrome interactions that may exacerbate the disease or syndrome and potentially inappropriate medications: drugs to be used with caution in older adults [14]. Likewise, STOPP criteria, invented and validated in European countries is also used to detect PIMs but based on the physiological systems, considering drug-disease and drug-drug interactions, dose and duration of treatments [12,13]. Several studies employing the use of both criteria have reported the presence of PIMs among elderly patients in Europe 42.1-75.4% [15] , in Qatar 38.2% [16] , in Brazil 29.9-39.6% [17] in Saudi Arabia 37.5%-57.6% [18] and in Nigeria 15.7-45.6% [19][20][21].
In Nigeria, there are few studies that have investigated PIP or the use of potential inappropriate medications among the elderly. These studies revealed PIP as a common occurrence among them [19][20][21][22]. However, some of these studies utilized Beers criteria alone [20][21][22], while some other compared Beers criteria with STOPP [19]. None of the studies so far conducted in Nigeria utilized both the AGS/Beers' and STOPP/START criteria. Thus, since there is no criteria outlining the use of medication appropriately or inappropriately among the elderly in the country, this study evaluated the prevalence of PIP and PIMs in the elderly using both the STOPP/START and AGS/Beers criteria with a view to advocating for a criteria that can be adapted for the country.  Inclusion and exclusion criteria: Case files of patients aged 60 years and above who attended the CTAGC, University College Hospital, Ibadan between 1st January 2016 and 31st December 2016 were retrieved and used in the study. Sixty years and above was the age adopted by the United Nations and the CTAGC as the definition of older persons. This is also supported by the short life expectancy in Nigeria which is 55/56 years (male/female) ratio according to the United Nations [3]. Case files of patients aged 60 years from other centres in the University College Hospital who did not attend the primary centre for the elderly were excluded from the study. Also, case files of patients without prescriptions, those with incomplete information such as age, sex, morbidity, and laboratory results were excluded from the study.

Data analysis
Data were sorted, coded and entered into Statistical Package for Social Sciences statistical software version 21.0 (SPSS, IBM Corporation, Armonk, NY, USA) for cleaning and analysis. Descriptive statistics were used to summarise the data. Continuous variables were presented as mean ± standard deviation (SD), while categorical variables were presented as frequency and percentages. Chi-square statistics was used to determine the association between polypharmacy (≥ 5 medications) and multimorbidity (presence of 2 or more diseases), and PIMs based on updated AGS/Beers 2015 and STOPP/START criteria. Where the rule of Chi-square test was violated in the analysis, Fisher Exact test p-values were reported for a 2 x 2 contingency table. The value of significance was set at p < 0.05.

Results
Three hundred and thirty-five case files were reviewed, with more females 219 (65.4%) than male.
The mean age of the patients was 69 ± 0.4 years (range 60-85 years). The mean number of medications per patient was 4.2 ± 1.4 (range 1-10) medications. Polypharmacy described as the use of 5 or more medications per patients was found in 147 (43.8%) patients and multi-morbidity was found in 296 (88.4%) of the studied patients. Hypertension 235 (70.1%) was the most prevalent disease state found in the elderly followed by osteoarthritis 64 (19.3%) and diabetes 19 (5.8%). Table   1. describes the demographic and clinical characteristics of the study population. and STOPP 124 (41.7%) than patients without multimorbidity. However, there was no significant association between multimorbidity and the two criteria. Polypharmacy was statistically significantly associated with PIMs in both the Beers p = 0.002 and STOPP criteria p=0.001. See Table 2.
The START criteria identified 29 PPOs, equivalent to 7.6 % of medications examined. These PPOs happened in 15 (4.4%) of the patients. More than half of the patients (57.4 %) had one PPO. The most common potential prescribing omissions were detected in the gastrointestinal tract system medications 13 (45%), associated with the lack of laxative use with continuous opioid use. Omissions in the musculoskeletal system medications were also common 10 (35.0 %), and was associated with the lack of bisphosphonates, calcium and vitamin D use. The third most common prescribing omission derived from the cardiovascular system, with lack of statin therapy use. See Table 5.  a Chi-square test, b Fisher Exact test, *P <0.05 was considered significant    [20,21,26]. NSAIDs when used for a long duration without gastroprotective agents, or as first line treatment for the management of pain and in the presence of underlying comorbidities such as congestive heart failure, chronic kidney disease and peptic ulcer in the elderly are classified as PIM [11]. Topical NSAIDs, and patches as alternative to oral have been recommended, however they are more expensive and there is presently no documented report to support its effectiveness in managing musculoskeletal pains such as osteoarthritis in the elderly. This probably has restricted physicians in countries with limited resources like Nigeria to the use of effective medicine for pain among elderly patients, thus the high use of oral NSAIDs in this study.
One of the top PIMs identified by STOPP in this study was in the cardiovascular system medications, Strength and weakness One of the drawbacks of this report was that the study was carried out in a single and only geriatric centre in Nigeria. This might affect the generalizability of the findings to elderly patients across Nigeria. In addition, this study did not apply other categories of the 2015 AGS/BEERS criteria, and this was primarily due to the design of the study, being a retrospective study and all the required information were not documented in the prescription and physician notes available. The version 2 STOPP/START criteria was validated for patients aged 65 years and above and our study used patients aged 60 years and above, this was due to the study design which compared the appropriateness of Beers' and STOPP/START criteria, Beers criteria was validated in > 60years and our study centre defines elderly as 60years. However, this study's strength involves the use of both Beers and STOPP/START criteria to identify the frequency of PIMs. These results will offer the literature valuable evidence considering potential inappropriate medications use among the elderly in this environment.
The potential prescribing omissions listed in the START criteria could be an invaluable resource in the improvement of elderly patient care. Consequently, the findings in this study shows the need of advocacy to adopt an existing criteria which will further assist in the reduction of potential inappropriate prescribing. However, the AGS/Beers and STOPP/START criteria limitations remains, these tools were developed for the USA and Europe, and adapting it for a resource limited nation like Nigeria may under-or over-estimate the findings because of the lower number and range of medications available in the country. It is also possible that some of the medications documented on the criteria may not have similar antagonistic effects on diverse population.

Conclusion
Potential inappropriate prescribing prevalence in this study was relatively high, irrespective of the tool used. The STOPP/START criteria identified a higher proportion of PIP compared with Beers criteria among elderly patients. The frequency of PIP should stimulate efforts to curtail potentially inappropriate prescribing and may require the need for advocating for a national criterion to be adopted by health care professionals in Nigeria. · Competing interests: The authors declare that they have no competing interests" in this section.

AGS -American Geriatrics
· Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sector · Acknowledgement: Not Applicable · Authors' contributions WAS had the original idea, developed study protocol, drafted manuscript, contributed in the data collection and data analysis. LAA developed study protocol, contributed in the data collection and data analysis. SS developed study protocol, contributed in the data collection and data analysis. OCA