Identifying Unintentional Medication Discrepancies at Admission among Elderly Inpatients in Vietnam

Background Elderly patients are at high risk of unintentional medication discrepancies during transition care as they are more likely to have multiple comorbidities and chronic diseases that require multiple medications. The main objective of the study was to measure the occurrence and identify risk factors for unintentional medication discrepancies in elderly inpatients during hospital admission. Methods A prospective observational study was conducted from July to December 2018 in a 800-bed geriatric hospital in Hanoi, North Vietnam. Patients over 60 years of age, admitted to one of selected internal medicine wards, taking at least one chronic medication before admission, and staying at least 48 hours were eligible for enrolment. Medication discrepancies of chronic medications before and after admission of each participant were identied by a pharmacist using a step-by-step protocol for the medication reconciliation process. The identied discrepancies were then classied as intentional or unintentional by an assessment group comprised of a pharmacist and a physician. A logistic regression model was used to identify risk factors of medication discrepancies. Results Among 192 enrolled patients, 328 medication discrepancies were identied; of which 87 (26.5%) were unintentional. 32.3% of patients had at least one unintentional medication discrepancy. The most common unintentional medication discrepancy was omission of drugs (75.9% of 87 medication discrepancies). The logistic regression analysis revealed a positive association between the number of discrepancies at admission and the type of treatment wards. Conclusions Medication discrepancies are common at admission among Vietnamese elderly inpatients. This study conrms the importance of obtaining a comprehensive medication history at hospital admission and supports implementing a medication reconciliation program to reduce the negative impact of medication discrepancy, especially for the elderly population.


Impact Of Findings On Practice
This is the rst study that assessed the occurrence of unintentional medication discrepancies and the associated risk factors in elderly patients at hospital admission in Vietnam.
A step-by-step protocol for the medication reconciliation process was developed according to the World Health Organization's High 5s programm to identify medication discrepancy in the study population.
The study supports the importance of implementing standard operating procedures to attain a complete preadmission medication history for patients as well as implementing a medication reconciliation program in Vietnam Background Medication discrepancies are de ned as the variations in drug regimens (1) and can occur during the transition between healthcare facilities, including on admission, transfer, and discharge (2). The discrepancies (e.g. medication omission, addition of a new medication, change in medication dose, or change in the route of administration), especially those that are unintentional, can often lead to preventable medication errors and potentially be harmful to patients (3,4). In practice, medication errors due to unintended discrepancies have been reported to occur in up to 50-70% of patients during transitions in care (5).
The majority of these medication discrepancies can be intercepted through medication reconciliation at all transitions in care (2). Many organizations have demonstrated that implementing medication reconciliation at all interface of care is an effective and necessary strategy for identifying medication discrepancies and thus ensuring patient safety (2) (6, 7). According to the World Health Organization (WHO), "medication reconciliation is the formal process in which health care professionals partner with patients to ensure accurate and complete medication information transfer at interfaces of care" (2). The Institute for Healthcare Improvement (IHI) de nes medication reconciliation as the process of creating the most accurate list possible of all medications a patient is taking and comparing that list against the physician's order at all transition of care (6). The medication reconciliation service has proven to be successful in identifying most discrepancies, preventing harm to patients and associating with signi cant nancial saving (4), (8), (9,10). Currently, medication reconciliation has become a standard healthcare practice recommended by the WHO (11) and many countries (7,(12)(13)(14).
Among the population groups, elderly patients have a high risk of medication discrepancies, with a reported prevalence of 49.5% to 81.9% during transitions in care (15)(16)(17)(18)(19). Elderly patients are at high risk of medication discrepancies for several reasons. Firstly, they are more likely to have multiple comorbidities and chronic diseases. The prevalence of chronic disease in elderly patients was shown to range from 55% to 98% according to a systematic review (20). With multiple comorbidities, these patients are likely to be prescribed more medications, thereby increasing the risk of inappropriate prescribing (21), drug-drug interactions, drug-disease interactions, adverse drug events (22), and medication errors (23). Elderly patients can also suffer from psychological (e.g. anxiety, depression, and dementia) and physiological factors (e.g. impaired hearing and vision function) that may impair their ability to communicate effectively with medical and healthcare staff, which may further contribute to medication discrepancies in this population. Elderly patients are, therefore, more vulnerable to medication discrepancies and should be a target population for medication reconciliation.
In Vietnam, obtaining the medication history from patients is the responsibility of doctors, nurses, and clinical pharmacists during ward rounds. However, the concept of medication reconciliation is still very new and has not been mentioned in any government documents or specialized professional practice standard guidelines. As such, there is no standard operating procedure for medication reconciliation in Vietnam. This is further attested by a literature search performed by our research team, showing no studies on this topic had been performed in Vietnam to date. Hence, the extent and clinical impact of unintentional medication discrepancies remain unknown as a potential clinical problem in Vietnam. Without this information, it is di cult to request the healthcare administrators to allocate appropriate resources to rectify this problem.

Aims of the study
The main objective of the present study was to assess the occurrence of unintentional medication discrepancies and identify the associated risk factors in elderly patients at hospital admission in Vietnam. The results are expected to support the importance of obtaining a comprehensive medication history at hospital admission and implementing a medication reconciliation program to reduce the negative impact of medication discrepancy, especially for the elderly population. This would also provide evidence to persuade the healthcare administrators in Vietnam to allocate additional resources to rectify this problem.

Ethics approval
This study was granted ethics approvals by The Hospital Science and Technology Committee at Friendship Hospital, Vietnam

Study setting and patient recruitment
This prospective observational study was conducted at Friendship Hospital, a 800-bed public geriatric hospital in Hanoi, which has 23 clinical units in total with 22,700 admissions in 2018. Patients over 60 years of age, admitted to 7 selected internal medicine units of the hospital, taking at least one chronic medication before admission, and staying at least 48 hours were eligible for enrolment. The selected internal medicine units were endocrine and metabolism, orthopedics, cardiovascular, respiratory, gastroenterology, psychiatry and neurology, and general internal medicine (coded from 01 to 07 respectively). Patients were excluded if they were unable to give consent due to their clinical conditions or refused to participate in the study. The patient recruitment process took place over 14 nonconsecutive weeks from July 2018 to December 2018, with two weeks of recruitment for each unit. During this period, all patients who met the selection criteria and gave informed consent were included in the study.

Data collection
For each enrolled participant, the following information was collected: age, gender, comorbidity, current admission diagnosis, treatment unit, outpatient management status (i.e. whether the patient was managed as an outpatient by the study hospital), and the available sources for patients' medication information (e.g. electronic medical records, paper-based outpatient medical records, and paper-based inpatient medical records). The patients' medication history and the current treatment during the hospital admission were collected as part of the medication reconciliation process described below.

Process of identifying medication discrepancies
At the time of the study, there was no standard operating procedure (SOP) available for healthcare staff to obtain the medication history from patients and to reconcile the information with the admission medication prescriptions. The physician or nurse would normally collect the information regarding patients' preadmission medications during medical examination and record this in the patients' paperbased medical record without a SOP to perform any reconciliation for discrepancy. To identify any medication discrepancies at admission, the research group conducted a process of medication reconciliation independent of but did not interfere with the normal practice of other healthcare professional staffs in delivering care to the patients.
Using the information from the WHO High 5s programme, a step-by-step protocol for the medication reconciliation process was developed and training was provided for a group of study data collectors. Overall, the process of medication reconciliation for each participant consisted of the following key steps.
Step 1: Obtain the Best Possible Medication History (BPMH) list for patients: The BPMH form suggested by the WHO High 5s programme was employed to obtain preadmission medication information of patients (2). The BPMH was obtained from multiple available sources, including patient interviews, computer-based medical record systems, and paper-based medical records. Patient interviews were conducted at the patients' bedside, using a structured form to guide the interview and record the data (Supplementary le 1. Interview guide).
Step 2: Identify medication discrepancies in chronic medications: The list of admission medication prescriptions (i.e., the rst 24 hours after admission of patients to the hospital) was collected from paper-based medical records for each patient. The list was then compared to the BPMH obtained by a study researcher as described above. Any differences between the chronic medications on the BPMH and admission medication prescription list was considered a medication discrepancy.
To examine the extent of the medication discrepancy resolution by physicians during the patients' hospital stay, the medication discrepancy was also assessed at 48 hours after admission and at the time of discharge using the same approach described above. After this time, each medication discrepancy was discussed with the physician to determine if it was intentional or unintentional. To ensure the accuracy of the process of medication discrepancy determination, several potential reasons such as diagnosis of a new clinical condition, occurrence of adverse drug events, or a speci c medication was unavailable in the Department of Pharmacy at the hospital, were considered. Medication discrepancies that were accepted by the physician as being unreasonable were classi ed as unintentional medication discrepancies. Each unintentional medication discrepancy was then classi ed by drug class (according to the Anatomical Therapeutic Chemical Classi cation System -ATC) (24) and type of unintentional medication discrepancy (including omission of medication, change of medication, extra medication, or difference in dose or dosing frequency).

Data analysis
The collected data were analyzed by using the Statistical Package for Social Sciences (SPSS), version 20.0 (IBM statistics, Armonk, NY, United States). Percent and frequency were used to describe medication discrepancy. Chi squared (χ2) test was conducted to identify potential relationships between medication discrepancy and explanatory variables. In addition, the Backward Stepwise (Wald) method was employed to identify appropriate multivariate logistic regression models and risk factors associated with unintentional medication discrepancies. The regression analysis results were expressed as odds ratio with 95% con dence intervals. The in uence of factors was considered to be statistically signi cant at p<0.05.

Results
Demographics and baseline characteristics of the participants During the study period, a total of 395 patients was admitted to the study units. Of these, 203 patients were excluded from the study -14 were admitted for less than 48 hours, 127 were not taking any chronic medications or had no chronic disease, 30 refused to participate in the study, and 32 were unable to give consent. There was a total of 192 patients eligible to be included in the study (Figure 1).
The demographics and baseline characteristics of these 192 patients are shown in Table 1. The average age of the study participants was relatively high (75.6 ± 7.0 years) and 77.1% were males. Polypharmacy (at least 5 medications) before admission was seen in almost half of the patients (44.8%). The most common chronic diseases in the study participants were hypertension (86.5%), hyperlipidemia (61.5%), type 2 diabetes (45.3%), chronic coronary syndrome (37.0%), and osteoarthritis (25.5%). The average number of co-morbidities was 5.1 ± 1.8.

Medication discrepancies
Among the 192 patients recruited, there were 328 chronic medication discrepancies identi ed between the BPMH list and the 24-hour medication prescription (intentional and unintentional), with a mean ± SD of 1.7 ± 1.4 discrepancies per patient. All of the identi ed discrepancies had no documented reason in either the paper-based medical records or electronic medical records of patients. After discussion with the managing physicians, 87 discrepancies were classi ed as unintentional in 32.3% of patients (n=62). The frequency of medication discrepancies among the study population is presented in Table 2. Note: * Mean ± Standard Deviation; MD = medication discrepancy; UMD = unintentional medication discrepancy Among the types of unintentional medication discrepancies, medication omission accounted for the highest proportion (75.9%), followed by medication change (21.8%) ( Table 3). Dose change was the least likely reason for the unintentional medication discrepancies identi ed (2.3%). After the rst 48 hours of admission, the number of unintentional medication discrepancies remained high (90.8%) and persisted until the time of discharge (77%) ( Table 3).

Risk factors associated with unintentional medication discrepancies
The occurrence of unintentional medication discrepancies was signi cantly higher among patients admitted to the orthopedics, respiratory, and gastroenterology units compared to those admitted to the endocrine and metabolism unit (odds ratios of 10.03, 5.44 and 6.98, respectively; p<0.05). In addition, the risk of medication discrepancy signi cantly increased among patients using a least 5 chronic medications (polypharmacy) before admission compared to patients taking only 1 or 2 chronic medications at preadmission (odds ratio 4.65, p < 0.05) ( Table 5).

Discussion
To the best of our knowledge, this is the rst study to examine the occurrence of medication discrepancies among inpatients in Vietnam. Our study focused on elderly patients, as they are a particularly vulnerable population to medication discrepancies and other drug-related problems (e.g., inappropriate indication, dose, or adverse effects). The results showed an average of 1.7 (SD 1.4) medication discrepancies per patient at the time of admission and 32.3% of the study participants had at least one unintentional medication discrepancy regarding their chronic medications.
To interpret the results meaningfully, we compared our ndings with similar studies conducted in other countries (from 2010 onwards). As shown in Table 6 (25) selected patients with at least 3 or 5 preadmission medications, whereas our study only required at least one preadmission medication. This may explain the lower rate of unintentional medication discrepancy in our current study when compared to those published studies. Furthermore, we only classi ed medication discrepancies as 'unintentional' after clari cation and approval from the managing physicians, this could have reduced the proportion of unintentional medication discrepancies identi ed. Despite this, our study still found a relatively high prevalence of unintentional medication discrepancies, thus suggesting the need of improvement in the current practice of obtaining the medication history from patients and reconciliating this with the medications prescribed at hospital admission in Vietnam. This study also found the number of unintentional medication discrepancies remained very high at 48 hours after admission (90.8%) and even persisted until the patient was discharged (77.0%). If these discrepancies were not identi ed and effectively communicated to the patient or the patient's general practitioner following hospital discharge, the unresolved medication discrepancies (e.g., omission of a vital medication) may continue inde nitely and can lead to adverse consequences for the patient.
The most frequent type of unintentional medication discrepancy identi ed was medication omissions (75.9%), followed by medication change (21.8%). Similarly, previous studies had also reported medication omission as the most common type of discrepancy (15,16,27,28). Potential reasons for the unintentional omission of medications among patients at hospital admission or discharge include incomplete information regarding the patients' preadmission medication lists, issues surrounding the anamnesis of patients during interviews, and the complexity of patients' medication regimens. These ndings suggest the need of strategies to identify and improve barriers in the transition of care pathways to ensure continuity and integration of care for the patient. Clinical pharmacists would be an invaluable resource to contribute in this area.
In term of medication class, unintentional medication discrepancy was identi ed mostly for cardiovascular drugs (e.g. lipid-modifying agents, antihypertensive agents, and antithrombotic agents), followed by blood glucose lowering drugs. Other medication reconciliation studies had also identi ed cardiovascular drugs as being one of the most frequent drug classes associated with medication discrepancies (15,16,25). Other frequently reported medication classes include drugs affecting the blood and hematopoietic system (16, 27), the nervous system (15), (16), and the gastrointestinal system (15), (27). This may suggest that some medication classes require special attention when implementing medication reconciliation procedures.
Associations between the number of unintentional medication discrepancies and the type of internal medicine unit as well as the number of medications at admission were found in the present study. The unintentional medication discrepancies were 10.03, 5.44 and 6.98 times more likely to occur among patients admitted to the orthopedics, respiratory, and gastroenterology units, respectively, compared to patients admitted to the endocrine and metabolism unit. Similar variations in the prevalence of unintentional medication discrepancy among hospital wards were also reported by other studies (27,29). These variations may be due to the lack of a standard operating procedure for medication reconciliation in the different units of the study hospital. The different charactersitics of patients admitted to these units and the different specialties of the physicians in these units may also contribute. In resource-limited settings such as Vietnamese hospitals, this information could help the hospital administrators to strategically assign resources.
Furthermore, the likelihood of medication discrepancy was also signi cantly increased among patients taking at least 5 chronic medications prior to hospital admission compared to patients taking 1 or 2 preadmission chronic medications. This nding was again consistent with other studies regarding the risk factors of unintentional medication discrepancies (15,29). These ndings suggest that medication reconciliation by clinical pharmacists can be prioritized to elderly inpatients with polypharmacy at hospital admission if resources are limited.
There are a few limitations that should be considered when interpreting the ndings of the present study. Firstly, the results may not represent the current practice of the whole country, as the study was only conducted at a single hospital in Vietnam. However, as mentioned above, the concept of 'medication reconciliation' is still very new in Vietnam and has not been mentioned in any o cial documents or specialized professional practice standards. Hence, there is a lack of standard operating procedures in Vietnamese hospitals for this practice. In addition, the study hospital is one of the biggest geriatric hospitals in Vietnam with large number of elderly patients admitted each year. Therefore, the current results are likely to be applicable to other Vietnamese hospitals. The second limitation is that the review of the medications prescribed was limited to only chronic medical conditions, which may have led to an underestimation of the prevalence of unintentional medication discrepancies. Lastly, the potential clinical impact of the unintentional medication discrepancies identi ed was not evaluated in the study due to a lack of appropriate assessment instrument. In fact, other studies have resorted to using a physician and a pharmacist to judge the clinical signi cance of the unintentional medication discrepancies (26, 27). Therefore, future studies about the clinical impact of unintentional medication discrepancies should be conducted in Vietnamese hospital settings to assess the severity of the problems. The cost-bene t analysis for the implementation of medication reconciliation services should also be explored to justify the resource allocation that is required.

Conclusion
This study found similar rate of medication discrepancies among elderly patients admitted to hospital in Vietnam compared to the results reported in other jurisdictions. The most frequent type of unintentional medication discrepancy was medication omission, which commonly occurred for drugs of the cardiovascular system. Another important observation from our study was that unintentional medication discrepancy persisted throughout the patients' hospital stay until discharge. Overall, our results support implementing a medication reconciliation program with o cially endorsed standard operating procedures to attain a complete preadmission medication history for patients in Vietnam. Consent to participate All participants have provided written consents to participate Consent to publication Not applicable Availability of data and material All data generated and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests The authors declare that they have no competing interests
Funding This research received no speci c grant from any funding agency in the public, commercial or not-for-pro t sectors.